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• v.155(1); 2022 Jan

Safety & effectiveness of COVID-19 vaccines: A narrative review

Francesco chirico.

1 Department of Public Health, Post-graduate School of Occupational Medicine, Catholic University of the Sacred Heart, Rome, Italy

Jaime A. Teixeira da Silva

2 Independent Researcher, Kagawa-Ken, Japan

Panagiotis Tsigaris

3 Department of Economics, Thompson Rivers University, Kamloops, British Columbia, Canada

Khan Sharun

4 Division of Surgery, ICAR-Indian Veterinary Research Institute, Bareilly, Uttar Pradesh, India

There are currently eight vaccines against SARS-CoV-2 that have received Emergency Use Authorization by the WHO that can offer some protection to the world’s population during the COVID-19 pandemic. Though research is being published all over the world, public health officials, policymakers and governments are collecting evidence-based information to establish the public health policies. Unfortunately, continued international travel, violations of lockdowns and social distancing, the lack of mask use, the emergence of mutant strains of the virus and lower adherence by a sector of the global population that remains sceptical of the protection offered by vaccines, or about any risks associated with vaccines, hamper these efforts. Here we examine the literature on the efficacy, effectiveness and safety of COVID-19 vaccines, with an emphasis on select categories of individuals and against new SARS-CoV-2 strains. The literature shows that these eight vaccines are highly effective in protecting the population from severe disease and death, but there are some issues concerning safety and adverse effects. Further, booster shots and variant-specific vaccines would also be required.

The World Health Organization (WHO) list of Emergency Use Authorization (EUA)-qualified COVID-19 vaccines (as on 20 December, 2021) contains eight vaccines, namely the three adenoviral-vectored vaccines ChAdOx1 nCoV-19 (University of Oxford/AstraZeneca), Ad26.CoV2.S (Janssen), Covishield, CrAdOxI, nCoV-19 (Serum Institute of India), two whole-inactivated coronavirus, which are the Covilo/BBIBP-CorV (SinoPharm/Beijing Institute of Biological Products), CoronaVac (Sinovac) and Covaxin, BBV152 (Bharat Biotech), and the messenger RNA (mRNA) vaccines mRNA-1273 (Moderna) and BNT162b2 (Pfizer-BioNTech) 1 . mRNA vaccines work by injecting mRNA that encodes the SARS-CoV-2 spike protein directly into the host and have several advantages over conventional vaccine types, including improved safety, low potential for mutations, lower risk of antigen degradation in vivo and the potential for rapid mass production at a lower cost 2 , although there are still challenges remaining regarding their pharmacological stability 3 .

Another mRNA vaccine, CureVac, was developed in the European Union (EU) by CureVac N.V. and the Coalition for Epidemic Preparedness Innovations, with the hope of being cheaper and lasting longer than other mRNA vaccines, but results on June 16, 2021 from a 40,000-person phase III two-dose trial found it 47 per cent effective at preventing the disease, which was lower than the ≥50 per cent requirement for approval by the WHO 4 . Other vaccines produced by Janssen, AstraZeneca, Sputnik-V and CanSino, use human and primate adenovirus vectors 5 . The vaccines manufactured by Novavax and GSK/Sanofi companies consist of purified pre-fusion stabilized SARS-CoV-2 spike protein, which is given in combination with an adjuvant to boost the immune response 6 . On June 1, 2021, the WHO validated the use of the Chinese Sinovac - CoronaVac COVID-19 vaccine for emergency use, although with interim policy recommendations 7 . CoronaVac is an inactivated vaccine with easy storage requirements 8 . It was only 51 per cent effective at preventing COVID-19 in late-stage trials 9 . The vaccine’s safety, immunogenicity and efficacy need to be tested across the three phases of clinical trials, although ‘protection against severe disease and death is difficult to assess only in phase 3 clinical trials’ 10 .

Vaccination against COVID-19 started in India on January 16, 2021 11 . The Indian government and States launched an extensive vaccination campaign against COVID-19, targeting 300 million beneficiaries of priority groups such as healthcare and frontline workers and individuals older than 50 12 . India’s drug regulator (Central Drugs and Standards Committee - CDSCO) approved restricted emergency use of Covishield and Covaxin in India. Covishield (AstraZeneca vaccine ChAdOx1/AZD1222), approved for EUA by the WHO, is a two-dose version of the Oxford/AstraZeneca vaccine manufactured by the Serum Institute of India 13 , while Covaxin (BBV152 vaccine) is an inactivated-virus vaccine 11 , 14 . Phase I (safety and immunogenicity) and phase II trial (immune response and safety) data of Covaxin are published 15 . A phase 3 study confirmed the clinical efficacy of BBV152 against symptomatic COVID-19 disease and safety monitoring and assessment did not raise concerns about the vaccine 16 .

In April 2021, the Indian Government approved Sputnik V as a third vaccine 12 . Sputnik V (Gam-COVID-Vac), which is a dual vector-based vaccine that combines type 26 and rAd5 recombinant adenovirus (rAd), exhibited 91.6 per cent efficacy against COVID-19 17 . Sinopharm’s BBIBP-CorV (Covilo) showed 79 per cent efficacy against symptomatic SARS-CoV-2 infection and hospitalization in a large multi-country phase III trial after administering two doses 21 days apart, but efficacy could not be determined in people aged 60+ and with comorbidities, and there was an underrepresentation of women 18 .

In October 2021, India crossed the one billion vaccine doses milestone and by January 16, 2022, 70 per cent adult population was fully vaccinated 19 .

Efficacy/effectiveness of current COVID-19 vaccines

A systematic review on the efficacy of vaccines covering studies from January 1 to May 14, 2021 identified 30 studies, showed 80-90 per cent vaccine efficacy against symptomatic and asymptomatic infections in fully vaccinated people in nearly all studies 20 . In clinical trials, three vaccines had higher (>90%) efficacy against COVID-19 infection [Pfizer-BioNTech (~95%), Moderna (~94%) and Sputnik V (~92%)] than the vaccines by Oxford-AstraZeneca (~70%) and Janssen (54-72%), against moderate and severe forms of COVID-19 infection 10 . The mRNA vaccines showed high efficacy against infection and a very high level of protection against severe disease, hospitalization and death while the risk of severe forms of COVID-19 infection and deaths was reduced by Moderna, Sputnik V, Janssen and Oxford-AstraZeneca vaccines. In contrast, this information was not available in the published trials for the Pfizer-BioNTech vaccine 20 , 21 . Compared to the Pfizer vaccine, the Moderna vaccine can be kept at higher temperatures, making it easier to transport and store 22 . Other vaccines produced by other companies, and with positive efficacy results, received EUA status in some countries 23 . The longitudinal assessment of vaccine participants is a necessary critical assessment because it provides information on whether vaccination can achieve long-lasting immunity 24 .

Although most evidence suggests that ‘immune responses elicited by SARS-CoV-2 infection are present and might protect against’ reinfection, but the experience with seasonal coronaviruses and the present experience with SARS-CoV-2 suggest that immunity to natural infection might wane over time, as reinfection cases occur 25 . For this reason, an extra booster dose can continue to offer protection 26 .

Regarding the interchangeability of COVID-19 vaccines, the WHO recommends using the same COVID-19 vaccine for both doses of a two-dose schedule 27 , but there is scientific evidence of the effectiveness of heterologous vaccination with AstraZeneca or Covishield as the first dose and an mRNA vaccine as the second dose 28 , 29 , 30 .

Safety and adverse effects of current COVID-19 vaccines

As shown in Table I , current vaccines have demonstrated considerable efficacy in diminishing mild, moderate and severe cases with a low risk of adverse events 21 . For some of these vaccines [such as Convidicea (AD5-nCoV), Janssen (Ad26.COV2.S), Sinopharm (BBIBP-CorV), Covaxin (BBV152) and Sinovac (CoronaVac)], there is the information available on their immunogenicity and safety from phase I and II vaccine recipients, but evidence of their effectiveness is not clear 21 . Due to urgency, health regulatory agencies such as the EMA in the EU and the Food and Drug Administration (FDA) in the US evaluated only short-term adverse effects before their authorization. Records of adverse events in trial results on the BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech vaccine) continued up to six months from the second dose 39 . Mild-to-moderate local responses such as discomfort, redness or inflammation at the injection site were the most commonly reported adverse effects in the clinical trials, while systemic events included fatigue, headache, body aches and fever 39 . There were four serious issues among BNT162b2 participants in a clinical trial: shoulder injury from vaccine administration, right axillary lymphadenopathy, paroxysmal ventricular arrhythmia and right leg paresthesia 39 . Another adverse reaction in the Pfizer-BioNTech trial was lymphadenopathy with 64 vaccine recipients (0.3%) versus only six in the placebo group (<0.1%) 39 . The clinical trial on the mRNA-1273 COVID-19 vaccine, manufactured by ModernaTX Inc., reported no serious adverse events, while moderate or mild adverse events included headache, fatigue, myalgia, chills and injection-site discomfort, but these were dose-dependent and more common after the second immunization 40 .

Type, regime, efficacy, safety, protection against variants and storage of COVID-19 vaccines listed by the World Health Organization: Findings from clinical trials and preliminary studies

Information gathered above from various sources can be also validated from: https://www.mckinsey.com /industries/pharmaceuticals-and-medical-products/our-insights/on-pins-and-needles-will-COVID-19-vaccines-save-the-world and https://www.statista.com /chart/23510/estimated-effectiveness-of-COVID-19-vaccine-candidates /. Cost per dose obtained from: https://www.statista.com /chart/23658/reported-cost-per-dose-of-COVID-19-vaccines/ and https://observer.com /2020/08/COVID19-vaccine- price-comparison-moderna-pfizer-novavax-johnson-astrazeneca /. All vaccines report mild-to-moderate local reactions ( e.g. , pain, redness, or swelling at the injection) and a few systemic events ( e.g ., fatigue, headache, body aches, and fever), For information on protection against variants see: https://www.businessinsider.in /science/news/one-chart-shows-how-well-covid-19-vaccines-work-against-the-3-most-worrisome-coronavirus-variants/articleshow/81472174.cms , WHO. Background document on the Bharat Biotech BBV152 Covaxin vaccine against COVID-19. Released on November 3, 2021. Available from: https://extranet.who.int /iris/restricted/bitstream/handle/10665/347044/WHO-2019-nCoV-vaccines-SAGE-recommendation-BBV152-background-2021.1-eng.pdf?sequence=1&isAllowed=y ; For the cost of Covaxin: https://www.dnaindia.com /india/report-bharat-biotech-announces-price-of-Covaxin-rs-600-for-states-rs-1200-for-private-hospitals-2887737.

Myocarditis and pericarditis were reported in individuals receiving mRNA vaccines (Pfizer-BioNTech BNT162b2 and Moderna SpikeVax), especially in young males after the second dose, so the US Centres for Disease Control and Prevention (CDC) and FDA developed educational material for vaccine recipients and providers that described the possibility of myocarditis and its symptoms to be able to recognize and manage it 41 . There are insufficient data to describe the efficacy, safety and effectiveness of the BNT162b2 in children under 16 and the SpikeVax vaccine in individuals under 18 42 . Although the balance of benefits and risks varied by age and gender, but the benefits of preventing the COVID-19 disease and associated hospitalizations, intensive care unit admissions and deaths outweighed the risks such as expected myocarditis cases after vaccination in all populations for which vaccination was recommended 41 . There are currently no alternatives to mRNA COVID-19 vaccines for youths, so on May 10, 2021, the FDA expanded the EUA of the Pfizer-BioNTech COVID-19 vaccine to include adolescents 12 through 15 yr of age 41 .

Anaphylaxis has been the only life-threatening condition reported during the vaccination campaign with the Pfizer-BioNTech vaccine, so it has to be appropriately managed and prevented 43 . Hypersensitivity-related adverse events for Pfizer-BioNTech and Moderna trial participants relative to the placebo groups were 0.12 and 0.4 per cent higher, respectively 39 , 40 . In addition, the Pfizer-BioNTech trial reported one ‘drug hypersensitivity reaction’ and one case of anaphylaxis, while Moderna reported two cases of ‘delayed hypersensitivity reactions’ 44 .

By December 23, 2020, among the 1,893,360 first doses of Pfizer-BioNTech vaccines administered in the US, only 0.2 per cent of adverse events were reported and submitted to the Vaccine Adverse Event Reporting System (VAERS) 45 . As of January 10, 2021, a reported 4,041,396 first doses of Moderna COVID-19 vaccine had been administered in the United States, and reports of 1,266 (0.03%) adverse events after receipt of Moderna COVID-19 vaccine were submitted to VAERS 46 .

Allergic reactions from the two available mRNA COVID-19 vaccines were due to polyethylene glycol (PEG) 47 , also known as macrogol, while for the AstraZeneca and Johnson and Johnson COVID-19 vaccines, the filler polysorbate 80, also known as Tween 80, has been implicated in allergic reactions 48 , 49 , 50 . Allergic reactions are rare, but the CDC recommends avoiding mRNA vaccines in individuals who had anaphylaxis in the past 42 , 51 . In addition, the CDC guidance indicates precaution for allergy due to ‘a potential cross-reactive hypersensitivity between ingredients in mRNA and adenovirus vector COVID-19 vaccines’ 52 .

The occurrence of thrombosis with thrombocytopenia syndrome was linked to adenovirus vector vaccines such as ChAdOx1 nCoV-19 (Oxford-AstraZeneca) and AD26.CoV2·S (Johnson and Johnson), raising concerns 43 . For example, a population-based cohort study in Denmark and Norway showed ‘increased rates of venous thromboembolic events, including cerebral venous thrombosis’ in recipients of ChAdOx1, more venous thromboembolic events were observed in the vaccinated cohort than expected in the general population, and the standardized morbidity ratio was significantly greater than unity 53 .

ChAdOx1 nCoV-19 vaccine induced immune thrombotic thrombocytopenia and cerebral venous sinus thrombosis with fatal intracerebral haemorrhaging 53 , 54 , 55 . Following administration of the Johnson & Johnson vaccine, a case of thrombocytopenia, elevated D-dimers and pulmonary emboli was found 56 . EMA reported other blood clots associated with thrombocytopenia, including arterial thromboses and splanchnic vein thrombosis, after administration of the AstraZeneca vaccine 57 . All patients in each series had high levels of antibodies against antigenic complexes of platelet factor 4, as seen in heparin-induced thrombocytopenia. Therefore, this condition was defined as ‘vaccine-induced immune thrombotic thrombocytopenia’, requiring high-dose immunoglobulins and certain non-heparin anticoagulants for treatment 57 , 58 . A case report of Guillain−Barre syndrome followed the administration of the first dose of the ChAdOx1 vaccine 59 , and two cases of autoimmune hepatitis were triggered by Covishield vaccination 60 .

The Coalition of Epidemic Preparedness Innovations (CEPI) questioned the use of alum and other adjuvants that might promote T-helper2 (Th2) responses 61 . Moreover, T-helper17 (Th17) inflammatory responses, which play a role in the pathogenesis of COVID-19-related pneumonia and oedema by promoting eosinophilic activation and infiltration, could also explain coronavirus-vaccine immune enhancement 62 . Therefore, an understanding of Th17 responses is critical for the successful clinical development and production of COVID-19 vaccines and plays a potential role in selecting vaccine dose, adjuvants and route 62 .

Do COVID-19 vaccines sensitize humans to antibody-dependent enhanced (ADE) breakthrough infection? ADE is a complex phenomenon that includes vaccine hypersensitivity (VAH), delayed-type hypersensitivity and/or an Arthus reaction 63 . VAH has a complex and poorly defined immunopathology post-vaccination outcome that may be associated with non-protective antibodies 64 . ADE in SARS-CoV and MERS-CoV infection showed the development of poorly or non-neutralizing antibodies after vaccination or infection enhance subsequent infections 65 . Several SARS-CoV and MERS-CoV vaccines have elicited a post-challenge VAH in laboratory animals. For example, in the 1960s, the formalin-inactivated measles vaccine in children caused VAH 8-12 months after the vaccination, leading to lung lesions, revealing damage to parenchymal tissue, pulmonary neutrophilia with abundant macrophages and lymphocytes and excess eosinophils 66 . Lessons learned from adverse effects caused by SARS-CoV and MERS-CoV vaccines may help to develop better immunotherapeutics and vaccines against SARS-CoV-2 65 .

Overvaccination in patients predisposed to autoimmune disease may enhance the possibility of developing an autoimmune response 63 . Since the mRNA vaccines against COVID-19 are the first mRNA vaccines authorized for the market, there is a possibility that these may generate strong type 1 interferon responses that could lead to inflammation and autoimmune conditions 67 .

A vaccine in the market requires safety monitoring surveillance to detect and evaluate rare adverse events not identified in prelicensure clinical trials. In the US, the CDC has three long-standing vaccine safety programmes: VAERS, the Vaccine Safety Datalink and the Clinical Immunization Safety Assessment 68 .

Efficacy of the vaccines against new viral strains

Considering that the SARS-CoV-2 virus, like other viruses, mutates 69 , 70 , why are some RNA vaccines effective against the new strains of the SARS-CoV-2 virus, while others are less, or not at all? These new variants result from mutations in the viral genomes, occurring due to the consequences of viral replication, which are advantageous to the survival of the virus. Among these variants, WHO, US CDC, and the EU’s European Centre for Disease Prevention identified some variants as being significant variants, referring to them as variants of concern (VOCs) and variants of interest (VOIs) ( Table II ). VOCs emerged as a more significant threat to public health due to their enhanced transmissibility and infectivity 71 . Global concern is the continued spread of the highly transmissible Delta variant, which has become predominant worldwide 72 , 73 and has better transmission potential (60%) than the alpha variant 74 . Currently, omicron variant is becoming the predominant strain resulting from a combination of increased transmissibility and the ability to evade natural and artificial immunization 75 . WHO monitors the global spread and epidemiology of VOCs and VOIs and coordinates laboratory investigations 76 .

Characteristics of SARS-CoV-2 variants of concern (VOC, Alpha, Beta, Gamma, Delta and omicron) and variants of interest (VOI, Lambda and Mu)

Last updated: 20 December 2021. Information obtained from WHO ( https://www.who.int /en/activities/tracking-SARS-CoV-2-variants/ ) there are a number of variants that are being monitored currently and can be found at the WHO as we as at the USA Center of Disease Control and Prevention found ( https://www.cdc.gov /coronavirus/2019-ncov/variants/variant-info.html ); CDC has no VOI listed and only two VOCs: Delta and Omicron; There is also information in the magazine about: https://www.businessinsider.com /COVID-19-vaccine-efficacy-variants-india-south-africa-brazil-uk-2021-5 ; for transmission see: https://www.aljazeera.com /news/2021/7/7/map-tracking-the-COVID-19-delta-variant . WHO, World Health Organization; CDC, Centres for Disease Control; VOI, variants of interest; VOCs, variants of concerns; N/A, not available

Several SARS-CoV-2 VOCs have emerged and were originally identified in the UK (variant B.1.1.7 or alpha), South Africa (B.1.351 or beta), Brazil (P.1 or gamma), India (B.1.617.2 or delta) and South Africa (B.1.1.529 or omicron) 77 . These VOCs are considered severe public health threats because of their association with higher transmissibility, morbidity, mortality and potential immune escape 78 by infection or vaccine-induced antibodies resulting from the accumulation of mutations in the spike protein 79 . In other words, these may alter the clinical manifestation of the disease and efficacy of available vaccines and therapeutics, as well as the ability of reverse transcription-polymerase chain reaction (RT-PCR) assays to detect the virus 80 .

Though the efficacy of the ChAdOx1 nCoV-19 vaccine against the alpha variant was similar to that reported in previous studies 81 , the vaccine conferred only minimal protection against COVID-19 infection caused by the Beta variant 82 . The NVX-CoV2373 vaccine (Novavax) also demonstrated efficacy against the Alpha and Beta variants of SARS-CoV-2 83 . The Novavax vaccine is 86 per cent efficacious against the Alpha variant and 60 per cent efficacious against the Beta variant 84 . Although the neutralization capacity of several COVID-19 vaccines (mRNA-1273, NVX-CoV2373, BNT162b2 and ChAdOx1 nCoV-19) was reduced against the Beta (B.1.351) variant 85 , but Covaxin conferred significant protection against both Beta (B.1.351) and Delta (B.1.617.2) variants 70 .

Similarly, the single-dose Janssen COVID-19 vaccine candidate demonstrated efficacy against the Beta variant 86 . The Moderna vaccine candidate (mRNA-1273) also demonstrated efficacy against the Alpha and Beta SARS-CoV-2 variants, findings that were based on in vitro neutralization studies conducted using serum collected from individuals vaccinated with the mRNA-1273 vaccine 87 . Therefore, South Africa adjourned campaigns to vaccinate its front-line health care workers (HCWs) with the Oxford-AstraZeneca vaccine after a small clinical trial suggested that it ineffectively prevented mild to moderate illness from the dominant variant in the country 88 . The results of a clinical trial confirmed that a two-dose regimen of the ChAdOx1 nCoV-19 (AstraZeneca) vaccine did not protect individuals against the mild-to-moderate B.1.351 variant 89 .

Mutations observed in the SARS-CoV-2 variants identified in the UK and South Africa had small effects on the effectiveness of the Pfizer-BioNTech vaccine 90 . A two-strain mathematical framework using Ontario (Canada) as a case study found that, given the levels of under-reporting and case levels at that time, ‘a variant strain was unlikely to dominate’ until the first quarter of 2021, and high vaccine efficacy was required across strains to make it possible to have an immune population in Ontario by the end of 2021 91 . The UK research showed that the Pfizer–BioNTech vaccine was 92 per cent effective against symptomatic cases of the alpha variant and offered 83 per cent protection against the Delta variant 92 . A study in Qatar found similar results: the Pfizer–BioNTech vaccine offered 90 per cent protection against the Alpha variant and 75 per cent protection against the Beta variant 93 . In a US-based study carried out during July 2021, 346 of the 469 COVID-19 cases (74%) among Massachusetts residents occurred in fully vaccinated people with two doses of Pfizer-BioNTech, Moderna, or a single dose of Janssen vaccine ≥14 days before exposure 94 . Genomic sequencing of testing identified the new Delta variant in 90 per cent of cases 86 . Even vaccinated people may get infected with COVID-19 due to the Delta variant, and on July 27, 2021, the US CDC released a recommendation to invite citizens to wear masks in indoor public environments where the risk of COVID-19 transmission is high 84 .

The neutralization potential of BBV152/Covaxin, the inactivated SARS-CoV-2 vaccine rolled out in India, was also effective against Beta and Delta variants, but since reduced neutralization activity may result in reduced vaccine effectiveness, further studies are needed for Covaxin against these two variants 78 . A single dose of Pfizer or AstraZeneca offered little protection against the Beta and Delta variants and a neutralizing response was generated against the Delta variant only after the administration of the second dose 74 . Despite being lower, the remaining neutralization capacity conferred by the Pfizer vaccine against Delta and other VOCs was protective 95 .

Until February 6, 2022, the WHO described eight variants of interest (VOIs), namely Epsilon (B.1.427 and B.1.429); Zeta (P.2); Eta (B.1.525); Theta (P.3); Iota (B.1.526); Kappa (B.1.617.1); Lambda (C.37)and Mu (B.1.621) 96 . However, there is still a lack of detailed knowledge about their transmissibility, infectivity, re-infectivity, immune escape and vaccine activity 61 . A preprint highlighted that the lambda variant (lineage C.37), which spread from Peru in December 2020, displayed increased infectivity and immune escape against the Coronovac vaccine 97 . Table II summarizes the profiles of the VOCs and VOIs. The most recent data on the variants reported in India are available at the Indian SARS-CoV-2 Genomic Consortia (INSACOG) website. The predominant SARS-CoV-2 variant currently circulating in India is Delta (B.1.617.2 and AY.4) 98 . Covaxin (BBV152) exhibited good protection (65.2%) against the Delta variant, and although a minor reduction in the neutralizing antibody titre was observed, the sera of vaccinated individuals still effectively neutralized the Delta, Delta AY.1 and B.1.617.3 variants 99 . In contrast, breakthrough infections were reported due to the Delta variant in individuals fully vaccinated with Covishield 100 .

Safety and efficacy of the vaccines in select categories of people

Another issue is that clinical trials are studies conducted on select categories of individuals, generally healthy people. Thus, concerns exist about safety and effectiveness in specific categories of people. For instance, there are doubts that all COVID-19 vaccines can stimulate an immune response in older individuals (≥65 yr), especially those with co-morbidities, such as hypertension, obesity and diabetes mellitus 101 . Older patients, especially those older than 65 and with co-morbidities, are more susceptible to a severe form of COVID-19 that can progress rapidly, often leading to death 102 . In general, the efficacy of vaccines in older people is not well studied. The impact of immunosenescence on vaccine safety is even more uncertain 2 . The presence of chronic diseases ( e.g ., diabetes) and fragility, including immunodepression, may be better forecasters of weak immunologic responses than age 103 .

Even though the safety and efficacy of COVID-19 vaccines in older people are critical to their health 2 , no studies have been done to examine the response of this category of individuals to all COVID-19 vaccines. Vaccines developed by the University of Oxford/AstraZeneca (ChAdOx1) and Janssen (Ad26.COV2) depend on the genetic alteration of adenoviruses that are inactivated, due to the replacement of the E1 gene with the spike gene 2 . The ChAdOx1 nCoV-19 (AZD1222) vaccine is better tolerated by older than younger people, and after the second dose, it has similar immunogenicity across all ages 104 . However, additional assessment of AZD1222 is planned 105 . A second trial on the Moderna vaccine showed binding- and neutralizing-antibody responses in older people (>55 yr), similar to previously reported vaccine recipients between 18 and 55 yr of age 40 .

Pregnant and lactating women are excluded from vaccine research because they are not recognized as a high-priority group, despite the risk of complications and poor perinatal outcomes 106 , and because of previous experience of pregnancies complicated by infection with other coronaviruses, such as SARS-CoV and MERS-CoV, making pregnant women vulnerable to severe SARS-CoV-2 disease 107 . A retrospective study based on the clinical criteria confirmed that pregnancy significantly increased the risk of severe COVID-19 108 . Based on a review of maternal and neonatal COVID-19 morbidity and mortality data, the COVID-19 vaccines should be administered to those at the highest risk of severe infection until the safety and efficacy of vaccines are thoroughly validated 109 . Therefore, in consultation with their obstetricians, pregnant women will need to consider the benefits and risks of COVID-19 vaccines. The US CDC, the American College of Obstetricians and Gynaecologists and the Society for Maternal-Foetal Medicine each issued guidance supporting vaccination in pregnant individuals 110 .

Another critical issue concerns COVID-19 vaccination in children. Children of any age are susceptible to SARS-CoV-2 infection, including severe disease manifestations. Previously healthy children are also at risk of severe COVID-19 and multisystem inflammatory syndrome in children (MIS-C) 68 . Children might differ from adults in terms of the safety, reactogenicity and immunogenicity of vaccines 68 . Paediatric clinical trials can offer direct and indirect benefits from COVID-19 vaccination 111 .

Updates on COVID-19 and vaccines

On November 26, 2021, the WHO designated B.1.1.529 (Omicron) as a new VoC, although its pathogenicity as well as its potential to evade immune response from vaccines and natural immunity is relatively unknown 112 . Since other variants could emerge in the future, coordinated global responses that address vaccines and lockdown measures against SARS-CoV-2, surveillance systems that monitor viral mutations and the effectiveness of vaccines, as well as overcoming vaccine and economic inequalities, are needed.

A third dose of the Pfizer-BioNTech vaccine is effective in protecting individuals against severe COVID-19-related outcomes, compared with receiving only two doses at least five months prior 113 . A booster of Moderna or Pfizer-BioNTech may produce antibodies against SARS-CoV-2 in organ transplant patients with an immunodepression state 114 , 115 . On August 13, 2021, the US FDA authorized a third dose of the Pfizer-BioNTech or Moderna vaccines for immunocompromised people, who are particularly at risk for severe disease 116 , and the EMA concluded that an extra dose of these COVID-19 vaccines may be given to these patients at least 28 days after their second dose 117 .

Financial support & sponsorship : None.

Conflicts of Interest : None.

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COVID-19 mRNA Vaccines: Lessons Learned from the Registrational Trials and Global Vaccination Campaign

Affiliations.

• 1 Biology and Nutritional Epidemiology, Independent Research, Copper Hill, USA.
• 2 Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, USA.
• 3 Biostatistics and Epidemiology, Independent Research, Research Triangle Park, USA.
• 4 Immunology and Public Health Research, Independent Research, Ottawa, CAN.
• 5 Epidemiology and Biostatistics, Independent Research, Basel, CHE.
• 6 Data Science, Independent Research, Los Angeles, USA.
• 7 Cardiology, Epidemiology, and Public Health, McCullough Foundation, Dallas, USA.
• 8 Cardiology, Epidemiology, and Public Health, Truth for Health Foundation, Tucson, USA.
• PMID: 38274635
• PMCID: PMC10810638
• DOI: 10.7759/cureus.52876

Retraction in

• Retraction: COVID-19 mRNA Vaccines: Lessons Learned from the Registrational Trials and Global Vaccination Campaign. Mead MN, Seneff S, Wolfinger R, Rose J, Denhaerynck K, Kirsch S, McCullough PA. Mead MN, et al. Cureus. 2024 Feb 26;16(2):r137. doi: 10.7759/cureus.r137. eCollection 2024 Feb. Cureus. 2024. PMID: 38414517 Free PMC article.

Our understanding of COVID-19 vaccinations and their impact on health and mortality has evolved substantially since the first vaccine rollouts. Published reports from the original randomized phase 3 trials concluded that the COVID-19 mRNA vaccines could greatly reduce COVID-19 symptoms. In the interim, problems with the methods, execution, and reporting of these pivotal trials have emerged. Re-analysis of the Pfizer trial data identified statistically significant increases in serious adverse events (SAEs) in the vaccine group. Numerous SAEs were identified following the Emergency Use Authorization (EUA), including death, cancer, cardiac events, and various autoimmune, hematological, reproductive, and neurological disorders. Furthermore, these products never underwent adequate safety and toxicological testing in accordance with previously established scientific standards. Among the other major topics addressed in this narrative review are the published analyses of serious harms to humans, quality control issues and process-related impurities, mechanisms underlying adverse events (AEs), the immunologic basis for vaccine inefficacy, and concerning mortality trends based on the registrational trial data. The risk-benefit imbalance substantiated by the evidence to date contraindicates further booster injections and suggests that, at a minimum, the mRNA injections should be removed from the childhood immunization program until proper safety and toxicological studies are conducted. Federal agency approval of the COVID-19 mRNA vaccines on a blanket-coverage population-wide basis had no support from an honest assessment of all relevant registrational data and commensurate consideration of risks versus benefits. Given the extensive, well-documented SAEs and unacceptably high harm-to-reward ratio, we urge governments to endorse a global moratorium on the modified mRNA products until all relevant questions pertaining to causality, residual DNA, and aberrant protein production are answered.

Keywords: autoimmune; cardiovascular; covid-19 mrna vaccines; gene therapy products; immunity; mortality; registrational trials; risk-benefit assessment; sars-cov-2 (severe acute respiratory syndrome coronavirus -2); serious adverse events.

Copyright © 2024, Mead et al.

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Conflict of interest statement

Steve Kirsch is the founder of the Vaccine Safety Research Foundation or VSRF (vacsafety.org) but receives no income from this entity

Figure 1. Analysis of Pfizer trial’s weekly…

Figure 1. Analysis of Pfizer trial’s weekly mortality over a 33-week period

This representation of…

Figure 2. Charts illustrating Pfizer trial irregularities…

Figure 2. Charts illustrating Pfizer trial irregularities in reporting of COVID-19 cases and humoral immune…

Figure 3. Cleveland Clinic study showing increasing…

Figure 3. Cleveland Clinic study showing increasing COVID-19 cases with increasing mRNA vaccinations

Cleveland Clinic…

Figure 4. Cleveland Clinic study showing increased…

Figure 4. Cleveland Clinic study showing increased COVID-19 cases for subjects most "up to date"…

Figure 5. VAERS reports of autoimmune disease…

Figure 5. VAERS reports of autoimmune disease per million doses of COVID-19 mRNA (2021-2023) compared…

Figure 6. Factors contributing to COVID-19 mRNA…

Figure 6. Factors contributing to COVID-19 mRNA vaccine inefficacy

COVID-19 vaccines may lose efficacy in…

Figure 7. Myocarditis reports in VAERS Domestic…

Figure 7. Myocarditis reports in VAERS Domestic Data as of September 29, 2023, plotted by…

Figure 8. Registrational trial for Pfizer, projected…

Figure 8. Registrational trial for Pfizer, projected three-year mortality If the six-month Pfizer trial had…

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• Covid-19: Pfizer...

Covid-19: Pfizer vaccine efficacy was 52% after first dose and 95% after second dose, paper shows

Read our latest coverage of the coronavirus outbreak.

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• Elisabeth Mahase

The Pfizer and BioNTech covid-19 vaccine may provide some early protection, starting 12 days after the first dose, the peer reviewed results of a phase III trial have found.

The study, published in the New England Journal of Medicine , 1 found that vaccine efficacy between the first and second doses was 52% (95% credible interval 29.5% to 68.4%), with 39 cases of covid-19 in the vaccine group and 82 cases in the placebo group.

Seven or more days after the second dose, vaccine efficacy then rose to 95% (90.3% to 97.6%), with eight covid-19 cases reported in the vaccine group and 162 cases in the placebo group.

The vaccine has so far been approved in Canada and in the UK, where it is already being rolled out to people over 80 and healthcare workers. In the US the Food and Drug Administration’s independent panel has voted in favour of emergency use authorisation for the vaccine, and the agency is expected to approve it within days. 2

Participants

From July to November 2020, 43 448 adults were randomly assigned at 152 sites worldwide (including in Argentina, Brazil, Germany, South Africa, Turkey, and the US) as part of the phase II/III trial of the BNT162b2 vaccine. A total of 21 720 people received two doses 21 days apart, and 21 728 received a placebo.

The paper reported that, seven days after the second dose, vaccine efficacy ranged from 89% to 100% across subgroups defined by age, sex, race, ethnicity, baseline body mass index, and the presence of coexisting conditions.

The study found 10 severe covid-19 cases after the first dose, nine of which were in the placebo group. After the second dose it showed one case in the vaccine group and four in the placebo group. 3

As of 9 October, 37 706 participants had a median of at least two months’ safety data available after a second dose. Among these participants 49% were female, 83% were white, 9% were black or African-American, 28% were Hispanic or Latinx, 35% had a body mass index of at least 30, and 21% had at least one pre-existing condition. The median age was 52, and 42% of participants were aged over 55.

Adverse events

In terms of safety, more people in the covid-19 vaccine group reported any adverse event (27%, compared with 12% taking a placebo) or a related adverse event (21% v 5%). The researchers said that this was mainly due to transient reactogenicity events, such as injection site pain.

Few participants in either group had severe or serious adverse events. Among the BNT162b2 recipients four related serious adverse events were reported and two recipients died (one from arteriosclerosis and one from cardiac arrest), as did four placebo recipients (two from unknown causes, one from haemorrhagic stroke, and one from myocardial infarction). However, none of the deaths was considered by the investigators to be related to the vaccine or placebo, and no covid-19 associated deaths were observed.

The researchers wrote, “The safety profile of BNT162b2 was characterised by short term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups.”

This article is made freely available for use in accordance with BMJ's website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.

• ↵ Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA covid-19 vaccine. N Engl J Med 2020. doi: 10.1056/NEJMoa2034577 . https://www.nejm.org/doi/full/10.1056/NEJMoa2034577?query=RP .
• ↵ Polack FP, Thomas SJ, Kitchin N, et al. Supplementary appendix to “Safety and efficacy of the BNT162b2 mRNA covid-19 vaccine.” N Engl J Med 2020. https://www.nejm.org/doi/suppl/10.1056/NEJMoa2034577/suppl_file/nejmoa2034577_appendix.pdf .

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Grading of Recommendations, Assessment, Development, and Evaluation (GRADE): Pfizer-BioNTech COVID-19 Vaccine

CDC vaccine recommendations are developed using an explicit evidence-based method based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.

A Grading of Recommendations, Assessment, Development and Evaluation (GRADE) review of the evidence for benefits and harms for Pfizer-BioNTech COVID-19 vaccine was presented to the Advisory Committee for Immunization Practices (ACIP) on August 30, 2021. GRADE evidence type indicates the certainty of estimates from the available body of evidence. Evidence certainty ranges from type 1 (high certainty) to type 4 (very low certainty). 1

The policy question was, "Should vaccination with Pfizer-BioNTech COVID-19 vaccine (2-doses, IM) be recommended for persons 16 years of age and older?" The potential benefits pre-specified by the ACIP COVID-19 Vaccines Work Group included prevention of symptomatic laboratory-confirmed COVID-19 (critical), hospitalization due to COVID-19 (critical), death due to COVID-19 (important) and asymptomatic SARS-CoV-2 infection, assessed using PCR (important). The two pre-specified harms were serious adverse events (SAEs) (including myocarditis and anaphylaxis) (critical) and reactogenicity (severe, grade ≥3) (important).

A systematic review of evidence on the benefits and harms of a two-dose regimen of Pfizer-BioNTech COVID-19 vaccine among persons aged ≥16 years was conducted, based on data available as of August 23, 2021. The evidence from one Phase I randomized controlled trial (RCT), 2 one Phase II/III RCT, 3 4 5 26 vaccine effectiveness studies, 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 and two vaccine safety surveillance systems 32 33 34 were assessed using a modified GRADE approach. 1 Pooled efficacy and effectiveness estimates were calculated when multiple sources had data on an outcome.

In terms of benefits, the available data from RCTs demonstrated that, compared with placebo, vaccination was associated with a lower risk of symptomatic laboratory-confirmed COVID-19 (relative risk [RR] 0.09, 95% confidence interval [CI] 0.07–0.11; evidence type 1), hospitalization due to COVID-19 (RR 0.02; 95% CI 0.00–0.12; evidence type 2), and death due to COVID-19 (RR 0.17, 95% CI 0.02–1.39; evidence type 2). The certainty of estimates regarding hospitalization and death due to COVID-19 was reduced due to imprecision.

The pooled vaccine effectiveness estimates from observational studies were consistent with these findings. Compared with no vaccination, vaccination with Pfizer-BioNTech COVID-19 vaccine was associated with a decreased risk of symptomatic laboratory-confirmed COVID-19 (RR 0.07, 95% CI 0.05–0.13; evidence type 2), hospitalization (RR 0.06, 95% CI 0.03–0.12; evidence type 2), and death due to COVID-19 (RR 0.04, 95% CI 0.02–0.09; evidence type 2). The certainty of each of these estimates was increased for a strong association. Vaccination was also associated with a decreased risk of asymptomatic SARS-CoV-2 infection (RR 0.11, 95% CI 0.10–0.12; evidence type 4); the evidence certainty type was downgraded for inconsistency.

In terms of harms, the available data from RCTs indicated that serious adverse events were balanced between the vaccine and placebo arms (RR 1.00; 95% CI 0.85 to 1.18, evidence type 2), and two serious adverse events were judged to be related to vaccination among more than 22,000 persons vaccinated. The certainty of this estimate was reduced due to imprecision. Reactogenicity grade ≥3 was associated with vaccination (RR 4.69; 95% CI 3.83–5.73, evidence type 1). About 11% of vaccine recipients versus 2% of placebo recipients reported grade ≥3 reactions. Two rare but serious adverse events, anaphylaxis and myocarditis, have been associated with vaccination in post-authorization safety surveillance (see results section and Table 3e ).

Introduction

On August 23, 2021, the U.S. Food and Drug Administration (FDA) approved the Biologics License Application (BLA) for Pfizer-BioNTech COVID-19 Vaccine (COMIRNATY®) for the prevention of COVID-19 in individuals aged ≥16 years. 35 As part of the process employed by the Advisory Committee for Immunization Practices (ACIP), a systematic review and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) assessment of the evidence for Pfizer-BioNTech COVID-19 vaccine was conducted and presented to ACIP. 1 There were no conflicts of interest reported by CDC and ACIP COVID-19 Vaccines Work Group members involved in the GRADE analysis.

ACIP adopted a modified GRADE approach in 2010 as the framework for evaluating the scientific evidence that informs recommendations for vaccine use. ACIP has made modifications to the GRADE approach by presenting assessed evidence as type 1, 2, 3, and 4, which corresponds to high, moderate, low, and very low certainty, whereas standard GRADE has high as level 4 and very low as level 1. Additionally, instead of presenting the overall certainty of evidence across all outcomes, ACIP presents the certainty of evidence for the benefits and harms separately. ACIP includes an option "ACIP recommends the intervention for individuals based on shared clinical decision-making" instead of providing a conditional recommendation for or against an intervention. GRADE was used to evaluate the efficacy and safety of a two-dose regimen of Pfizer-BioNTech COVID-19 vaccine among persons aged ≥16 years. Evidence of benefits and harms were reviewed based on the modified GRADE approach. 1

The policy question was, "Should vaccination with Pfizer-BioNTech COVID-19 vaccine (2-doses, IM) be recommended for persons 16 years of age and older?" ( Table 1 ).

We conducted a systematic review of evidence on the benefits and harms of a two-dose regimen of Pfizer-BioNTech COVID-19 vaccine (see Appendix 2 for databases and search strategies). We assessed outcomes and evaluated the quality of evidence using the GRADE approach. Patient-important outcomes (including benefits and harms) for assessment were selected by the Work Group during Work Group calls and via online surveys where members were asked to rate and rank the importance of relevant outcomes.

We identified RCTs through clinicaltrials.gov. Relevant Phase I, II, or III RCTs of COVID-19 vaccine were included if they: 1) involved human subjects; 2) reported primary data; 3) included adults (aged ≥16 years) at risk for SARS-CoV-2 infection; 4) included data relevant to the efficacy and safety outcomes being measured; 5) included data for the dosage being recommended (30 μg, 2 doses at 0 and 21 days). We identified relevant observational studies through an ongoing systematic review conducted by the International Vaccine Access Center (IVAC) and the World Health Organization (WHO). 36 Relevant observational studies, using case-control, test-negative, or cohort designs, were restricted to the defined population, intervention, comparison, and outcome outlined in the policy question. Outcomes were assessed starting at least 7 days after 2 nd dose. We included only 2-dose Pfizer-BioNTech vaccine effectiveness estimates, with combined mRNA vaccine effectiveness estimates excluded. We included studies of general populations and special populations. In addition, efforts were made to obtain unpublished and other relevant data by hand-searching reference lists, and consulting with vaccine manufacturers and subject matter experts. We included observational safety data from two vaccine safety surveillance systems based on input from ACIP's COVID-19 Vaccines Safety Technical (VaST) Work Group: Vaccine Safety Datalink (VSD) and Vaccine Adverse Event Reporting System (VAERS). Characteristics of all included studies and surveillance systems are shown in Appendix 1. 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34

Two reviewers evaluated all studies for study limitations (risk of bias) using the Cochrane Risk of Bias (RoB) tool for RCTs and the Newcastle-Ottawa Scale (NOS) for observational studies. RoB comprises a series of questions structured into domains focusing on different aspects of trial design, conduct, and reporting. Based on question responses, judgement can be "low", "moderate", or "high" risk of bias. NOS is a 9-point scale which assesses study limitations related to participant selection and comparability, and assessment of outcome (cohort studies) or ascertainment of exposure (case-control studies). Studies with NOS scores <7 were considered to have serious study limitations.

From the RCT data, relative risks (RR) were calculated from numerators and denominators available in the body of evidence. Vaccine efficacy estimates were defined as 100% x (1-RR). Vaccine effectiveness estimates and 95% CIs were taken from the published/preprint studies, as defined by the authors using a variety of study designs and analytical approaches; adjusted estimates were used when available. When multiple studies were available, pooled estimates were calculated using random effects (>3 studies) or fixed effects (≤2 studies) meta-analysis (R meta package). When multiple studies provided estimates based on overlapping study populations, the study with the most comprehensive population and follow-up time was selected for inclusion in the pooled estimate. Because there was a relatively large body of evidence from vaccine effectiveness studies, with many available only in the preprint literature, an a priori decision was made to exclude studies judged to have serious study limitations from the main pooled estimate used for GRADE. Sensitivity analyses were performed to assess the influence of study characteristics (e.g., special populations vs. full population, preprint vs. peer-reviewed, standard vs. extended dosing interval, cohort vs. case-control/test-negative study design, study limitations, and circulating variants). The evidence certainty assessment for randomized and observational studies addressed risk of bias, inconsistency, indirectness, imprecision, and other characteristics. The GRADE assessment across the body of evidence for each outcome was presented in an evidence profile.

The results of the GRADE assessment were presented to ACIP on August 30, 2021.

Outcomes of interest included individual benefits and harms. Indirect effects of vaccination (e.g., societal benefits) were not considered as part of GRADE. Benefits of interest deemed critical were prevention of symptomatic laboratory-confirmed COVID-19 and prevention of hospitalization due to COVID-19 (Table 2). Other important benefits included prevention of death due to COVID-19 and prevention of asymptomatic SARS-CoV-2 infection. The critical harm of interest was serious adverse events (SAEs), including myocarditis and anaphylaxis; reactogenicity grade ≥3 was deemed an important harm.

After screening 86 records, 45 were excluded from full-text review because they were a different study design (i.e. screening method, n=2), a different intervention (e.g., a different vaccine or a different dose, n=28), or a different outcome that did not directly align with the PICO outcomes (e.g., any infection instead of symptomatic COVID-19 or asymptomatic infection, n=15). Of the 41 records that were deemed eligible for full-text review, 1 was excluded for not having primary data, 4 were excluded because they assessed a different intervention, and 4 were excluded because they assessed a different outcome. The remaining 33 records, which reported data on 29 studies or surveillance systems, were included in the evidence synthesis and GRADE evidence assessment (Appendix 1). 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 Data were reviewed from four RCT records, including one publication from a Phase I trial, one publication and one preprint from the same Phase II/III trial, and additional data provided by the sponsor. 2 3 4 5 Data were reviewed from 26 vaccine effectiveness studies. 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 Two vaccine safety surveillance systems, VSD and VAERS, included data for SAEs. 32 33 34

In the Phase II/III RCT, using data on all blinded follow-up (up to 6 months or the unblinding date of March 13, 2021), the Pfizer-BioNTech COVID-19 vaccine reduced symptomatic COVID-19 when compared to placebo (vaccine efficacy: 91.1% (95% CI 88.8–93.1%)) (Table 3a). For hospitalization due to COVID-19, 31 events occurred, all in the placebo group. Vaccine efficacy against hospitalization due to COVID-19 was 100% (95% CI 87.6–100%) (Table 3b). Deaths due to COVID-19 were uncommon, one in the vaccine group and six in the placebo group (83% (-39–98%)) (Table 3c). Numbers of SAEs were comparable between the vaccine group and the placebo group across the two RCTs (Phase II/III: 268/21,926 (1.2%) vs. 268/21,921 (1.2%); Phase I: 1/24 (4.2%) vs. 0/6 (0.0%)); there were no cases of vaccine-associated enhanced disease or vaccine-related deaths (Table 3e). Grade ≥3 reactions generally were not uncommon and occurred more frequently in the vaccine than placebo groups (Table 3f).

Seventeen vaccine effectiveness studies reported data on symptomatic laboratory-confirmed COVID-19 (Table 3a), 13 reported data on hospitalization due to COVID-19 (Table 3b), 6 reported data on death due to COVID-19 (Table 3c), and 5 reported data on asymptomatic SARS-CoV-2 infection (Table 3d). The pooled vaccine effectiveness estimates from the observational studies demonstrated that the Pfizer-BioNTech COVID-19 vaccine reduced symptomatic COVID-19 when compared to no vaccination (pooled vaccine effectiveness: 92.4% (95% CI: 87.5–95.3%), based on 8 studies). 6 10 11 14 17 18 21 31 The pooled vaccine effectiveness against hospitalization due to COVID-19 was 94.3% (95% CI 87.9–97.3%), based on 8 studies. 13 15 17 21 22 25 28 30 The pooled vaccine effectiveness for prevention of death due to COVID-19 was 96.1% (95%CI 91.5–98.2%), based on 4 studies. 13 15 17 25 The pooled vaccine effectiveness against asymptomatic SARS-CoV-2 infection was 89.3% (95% CI 88.4–90.1%), based on 2 studies. 17 24

Observational data on serious adverse events were reviewed. A rapid cycle analysis from VSD evaluated chart-reviewed cases of myocarditis occurring among persons aged 18–39 years following dose 2 of the Pfizer-BioNTech COVID-19 vaccine (Table 3e). 34 The rates of myocarditis were 368 per million person-years (9/24,432) in the 0–7-day risk interval and 48 per million person-years (3/62,481) in vaccinated comparators (adjusted rate ratio: 9.1 (95%CI 2.1–48.6)). Data from VAERS showed an elevated ratio of observed to expected myocarditis cases in the 7-day interval following vaccination among females in age groups 16–24 years and among males in age groups 16–49 years, with higher observed/expected ratios in males than females. 33 A rapid cycle analysis of data from VSD evaluated chart-reviewed cases of anaphylaxis among all vaccinated persons aged ≥12 years. Based on events occurring in a 0–1 day risk interval after vaccination, the estimated incidence of confirmed anaphylaxis was 5.0 (95% CI 3.5–6.9) per million doses. 34 The absolute reporting rate to VAERS was 4.7 per million doses administered. 32

GRADE Summary

The initial GRADE evidence level was type 1 (high) for randomized controlled trials and type 3 (low) for the observational data (Table 4). In terms of benefits, the RCT data indicate that the vaccine reduces the risk of symptomatic laboratory-confirmed COVID-19, and no serious concerns impacting certainty were identified for this outcome (type 1, high). Observational data for symptomatic laboratory-confirmed COVID-19 indicated a similar risk reduction with vaccination, and the certainty was upgraded one point for a strong association (type 2, moderate). The certainty of the evidence from RCTs for hospitalization due to COVID-19 was downgraded one point for serious concern of imprecision (type 2, moderate). Observational data for hospitalization due to COVID-19 indicated a similar risk reduction with vaccination, and the certainty was upgraded one point for a strong association (type 2, moderate). The certainty of the evidence for death due to COVID-19 was downgraded one point for serious concern of imprecision (type 2, moderate). Observational data for death due to COVID-19 concurred with a strong risk reduction with vaccination, and the certainty was upgraded one point for a strong association (type 2, moderate). The body of evidence for prevention of asymptomatic SARS-CoV-2 infection came from observational studies and was downgraded one point for serious concern for inconsistency (type 4, very low). The certainty of evidence for serious adverse events was downgraded one point for serious concern of imprecision related to sample size (type 2, moderate). Observational data on specific serious adverse events (i.e., myocarditis among persons aged 18–39 years and anaphylaxis among persons aged 12 years and older) demonstrated these events are rare (evidence type 3, low). No serious concerns impacted the certainty of estimates of reactogenicity from RCTs (type 1, high).

The summary of evidence types is shown in Table 5. The final evidence types were type 1 for symptomatic laboratory-confirmed COVID-19, type 2 for hospitalization due to COVID-19 and death due to COVID-19, type 4 for asymptomatic SARS-CoV-2 infection, type 2 for serious adverse events, and type 1 for reactogenicity.

Table 1: Policy Question and PICO

Abbreviations : IM = intramuscular.

Table 2: Outcomes and Rankings

a Three options: 1. Critical; 2. Important but not critical; 3. Not important for decision making

Table 3a: Summary of Studies Reporting Symptomatic Laboratory-confirmed COVID-19

References in this table: 4 5 6 7 8 9 10 11 12 14 17 18 19 20 21 22 24 26 29 31

a Pre-print

b Assessed using a primary outcome of the RCT, defined as SARS-CoV-2 RT-PCR-positive symptomatic illness, in seronegative adults, ≥7 days post second dose. Seronegative status was not a criterion for inclusion of observational studies.

c Additional data provided by sponsor

d Vaccine effectiveness estimate included in main pooled analysis used for GRADE.

e Vaccine effectiveness estimate not included in main pooled analysis used for GRADE because study population overlapped with another study that was included.

f Vaccine effectiveness estimate not included in main pooled analysis used for GRADE because of study limitations related to selection and comparability.

Table 3b: Summary of Studies Reporting Hospitalization due to COVID-19

References in this table: 3 4 5 8 9 12 13 15 16 17 21 22 23 25 27 28 30

a Pre-print.

b Additional data provided by study sponsor.

c Outcome defined as hospitalization or death.

f Vaccine effectiveness estimate not included in main pooled analysis used for GRADE; a different variant-specific estimate from the same study was included.

Table 3c: Summary of Studies Reporting Death due to COVID-19

References in this table: 3 4 5 13 15 16 17 25 27

b Additional data provided by sponsor.

c Vaccine effectiveness estimate included in main pooled analysis used for GRADE.

d Vaccine effectiveness estimate not included in main pooled analysis used for GRADE because study population overlapped with another study that was included.

Table 3d: Summary of Studies Reporting Asymptomatic SARS-CoV-2 infection

References in this table: 7 17 24 26 29

b Vaccine effectiveness estimate not included in main pooled analysis used for GRADE because study population overlapped with another study that was included.

d Vaccine effectiveness estimate not included in main pooled analysis used for GRADE because of study limitations related to selection and comparability.

Table 3e: Summary of Studies Reporting Serious Adverse Events a

References in this table: 2 3 4 5 32 33 34

a Included all randomized participants who received at least 1 dose of vaccine.

c One SAE of neuritis was reported from the phase 1 trial that had not been identified at the time of the Walsh publication. This SAE was deemed unrelated to vaccination.

d Four serious adverse events were deemed by blinded investigators to be related to vaccination. These included: shoulder injury related to vaccine administration, ventricular arrhythmia, lymphadenopathy, and lower back pain and bilateral lower extremity pain with radicular paresthesia. Through further investigation by the FDA, only two were classified as related to vaccination: shoulder injury and lymphadenopathy.

e Risk evaluated in a 7-day interval following vaccination.

f Reported cases and expected number of cases were examined by age group (16–17, 18–24, 25–29, 30–39, 40–49, 50–64, ≥65 years) and sex.

g Risk evaluated in a 0–1 day risk interval after vaccination.

h Risk evaluated in a 7-day interval following dose 2

Table 3f: Summary of Studies Reporting Reactogenicity a

References in this table: 2 3 4 5

a Grade 3 or worse. Grade 3 local reactions include pain at injection site that prevents daily activity, redness > 10 cm, and swelling > 10 cm. Grade 3 systemic events include vomiting that requires IV hydration, diarrhea of 6 or more loose stools in 24 hours, or headache, fatigue/tiredness, chills, new or worsened muscle pain, or new or worsened joint pain that prevent daily routine activity.

Table 4: Grade Summary of Findings Table

CI: Confidence interval; RR: Risk ratio

Explanations

a. Risk of bias related to blinding of participants and personnel was present. Although participants and study staff were blinded to intervention assignments, they may have inferred receipt of vaccine or placebo based on reactogenicity. This was deemed unlikely to overestimate efficacy or underestimate risk of serious adverse events, therefore the risk of bias was rated as not serious.

b. The RCT excluded persons with prior COVID-19 diagnosis, pregnant or breastfeeding women, and persons who were immunocompromised. The population included in the RCT may not represent all persons aged >=16 years.

c. Absolute risk was calculated using the observed risk among placebo recipients in the available body of evidence from randomized controlled trials. Absolute risk estimates should be interpreted in this context.

d. 17 studies were available in the body of evidence. 8 were excluded because the study population was already represented, and 1 was excluded due to serious study limitations.

e. The body of evidence includes preprints.

f. Although I 2 value was high (95.0%), no serious concern for inconsistency was judged because all studies showed a high degree of vaccine effectiveness, with point estimates ranging from 87% to 97%. In a sensitivity analysis including results from one study with study limitations identified that had a vaccine effectiveness estimate of 56%, the pooled RR was 0.10 (95% CI 0.05–0.18), and I 2 was 98.1%.

g. Data on numerators and denominators were not consistently reported in the available body of evidence. The n shown excludes events from studies that did not report the number of cases. The N is not included because studies variously provided person-time or number of persons. In addition to the numerators from cohort studies shown, the body of evidence included at least 85 cases and 54,603 controls from case-control or test-negative studies.

h. Pooled RR based on a random effects meta-analysis, using adjusted vaccine effectiveness estimates on a log scale.

i. Risk of bias was considered due to concern about misclassification of outcome. Hospitalization due to COVID-19 is not specified in the study protocol, and the data shown include only persons who met the protocol definition of COVID-19 using an approved assay or confirmation in a central laboratory; it was unclear if constructing a non-protocol measure may have resulted in bias. Data on all hospitalizations due to COVID-19 diagnosed by any assay after dose 1 were also obtained and reviewed. Two hospitalizations due to COVID-19 occurred among 21,909 persons in the vaccine arm and 59 occurred among 21,908 persons in the placebo arm (RR 0.03, 95% CI 0.01–0.14); the similar efficacy diminished concerns regarding risk of bias.

j. Serious concerns of imprecision due to fragility in the estimate was present because there were only 31 events observed from a single RCT.

k. RR calculated using a standard continuity correction of 0.5.

l. 13 studies were available in the body of evidence. 5 were excluded because the study population was already represented.

m. Although I 2 value was high (91.7%), no serious concern for inconsistency was judged because all studies showed a high degree of vaccine effectiveness, with point estimates ranging from 84% to 99%.

n. Definitions varied by study. Indirectness was considered given COVID-19 was not necessarily confirmed as the cause of hospitalizations, but this was deemed not serious.

o. Data on numerators and denominators were not consistently reported in the available body of evidence. The n shown excludes events from studies that did not report the number of cases. The N is not included because studies variously provided person-time or number of persons. In addition to the numerators from cohort studies shown, the body of evidence included at least 95 cases and 1,359 controls from case-control or test-negative studies.

p. Risk of bias was considered due to possible misclassification of outcomes. One death in a vaccine recipient and 3 deaths among placebo recipients were in persons who had been diagnosed with COVID-19 based on local clinical nucleic acid amplification tests that were not protocol approved; these diagnoses were not confirmed by the central study laboratory and were not counted in the efficacy estimates for symptomatic laboratory-confirmed COVID-19 or hospitalization due to COVID-19. In an analysis using only protocol approved or central laboratory confirmed cases resulting in death, with a standard continuity correction applied, the relative risk was 0.14 (95% CI 0.01–2.77).

q. Serious concern for imprecision was present due to the small number of events that were observed. In addition to a 95% confidence interval crossing the line of no effect, there was concern for fragility in the estimate due to the small number of events.

r. Calculated risk among placebo arm in available body of evidence from RCT was 0.03%, but it appears lower here due to rounding.

s. 6 studies were available in the body of evidence. 2 were excluded because the study population was already represented.

t. The relative risk shown is from a pooled analysis of 4 cohort studies conducted in different populations. I 2 was 48.8%.

u. Definitions varied by study. Indirectness was considered given COVID-19 was not necessarily confirmed as the cause of deaths, but this was deemed not serious.

v. Data on numerators and denominators were not consistently reported in the available body of evidence. The n shown excludes events from studies that did not report the number of cases. The N is not included because the type of denominator varied across studies (e.g., person-time or number of persons).

w. 5 studies were available in the body of evidence. 2 were excluded because the study population was already represented, and one study was excluded due to study limitations.

x. Serious concern for inconsistency was present (I 2 = 98.1%). The magnitude of the relative risks from the two studies in the body of evidence varied widely, possibly reflecting different prevalence of circulating SARS-CoV-2 variants at the time of data collection or differences in study methods. In a sensitivity analysis including results from one study with study limitations identified that had a vaccine effectiveness estimate of 35.9%, the pooled RR was 0.12% (95% CI 0.11–0.13), and I 2 was 99.1%.

y. Pooled RR based on a fixed effects meta-analysis, using adjusted vaccine effectiveness estimates on a log scale. Fixed effects model was used for this analysis due to imprecise estimates of the between-studies variance.

z. Absolute risk was calculated using the observed risk of symptomatic COVID-19 among placebo recipients in the available body of evidence from randomized controlled trials. Absolute risk estimates should be interpreted in this context.

aa. Risk of bias related to blinding of participants was present. Although participants and study staff were blinded to intervention assignments, they may have inferred receipt of vaccine or placebo based on reactogenicity. Some reactogenicity outcomes may also have been reported as serious adverse events, and experiences of reactions immediately after vaccination could have influenced recall or reporting of subsequent serious adverse events. This was rated as not serious.

ab. Serious concern for imprecision was present. The confidence interval indicates that both reduced and increased risk of serious adverse events are possible.

ac. Pooled RR based on a fixed effects meta-analysis. Fixed effects model was appropriate for this analysis because these RCTs used the same protocol and were conducted in similar populations.

ad. A rapid cycle analysis from Vaccine Safety Datalink (VSD) evaluated chart-reviewed cases of myocarditis among persons aged 18–39 years, following dose 2. Based on events occurring in a 7-day risk interval after vaccination vs. a comparison interval in vaccinated individuals, the adjusted rate ratio was 9.1% (95% CI 2.1–48.6). The rates of myocarditis were 368 per 1 million person-years (9/24,432) in the 0–7 day risk interval and 48 per 1 million person-years (3/62,481) in vaccinated comparators.

ae. Data from the national Vaccine Adverse Event Reporting System (VAERS) showed an elevated ratio of observed to expected myocarditis cases in the 7-day interval following vaccination among females in age groups 16–24 years, and among males in age groups 16–49 years, with higher observed/expected ratios in males than females. Although VAERS data are subject to the limitations of a passive surveillance system, the elevated risk of myocarditis following Pfizer vaccination is consistent with that observed in VSD.

af. A rapid cycle analysis of data from VSD evaluated chart-reviewed cases of anaphylaxis among all vaccinated persons aged 12 and older. Based on events occurring in a 0-1 day risk interval after vaccination, the estimated incidence of confirmed anaphylaxis was 5.0 (95% CI 3.5-6.9) per million doses. The absolute reported rate to VAERS was 4.7 per million doses administered.

Table 5: Summary of Evidence for Outcomes of Interest

Appendix 1. Studies Included in the Review of Evidence

Randomized controlled trial.

Observational Cohort Studies

References in this table: 6 7 8 9 12 13 14 15 16 17 21 23 24 25 26 27 31

Observational Case-Control Studies

References in this table: 10 11 18 19 20 22 28 29 30

Safety Surveillance

References in this table: 32 33 34

b Additional data provided by sponsor

c This was a primary outcome of the RCT, defined as SARS-CoV-2 RT-PCR-positive symptomatic illness, in seronegative persons aged ≥18 years, ≥7 days post second dose. In a secondary analysis among seronegative and seropositive persons, the efficacy was Grade 3 or worse.

d Grade 3 local reactions include pain at injection site that prevents daily activity, redness > 10 cm, and swelling > 10 cm. Grade 3 systemic events include vomiting that requires IV hydration, diarrhea of 6 or more loose stools in 24 hours, or headache, fatigue/tiredness, chills, new or worsened muscle pain, or new or worsened joint pain that prevent daily routine activity.

e Not reported

Appendix 2. Databases and strategies used for systematic review

View the complete list of GRADE evidence tables‎

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ACIP comprises medical and public health experts who develop recommendations on the use of vaccines in the civilian population of the United States.

COVID-19 vaccines: Get the facts

Looking to get the facts about COVID-19 vaccines? Here's what you need to know about the different vaccines and the benefits of getting vaccinated.

As the coronavirus disease 2019 (COVID-19) continues to cause illness, you might have questions about COVID-19 vaccines. Find out about the different types of COVID-19 vaccines, how they work, the possible side effects, and the benefits for you and your family.

COVID-19 vaccine benefits

What are the benefits of getting a covid-19 vaccine.

Staying up to date with a COVID-19 vaccine can:

• Help prevent serious illness and death due to COVID-19 for both children and adults.
• Help prevent you from needing to go to the hospital due to COVID-19 .
• Be a less risky way to protect yourself compared to getting sick with the virus that causes COVID-19.
• Lower long-term risk for cardiovascular complications after COVID-19.

Factors that can affect how well you're protected after a vaccine can include your age, if you've had COVID-19 before or if you have medical conditions such as cancer.

How well a COVID-19 vaccine protects you also depends on timing, such as when you got the shot. And your level of protection depends on how the virus that causes COVID-19 changes and what variants the vaccine protects against.

Talk to your healthcare team about how you can stay up to date with COVID-19 vaccines.

Should I get the COVID-19 vaccine even if I've already had COVID-19?

Yes. Catching the virus that causes COVID-19 or getting a COVID-19 vaccination gives you protection, also called immunity, from the virus. But over time, that protection seems to fade. The COVID-19 vaccine can boost your body's protection.

Also, the virus that causes COVID-19 can change, also called mutate. Vaccination with the most up-to-date variant that is spreading or expected to spread helps keep you from getting sick again.

Researchers continue to study what happens when someone has COVID-19 a second time. Later infections are generally milder than the first infection. But severe illness can still happen. Serious illness is more likely among people older than age 65, people with more than four medical conditions and people with weakened immune systems.

Safety and side effects of COVID-19 vaccines

What covid-19 vaccines have been authorized or approved.

The COVID-19 vaccines available in the United States are:

• Pfizer-BioNTech COVID-19 vaccine 2024-2025 formula, available for people age 6 months and older.
• Moderna COVID-19 vaccine 2024-2025 formula, available for people age 6 months and older.
• Novavax COVID-19 vaccine 2024-2025 formula, available for people age 12 years and older.

These vaccines have U.S. Food and Drug Administration (FDA) emergency use authorization or approval.

In June 2024, the FDA recommended COVID-19 vaccine updates to target a strain of the COVID-19 virus called JN.1. But JN.1 soon began to fade from the community. Strains that evolved from it began to spread at higher levels. As the virus continued to change, the FDA updated its guidance and asked vaccine makers to focus on a JN.1 strain subtype called KP.2.

The Pfizer-BioNTech and Moderna COVID-19 vaccines for 2024-2025 focus on building protection against the KP.2 virus strain. The Novavax COVID-19 vaccine, adjuvanted 2024-2025 formula will focus on the JN.1 strain.

In December 2020, the Pfizer-BioNTech COVID-19 vaccine two-dose series was found to be both safe and effective in preventing COVID-19 infection in people age 18 and older. This data helped predict how well the vaccines would work for younger people. The effectiveness varied by age. Since 2020, the vaccine has been updated yearly to better protect against the strains of COVID-19 spreading in the community. The currently approved vaccine is Pfizer-BioNTech COVID-19 vaccine 2024-2025 formula.

The Pfizer-BioNTech vaccine is approved under the name Comirnaty for people age 12 and older. The FDA authorized the vaccine for people age 6 months to 11 years. The number of shots in this vaccination series varies based on a person's age and COVID-19 vaccination history.

In December 2020, the Moderna COVID-19 vaccine was found to be both safe and effective in preventing infection and serious illness among people age 18 or older. The vaccine's ability to protect younger people was predicted based on that clinical trial data. Since 2020, the vaccine has been updated yearly to better protect against the changing strains of COVID-19. The currently approved vaccine is Moderna COVID-19 vaccine 2024-2025 formula.

The FDA approved the vaccine under the name Spikevax for people age 12 and older. The FDA authorized use of the vaccine in people age 6 months to 11 years. The number of shots needed varies based on a person's age and COVID-19 vaccination history.

In July 2022, this vaccine was found to be safe and effective and became available under an emergency use authorization for people age 18 and older. In August 2022, the FDA authorized the vaccine for people age 12 and older. Since then, the vaccine has been updated yearly to better protect against the changing strains of COVID-19. The currently approved vaccine is Novavax COVID-19 vaccine, adjuvanted 2024-2025 formula.

How do the COVID-19 vaccines work?

COVID-19 vaccines help the body get ready to clear out infection with the virus that causes COVID-19.

Both the Pfizer-BioNTech and the Moderna COVID-19 vaccines use genetically engineered messenger RNA (mRNA). The mRNA in the vaccine tells your cells how to make a harmless piece of virus that causes COVID-19.

After you get an mRNA COVID-19 vaccine, your muscle cells begin making the protein pieces and displaying them on cell surfaces. The immune system recognizes the protein and begins building an immune response and making antibodies. After delivering instructions, the mRNA is immediately broken down. It never enters the nucleus of your cells, where your DNA is kept.

The Novavax COVID-19 adjuvanted vaccine is a protein subunit vaccine. These vaccines include only protein pieces of a virus that cause your immune system to react the most. The Novavax COVID-19 vaccine also has an ingredient called an adjuvant that helps raise your immune system response.

With a protein subunit vaccine, the body reacts to the proteins and creates antibodies and defensive white blood cells. If you later become infected with the COVID-19 virus, the antibodies will fight the virus. Protein subunit COVID-19 vaccines don't use any live virus and can't cause you to become infected with the COVID-19 virus. The protein pieces also don't enter the nucleus of your cells, where your DNA is kept.

Can a COVID-19 vaccine give you COVID-19?

No. The COVID-19 vaccines available in the U.S. don't use the live virus that causes COVID-19. Because of this, the COVID-19 vaccines can't cause you to become sick with COVID-19.

It can take a few weeks for your body to build immunity after getting a COVID-19 vaccination. As a result, it's possible that you could become infected with the virus that causes COVID-19 just before or after being vaccinated.

What are the possible general side effects of a COVID-19 vaccine?

Some people have no side effects from the COVID-19 vaccine. For those who get them, most side effects go away in a few days.

A COVID-19 vaccine can cause mild side effects after the first or second dose. Pain and swelling where people got the shot is a common side effect. That area also may look reddish on white skin. Other side effects include:

• Fever or chills.
• Muscle pain or joint pain.
• Tiredness, called fatigue.
• Upset stomach or vomiting.
• Swollen lymph nodes.

For younger children up to age 4, symptoms may include crying or fussiness, sleepiness, loss of appetite, or, less often, a fever.

In rare cases, getting a COVID-19 vaccine can cause an allergic reaction. Symptoms of a life-threatening allergic reaction can include:

• Breathing problems.
• Fast heartbeat, dizziness or weakness.
• Swelling in the throat.

If you or a person you're caring for has any life-threatening symptoms, get emergency care.

Less serious allergic reactions include a general rash other than where you got the vaccine, or swelling of the lips, face or skin other than where you got the shot. Contact your healthcare professional if you have any of these symptoms.

You may be asked to stay where you got the vaccine for about 15 minutes after the shot. This allows the healthcare team to help you if you have an allergic reaction. The healthcare team may ask you to wait for longer if you had an allergic reaction from a previous shot that wasn't serious.

Contact a healthcare professional if the area where you got the shot gets worse after 24 hours. And if you're worried about any side effects, contact your healthcare team.

Are there any long-term side effects of the COVID-19 vaccines?

The vaccines that help protect against COVID-19 are safe and effective. Clinical trials tested the vaccines to make sure of those facts. Healthcare professionals, researchers and health agencies continue to watch for rare side effects, even after hundreds of millions of doses have been given in the United States.

Side effects that don't go away after a few days are thought of as long term. Vaccines rarely cause any long-term side effects.

If you're concerned about side effects, safety data on COVID-19 vaccines is reported to a national program called the Vaccine Adverse Event Reporting System in the U.S. This data is available to the public. The U.S. Centers for Disease Control and Protection (CDC) also has created v-safe, a smartphone-based tool that allows users to report COVID-19 vaccine side effects.

If you have other questions or concerns about your symptoms, talk to your healthcare professional.

Can COVID-19 vaccines affect the heart?

In some people, COVID-19 vaccines can lead to heart complications called myocarditis and pericarditis. Myocarditis is the swelling, also called inflammation, of the heart muscle. Pericarditis is the swelling, also called inflammation, of the lining outside the heart.

Symptoms to watch for include:

• Chest pain.
• Shortness of breath.
• Feelings of having a fast-beating, fluttering or pounding heart.

If you or your child has any of these symptoms within a week of getting a COVID-19 vaccine, seek medical care.

The risk of myocarditis or pericarditis after a COVID-19 vaccine is rare. These conditions have been reported after COVID-19 vaccination with any of the vaccines offered in the United States. Most cases have been reported in males ages 12 to 39.

These conditions happened more often after the second dose of the COVID-19 vaccine and typically within one week of COVID-19 vaccination. Most of the people who got care felt better after receiving medicine and resting.

These complications are rare and also may happen after getting sick with the virus that causes COVID-19. In general, research on the effects of the most used COVID-19 vaccines in the United States suggests the vaccines lower the risk of complications such as blood clots or other types of damage to the heart.

If you have concerns, your healthcare professional can help you review the risks and benefits based on your health condition.

Things to know before a COVID-19 vaccine

Are covid-19 vaccines free.

In the U.S., COVID-19 vaccines may be offered at no cost through insurance coverage. For people whose vaccines aren't covered or for those who don't have health insurance, options are available. Anyone younger than 18 years old can get no-cost vaccines through the Vaccines for Children program.

Can I get a COVID-19 vaccine if I have an existing health condition?

Yes, COVID-19 vaccines are safe for people who have existing health conditions, including conditions that have a higher risk of getting serious illness with COVID-19.

The COVID-19 vaccine can lower the risk of death or serious illness caused by COVID-19. Your healthcare team may suggest that you get added doses of a COVID-19 vaccine if you have a moderately or severely weakened immune system.

Cancer treatments and other therapies that affect some immune cells also may affect your COVID-19 vaccine. Talk to your healthcare professional about timing additional shots and getting vaccinated after immunosuppressive treatment.

Talk to your healthcare team if you have any questions about when to get a COVID-19 vaccine.

Is it OK to take an over-the-counter pain medicine before or after getting a COVID-19 vaccine?

Don't take medicine before getting a COVID-19 vaccine to prevent possible discomfort. It's not clear how these medicines might impact the effectiveness of the vaccines. It is OK to take this kind of medicine after getting a COVID-19 vaccine, as long as you have no other medical reason that would prevent you from taking it.

Allergic reactions and COVID-19 vaccines

What are the signs of an allergic reaction to a covid-19 vaccine.

Symptoms of a life-threatening allergic reaction can include:

If you or a person you're caring for has any life-threatening symptoms, get emergency care right away.

Less serious allergic reactions include a general rash other than where you got the vaccine, or swelling of the lips, face or skin other than where the shot was given. Contact your healthcare professional if you have any of these symptoms.

Tell your healthcare professional about your reaction, even if it went away on its own or you didn't get emergency care. This reaction might mean that you are allergic to the vaccine. You might not be able to get a second dose of the same vaccine. But you might be able to get a different vaccine for your second dose.

Can I get a COVID-19 vaccine if I have a history of allergic reactions?

If you have a history of severe allergic reactions not related to vaccines or injectable medicines, you may still get a COVID-19 vaccine. You're typically monitored for 30 minutes after getting the vaccine.

If you've had an immediate allergic reaction to other vaccines or injectable medicines, ask your healthcare professional about getting a COVID-19 vaccine. If you've ever had an immediate or severe allergic reaction to any ingredient in a COVID-19 vaccine, the CDC recommends not getting that specific vaccine.

If you have an immediate or severe allergic reaction after getting the first dose of a COVID-19 vaccine, don't get the second dose. But you might be able to get a different vaccine for your second dose.

Pregnancy, breastfeeding and fertility with COVID-19 vaccines

Can pregnant or breastfeeding women get the covid-19 vaccine.

The CDC recommends getting a COVID-19 vaccine if:

• You are planning to or trying to get pregnant.
• You are pregnant now.
• You are breastfeeding.

Staying up to date on your COVID-19 vaccine helps prevent severe COVID-19 illness. It also may help a newborn avoid getting COVID-19 if you are vaccinated during pregnancy.

People at higher risk of serious illness can talk to a healthcare professional about additional COVID-19 vaccines or other precautions. It also can help to ask about what to do if you get sick so that you can quickly start treatment.

Children and COVID-19 vaccines

If children don't often experience severe illness with covid-19, why do they need a covid-19 vaccine.

While rare, some children can become seriously ill with COVID-19 after getting the virus that causes COVID-19 .

A COVID-19 vaccine might prevent your child from getting the virus that causes COVID-19 . It also may prevent your child from becoming seriously ill or having to stay in the hospital due to the COVID-19 virus.

After a COVID-19 vaccine

Can i stop taking safety precautions after getting a covid-19 vaccine.

You can more safely return to activities that you might have avoided before your vaccine was up to date. You also may be able to spend time in closer contact with people who are at high risk for serious COVID-19 illness.

But vaccines are not 100% effective. So taking other action to lower your risk of getting COVID-19 still helps protect you and others from the virus. These steps are even more important when you're in an area with a high number of people with COVID-19 in the hospital. Protection also is important as time passes since your last vaccination.

If you are at higher risk for serious COVID-19 illness, basic actions to prevent COVID-19 are even more important. Some examples are:

• Avoid close contact with anyone who is sick or has symptoms, if possible.
• Use fans, open windows or doors, and use filters to move the air and keep any germs from lingering.
• Wash your hands well and often with soap and water for at least 20 seconds. Or use an alcohol-based hand sanitizer with at least 60% alcohol.
• Cough or sneeze into a tissue or your elbow. Then wash your hands.
• Clean and disinfect high-touch surfaces. For example, clean doorknobs, light switches, electronics and counters regularly.
• Spread out in crowded public areas, especially in places with poor airflow. This is important if you have a higher risk of serious illness.
• The CDC recommends that people wear a mask in indoor public spaces if COVID-19 is spreading. This means that if you're in an area with a high number of people with COVID-19 in the hospital a mask can help protect you. The CDC suggests wearing the most protective mask possible that you'll wear regularly, that fits well and is comfortable.

Can I still get COVID-19 after I'm vaccinated?

COVID-19 vaccination will protect most people from getting sick with COVID-19. But some people who are up to date with their vaccines may still get COVID-19. These are called vaccine breakthrough infections.

People with vaccine breakthrough infections can spread COVID-19 to others. However, people who are up to date with their vaccines but who have a breakthrough infection are less likely to have serious illness with COVID-19 than those who are not vaccinated. Even when people who are vaccinated get symptoms, they tend to be less severe than those felt by unvaccinated people.

Researchers continue to study what happens when someone has COVID-19 a second time. Reinfections and breakthrough infections are generally milder than the first infection. But severe illness can still happen. Serious illness is more likely among people older than age 65, people with more than four medical conditions and people with weakened immune systems.

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• Benefits of getting a COVID-19 vaccine. Centers for Disease Control and Prevention. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/vaccine-benefits.html. Accessed April 15, 2024.
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• Introduction
• Conclusions
• Article Information

This figure presents serum binding and functional antibody responses following COVID-19 vaccination and SARS-CoV-2 infection among women 45 years or younger.

A and B, Each panel compares vaccine antibody responses at 2 through 8 weeks after the second dose to nonpregnant and pregnant women who were unvaccinated and infected. Thirteen women (7 nonpregnant, 4 pregnant, and 2 lactating) who had baseline samples collected within 7 days of their first vaccine dose were selected based on the earliest sample availability and were analyzed as a negative assay control.

C, D, and E, Systems serology was used to quantify spike-specific antibody–dependent neutrophil phagocytosis (ADNP), antibody–dependent complement deposition (ADCD), and antibody–dependent monocyte cellular phagocytosis (ADCP).

For an explanation of antibody binding, neutralizing, and systems serology assays see Table 2 . The red bars indicate the median; the dotted lines in panels A and B, the limit of detection; C3, complement component 3; NT50, neutralizing antibody titer serum dilution.

A and B, The paired sera samples from maternal blood and cord blood at delivery were used to measure transplacental transfers of the SARS-CoV-2 receptor binding domain (RBD) and binding neutralizing antibody levels after 2 doses of vaccines compared with levels in women who were not vaccinated but were infected with SARS-CoV-2.

C, D, and E, Paired sera samples and breast milk from lactating participants were used to assess IgG and IgA RBD binding antibody and neutralizing antibody levels and compare them between women who were vaccinated and women who were not vaccinated but were infected with SARS-CoV-2. Three participants (green data points) were vaccinated during pregnancy and provided breast milk in the immediate postpartum period. These 3 participants are included as vaccinated in the figure and are included in Table 1 with the pregnant group.

An explanation of binding and neutralizing assays can be found in Table 2 . The red bars indicate the median and the dotted lines, the limit of detection.

Peripheral blood mononuclear cells (PBMCs) following 2 doses of vaccines were stimulated with SARS-CoV-2 USA-WA1/2020 spike peptides. The T-cell responses were measured using IFN-γ enzyme-linked immunospot (ELISPOT) assays and multiparameter intracellular cytokine staining assays to assess IFN-γ total CD4 T cells, CD45RA − CD27 + central memory CD4 T cells, total CD8 T cells, and CD45RA − CD27 + central memory CD8 T cells.

The red bars indicate the median and the dotted lines, the limit of detection. See Table 2 for an explanation of ELISPOT and ICS assays.

Serum receptor binding domain (RBD) IgG binding antibody titers and neutralizing antibody titers (NT50) were compared with SARS-CoV-2 wild-type USA-WA1/2020 and variants of concern B.1.1.7 and B.1.351 following 2 doses of vaccines, as well as in cord blood and in breast milk. Peripheral blood mononuclear cells (PBMCs) were stimulated with SARS-CoV-2 wild-type USA-WA1/2020, B.1.1.7, and B.1.351 spike peptides. IFN-γ T-cell responses were measured using enzyme-linked immunospot (ELISPOT) assays and multiparameter intracellular cytokine staining assays gated on total CD4 T cells, CD45RA − CD27 + central memory CD4 T cells, total CD8 T cells, and CD45RA − CD27 + central memory CD8 T cells.

The red bars indicate the median and the dotted lines, the limit of detection. See Table 2 for an explanation of antibody binding and neutralizing assays and ELISPOT and ICS assays.

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Collier AY , McMahan K , Yu J, et al. Immunogenicity of COVID-19 mRNA Vaccines in Pregnant and Lactating Women. JAMA. 2021;325(23):2370–2380. doi:10.1001/jama.2021.7563

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Immunogenicity of COVID-19 mRNA Vaccines in Pregnant and Lactating Women

• 1 Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
• 2 Harvard Medical School, Boston, Massachusetts
• 3 Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts
• 4 Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts
• 5 SeromYx Systems Inc, Cambridge, Massachusetts
• 6 Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts
• Viewpoint COVID-19 Vaccination in Pregnant and Lactating Women Emily H. Adhikari, MD; Catherine Y. Spong, MD JAMA
• Viewpoint Involving Pregnant Individuals in Clinical Research on COVID-19 Vaccines Diana W. Bianchi, MD; Lisa Kaeser, JD; Alison N. Cernich, PhD JAMA
• JAMA Insights Caring for Pregnant and Postpartum Women During the COVID-19 Pandemic Sonja A. Rasmussen, MD, MS; Denise J. Jamieson, MD, MPH JAMA
• Medical News & Perspectives Pregnant People Getting Mixed Messages About COVID-19 Vaccines Rita Rubin, MA JAMA
• Original Investigation Immunogenicity of the Ad26.COV2.S COVID-19 Vaccine Kathryn E. Stephenson, MD, MPH; Mathieu Le Gars, PhD; Jerald Sadoff, MD; Anne Marit de Groot, PhD; Dirk Heerwegh, PhD; Carla Truyers, PhD; Caroline Atyeo, BS; Carolin Loos, PhD; Abishek Chandrashekar, MS; Katherine McMahan, BS; Lisa H. Tostanoski, PhD; Jingyou Yu, PhD; Makda S. Gebre, MS; Catherine Jacob-Dolan, BS; Zhenfeng Li, MS; Shivani Patel, BA; Lauren Peter, BA; Jinyan Liu, PhD; Erica N. Borducchi, PhD; Joseph P. Nkolola, PhD; Morgana Souza, BA; Chen Sabrina Tan, MD; Rebecca Zash, MD; Boris Julg, MD, PhD; Ruvandhi R. Nathavitharana, MD, MPH; Roger L. Shapiro, MD; Ahmed Abdul Azim, MD; Carolyn D. Alonso, MD; Kate Jaegle, MSN; Jessica L. Ansel, MSN; Diane G. Kanjilal, BSN; Caitlin J. Guiney, MSN; Connor Bradshaw, BS; Anna Tyler, BS; Tatenda Makoni, BS; Katherine E. Yanosick, BS; Michael S. Seaman, PhD; Douglas A. Lauffenburger, PhD; Galit Alter, PhD; Frank Struyf, MD; Macaya Douoguih, MD; Johan Van Hoof, MD; Hanneke Schuitemaker, PhD; Dan H. Barouch, MD, PhD JAMA
• Original Investigation BNT162b2 Vaccination and SARS-CoV-2 Infection in Pregnant Women Inbal Goldshtein, PhD; Daniel Nevo, PhD; David M. Steinberg, PhD; Ran S. Rotem, ScD; Malka Gorfine, PhD; Gabriel Chodick, PhD; Yaakov Segal, MD JAMA
• Research Letter Spontaneous Abortion Following COVID-19 Vaccination During Pregnancy Elyse O. Kharbanda, MD, MPH; Jacob Haapala, MPH; Malini DeSilva, MD, MPH; Gabriela Vazquez-Benitez, PhD; Kimberly K. Vesco, MD, MPH; Allison L. Naleway, PhD; Heather S. Lipkind, MD, MS JAMA
• Research Letter Receipt of COVID-19 Booster Dose Among Fully Vaccinated Pregnant Individuals Aged 18 to 49 Years by Key Demographics Hilda Razzaghi, PhD; Mehreen Meghani, MPH; Bradley Crane, MS; Sascha Ellington, PhD; Allison L. Naleway, PhD; Stephanie A. Irving, MHS; Suchita A. Patel, DO JAMA

Question   What is the immunogenicity of COVID-19 messenger RNA (mRNA) vaccines in pregnant and lactating women?

Findings   In this cohort study involving 103 women who received a COVID-19 mRNA vaccine, 30 of whom were pregnant and 16 of whom were lactating, immunogenicity was demonstrated in all, and vaccine-elicited antibodies were found in infant cord blood and breast milk. Pregnant and nonpregnant vaccinated women developed cross-reactive immune responses against SARS-CoV-2 variants of concern.

Meaning   In a small convenience sample, COVID-19 mRNA vaccines were immunogenic in pregnant and lactating women and induced immune responses against SARS-CoV-2 variants.

Importance   Pregnant women are at increased risk of morbidity and mortality from COVID-19 but have been excluded from the phase 3 COVID-19 vaccine trials. Data on vaccine safety and immunogenicity in these populations are therefore limited.

Objective   To evaluate the immunogenicity of COVID-19 messenger RNA (mRNA) vaccines in pregnant and lactating women, including against emerging SARS-CoV-2 variants of concern.

Design, Setting, and Participants   An exploratory, descriptive, prospective cohort study enrolled 103 women who received a COVID-19 vaccine from December 2020 through March 2021 and 28 women who had confirmed SARS-CoV-2 infection from April 2020 through March 2021 (the last follow-up date was March 26, 2021). This study enrolled 30 pregnant, 16 lactating, and 57 neither pregnant nor lactating women who received either the mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) COVID-19 vaccines and 22 pregnant and 6 nonpregnant unvaccinated women with SARS-CoV-2 infection.

Main Outcomes and Measures   SARS-CoV-2 receptor binding domain binding, neutralizing, and functional nonneutralizing antibody responses from pregnant, lactating, and nonpregnant women were assessed following vaccination. Spike-specific T-cell responses were evaluated using IFN-γ enzyme-linked immunospot and multiparameter intracellular cytokine–staining assays. Humoral and cellular immune responses were determined against the original SARS-CoV-2 USA-WA1/2020 strain as well as against the B.1.1.7 and B.1.351 variants.

Results   This study enrolled 103 women aged 18 to 45 years (66% non-Hispanic White) who received a COVID-19 mRNA vaccine. After the second vaccine dose, fever was reported in 4 pregnant women (14%; SD, 6%), 7 lactating women (44%; SD, 12%), and 27 nonpregnant women (52%; SD, 7%). Binding, neutralizing, and functional nonneutralizing antibody responses as well as CD4 and CD8 T-cell responses were present in pregnant, lactating, and nonpregnant women following vaccination. Binding and neutralizing antibodies were also observed in infant cord blood and breast milk. Binding and neutralizing antibody titers against the SARS-CoV-2 B.1.1.7 and B.1.351 variants of concern were reduced, but T-cell responses were preserved against viral variants.

Conclusion and Relevance   In this exploratory analysis of a convenience sample, receipt of a COVID-19 mRNA vaccine was immunogenic in pregnant women, and vaccine-elicited antibodies were transported to infant cord blood and breast milk. Pregnant and nonpregnant women who were vaccinated developed cross-reactive antibody responses and T-cell responses against SARS-CoV-2 variants of concern.

Pregnant women with symptomatic COVID-19 have a higher risk of intensive care unit admission, mechanical ventilation, and death compared with other women in their reproductive years. 1 Increases in preterm birth and stillbirth also have been observed in pregnancies complicated by COVID-19. 2 Maternal-fetal virus transmission in utero is rare, 2 and it appears that newborns receive passive immunity through antibody transfer via the placenta and from breast milk following natural infection. 3 , 4 Vaccination during pregnancy has reduced maternal morbidity and mortality from influenza and neonatal morbidity from pertussis through passive immunity. 5 , 6

The theoretical risks of COVID-19 vaccination in pregnancy and during lactation are limited, and the current vaccines have a favorable safety profile and high efficacy in nonpregnant individuals. The Centers for Disease Control and Prevention 7 recommended that pregnant and lactating women have access to the available COVID-19 vaccines. In the month following Emergency Use Authorization of 2 COVID-19 messenger RNA (mRNA) vaccines in December 2020, 11 087 pregnant women received a COVID-19 vaccine in the United States. 8 However, pregnant and lactating women were excluded from phase 3 vaccine efficacy trials 9 - 11 ; thus, data on vaccine safety and immunogenicity in these populations remain limited.

New genetic variants have evolved from the initial SARS-CoV-2 sequence. The D614G variant is associated with enhanced infectivity, 12 the B.1.1.7 variant is associated with greater transmissibility, 13 and the B.1.351 variant appears to evade natural immunity from prior infection 14 , 15 and partially escapes from neutralizing antibodies. The objective of this study was to assess the immunogenicity of the current COVID-19 mRNA vaccines in pregnant and lactating women against both the original SARS-CoV-2 USA-WA1/2020 strain as well as against the B.1.1.7 and B.1.351 variants of concern.

The Beth Israel Deaconess Medical Center institutional review board approved this study and the parent biorepository study; participants provided written informed consent. We conducted an exploratory, descriptive cohort study of women 18 years or older who had received a COVID-19 vaccine from December 2020 through March 2021 or had had confirmed SARS-CoV-2 infection from April 2020 through March 2021 using samples collected in a larger hospital-wide, prospective data and tissue biorepository. The date of the last follow-up was March 26, 2021.

To recruit participants planning to be vaccinated, we screened clinic schedules; to recruit participants with confirmed infection, we also screened inpatient admissions. Participants also self-referred from flyers posted in the hospital. All participants provided blood, some provided infant cord blood at delivery, and some provided breast milk. Samples were collected close to each vaccine dose and 2 to 8 weeks after the second dose for the mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine. The analysis presented herein includes pregnant, lactating, and nonpregnant women aged 18 to 45 years who were vaccinated or infected ( Table 1 ). To further characterize the study population, participants were asked to provide their race and ethnicity based on specified categories for each; they could select multiple race categories. Participants also reported if they had fever symptoms following either vaccine dose.

SARS-CoV-2 spike receptor binding domain (RBD)–specific binding antibodies in serum and milk were assessed by enzyme-linked immunosorbent assay (ELISA) ( Table 2 ). The 96-well plates were coated with 2 μg/mL of wild-type SARS-CoV-2, variant B.1.1.7 (containing mutation N501Y) (A.G. Schmidt), 16 or B.1.351 (containing mutations K417N, E484K, N501Y) RBD protein in 1× Dulbecco phosphate-buffered saline (DPBS) and incubated at 4 °C overnight.

After incubation, plates were washed once with wash buffer (0.05% Tween 20 in 1× DPBS) and blocked with 350 μL of casein block solution per well for 2 to 3 hours at room temperature. Following incubation, block solution was discarded and plates were blotted dry. Serial dilutions of heat-inactivated serum or breast milk diluted in Casein block were added to wells, and plates were incubated for 1 hour at room temperature, prior to 3 more washes and a 1-hour incubation with a 1:4000 dilution of anti–human IgG horseradish peroxidase (HRP) (Invitrogen, ThermoFisher Scientific) or a 1:1000 dilution of anti–human IgA HRP (Bethyl Laboratories Inc) at room temperature in the dark. Plates were washed 3 times, and 100 μL of SeraCare KPL TMB SureBlue Start solution was added to each well; plate development was halted by adding 100 μL of SeraCare KPL TMB Stop solution per well. The absorbance at 450 nm, with a reference at 650 nm, was recorded with a VersaMax microplate reader (Molecular Devices). For each sample, the ELISA end point titer was calculated using a 4-parameter logistic curve fit to calculate the reciprocal serum dilution that yields a corrected absorbance value (450 nm-650 nm) of 0.2. Interpolated end point titers were reported.

The SARS-CoV-2 pseudoviruses expressing a luciferase reporter gene were generated in a similar approach, described previously. 3 , 17 - 19 In brief, the packaging construct psPAX2 (AIDS Resource and Reagent Program), luciferase reporter plasmid pLenti-CMV Puro-Luc (Addgene), and spike protein expressing pcDNA3.1-SARS-CoV-2 SΔCT were cotransfected into HEK293T cells with calcium phosphate. Pseudoviruses were also generated using spike plasmids harboring mutations found in the USA-WA1/2020 variant (mutation D614G), B.1.1.7 variant (Global Initiative on Sharing All Influenza Data [GISAID] accession number, EPI_ISL_601443), and B.1.351 variant (GISAID accession number, EPI_ISL_712096). The supernatants containing the pseudotype viruses were collected 48 hours after transfection; pseudotype viruses were purified by filtration with a 0.45-μm filter.

To determine the neutralization activity of human adult and infant cord blood serum and whole breast milk, HEK293T-hACE2 cells were seeded in 96-well tissue culture plates at a density of 1.75 × 10 4 cells per well overnight. Three-fold serial dilutions of heat-inactivated serum samples were prepared and mixed with 50 μL of pseudovirus. The mixture was incubated at 37 °C for 1 hour before adding to HEK293T-hACE2 cells. After 48 hours, cells were lysed in Steady-Glo Luciferase Assay (Promega Corp) according to the manufacturer’s instructions. SARS-CoV-2 neutralization titers (NT50) were defined as the sample dilution at which a 50% reduction in relative light units was observed relative to the average of the virus control wells.

For the functional analysis of sera samples, bead-based assays were used to quantify antibody–dependent cellular phagocytosis (ADCP), antibody–dependent neutrophil phagocytosis (ADNP), and antibody–dependent complement deposition (ADCD), as previously described. 19 Fluorescent streptavidin beads (ThermoFisher) were coupled to biotinylated SARS-CoV-2 Spike trimer (LakePharma) and incubated with diluted serum (ADCP and ADNP, 1:100; ADCD, 1:10). For ADCP, THP-1 cells (ATCC), derived from a human monocytic cell line, were added to the immune complexes and incubated for 16 hours at 37 °C. For ADNP, primary neutrophils were isolated using an ammonium chloride potassium lysis buffer from whole blood.

After a 1-hour incubation at 37 °C, neutrophils were stained with an anti-CD66b PacBlue detection antibody (Biolegend). For the ADCD assay, lyophilized guinea pig complement component 3b (C3b) (Sigma) was resuspended according to manufacturer’s instructions and diluted in a gelatin veronal buffer with calcium and magnesium (Boston BioProducts). After incubation, C3 was detected with fluorescein-conjugated goat IgG fraction to guinea pig complement C3 (MPbio). For ADCP, events were gated on bead-positive cells, whereas neutrophils were defined as CD66b positive followed by gating on bead-positive neutrophils for ADNP. ADCP and ADNP data were reported as the phagocytic score, calculated using the following formula: phagocytic score = {[percentage of bead-positive cells] × [geometric mean MFI (mean fluorescence index) for bead-positive cells]}/1000. ADCD was reported as the MFI of C3 deposition.

Enzyme-linked immunospot (ELISPOT) assay plates were coated with mouse anti–human IFN-γ monoclonal antibody (MabTech) at 1 μg per well and incubated overnight at 4 °C. Plates were washed with DPBS and blocked with R10 media (RPMI with 10% heat-inactivated fetal bovine serum [FBS] with 1% of 100× penicillin-streptomycin, 1 M of HEPES buffer, 100 mM of sodium pyruvate, 200 mM of L-glutamine, and 0.1% of 55 mM of 2-mercaptoethanol) for 2 to 4 hours at 37 °C. Peptides from wild-type, B.1.1.7, and B.1.351 variant spike (21st Century Biochemicals) were prepared and plated at a concentration of 2 μg per well, and 100 000 cells per well were added to the plate.

The peptides and cells were incubated for 15 to 20 hours at 37 °C. All steps following this incubation were performed at room temperature. The plates were washed with an ELISPOT wash buffer and incubated for 2 to 4 hours with 1 μg/mL of biotinylated mouse anti–human IFN-γ monoclonal antibody (MabTech). The plates were washed again and incubated for 2 to 3 hours with 1.33 μg/mL of conjugated goat antibiotin alkaline phosphatase (Rockland Inc). The final wash was followed by adding nitor-blue tetrazolium and 5-bromo-4-chloro-3-indolyphosphate p -toludine salt (NBT/BCIP chromogen) substrate solution for 7 minutes. The chromogen was discarded, and the plates were washed with water and dried in a dim place for 24 hours. Plates were scanned and counted on an immunospot analyzer (Cellular Technologies Ltd).

Peripheral blood mononuclear cells were resuspended at a concentration of 10 6 cells in 100 μL of R10 media supplemented with a CD49d monoclonal antibody (1 μg/mL) and a CD28 monoclonal antibody (1 μg/mL). Each sample was assessed with mock (100 μL of R10 plus 0.5% dimethyl sulfoxide; background control), peptides (2 μg/mL), and/or 10 pg/mL of phorbol myristate acetate and 1 μg/mL of ionomycin (Sigma-Aldrich) (100 μL; positive control) and incubated at 37 °C for 1 hour. After incubation, 0.25 μL of GolgiStop (BD Bioscience), which contains monensin, and 0.25 μL of GolgiPlug (BD Bioscience), which contains brefeldin A, in 50 μL of R10 was added to each well and incubated at 37 °C for 8 hours and then held at 4 °C overnight.

The next day, the cells were washed twice with DPBS, stained with aqua live-or-dead dye for 10 minutes, and then stained with predetermined titers of monoclonal antibodies (mAbs) against CD279 (clone EH12.1, BB700), CD4 (clone L200, BV711), CD27 (clone M-T271, BUV563), CD8 (clone SK1, BUV805), and CD45RA (clone 5H9, APC H7) for 30 minutes. Cells were then washed twice with a 2% FBS-DPBS buffer and incubated for 15 minutes with 200 μL of BD CytoFix/CytoPerm fixation/permeabilization solution. Cells were washed twice with 1× Perm Wash buffer (BD Biosciences Perm/Wash Buffer 10× in the CytoFix/CytoPerm Fixation/ Permeabilization kit diluted with MilliQ water and passed through 0.22-μm filter) and stained intracellularly with mAbs against Ki67 (clone B56, BB515), IL-21 (clone 3A3-N2.1, PE), CD69 (clone TP1.55.3, ECD), IL-10 (clone JES3-9D7, PE CY7), IL-13 (clone JES10-5A2, BV421), IL-4 (clone MP4-25D2, BV605), TNF (clone Mab11, BV650), IL-17 (clone N49-653, BV750), IFN-γ (clone B27; BUV395), IL-2 (clone MQ1-17H12, BUV737), IL-6 (clone MQ2-13A5, APC), and CD3 (clone SP34.2, Alexa 700) for 30 minutes. Cells were washed twice with 1× Perm Wash buffer and fixed with 250 μL of freshly prepared 1.5% formaldehyde. Fixed cells were transferred to a 96-well round bottom plate and analyzed by BD FACSymphony system.

Descriptive statistics were calculated using SAS 9.4 (SAS Institute Inc) and GraphPad Prism 8.4.3 (GraphPad Software). Data are presented as median with interquartile range (IQR) or proportion with standard deviation (SD).

The hospital-wide biorepository enrolled 103 women aged 18 to 45 years who received an mRNA COVID-19 vaccine and had serum available for analysis; an additional 4 individuals declined to participate. Among these 103 participants, 30 were pregnant; 16 were lactating; and 57 were neither pregnant nor lactating ( Table 1 ). Samples were obtained a median of 21 days (IQR, 17-27 days) after the second vaccine dose from nonpregnant women, 21 days (IQR, 14-36 days) from pregnant women, and 26 days (IQR, 19-31 days) from lactating women. Nine pregnant women delivered during the study and contributed infant cord blood. Fifty-six participants (54%) received BNT162b2; 47 (46%) received mRNA-1273. Prior SARS-CoV-2 infection was diagnosed in 4 (4%) of the vaccinated participants. Among pregnant participants, 5 (17%) received their first vaccine dose in the first trimester, 15 (50%) in the second, and 10 (33%) in the third.

The hospital-wide biorepository also enrolled 70 women aged 18 to 45 years who were tested for SARS-CoV-2, including 60 pregnant women; an additional 76 individuals declined to participate. The analysis presented herein includes 22 pregnant and 6 nonpregnant unvaccinated women with SARS-CoV-2 infection as comparators who had serum available for analysis. These participants were more likely to self-identify as Black or Hispanic than were the vaccinated women ( Table 1 ). Among women who had not been vaccinated but had been infected, the median time from symptom onset (or positive polymerase chain reaction [PCR] test result among those who were asymptomatic) to sample collection was 12 days (IQR, 10-20 days) for nonpregnant women and 41 days (IQR, 15-140 days) for pregnant women. Among participants infected but not vaccinated, 1 nonpregnant (17%) and 3 pregnant (14%) women experienced severe disease.

After the second dose, fever was reported in 27 nonpregnant (52%, SD; 7%), 4 pregnant (14%; SD, 6%), and 7 lactating (44%; SD, 12%) women ( Table 1 ). Among nonpregnant women, 5 did not report whether they had a fever within 48 hours after the first or second dose; 1 pregnant woman did not report whether she had a fever after the second dose. No severe adverse events or pregnancy or neonatal complications were observed.

The median RBD–IgG binding antibody titers in nonpregnant (37 839), pregnant (27 601), and lactating (23 497) women after the second vaccine dose were higher than their baseline prevaccination titers (28) ( Figure 1 A). Among pregnant women, median binding antibody titer was 27 601 following vaccination and was 1321 after infection. The median binding antibody titer was 37 839 following vaccination and was 771 after infection in nonpregnant women. Similarly, the median pseudovirus NT50 in vaccinated nonpregnant (901), pregnant (910), and lactating individuals (783) were higher than the prevaccination titers (20) ( Figure 1 B). Among those who were not vaccinated but were infected, the median NT50 values were 148 among those who were pregnant and 193 among those who were not pregnant. Among vaccinated individuals, ADNP activity was quantified with median phagocytic score of 58 in nonpregnant, 27 in pregnant, and 12 in lactating individuals ( Figure 1 C). The median MFI for ADCD among vaccinated nonpregnant women was 376; pregnant women, 402; and lactating women, 333 ( Figure 1 D). The median phagocytic score for ADCP among vaccinated nonpregnant women was 277; for pregnant women, 282; and for lactating women, 249 ( Figure 1 E).

Nine paired maternal and infant cord blood samples were used to evaluate transplacental transfer of vaccine–elicited binding and neutralizing antibodies. Median maternal serum RBD IgG binding antibody titers at delivery were 14 953 compared with 19 873 in cord blood ( Figure 2 A). The median maternal NT50 at delivery was 1016 compared with 324 in cord blood ( Figure 2 B). In the unvaccinated infected maternal and infant dyads, the median RBD IgG binding antibody titers at delivery were 1342 in maternal sera and 635 in cord blood ( Figure 2 A), and the median NT50 was 151 in maternal sera compared with 164 in cord blood ( Figure 2 B).

RBD IgG and IgA binding antibodies and neutralizing antibodies were assessed in breast milk following vaccination and infection. The median serum IgG binding antibody titer was 25 055 after vaccination and 1593 following natural infection. Median breast milk IgG titer was 97 in vaccinated and 203 in infected individuals ( Figure 2 C). The median serum IgA–binding antibodies were 820 after vaccination and 152 after infection. The median breast milk IgA binding antibodies were 25 after vaccination and 1940 after infection ( Figure 2 D). The median NT50 in breast milk was 75 following vaccination and 153 following infection ( Figure 2 E).

Spike-specific T-cell responses were evaluated in 18 pregnant, 7 lactating, and 12 nonpregnant individuals with available peripheral blood mononuclear cells (PBMCs). The median ELISPOT responses in vaccinated pregnant individuals was 270 spot-forming cells (SFCs) per million PBMCs, 185 SFCs per million PBMCs in lactating, and 435 SFCs per million PBMCs in nonpregnant women. The percent of spike-specific IFN-γ production by CD4 T cells, CD4 central memory T cells, CD8 T cells, and CD8 central memory T cells were comparable in pregnant, lactating, and nonpregnant women ( Figure 3 ).

Serum RBD IgG binding antibodies and neutralizing antibodies to the B.1.1.7 and B.1.351 variants of concern were evaluated. 20 Binding antibody responses were comparable against wildtype USA-WA1/2020 and B.1.1.7 RBD proteins in nonpregnant, pregnant, and lactating women and in infant cord samples but were lower for the B.1.351 RBD protein ( Figure 4 A). The median neutralizing antibody titer in nonpregnant, pregnant, and lactating women was lower by 3.5-fold for the B.1.1.7 variant and 6-fold lower for the B.1.351 variant than for the USA-WA1/2020 variant ( Figure 4 B).

Spike-specific T-cell responses were also compared with the wildtype USA-WA1/2020, B.1.1.7, and B.1.351 peptides by ELISPOT and ICS assays following vaccination. There were no differences in ELISPOT responses , CD4 T-cell responses, CD4 central memory T-cell responses, CD8 T-cell responses, or CD8 central memory T-cell responses across these variants.

COVID-19 mRNA vaccines were immunogenic, as quantified by both humoral and cellular immune responses, in pregnant, lactating, and nonpregnant, nonlactating women. Following the second dose of the mRNA vaccines, 13% of pregnant women and 47% of nonpregnant women reported fever. These findings need to be confirmed using the national v-safe Centers for Disease Control and Prevention registry. 21 Moreover, similar to prior studies, 22 this study validates that vaccination elicits higher antibody responses than does infection.

The detection of binding and neutralizing antibodies in infant cord blood suggests efficient transplacental transfer of maternal antibodies. As with the recommendation for diphtheria and tetanus toxoids and acellular pertussis vaccination in pregnancy to protect vulnerable newborns against pertussis, maternal COVID-19 vaccination in pregnancy may confer similar benefits for newborns who may be ineligible for vaccination. Vaccination also elicited binding and neutralizing antibodies in breast milk, although IgA responses were low in breast milk, with the exception of early breast milk from participants receiving a vaccine during pregnancy. Differential breast milk IgG- and IgA-antibody production specific to respiratory pathogens has been described in the setting of maternal infection and vaccination, 23 and future work should focus on delineating the timing of vaccination that optimizes delivery of breast milk antibodies to neonates. Other studies have similarly reported spike–specific binding antibodies in breast milk following vaccination. 24 The results of this study complement these studies by demonstrating neutralizing antibodies in both cord blood and breast milk, suggesting the possibility that newborns may be protected by maternal vaccination.

Consistent with recent reports, 15 , 25 , 26 reduced serum neutralizing antibody titers were evident against the B.1.1.7 variant that was originally identified in the UK and particularly against the B.1.351 variant that was originally identified in South Africa. Both vaccinated pregnant women and infant cord blood showed reductions in neutralizing antibody titers against these variants. In contrast, minimal reductions were observed against these variants for nonneutralizing antibody binding and for CD4 and CD8 T-cell responses in both pregnant and nonpregnant women following vaccination. These data suggest that there may be greater cross-reactivity for functional nonneutralizing antibodies and cellular immune responses than for neutralizing antibodies against SARS-CoV-2 variants of concern. The mechanistic roles of these different immune responses in protecting against COVID-19 infection and disease remain to be determined, but data from nonhuman primates suggest that both humoral and cellular immune responses may contribute to protection. 17

This study has several limitations. First, the study size is small, and thus conclusions about vaccine safety and tolerability could not be made. Second, the correlates of immunogenicity and protection against COVID-19 infection and disease have not yet been determined. Third, as a cohort study rather than a randomized clinical trial, any differences in the findings among the groups cannot be assumed to be causal. Fourth, given the reliance on a convenience sample of women who were willing to be vaccinated, the generalizability of the findings may be limited. Fifth, immune responses were evaluated at a short interval after vaccination; thus, conclusions regarding durability cannot be drawn from these results.

In this exploratory analysis of a convenience sample, receipt of a COVID-19 messenger RNA vaccine was immunogenic in pregnant women, and vaccine-elicited antibodies were transported to infant cord blood and breast milk. Pregnant and nonpregnant women who were vaccinated developed cross-reactive antibody responses and T-cell responses against SARS-CoV-2 variants of concern.

Corresponding Author: Dan H. Barouch, MD, PhD, Center for Virology and Vaccine Research, 330 Brookline Ave, E/CLS-1043, Boston, MA 02115 ( [email protected] ).

Accepted for Publication: April 27, 2021.

Published Online: May 13, 2021. doi:10.1001/jama.2021.7563

Author Contributions: Drs Collier and Barouch had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Collier, Alter, Barouch.

Acquisition, analysis, or interpretation of data: Collier, McMahan, Yu, Tostanoski, Aguayo, Ansel, Chandrashekar, Patel, Apraku Bondzie, Sellers, Barrett, Sanborn, Wan, Chang, Anioke, Nkolola, Bradshaw, Jacob-Dolan, Feldman, Gebre, Borducchi, Liu, Schmidt, Suscovich, Linde, Hacker, Barouch.

Drafting of the manuscript: Collier, McMahan, Yu, Chang, Anioke, Barouch.

Critical revision of the manuscript for important intellectual content: Collier, Tostanoski, Aguayo, Ansel, Chandrashekar, Patel, Apraku Bondzie, Sellers, Barrett, Sanborn, Wan, Chang, Nkolola, Bradshaw, Jacob-Dolan, Feldman, Gebre, Borducchi, Liu, Schmidt, Suscovich, Linde, Alter, Hacker, Barouch.

Statistical analysis: Collier, Yu, Tostanoski, Chang, Hacker.

Obtained funding: Schmidt, Barouch.

Administrative, technical, or material support: Collier, McMahan, Yu, Aguayo, Ansel, Chandrashekar, Patel, Apraku Bondzie, Sellers, Barrett, Sanborn, Chang, Anioke, Bradshaw, Feldman, Gebre, Liu, Suscovich, Linde, Barouch.

Supervision: Collier, McMahan, Ansel, Nkolola, Schmidt, Alter, Barouch.

Other - Performing assays: Wan.

Other - methodology, resources, data curation: Alter.

Conflict of Interest Disclosures: Dr Suscovich reported that he is an employee at and owns shares of SeromYx Systems Inc. Dr Linde reported that she is an employee of SeromYx Systems Inc. Dr Alter reported cofounding and serving as a consultant to, and having a patent pending through SeromYx Systems Inc. Dr Barouch reported receiving grants from National Institutes of Health (NIH), the Henry M. Jackson Foundation of the Walter Reed Army Institute of Research, the Bill and Melinda Gates Foundation, the Defense Advanced Research Projects Agency, Gilead, Intima, Alkermes, CureVac, South Africa Medical Research Council, amfAR, Ragon Institute, MassCPR, Sanofi, Legend, and Zentalis; receiving personal fees from SQZ Biotech; and having a patent for COVID-19 vaccines licensed to Janssen with no premarket royalties or payments of any kind. No other disclosures were reported.

Funding/Support: This study was funded by grant CA260476 from the National Institutes of Health (NIH), and grants from the Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, Harvard, the Massachusetts Consortium for Pathogen Readiness, and the Musk Foundation (DHB); AI146779 from the NIH (AGS); HD000849 from the Reproductive Scientist Development Program from the Eunice Kennedy Shriver National Institute of Child Health & Human Development and from Burroughs Wellcome Fund (AYC), AI007387 from the Multidisciplinary AIDS Training Program (LHT), and TR002541 from the Harvard Clinical and Translational Science Center (MRH).

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We thank the participants and their families, the frontline health care providers, and the Center for Virology and Vaccine Research, the Harvard Catalyst Clinical Research Center, the office of the Beth Israel Deaconess Medical Center Chief Academic Officer, and the Department of Obstetrics and Gynecology for enrollment, collection, and processing samples for the Beth Israel Deaconess Medical Center COVID-19 Biorepository.

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Panic in the pandemic: determinants of vaccine hesitancy and the dilemma of public health information sharing during the covid-19 pandemic in sri lanka.

1. Introduction

1.1. overview of vaccine hesitancy.

• Confidence—Lack of confidence in the vaccine’s effectiveness, efficacy, and safety, as well as the competency of health care workers (HCWs) who deliver the vaccines. The motivation and objectives behind the vaccination campaigns are often questioned.
• Convenience—Questions on being physically able to visit the site of vaccine delivery, affordability of the vaccine, understanding the instructions given (Health Literacy), and acceptance of vaccination within the cultural norms.
• Complacency—Ability to perceive the risk of getting infected with the disease vs. being protected by the vaccine.
• Collective Responsibility—Willingness to protect others.
• Calculations—Engagement in gathering extensive information.
• Contextual—Communication and media environment, influential leaders/gatekeepers, religion/culture/gender/economy/social status, politics, and policies.
• Individual/Group—Beliefs and attitudes on prevention, personal or family experiences in previous vaccinations, perceived risk and benefit, trust in the health care system and HCWs, etc.
• Vaccine/Vaccine Specific Influencers—Vaccine schedule, cost, design, and mode of delivery in the vaccination programme, reliability of vaccination equipment and the strength of recommendation by a health care professional.

1.2. COVID-19 Pandemic and Vaccination Status in Sri Lanka

2. materials and methods, 2.1. household survey, 2.2. statistical analysis, 2.3. semi-structured interviews, 2.4. ethical considerations, 3.1. factors affecting delayed vaccination and rejection of vaccination by the respondents.

“ I am newly married, and my husband and I are expecting a baby. We have been planning a baby for the past three years. We met several doctors and did some religious and ritualistic performances to have a child without further delay. Several of our colleagues and relatives advised us to consider this situation before getting a vaccine because many people suspect that vaccine impacts people’s fertility. This may be false or a rumour, but we have no option. No one knows what is happening… ” (Female, age 27, urban, higher education, a public servant)

“ I am suffering from high blood pressure, cholesterol and blood sugar. Also, I have gone through a stem treatment for blocking a valve in the heart. Several educated people, including some professionals, said that some vaccines make blood clots, which will harm patients with cardiovascular treatments. So, I went completely insane because of this information and even had a long time to get the first vaccine. After seeing people getting vaccines fearlessly, I decided to take the first two doses and did not get the third vaccine due to various concerns over different channels… ” (Male, age 66, urban, higher education, a retired executive officer of public service)

“ I was waiting to accept the second dose because many information sources informed that there were discrepancies of vaccine’s effectiveness as the vaccine has produced without enough trials… ” (Male, age 25, higher education, urban)

“ In the first stage, our community members hated to accept the vaccine because they thought it was against some religious principles. However, once cremation was started by the authorities, no one wanted to die as cremation was an extreme barrier to seeing the god. Thus, vaccine acceptance increased significantly… ” (Religious leader, age 64, rural)

3.2. Knowledge of Vaccines and the Vaccination Process

3.2.1. knowledge of vaccine development, country of origin, and manufacturer process, 3.2.2. knowledge of the vaccine outcomes, 3.2.3. knowledge of potential side effects of the vaccine.

“ I am 6 months pregnant. This is my first baby. I am scared because of side effects of vaccines that people talk about. I have a fear that if I take the vaccine, that will impact my baby… ” (Female, age 25, rural, secondary education, no occupation)

“ How can we believe the vaccine? There may be unseen side effects. Even paracetamol has side effects. Our peers were discussing the risk of malfunction or dysfunction of organs, especially genital organs (smiling). Many of my friends are afraid to take the vaccine due to this fact. We need to get married and have kids in the future. Who can guarantee that there are no such effects of the vaccines…(smiling) ” (female, age 22, urban, tertiary education, IT officer in profession)

3.3. Public Health Information and Related Factors Affecting Vaccine Intake by the Respondents

“ We have no idea about vaccines, the impact of vaccines, and presumed side effects, which people discuss in some informal forums. When we had something to confirm, we used to ask our younger son. He is searching Facebook and telling us what is right and wrong…” (Female, age 54, rural, secondary education, housemate).

Factors Affecting Satisfaction with Public Health Information Sharing among Respondents Regarding Vaccines

“ I am involved in public health-related activities at the local level. We are a group that works closely with the community. People ask all doubtful matters from us as they trust us. However, we also faced a challenging situation due to the inconsistency of messages delivered by authorities and officers. We know that COVID-19 is a new challenge, and many of us are learning things by doing. However, we also experienced pathetic contradictions since several officials publicly shared different views on some significant issues associated with COVID-19 in the first half of the pandemic… ” (Male, age 52, urban, higher education, public health inspector)

4. Discussion

• Low density of information: estate communities, Indigenous communities, and some communities in remote rural areas and low-income settings have comparatively limited access to information sources due to a lack of information infrastructures, such as internet facilities, devices, and accessibility to reliable data, and lack of public health professionals to engage in such information sharing and discussions. Further, people with insufficient education levels to understand health information shared by different sources also suffer from a scarcity of information on the cause. Hence, rumours are highly prevalent in such settings due to inadequate information, which causes a dilemma of “ what to believe and what not ”.
• High density of information: Youth, educated people, and some communities, such as urban, semi-urban, and rural areas near urban centres, have too much information coming from various sources, such as internet-based channels, electronic media, social media, professional networks, and primary community networks. In this milieu, people have too much information, complicating their decision-making.

5. Conclusions

Supplementary materials, author contributions, institutional review board statement, informed consent statement, data availability statement, acknowledgments, conflicts of interest.

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Kamalrathne, T.; Jayasekara, J.R.; Amaratunga, D.; Haigh, R.; Kodituwakku, L.; Rupasinghe, C. Panic in the Pandemic: Determinants of Vaccine Hesitancy and the Dilemma of Public Health Information Sharing during the COVID-19 Pandemic in Sri Lanka. Int. J. Environ. Res. Public Health 2024 , 21 , 1268. https://doi.org/10.3390/ijerph21101268

Kamalrathne T, Jayasekara JR, Amaratunga D, Haigh R, Kodituwakku L, Rupasinghe C. Panic in the Pandemic: Determinants of Vaccine Hesitancy and the Dilemma of Public Health Information Sharing during the COVID-19 Pandemic in Sri Lanka. International Journal of Environmental Research and Public Health . 2024; 21(10):1268. https://doi.org/10.3390/ijerph21101268

Kamalrathne, Thushara, Jayasekara R. Jayasekara, Dilanthi Amaratunga, Richard Haigh, Lahiru Kodituwakku, and Chintha Rupasinghe. 2024. "Panic in the Pandemic: Determinants of Vaccine Hesitancy and the Dilemma of Public Health Information Sharing during the COVID-19 Pandemic in Sri Lanka" International Journal of Environmental Research and Public Health 21, no. 10: 1268. https://doi.org/10.3390/ijerph21101268

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Investing in Vaccines to Mitigate Harm from COVID-19 and Future Pandemics

University of Chicago, Becker Friedman Institute for Economics Working Paper No. 2024-118

32 Pages Posted: 23 Sep 2024

Rachel Glennerster

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Claire McMahon

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Catherine Che

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Christopher M. Snyder

Dartmouth College - Department of Economics; National Bureau of Economic Research

Sarrin Chethik

Date Written: September 23, 2024

This paper evaluates the social value of investing in vaccine research, development, and manufacturing capacity for pandemic preparedness and response. Rapid vaccination during pandemics can significantly reduce mortality, economic losses, and societal disruptions. However, vaccine manufacturers often lack sufficient incentives for speed and capacity expansion. Strategic policies by governments and international organizations could enhance these incentives and improve equitable vaccine distribution.

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In the rare event of a vaccine injury, Australians should be compensated

This article by Professor Nicholas Wood from The Children's Hospital at Westmead Clinical School, University of Sydney, Senior Lecturer Sophie Wenn from the Faculty of Medicine, The University of Queensland and Tim Ford, Senior Lecturer in Paediatrics at the School of Medicine, The University of Western Australia originally appeared in The Conversation on 24 September 2024.

Vaccination is one of the most effective methods to protect individuals and the broader public from disease. Vaccines are typically given to healthy people to prevent disease, so the bar for safety is set high.

People benefit from vaccination at an individual level because they’re protected from disease. But for some vaccines, strong community uptake leads to “herd immunity”. This means people who are unable to be vaccinated can be protected by the “herd”.

As with any prescribed medicine, vaccines can cause side effects. In the rare case that COVID vaccines did cause a specified serious injury (the scheme listed certain conditions that a person could claim for), Australians have been able to claim compensation. But this ends at the end of this month.

From then, Australians won’t be able to access no-fault compensation for any vaccine injury – from COVID or any others.

Why compensate people for vaccine injuries?

Fortunately, serious vaccine injuries are rare. Most are not a result of error in vaccine design, manufacturing or delivery, but are a product of a small but inherent risk.

As a result, people who suffer serious vaccine injuries cannot get compensation through legal mechanisms. This is because they can’t demonstrate the injury was caused through negligence.

Vaccine injury compensation schemes compensate people who have a serious vaccine injury following administration of properly manufactured vaccines.

The COVID vaccine claims scheme

In 2021, in recognition of the rare risk of a serious vaccine injury, and in support of the roll out of the COVID vaccine program, the Australian government introduced a COVID vaccine claims scheme.

The aim was to provide a simple, streamlined process to compensate people who suffered a moderate to severe vaccine injury, without the need for complex legal proceedings. It was limited to TGA-approved COVID vaccines, and to specific reactions.

The Australian government has said the scheme will close this month and claims need to be lodged before September 30 2024.

Following its closure, Australia will not have a vaccine injury compensation scheme.

Australia is lagging internationally

Australia lags behind 25 other countries including the United States, United Kingdom and New Zealand which have comprehensive no-fault vaccine injury compensation schemes. These cover both COVID and non-COVID vaccines.

The schemes are based on the ethical principle of “reciprocal justice”. This acknowledges that people acting to benefit not just themselves but also the community (for the benefit of the “herd”) should be compensated by the same community if it has resulted in harm.

So what happens in Australia now?

In Australia, people with non-COVID vaccine injuries or COVID vaccine injuries not covered by the current claims scheme must bear the costs associated with their injury by themselves or access publicly funded health care. They will not receive any compensation for their injury and suffering.

Australia’s National Disability Insurance Scheme (NDIS) provides funding support to access therapies for people with a permanent and significant disability. However, it does not cover temporary vaccine-related injuries.

Participants with vaccine injuries as a result of taking part in a clinical vaccine trial are compensated. This typically includes income-replacement, personal assistance expenses and reimbursement of expenses resulting from the incident, including medical expenses.

In Australia, we also have strong compulsion for people to receive routine vaccines through legislative requirements such as No Jab No Pay (which requires children to be immunised to receive some government payments) and, in some states, No Jab No Play (which requires children be fully immunised to attend childcare).

Countries such as ours that mandate vaccination without providing no-fault injury compensation schemes for rare vaccine injury could be abrogating the social contract by not protecting the individual and community.

It’s time to set up an Australian scheme

The Australian immunisation system is among the most comprehensive in the world. Our government-funded national immunisation program provides free vaccines for infants, children and adults for at least 15 diseases.

We also have a whole-of-life immunisation register and comprehensive vaccine safety surveillance system.

A recent Senate committee recommended: " the Australian government consider the design and compensation arrangements of a no-fault compensation scheme for Commonwealth-funded vaccines in response to a future pandemic event."

Vaccines are designed to be very safe and effective. But the “insurance policy” of an injury compensation scheme, if designed and communicated appropriately, should build trust and give confidence to health workers and the general public to support our national vaccine program. This is particularly important given the reductions in uptake of routine vaccines.

How should it work?

A no-fault vaccine injury compensation scheme could be funded via a vaccine levy system, as is done in the US, where an excise tax is imposed on each dose of vaccine.

An effective vaccine injury compensation scheme needs to be:  accessible, with low legal and financial barriers;  transparent, with clear decision-making processes, compensation frameworks and funding responsibilities;  timely, with short, clear timeframes for decision-making; fair, with people compensated adequately for the harm they’ve suffered.

Legislation to introduce and allocate funds to support an Australian injury compensation scheme for all vaccines is overdue. The draft National Immunisation Strategy 2025–2030 hinted at the opportunity to explore the feasibility of a no fault compensation scheme for all vaccines the Australian government funds, without committing to such a program.

An Australian vaccine injury scheme, covering all national immunisation program vaccines, not just pandemic use vaccines, should be seen as a crucial component of our public health system and a social responsibility commitment to all Australians.

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