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Vaccines FAQ

Last reviewed: January 13, 2022

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Developed by the COVID-19 Real Time Learning Network Editorial Staff with input from Drs. Robin Avery, Michael Boeckh, Andrea Cox, Anna Durbin, Kathy Edwards, Hana El Sahly, Josh Hill, Mike Ison, Catherine Liu, Kathy Neuzil, Paul Offit, Tom Shimabukuro and Keipp Talbot.

 

Featured FAQs

Q: What is known about the “Omicron” variant of SARS-CoV-2?

A: The Omicron variant (B.1.1.529) was identified as a “variant of concern” by the World Health Organization on Nov. 26, 2021. This variant was first reported to WHO from South Africa on Nov. 24, 2021, but has since been identified in multiple countries around the world, including the United States. The earliest sample known to contain this variant was collected in South Africa on Nov. 9, 2021.

The Omicron variant differs from previous variants of SARS-CoV-2 in the increased number of mutations present in the spike protein (37), relative to previous variants such as beta (10) and delta (9). These mutations may have implications for diagnostic testing, transmissibility, and neutralization by vaccine-induced antibodies. The impact on disease severity remains to be characterized. For more details and literature about Omicron please visit the SARS-CoV-2 variants page. 

Transmission:

Preliminary epidemiological data reported from South Africa suggest an increased risk of reinfection with the omicron variant as compared with other variants of concern. A recent sharp increase in cases in almost all provinces in South Africa coincided with the detection of the Omicron variant, and spike mutations such as Q498R and N501Y have been previously characterized as resulting in increased binding affinity for the ACE2 receptor, suggesting a molecular basis for more efficient spread. However, despite these preliminary observations, estimates of relative transmissibility are at risk for bias due to the nature of case detection early in an outbreak. As more widespread surveillance is established in the coming weeks, the risk of transmission of the Omicron variant relative to the delta variant will be better defined. 

Diagnostics:

Like the Alpha and Eta variants, the dominant BA.1 lineage of the Omicron variant has a deletion at amino acid position 69/70 that results in failure to detect the spike gene (commonly referred to as “S gene target failure”) specifically with the ThermoFisher TaqPath SARS-CoV-2 PCR assay. Since other targets of this particular assay remain detectable, S gene target failure can be used as a potential rapid surveillance marker for infections caused by Omicron, with the caveat that further confirmation is usually necessary because other SARS-CoV-2 variants can also have this signature. The less prevalent BA.2 lineage of Omicron does not have this deletion and therefore S gene target failure cannot be used as a surrogate surveillance marker. The impact of these mutations on other commonly used PCR platforms such as those from Roche, Cepheid, Biofire and Hologic, is under evaluation, but preliminary evidence suggests no loss in sensitivity. 

With regard to rapid antigen tests, the majority of these assays detect the nucleocapsid rather than spike protein and are therefore anticipated to be unaffected by the mutations specific to the Omicron variant. 

Immune escape:

Several mutations in the Omicron spike protein have been previously characterized and associated with decrements in vaccine efficacy. Studies to evaluate antibody neutralization using pseudoviral constructs using the Omicron spike protein are underway to determine if any of the newly identified mutations are also associated with decreased neutralization activity. 

Disease severity:

There are too few clinical data available to understand if the Omicron variant is associated with more severe COVID-19 or with unique symptoms. Many of the reported cases to date are reinfections and among young previously healthy individuals and have been mild. As additional case data are collected, the impact of the Omicron variant on disease epidemiology will become clearer.  

Q: Who should get a COVID-19 vaccine booster and when?

A: In the U.S., all adults aged 18 and older should receive a single booster dose of any COVID-19 vaccine under a revised eligibility policy that was FDA-authorized and CDC-recommended in November 2021 (the FDA has also authorized the use of booster doses for individuals aged 12-17 years who received the Pfizer-BioNTech vaccine). Single booster doses of any product approved or authorized in the U.S. may be administered as a booster at least six months after completion of a primary mRNA vaccination series or at least two months after primary vaccination with the single-dose J&J/Janssen COVID-19 vaccine. 

For up-to-date guidance and evidence synthesis, refer to our Vaccine Dosing & Schedule page. 

Q: What is the rationale and evidence for booster shots?

Booster doses of COVID-19 vaccines are one potential strategy to address the issue of waning immunity. The role of booster doses in this context relies on several assumptions, for which there is emerging supportive evidence:

Immune responses to SARS-CoV-2 vaccines have waned.

Evidence:
There is now extensive evidence that COVID-19 vaccine-induced antibodies decrease over time. One study compared the kinetics of humoral and cellular responses between recipients of the Pfizer-BioNTech, Moderna and Johnson & Johnson/Janssen COVID-19 vaccines.  In this study, the mRNA COVID-19 vaccines elicited robust neutralizing antibody responses shortly after vaccination that then decayed significantly over 8 months (Collier, October 2021).

In another prospective 6-month longitudinal immunogenicity study of nearly 5,000 health care workers aged 18 years and older at Sheba Medical Center in Israel who received two doses of the Pfizer-BioNTech COVID-19 vaccine, anti–SARS-CoV-2 spike antibody titers reached their peak between days 4 and 30 after the second dose of vaccine, then consistently declined over the entire study period, ultimately decreasing by a factor of 18.3 after 6 months. Neutralizing antibodies also decreased, but the rate of decline slowed after 3 months (Levin, October 2021).

Limitations:
Declines in antibody concentrations may not correlate with a decrement in memory responses, which may be more relevant for protection against severe disease. In a longitudinal study of humoral and cell-mediated immune responses to SARS-CoV-2 following mRNA COVID-19 vaccination (mostly the Pfizer-BioNTech COVID-19 vaccine), although anti-spike antibodies waned over 6 months, memory B- and T-cell responses were durable over the same time period (Goel, October 2021).

Furthermore, decrements in antibody responses demonstrate an imperfect correlation with waning clinical protection. As an example, in longitudinal immunogenicity and efficacy analyses of data from the Phase 1-3 clinical trials of the Pfizer-BioNTech COVID-19 vaccine, neutralizing antibody titers against wildtype SARS-CoV-2 decreased 6- to 13-fold over the 8 months after the second dose of vaccine (Falsey, September 2021). Vaccine efficacy against symptomatic infection did decrease from 96% to 84% but remained >96% against severe COVID-19 (Thomas, September 2021).

Waning immunity is (or is predicted to be) a significant driver of breakthrough infections, and in particular, severe cases.

Evidence:
There is accumulating evidence that neutralizing antibody concentrations correlate with the risk for symptomatic SARS-CoV-2 infection. For example, in a prospective cohort study of vaccinated health care workers in Israel, investigators identified 39 episodes of breakthrough infection for which preinfection neutralizing antibody concentrations were available. When compared with matched individuals who did not experience breakthrough infection, those who experienced breakthrough had lower concentrations of neutralizing antibodies (Bergwerk, July 2021). One study incorporated the observed kinetics of antibody decay following SARS-CoV-2 vaccines to model COVID-19 vaccine effectiveness over time and predicted a decline in vaccine effectiveness by 6 months (Khoury, July 2021). Multiple population-based vaccine effectiveness studies have since shown that mRNA COVID-19 vaccine effectiveness against symptomatic infection decreases with increasing time since vaccination, including in the U.S. (Self, September 2021; Fowlkes, August 2021; Tartof, October 2021), UK (Pouwels, October 2021; Public Health England report, September 2021) and Israel (Mizrahi, November 2021; Goldberg, October 2021). In addition, in a 6-month follow-up study of participants in the multinational Phase 2/3 trial of the Pfizer-BioNTech COVID-19 vaccine, before the emergence of the Delta variant, vaccine efficacy against infection had decreased to 84% by 6 months (Thomas, September 2021).

Limitations:
In all these studies, vaccine effectiveness against severe disease has remained high (>90%), even in the context of widespread circulation of the Delta variant. Additionally, the follow-up period for most of these studies also coincided with a relaxation of control measures (e.g., masking, social distancing, etc.) which may differentially impact the likelihood of exposure among vaccinated and unvaccinated individuals, and there may have been other important baseline differences between the groups who were vaccinated at different times that influenced their likelihood of infection.

Booster doses meaningfully augment immune responses (quantitatively or qualitatively) against SARS-CoV-2 (and relevant variants).

Evidence: 
Data for augmented immune responses following booster doses come from several studies. In a substudy of the Phase I clinical trial of the Pfizer-BioNTech COVID-19 vaccine, 23 participants received a booster dose of the vaccine at approximately 8 months after completion of the primary series. One month after the booster dose, neutralizing antibody titers against both wildtype virus and the Beta (B.1.351) and Delta (B.1.617.2) variants had increased to levels higher than at one month after the primary series (Falsey, September 2021). In another study of 97 Israeli healthcare workers aged 60 years and up who received a third dose of the Pfizer-BioNTech COVID-19 vaccine approximately 6-7 months after their primary series, the additional vaccine dose significantly increased anti-spike IgG antibody titers measured 10-19 days after vaccination (Eliakim-Raz, November 2021). 

Data were also presented for review by the Vaccines and Related Biological Products Advisory Committee in response to Pfizer’s biologics license application supplement seeking approval for a booster dose of its COVID-19 vaccine. A press release from Moderna described a study of 344 participants enrolled in a Phase 2 study of the Moderna COVID-19 vaccine who received a 50 µg booster dose at 6 months following completion of the primary series. In this press release, neutralizing antibody titers following the booster dose were reported to exceed those described in the Phase 3 trial. Additionally, the booster dose elicited robust antibody responses against SARS-CoV-2 variants of concern, including Beta (B.1.351), Gamma (P.1) and Delta (B.1.617.2). 

The two largest studies were multicenter studies that compared the safety and immunogenicity of a variety of different booster vaccines, including heterologous doses. In an interim analysis of a multicenter trial conducted at 10 sites in the U.S., the investigators reported immune responses following heterologous and homologous booster doses among >400 participants who had previously been vaccinated with either two doses of an mRNA COVID-19 vaccine or one dose of the Johnson & Johnson/Janssen COVID-19 vaccine (at least 12 weeks earlier). In this study, a booster dose with any product augmented antibody concentrations, but heterologous boosts (“mixed” regimens) elicited a more robust response than homologous boosts (“matched” regimens) (Atmar, October 2021 – preprint, not peer-reviewed).  

In another large study conducted in the UK, the investigators reported immune responses following heterologous and homologous boosters among >2800 participants who had previously received either two doses of the Oxford-AstraZeneca or Pfizer-BioNTech COVID-19 vaccine (at least 10-12 weeks earlier). Participants were randomized to receive boosts with the Oxford-AstraZeneca, Pfizer-BioNTech, Moderna, or Johnson & Johnson/Janssen COVID-19 vaccines, as well as the Novavax COVID-19 vaccine, the CureVac mRNA COVID-19 vaccine, and an inactivated vaccine. All the booster vaccines augmented immune responses following a Pfizer-BioNTech COVID-19 vaccine series, with the two currently authorized mRNA COVID-19 vaccines demonstrating the greatest effect (Munro, December 2021). 

Limitations: 

The durability of these augmented immune responses is unknown. In a longitudinal study of immune responses to SARS-CoV-2 following mRNA COVID-19 vaccination (mostly the Pfizer-BioNTech COVID-19 vaccine), the investigators separately analyzed the kinetics of the immune response in individuals with and without prior SARS-CoV-2 infection. For those with prior infection, the primary vaccine series may be considered a “booster.” In this group, antibody, memory B-cell and T-cell responses were augmented by vaccination but had declined nearly back to baseline by 6 months (Goel, October 2021). 

These augmented immune responses translate into increased vaccine effectiveness against SARS-CoV-2 infection and severe disease.

Evidence:
Multiple studies have evaluated the clinical effectiveness of a COVID-19 vaccine booster dose. These are mostly observational cohort studies based in Israel, which was one of the first countries to institute a booster vaccination program. Additionally, to date the data are limited to follow up periods when Delta was the predominant circulating variant, prior to the emergence of Omicron. Together, the data indicate that a third dose of Pfizer-BioNTech COVID-19 vaccine provides a significant protective effect against symptomatic COVID-19 (Bar-On, September 2021Saciuk, November 2021Bar-On, December 2021), COVID-19 hospitalization and death compared with two doses of vaccine (Barda, October 2021Arbel, December 2021). 

Limitations:
The durability of this improvement in vaccine effectiveness is unknown, especially in the context of emerging variants such as Omicron. These studies also did not specifically evaluate the effectiveness of booster doses after other primary series of COVID-19 vaccines. 

Q: What is waning immunity and how do we know if it is occurring?

A: Waning immunity refers to a phenomenon where an individual’s initial immune response to a vaccine diminishes over time and thus makes them vulnerable to natural infection (despite vaccination), often referred to as “breakthrough infection.” There is now extensive evidence that COVID-19 vaccine-induced antibodies decrease over time. However, this may have varying implications for clinical protection against symptomatic SARS-CoV-2 infection and severe COVID-19.

Evidence for whether waning immunity is leading to “waning protection” is almost always indirect because there are many factors that can influence vaccine effectiveness over time that are independent of waning immune responses. In fact, observations of waning protection, which may be suggested by lower population-level vaccine effectiveness estimates over time or rates of breakthrough infection out of proportion to what is expected, need not be attributable to waning immune responses.

Other factors that can contribute to time-dependent estimates of vaccine effectiveness include:

  • Changes in behavior, policy or local disease epidemiology that influence the “force of infection” (likelihood of being exposed/infected) over time. This means that the vaccine efficacy estimates determined in clinical trials are not fixed characteristics of the vaccines and cannot be extrapolated to all contexts.

  • Evolution of the pathogen that results in diminished protection conferred by vaccine-induced immune responses, such as novel variants. In other words, vaccine-induced immunity may be preserved, but may be less effective against a different version of the pathogen.

  • Differences in the comparison groups used to estimate vaccine effectiveness – for example, the unvaccinated population may experience fewer cases because it has a higher level of immunity (than what is assumed) because of natural infections that have accumulated over time; alternatively, individuals who were vaccinated earlier in the pandemic may differ from more recent vaccinees in their likelihood to have a poor initial response to the vaccine or to be exposed to SARS-CoV-2.

These issues are relevant because the relative contribution of these factors should inform the optimal use of vaccine “boosters” at a population level.

The key studies that contribute to our current understanding of waning protection, and their limitations, are summarized here:

Population-level evidence of decreasing vaccine effectiveness over calendar time

Several population-level observational studies have shown that COVID-19 vaccine effectiveness against infection has decreased over time (or that the incidence rate of SARS-CoV-2 infections in vaccinated individuals has increased over time) since the vaccines were first introduced (Rosenberg, September 2021; Scobie, September 2021; Fowlkes, August 2021; Nanduri, August 2021; Keehner, September 2021). Importantly, many of these same studies (and others) have shown that vaccine effectiveness against severe COVID-19 has remained stable (Bajema, September 2021; Tenforde, August 2021). Given that the follow-up period for these studies spanned the time period when the Delta variant emerged, several of these studies stratified their analysis by time period, calculating vaccine effectiveness before and after Delta became predominant. In these analyses, vaccine effectiveness was essentially preserved (compared with vaccine efficacy estimates from clinical trials) before the emergence of Delta but decreased following the emergence of Delta.

Key limitations: None of these studies adjusted their VE estimates by time since vaccination, none computed SARS-CoV-2 variant-specific VE estimates, and the follow-up period for all these studies also coincided with a relaxation of control measures (e.g., masking, social distancing, etc.).

Individual-level evidence of decreasing vaccine effectiveness by time since vaccination

Some studies have specifically evaluated the potential role of waning immunity by stratifying VE calculations by time since vaccination. Studies from the U.S. (Self, September 2021; Fowlkes, August 2021; Tartof, October 2021), UK (Pouwels, October 2021; Public Health England report, September 2021) and Israel (Mizrahi, July 2021 – preprint, not peer-reviewed; Goldberg, August 2021 – preprint, not peer-reviewed) all suggest that a longer time period since the second dose of an mRNA COVID-19 vaccine is associated with decreased VE against symptomatic infection. Notably, VE against severe disease appears essentially preserved. In addition, in a 6-month follow-up study of participants in the multinational Phase 3 trial of the Pfizer-BioNTech COVID-19 vaccine, before the emergence of the Delta variant, VE against infection had decreased to 84% by 6 months, but VE against severe disease remained >90% (Thomas, September 2021).

Key limitations: Not all these studies computed SARS-CoV-2 variant-specific VE estimates, the follow-up period for most of these studies also coincided with a relaxation of control measures (e.g., masking, social distancing, etc.), and there may have been important differences between the groups who were vaccinated at different times that influenced their likelihood of infection.

Q: What is known about SARS-CoV-2 variants “Delta plus” (also known as Delta with K417N), Lambda and Mu?

A: Although the Delta variant (B.1.617.2) has become the dominant SARS-CoV-2 variant in many countries, while SARS-CoV-2 continues to circulate worldwide, new variants will continue to emerge.

The “Delta plus” variant is a sublineage of the Delta variant (Pango lineage B.1.617.2 AY1) that was first identified in June 2021 in India. The Delta plus variant has been identified in multiple countries, but its prevalence remains low compared with the parent lineage (B.1.617.2). This variant contains the same mutations as the Delta variant plus an additional mutation in the spike protein, K417N, which had previously been identified in the Beta (B.1.351) and Gamma (P.1.) lineages. Mutations at this site are predicted to result in decreased antibody binding to the spike protein, though not to the same degree as other mutations such as E484K, and have been associated with decreased neutralization by monoclonal antibodies from both convalescent and postvaccination sera (Harvey, June 2021; Wang, April 2021).

The Lambda variant (Pango lineage C.37) was first identified in November 2020 in Peru, where it is now the dominant variant. It has since been identified in multiple countries, but its prevalence outside of Peru remains low. This variant contains multiple unique mutations, including L452Q. Mutations at this position (including L452R in Delta) have been associated with decreased neutralization by monoclonal antibodies and convalescent sera (Liu, March 2021).

The Mu variant (Pango lineage B.1.621) was first identified in January 2021 in Colombia. It has since been identified in multiple countries, but its prevalence outside of Colombia remains low. This variant contains two key mutations, N501Y and E484K, that overlap with the Beta and Gamma  variants of concern, which confer decreased susceptibility to neutralization by monoclonal antibodies, as well as convalescent and postvaccination sera (Harvey, June 2021; Wang, April 2021).

Notably, the Delta plus, Lambda, and Mu variants have not risen to the level of Variant of Concern  designation by WHO or CDC. To date, there are no clinical data about the clinical effectiveness of monoclonal antibodies or currently authorized COVID-19 vaccines against these variants.

Q: What is known about “mixing and matching” vaccine doses of different types?

A: In the U. S., the CDC currently recommends completing a primary series of a two-dose vaccine (or three-doses for certain immunocompromised patients) with the same product, whenever possible.

For booster vaccination, FDA has authorized the use of heterologous (or “mix and match”) booster doses for currently available COVID-19 vaccines (i.e., FDA-authorized or approved). Interim CDC guidance addresses clinical considerations related to heterologous booster doses, including patient benefit-risk considerations when selecting which booster dose to receive. 

For up-to-date guidance and evidence synthesis, refer to our Vaccine Dosing & Schedule page. 

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Efficacy of COVID-19 Vaccines 

Q: How effective are current COVID-19 vaccines against emerging SARS-CoV-2 variants of concern? 

A: The Phase 3 trials of most currently available COVID-19 vaccines began prior to the emergence of most SARS-CoV-2 variants of concern; therefore, their efficacy against these variants can only be extrapolated from post-authorization observational studies conducted in countries where these vaccines are in use and where variants are highly prevalent. 

Of note, vaccine effectiveness can be measured using a variety of different outcomes, including prevention of transmission (which would encompass reduction in asymptomatic and symptomatic infections), reduction in symptomatic illness, and reduction in severe disease, hospitalization, or death due to COVID-19. Although all these outcomes may be relevant from a public health perspective, prevention of severe disease, hospitalization and death are most relevant to the individual vaccine recipient.  

The Real-Time Learning Network has assembled a summary table of available data about vaccine and monoclonal antibody effectiveness against SARS-CoV-2 variants of concern, focusing on two outcomes – symptomatic infection and severe disease. Most of the available vaccine effectiveness data pertain to mRNA COVID-19 vaccines (largely Pfizer-BioNTech) or the Oxford-AstraZeneca COVID-19 vaccine. Finally, comparative vaccine effectiveness data depend on which variants were co-circulating at the time the analysis was done, thus estimates of vaccine effectiveness against Alpha were compared with ancestral strains (e.g., D614G), whereas estimates of vaccine effectiveness against Delta are compared with Alpha. 

Delta variant 
There are emerging data about vaccine effectiveness against the Delta variant. In a press release (not published, not peer-reviewed), public health authorities in Israel reported substantially decreased effectiveness of the Pfizer-BioNTech COVID-19 vaccine against symptomatic infection during the time period that Delta became the dominant circulating variant in that country. However, they also reported that vaccine effectiveness against severe illness and hospitalization was still >90%. Of note, these data are preliminary and have not been published. 

Investigators from Public Health England conducted a test-negative case-control study to evaluate the effectiveness of both the Pfizer-BioNTech and Oxford-AstraZeneca COVID-19 vaccines against the Delta variant over the time period when this variant emerged in the UK. In this analysis, a single dose of either vaccine had significantly lower effectiveness against SARS-CoV-2 infection due to Delta compared with Alpha (30.7% vs. 48.7%). However, after two doses, vaccine effectiveness was only slightly lower (88.0% vs. 93.7% for Pfizer-BioNTech and 67.0% vs. 74.5% for Oxford-AstraZeneca) (Bernal, July 2021). In a parallel analysis, vaccine effectiveness of two doses of both vaccines was >90% against hospitalization due to the Delta variant (Stowe, May 2021 -preprint not peer-reviewed). A cohort analysis of SARS-CoV-2 infections in Scotland similarly found decreased effectiveness of the Pfizer-BioNTech and Oxford-AstraZeneca COVID-19 vaccines against S gene target positive cases (a laboratory surrogate for Delta variant during the time period of the study) compared with S gene target negative cases (a laboratory surrogate for Alpha variant), but no difference in effectiveness against hospitalization due to the two variants (Sheikh, June 2021). Finally, a test-negative case-control study in Canada found that single doses of the Pfizer-BioNTech and Moderna COVID-19 vaccines were less protective against symptomatic infection due to the Delta variant compared with Alpha, but that two doses restored their protective effect comparable to that against Alpha – two doses of either the Pfizer-BioNTech, Moderna, or Oxford-AstraZeneca vaccines were >90% effective against hospitalization or death due to the Delta variant (Nasreen, July -preprint not peer-reviewed). 

Other variants 
mRNA COVID-19 vaccines 
Alpha: In an analysis of a mass vaccination campaign among U.K. health care workers with the Pfizer-BioNTech COVID-19 vaccine, the investigators measured the incidence of new SARS-CoV-2 infections from Dec. 8, 2020 to Feb. 5, 2021, when the B.1.1.7 variant accounted for >50% of circulating SARS-CoV-2 strains (Hall, April 2021). In this study, vaccine effectiveness was 70% (95% CI, 55-85) against SARS-CoV-2 infection (asymptomatic and symptomatic cases) starting 21 days after the first dose, and increased to 85% (95% CI, 74-96) starting 7 days after the second dose. 

In a separate study of nationwide SARS-CoV-2 surveillance data from Israel following a mass vaccination campaign with the Pfizer-BioNTech COVID-19 vaccine, vaccine effectiveness was 90.5% against symptomatic SARS-CoV-2 infection starting 7 days after dose 2. The prevalence of the B.1.1.7 variant was estimated to be 95%, based on the rate of spike gene target failure at one of the testing sites from which surveillance data were reported (Haas, May 2021). 

In another analysis of the impact of a mass vaccination campaign with the Pfizer-BioNTech COVID-19 vaccine in Qatar, the investigators estimated the prevalence of the B.1.1.7 variant to be 44.5%. In this study, vaccine effectiveness was 89.5% against any documented infection with the B.1.1.7 variant. Vaccine effectiveness against severe, critical or fatal SARS-CoV-2 infection due to any variant was 97.4% (Abu-Raddad, May 2021). 

Finally, in a test-negative design study of SARS-CoV-2 infections in Canada, the investigators found the vaccine effectiveness of the Pfizer-BioNTech vaccine to be 89% against Alpha  (Nasreen, July -preprint not peer-reviewed). 

Beta: In an analysis of the impact of a mass vaccination campaign with the Pfizer-BioNTech COVID-19 vaccine in Qatar, the investigators estimated the prevalence of the B.1.351 variant to be 50% respectively. In this study, vaccine effectiveness was 75% against any documented infection with the B.1.351 variant. Vaccine effectiveness against severe, critical or fatal SARS-CoV-2 infection due to any variant was 97.4% (Abu-Raddad, May 2021). In a separate test-negative design study of SARS-CoV-2 infections in Canada, the investigators found the vaccine effectiveness of the Pfizer-BioNTech vaccine to be 84% against Beta/Gamma (Nasreen, July -preprint not peer-reviewed). 

Gamma: There are limited data specifically focused on mRNA COVID-19 vaccine effectiveness against the Gamma variant. Given the overlap in mutations present in this variant and the Beta variant, it is assumed that vaccine performance against this variant would be similar to that observed against Beta. 

Viral vector COVID-19 vaccines 
Alpha: In a post-hoc analysis of the Phase 2/3 clinical trial of ChAdOx1 conducted in the U.K., where the B.1.1.7 variant emerged in late 2020, vaccine efficacy was 70.4% against symptomatic COVID-19 due to the B.1.1.7 variant, and 81.5% against symptomatic COVID-19 due to non-B.1.1.7 variants, but this difference was not statistically significant (Emary, April 2021). 

Beta: The Phase 3 trial of Ad26.COV2.S was conducted in multiple countries, where new SARS-CoV-2 variants did emerge, and strain sequencing analyses of COVID-19 cases in the study are being performed. As of Feb. 12, 2021, 71.7% of cases reported in the trial had been sequenced. In subgroup analyses of vaccine efficacy against moderate to severe/critical COVID-19 by country of participation, vaccine efficacy was lower in South Africa (vaccine efficacy of 52.0%; 95% CI, 30.3-67.4) compared to the United States (vaccine efficacy of 74.4%; 95% CI, 65.0-81.6). In the United States, 96.4% of strain sequences were identified as SARS-CoV-2 Wuhan-H1 variant D614G, whereas in South Africa, 94.5% of strain sequences were identified as 20H/501Y.V2 variant (B.1.351) (Sadoff, April 2021). 

One of the Phase 3 trials of ChAdOx1 was conducted in South Africa. During that study, 41 (97.6%) of the 42 SARS-CoV-2 viruses involved in primary endpoint analyses were sequenced, of which 39 (95.1%) were the B.1.351 variant. There were 19 COVID-19 cases among ChAdOx1 recipients (15 mild, 4 moderate, 0 severe) and 23 among placebo recipients (17 mild, 6 moderate, 0 severe), giving an overall vaccine efficacy of 21.9% (95% CI, -49.9-59.8), suggesting that ChAdOx1 is not protective against the B.1.351 variant. As further evidence of this difference in efficacy, the investigators in this study conducted a post-hoc analysis of vaccine efficacy limited to cases occurring before Oct. 31, 2020 (i.e., before the B.1.351 variant emerged in South Africa). In this analysis, vaccine efficacy was determined to be 75.4% (95% CI, 8.7-95.5), similar to the reported vaccine efficacy in Phase 3 trials (Madhi, February 2021). 

Gamma: There are limited data specifically focused on mRNA COVID-19 vaccine effectiveness against the Gamma variant. Given the overlap in mutations present in this variant and the Beta variant, it is assumed that vaccine performance against this variant would be similar to that observed against Beta. 

Q: Are the mRNA vaccines more efficacious than the viral vector vaccines? 

A: None of the COVID-19 vaccines have been directly compared head-to-head in the same population, and so the point estimates of vaccine efficacy for the mRNA vaccines (Moderna and Pfizer-BioNTech) and viral vector vaccines (Johnson & Johnson/Janssen and Oxford-AstraZeneca) cannot be directly compared with each other. The clinical trials for these vaccines were conducted at different times in different populations. Furthermore, the outcomes used to calculate the efficacy estimates differed between the studies (see previous question). The Pfizer-BioNTech, Moderna and Johnson & Johnson/Janssen vaccines have all been evaluated for emergency use authorization and met the efficacy criteria pre-specified by the FDA. They all have high efficacy, especially against severe COVID-19. 

Q: What do we know about breakthrough SARS-CoV-2 infections in vaccinated individuals? 

A: Our knowledge of SARS-CoV-2 breakthrough infections after vaccination is still evolving. Importantly, breakthrough infections occur at a much lower incidence compared with infections in unvaccinated individuals, therefore the occurrence of breakthrough infections does not diminish the critical importance of vaccination against COVID-19. 

To date, the data suggest that most breakthrough infections are associated with mild illness or are asymptomatic. There are insufficient published data on the virologic and immunologic aspects of breakthrough infections to be able to draw definitive conclusions regarding risk assessment (for breakthrough infection) after vaccination, transmissibility of breakthrough infection (symptomatic or asymptomatic), or appropriate management. Below are critical summaries of selected reports of breakthrough SARS-CoV-2 infections in the published literature: 

  • In an analysis of breakthrough SARS-CoV-2 infections reported to CDC through April 30, 2021, investigators described 10,262 cases, of which 27% (n=2,725) were asymptomatic, 10% (n=995) were hospitalized at the time of their infection and 2% (n=160) died. Notably, 29% of hospitalized patients with a reported breakthrough infection were asymptomatic or hospitalized for another reason and 18% of the deaths were asymptomatic at the time their breakthrough infection was identified or died from another cause. Only 5% (n=555) of the breakthrough infections had sequencing data available, and nearly two-thirds (64%, n=356) were identified as variants of concern (CDC, May 2021).  
  • In one of the largest case series of breakthrough infections reported to date, CDC investigators described a cluster of SARS-CoV-2 infections associated with large public gatherings in Barnstable County, Massachusetts (CDC, August 2021). This investigation described 469 COVID-19 cases, of which 346 (74%) occurred in fully vaccinated individuals. Notably, of the 133 infections for which genome sequencing data were available, 119 (89%) were due to the Delta variant. Of the 346 breakthrough cases, 274 (79%) reported symptoms, 4 (1.2%) were hospitalized, and none died. In this study the investigators reported cycle threshold (Ct) values as a surrogate for viral load and noted that the median Ct values in vaccinated individuals were similar to those who were unvaccinated, partially vaccinated, or with unknown vaccination status. 
    • Key limitations of this report include: incomplete data on the exposed population (which limits our ability to assess the relative incidence of infection in vaccinated and unvaccinated individuals); use of a surrogate measure of viral load (that does not distinguish between culturable virus, total RNA, or subgenomic RNA); and no description of the approach to viral detection (specimen type, timing of specimen in course of illness, etc.). 
  • In a separate study, investigators in Israel analyzed a cohort of 39 breakthrough cases (<1% of the 1497 fully vaccinated healthcare workers that underwent PCR testing) and found that the majority (N=26, or 67%) were mild (and none required hospitalization) and the remainder were asymptomatic. Although 29 (74%) of the case patients had a cycle threshold (Ct) value of <30 at some point during their infection, no secondary infections were documented. Of note, the time point of this low Ct value was not reported or compared with an unvaccinated cohort (Bergwerk, July 2021). 
  • In an analysis of SARS-CoV-2 infections identified through the HEROES-RECOVER network, an ongoing prospective cohort study of healthcare personnel, first responders, and other essential and frontline workers – investigators described 204 cases, of which 5 (2.5%) were fully vaccinated and 11 (5.4%) were partially vaccinated (the remaining >92% of cases were unvaccinated). Vaccinated or partially vaccinated individuals had fewer febrile symptoms and had fewer days of symptoms compared with unvaccinated individuals. In this study the investigators used quantitative RT-PCR to measure SARS-CoV-2 viral load in mid-turbinate nasal swabs and found that vaccinated individuals and lower viral loads and a shorter duration of RNA detection compared with unvaccinated individuals (Thompson, July 2021). 

Q: What is known about the impact of COVID-19 vaccination on SARS-CoV-2 transmission? 

A: There are limited data about the transmissibility of SARS-CoV-2 breakthrough infections, and apart from isolated case reports (Kernéis, August 2021), most of what is known is based on indirect evidence. Transmissibility depends on a variety of factors, including (but not limited to) the magnitude and duration of viral shedding. Prior to the emergence of the Delta variant, there was some evidence that COVID-19 vaccination may be associated with lower peak viral loads (Levine-Tiefenbrun, March 2021). Importantly, the increased transmissibility of the Delta variant has been attributed to higher viral loads and earlier viral shedding compared with ancestral strains of SARS-CoV-2 (Li, July 2021 -pre-print not peer-reviewed), which may have implications for the effect of COVID-19 vaccines on transmission of Delta. In a still unpublished study of Delta infections in Singapore, the investigators evaluated viral and serologic kinetics of infection in vaccinated and unvaccinated individuals – they found that although both vaccinated and unvaccinated individuals had similar initial cycle threshold (Ct) values, Ct values increased much faster (e.g., viral loads decreased much faster) in vaccinated individuals compared with unvaccinated individuals (Chia, July 2021 -pre-print not peer-reviewed). 

Prior to the emergence of Delta, in two large studies of household contacts of vaccinated and unvaccinated individuals with SARS-CoV-2 infection in the UK (Shah, March 2021 -preprint not peer-reviewed) and Netherlands (de Gier, August 2021), the risk of secondary infection was lower in contacts of vaccinated individuals compared with unvaccinated individuals. These findings are suggestive that COVID-19 vaccination may be associated with less transmission to close contacts – if these conclusions can be generalized to Delta remains to be seen. 

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COVID-19 Vaccines & Immunity 

Q: What is the utility of laboratory testing to determine if an individual has mounted an adequate immune response following COVID-19 vaccination?  

A: There is no established immunologic correlate of protection against SARS-CoV-2, and none of the commercially available immune assays (antibody or T cell) are FDA-approved to assess protective immunity against SARS-CoV-2 infection. This means it is not possible to reliably infer immunity from the results of such tests. As such, there is no current recommendation from the CDC or FDA to use currently available immune assays (antibody or T cell) against SARS-CoV-2 to assess for a protective immune response after vaccination. Furthermore, CDC does not recommend additional doses of COVID-19 vaccines based on the results of these tests.   

Q: How does natural immunity compare with vaccine-induced immunity to COVID-19?    

A: There are limited data comparing natural and vaccine-induced immunity to COVID-19. Observational studies of rates of reinfection among seropositive individuals cannot be directly compared with data from vaccine clinical trials or post-authorization studies of vaccine recipients. These studies were conducted in different populations, during different phases of the pandemic (when different control measures were in place and different variants were circulating) and using different methods of case ascertainment. Furthermore, in ecological studies that have examined rates of reinfection among previously infected individuals, the period of observation for reinfections was less than one year (and in some cases, just a few months) after initial infection, which limits any conclusions about the long-term durability of protection after natural infection.  

A few studies have compared the incidence of SARS-CoV-2 infection between individuals with evidence of either prior infection or vaccination in the same population over the same time period. These have found that the risk of infection was similarly low in those who had been previously infected or vaccinated (Bertollini, June 2021Lumley, July 2021Shrestha, June 2021 -preprint, not peer-reviewed).   

Notably, these studies have several key limitations that constrain what can be concluded about the need for vaccination of previously infected individuals. First, other than age and sex, none of these studies reported baseline characteristics of previously infected individuals, such as comorbidities, immune status or severity of initial COVID-19 illness – factors that have been shown to influence the magnitude and durability of the immune response generated by natural infection, which likely also influences its protective effect. Thus, it remains unclear if the findings from these studies can be extrapolated to all individuals with laboratory evidence of prior infection. Second, the duration of follow-up in all these studies is at most a few months; therefore, the durability of protection from natural infection versus vaccination cannot be determined.  

Finally, there are emerging data that in vitro immune responses following natural infection — especially mild infections — may not be as robust as compared with vaccine-induced responses, including against novel SARS-CoV-2 variants of concern (Marot, May 2021Greaney, June 2021Caniels, June 2021 -preprint, not peer-reviewedHerzberg, June 2021 -preprint, not peer-reviewedPsichogiou, June 2021 – preprint, not peer-reviewed).    

Q: What is the evidence regarding waning immunity after COVID-19 vaccination (or natural infection)?  

A: There are limited clinical data on waning immunity after COVID-19 vaccination. Since COVID-19 vaccines only began to be used in the general population in late 2020, studies are naturally limited in their ability to determine the effect of time on vaccine effectiveness. In addition, it is possible that in the future emerging variants of concern could evade vaccine-induced immunity enough to result in high rates of severe disease, which would make it difficult to discern whether vaccine effectiveness was decreasing due to waning immunity or vaccine escape.  

Notably, population-based studies whose primary objective was to compare the effectiveness of COVID-19 vaccines against emerging variants (for example, Alpha vs. Delta) found that the Pfizer-BioNTech, Moderna, and Oxford-AstraZeneca vaccines were as effective against the Alpha variant as they were in earlier phases of vaccine roll-out (Bernal, July 2021Nasreen, July -preprint, not peer-reviewed).  

As detailed in another FAQ, observational studies of previously infected individuals have demonstrated a protective effect of natural infection against re-infection; however, the duration of follow-up in all these studies is at most a few months; therefore, the durability of protection from natural infection cannot be determined.  

Q: What is known about natural immunity following SARS-CoV-2 infection?   

A: Multiple studies have demonstrated durable humoral (Rodda, January 2021Dan, February 2021Sokal, March 2021Turner, May 2021Anand, June 2021Cohen, June 2021 -preprint, not peer-reviewed) and cell-mediated (Rodda, January 2021Dan, February 2021Kang, March 2021Breton, April 2021Cohen, June 2021 -preprint, not peer-reviewed) immune responses to SARS-CoV-2 in individuals several months after recovery from SARS-CoV-2 infection. Some studies have also shown that these immune responses vary based on the severity of initial infection, with severe COVID-19 (i.e., requiring hospitalization, intensive care unit admission or mechanical ventilation) being associated with more robust antibody and T cell responses (Lynch, January 2021Kang, March 2021Betton, April 2021). Our understanding of the longevity of these responses is still evolving and naturally limited by the timeframe since the pandemic began.    

In addition to in vitro studies, there is also compelling evidence that natural SARS-CoV-2 infection can decrease the risk of reinfection with SARS-CoV-2. For example, in large observational cohort studies in the U.S. (Sheehan, March 2021Letizia, April 2021Harvey, May 2021Rennert, May 2021Shrestha, June 2021 -preprint, not peer-reviewed), U.K. (Lumley, February 2021Hall, May 2021Lumley, July 2021), Denmark (Hansen, March 2021), Italy (Vitale, May 2021Manica, July 2021), France (Dimeglio, January 2021), Switzerland (Leidi, July 2021) and Qatar (Abu-Raddad, December 2020Bertollini, June 2021), prior documented infection with SARS-CoV-2 (based on a PCR or antibody result) was associated with a decreased rate of subsequent infection in the ensuing months, including up to 12 months after the initial infection.   

Despite these observations from laboratory and ecological studies, it is also clear that SARS-CoV-2 reinfections do occur. Although reinfections tend to be milder (Qureshi, April 2021Abu Raddad, May 2021), severe (and even fatal) cases have been reported (Tillet, January 2021Cavanaugh, February 2021Qureshi, April 2021).   

Importantly, how the magnitude and durability of the protective effect of natural infection varies by baseline factors such as age, comorbidities or immune status, or the severity of the initial SARS-CoV-2 infection, remains unclear. For example, in one study, the protective effect of prior infection observed among individuals aged greater than 65 years was significantly lower than that observed for the entire cohort (Hansen, March 2021). Furthermore, the follow-up period of most of the published observational studies of natural immunity occurred prior to the spread of SARS-CoV-2 variants against which immune responses may be less robust. In one analysis of U.K. health care workers, the degree of protection conferred by seropositivity did not vary based on whether the infecting strains were Alpha/B.1.1.7 (inferred based on S-gene target failure, or SGTF) or not (Lumley, July 2021). The protective effect of prior infection with historical SARS-CoV-2 variants against reinfections due to other novel variants of concern remains poorly characterized.   

Q: What tests can be used to document prior SARS-CoV-2 infection, and how does one interpret the results?    

A: Measures of the immune response to SARS-CoV-2 antigens (either antibody or T cell responses) can identify individuals previously infected with SARS-CoV-2. Currently, only antibody assays are commercially available. For vaccinated individuals, to differentiate between the immune response to past infection versus the COVID-19 vaccine itself — which all use the spike protein as the vaccine antigen — immune responses to non-spike SARS-CoV-2 antigens (i.e., nucleocapsid) should be measured.   

The performance characteristics of commercial antibody assays are variable. In general, a positive antibody test result in an unvaccinated individual (or a positive anti-nucleocapsid antibody response in a vaccinated individual) is strong evidence for prior SARS-CoV-2 infection. However, a negative result does not exclude prior infection, because antibodies may wane to undetectable levels within a few months of infection. For more details, please refer to the Overview of Testing for SARS-CoV-2 (COVID-19) and Interim Guidelines for COVID-19 Antibody Testing pages maintained by CDC.    

Importantly, none of the commercially available antibody assays are FDA-approved to assess protective immunity against SARS-CoV-2. Baseline serologic testing to assess for prior infection solely for the purpose of vaccine decision-making is not recommended, and CDC does not recommend “exempting” previously infected individuals from vaccination. Indeed, in one study of five FDA-approved antibody assays, neutralizing antibody concentrations in two seropositive individuals that were protected against reinfection during a wildtype SARS-CoV-2 outbreak on a fishing vessel were similar to those in five fully vaccinated individuals that experienced breakthrough infections with SARS-CoV-2 variants of concern (Bradley, June 2021). This underscores the point that serostatus may not be entirely predictive of general protection from or vulnerability to the virus, particularly variants of concern.    

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Safety of COVID-19 Vaccines

Q: What is the association between mRNA COVID-19 vaccines and myocarditis/pericarditis?  

A: Since April 2021, both CDC and the European Medicines Agency have been assessing cases of myocarditis and pericarditis temporally associated with mRNA COVID-19 vaccination. Based on data reported to the Vaccine Adverse Event Reporting System in the United States, such cases of myopericarditis occurred mostly in adolescent males and young adults aged 16 years or older and typically occurred within a few days of the second dose of an mRNA COVID-19 vaccine.  

Several small case series of myocarditis following COVID-19 vaccination have since been published (Marshall, June 2021Rosner, June 2021Abu Mouch, June 2021). These reports describe a total of 20 individuals — all male, 85% (17 out of 20) under the age of 30 and 95% (19 out of 20) having received an mRNA COVID-19 vaccine (18 Pfizer-BioNTech and 1 Moderna). Symptomatic myocarditis occurred within 4 days of receipt of the second dose of mRNA COVID-19 vaccine in 85% (17 out of 20) of these individuals. All of these patients had brief hospitalizations and made a full recovery.  

In a presentation of VAERS safety data to the FDA Vaccines and Related Biological Products Advisory Committee, a total of 789 cases of myocarditis/pericarditis following mRNA COVID-19 vaccines were identified (216 after the first dose, 573 after the second dose). The observed rate of myocarditis/pericarditis was higher than what would be expected based on population-level background incidence rates. The median age at time of onset was 30 years (range 12-94) for cases after dose #1 and 24 years (range 14-87) for cases after dose #2. The majority of cases (75%) occurred in males.  

The mechanism of myocarditis/pericarditis following mRNA COVID-19 vaccination remains unclear. Monitoring and follow-up of cases of myocarditis/pericarditis following COVID-19 vaccination is ongoing.  

Q: In comparing the mRNA COVID-19 vaccines and the Ad26.COV2.S vaccine, which is safer and will have fewer side effects for people? 

A: In the Phase 3 trial data submitted to FDA, the most common solicited adverse reactions among Ad26.COV2.S vaccinated individuals were injection site pain (48.6%), headache (38.9%), fatigue (38.2%), muscle pain (33.2%), nausea (14.2%) and fever (9.0%). These were more common in patients younger than 60 years of age. Overall, these rates were lower than those reported for both mRNA vaccines; however, all the currently authorized COVID-19 vaccines are safe. 

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COVID-19 Vaccination by Patient Population

Q: What is the current recommendation regarding additional vaccine doses in immunocompromised patients? 

A: In August 2021 FDA amended the emergency use authorizations (EUAs) for both the Pfizer-BioNTech and Moderna COVID-19 vaccines to allow for the use of a third dose of both products in certain immunocompromised patients. CDC’s Advisory Committee on Immunization Practices (ACIP) subsequently recommended consideration of a third dose of mRNA vaccine for the following patient populations: 

  • Active treatment for solid tumor and hematologic malignancies 
  • Receipt of solid-organ transplant and taking immunosuppressive therapy 
  • Receipt of CAR-T-cell or hematopoietic stem cell transplant (within 2 years of transplantation or taking immunosuppression therapy) 
  • Moderate or severe primary immunodeficiency (e.g., DiGeorge syndrome, Wiskott-Aldrich syndrome) 
  • Advanced or untreated HIV infection 
  • Active treatment with high-dose corticosteroids (i.e., ≥20mg prednisone or equivalent per day), alkylating agents, antimetabolites, transplant-related immunosuppressive drugs, cancer chemotherapeutic agents classified as severely immunosuppressive, tumor-necrosis (TNF) blockers, and other biologic agents that are immunosuppressive or immunomodulatory. 

The third vaccine dose should ideally be the same product as the initial two-dose mRNA COVID-19 vaccine series that the patient received (Pfizer-BioNTech or Moderna) – however, if that product is not available, the other mRNA COVID-19 vaccine can be used. The third dose should be administered at least 28 days after completion of the initial two-dose mRNA COVID-19 vaccine series. 

There are no current recommendations to administer additional mRNA COVID-19 vaccine doses to prior recipients of the Johnson & Johnson/Janssen COVID-19 vaccine, or to administer additional doses of the Johnson & Johnson/Janssen COVID-19 vaccine. 

Given the potential for a less robust immune response to COVID-19 vaccines among immunocompromised individuals, CDC continues to recommend that these individuals continue appropriate precautions (masking, social distancing, etc.) even after vaccination. 

Q: What is the benefit of vaccinating individuals who have had COVID-19? 

A: Multiple studies have shown that previously infected individuals mount a robust immune response following receipt of COVID-19 vaccines, even after just a single dose. Furthermore, there are accumulating data that vaccination after prior infection can boost immune responses against SARS-CoV-2 variants of concern – in fact, the vaccine response in previously infected individuals may be superior to that in individuals without prior infection (Wang, June 2021Stamatatos, June 2021Reynolds, June 2021Lyski, June 2021 -preprint, not peer-reviewedLeier, June 2021 -preprint, not peer-reviewedUrbanowicz, August 2021). 

Although the clinical trials of COVID-19 vaccines excluded seropositive individuals from their efficacy calculations, there are emerging data that vaccination can also confer protection against reinfection. In a case-control study of SARS-CoV-2 reinfections in Kentucky, investigators found that individuals who had had natural infection in 2020 and who did not receive a vaccine had 2.34 times the odds of reinfection compared with individuals who had natural infection and then subsequently received a COVID-19 vaccine (Cavanaugh, August 2021). 

Q: What is known about the safety of the COVID-19 vaccines in pregnant or lactating individuals? 

A: Pregnant people were excluded from the pre-authorization studies of all the COVID-19 vaccines. A small number of pregnancies did occur during the Phase 3 trials (23 in the Pfizer-BioNTech trial, 13 in the Moderna trial and 8 in the Johnson & Johnson/Janssen trial), but too few to draw any meaningful conclusions about safety. Thus, our knowledge of the safety of COVID-19 vaccines in pregnancy comes from post-authorization studies. 

In an analysis of safety data collected through v-safe and VAERS (Shimabukuro, April 2021), investigators found 35,691 individuals who were identified as pregnant (30,887 or 86.5% were pregnant at the time of vaccination) and who had received a COVID-19 vaccine between Dec. 14, 2020 and Feb. 28, 2021. During this time, only the Pfizer-BioNTech and Moderna COVID-19 vaccines were authorized for emergency use in the U.S. Overall, local and systemic reactogenicity events occurred at a similar rate between pregnant and non-pregnant women. 

The authors also analyzed the v-safe pregnancy registry, which included data from 3,958 pregnant people who had received a COVID-19 vaccine. Of these, nearly all (>98%) were between age 25-44 years, 2,136 (54%) had received the Pfizer-BioNTech COVID-19 vaccine and 1,822 (46%) had received the Moderna COVID-19 vaccine; additionally, 1,132 (28.6%) received their first dose of vaccine in the first trimester, 1,714 (43.3%) received it in the second trimester, and 1,019 (25.7%) received it in the third trimester. There were 827 individuals who completed their pregnancy during this time period, of whom 712 individuals delivered 724 live-born infants; of these 9.4% were born preterm, 3.2% were small for gestational age, and 2.2% had major congenital anomalies. These rates were similar to those reported for pregnancies prior to the pandemic; thus, no safety signal was identified for the mRNA COVID-19 vaccines in pregnancy. 

No clinical safety data specific to the Johnson & Johnson/Janssen COVID-19 vaccine have been published, and the Phase 3 trial of Ad26.COV2.S excluded individuals who were pregnant at the time of screening or planned to become pregnant within 3 months of vaccination. Only 8 pregnancies occurred during the conduct of that study through Jan. 22, 2021 (4 in the vaccine group, 4 in the placebo group), thus no conclusions about safety can be drawn. 

The Pfizer-BioNTech, Moderna and Johnson & Johnson/Janssen COVID-19 vaccine EUAs/approvals do not exclude pregnant or lactating individuals. Per CDC ACIP recommendations, people who are pregnant or breastfeeding may choose to be vaccinated with any of these vaccines. There is no recommendation for routine pregnancy testing before receipt of a COVID-19 vaccine. Those who are trying to become pregnant do not need to avoid pregnancy after COVID-19 vaccination. The EUA for the Johnson & Johnson/Janssen vaccine has been updated to include information about the risk of thrombosis with thrombocytopenia syndrome in women under age 50 (who are of childbearing age). 

The American College of Obstetricians and Gynecologists maintains updated recommendations regarding COVID-19 vaccination in pregnant and lactating individuals. 

Q: Can the COVID-19 vaccines make people of child-bearing age infertile? 

A: No. There is no evidence linking any of the COVID-19 vaccines to infertility. This myth arose as a result of misinformation circulated on the internet regarding the antigen created by these vaccines (the SARS-CoV-2 spike protein) and its supposed similarity to a protein important for placental attachment (syncytin-1). None of the COVID-19 vaccines contain syncytin-1, nor does the genetic material used in the vaccines encode for syncytin-1. Furthermore, the SARS-CoV-2 spike protein that is generated as a result of vaccination with the currently available COVID-19 vaccines has no structural similarity to syncytin-1, and no data indicate that the antibodies formed as a result of COVID-19 vaccination target syncytin-1.

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COVID-19 Vaccine Practical Considerations

Q: Do COVID-19 vaccines affect the performance of SARS-CoV-2 diagnostic tests?   

A: Receipt of a COVID-19 vaccine will not affect the result of PCR or antigen-based tests for SARS-CoV-2 infection. Antibody-based tests may or may not be affected by prior COVID-19 vaccination depending on the type of assay being used. Assays that measure IgM or IgG antibodies against SARS-CoV-2 nucleocapsid protein will not be affected by currently authorized COVID-19 vaccines because the vaccine does not contain or encode the nucleocapsid protein. Assays that measure antibodies against SARS-CoV-2 spike protein may be variably affected by prior vaccination; however, none of the currently available anti-spike antibody assays is authorized for assessing post-vaccination immunity. 

Q: Are there recommendations to test for antibodies to the vaccine after administration? 

A: No. At this time antibody testing is not recommended to assess for immunity to COVID-19 following vaccination with any COVID-19 vaccine. A correlate of protection against SARS-CoV-2 infection has not been definitively established; therefore, the results of antibody testing following vaccination should not be used to make vaccination decisions. 

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