Facebook Twitter LinkedIn Email

Vaccines FAQ

Last Updated: March 5, 2021

On this page:

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.

Mechanisms of COVID-19 Vaccines

Q: What are mRNA vaccines and how do they work?  

A: mRNA vaccines contain messenger RNA, a single-stranded RNA molecule that complements DNA. MRNA is created in the nucleus when DNA is transcribed by RNA polymerase to create pre-MRNA (Zipursky, 2000). Pre-MRNA is then spliced into mRNA, which is exported from the nucleus to the cytoplasm and “read” by ribosomes (the translation machinery of cells). Ribosomes then make proteins.  

mRNA vaccines use lab-created mRNA encapsulated within nanoparticles. mRNA vaccines deliver mRNA directly to the cytoplasm. Once the mRNA is in the cytoplasm ribosomes translate it, which results in the creation of a protein antigen that triggers an immune response (Schlake, 2012). The mRNA does not enter the nucleus, and therefore cannot be incorporated into the genome. Its presence in the cell is transient, and it is quickly metabolized and eliminated via cellular processing mechanisms (Mulligan, 2020). mRNA vaccines do not utilize any element of an organism. Unlike conventional vaccines, which can take months to produce, mRNA vaccines can be created quickly and are more easily scaled because they use an organism’s genetic code.   

Two mRNA vaccines are available under emergency use authorization by FDA: the Pfizer-BioNTech COVID-19 vaccine and Moderna COVID-19 vaccine, the latter of which was developed in partnership with the National Institute of Allergy and Infectious Diseases. Both vaccines are lipid nanoparticle-formulated, nucleoside-modified mRNA vaccines encoding the prefusion spike glycoprotein of SARS-CoV-2, the virus that causes COVID-19.    

Q: Does the mRNA delivered by the vaccines “deteriorate” in the cell, or is it actively extruded from the cell?  

A: The mRNA is degraded quickly by normal intracellular processes. The cell breaks down and gets rid of the mRNA soon after it has been translated by the ribosome.  

Q: How long does the spike protein remain on the cell surface?  

A: The spike protein can be found in three different ways after translation within the cell. The protein can be presented on the cell surface in its native expression form. It is also processed within the cell so different peptides that make up the protein are expressed in the context of major histocompatibility complex class I and MHC class II. MHC proteins play a key role in the adaptive branch of the immune system, presenting peptides on the cell surface for recognition by T cells. The protein may also be secreted and then taken up by antigen presenting cells and re-processed. The protein may be found on the surface of the cell in either its peptide form or its native form, likely until the cell dies or interacts with other immune cells. 

Q: How long does the spike protein made by the body (via encoding through the mRNA vaccine) last in the body?  

A: The protein lasts the same amount of time as other proteins made by the body. Exact time is not known, but it is estimated to be a few weeks.  

Q: Since the Janssen COVID-19 vaccine is vector associated, may it be transmitted in vivo?

A: The viral vector used in the Ad26.COV2.S vaccine is replication incompetent. This means it does not replicate within the human body, and there is no possibility for transmission of the viral vector to other individuals.

Q: Can the vaccine mRNA alter cellular DNA?  

A: For the vaccine mRNA to alter someone’s DNA, several events would need to occur. First, mRNA would need to enter the cell nucleus, where DNA resides. However, vaccine mRNA does not have the nuclear access signals that would allow it to enter the nucleus — it can’t get in. Second, once in the nucleus, the mRNA would have to be converted to DNA. This would require an enzyme called reverse transcriptase, which the mRNA vaccines don’t contain. Third, an enzyme called integrase is needed for mRNA to insert itself into DNA; the mRNA vaccines don’t contain integrase.  

In short, the mRNA vaccines lack all of the basic requirements necessary to alter DNA. The vaccine mRNA remains in the cell cytoplasm for just a few days before it is destroyed. Of note, there are more than 200,000 cellular mRNAs per cell, each making a host of proteins and enzymes. The mRNA vaccines introduce only a few copies of mRNA into cells.  

Q: Can mRNA alter cellular RNA?  

A: No. The vaccine mRNA is delivered to the cytoplasm, where it is translated by ribosomes, resulting in the creation of the SARS-CoV-2 spike protein. It is then degraded.  

Q: Is this mRNA self-amplifying?  

A: No, the vaccine mRNA is not self-amplifying

Q: If the Pfizer-BioNTech or Moderna mRNA is introduced into a cell in which HIV-1 is replicating, will any portion of the vaccine mRNA be reverse transcribed into DNA?  

A: HIV-1 replication occurs in the cell nucleus; the mRNA delivered by the mRNA COVID-19 vaccines does not enter the nucleus. Rather, it stays in the cytoplasm to be translated. Therefore, the mRNA cannot be transcribed into DNA.  

 

Efficacy of COVID-19 Vaccines 

Q: What does “vaccine efficacy” mean, and how was efficacy measured in the Pfizer-BioNTech and Moderna vaccine trials — disease or infection prevention?  

A: The primary efficacy endpoint in both trials was clinical disease; reduction in infection was not assessed as a primary endpoint, although additional data utilizing serologic endpoints are being collected in both the Moderna and Pfizer-BioNTech trials. When the term “vaccine efficacy” is discussed in relation to these vaccines, it generally refers to efficacy at preventing clinical disease unless otherwise specified. More information on the efficacy of these vaccines is available on the Pfizer-BioNTech COVID-19 Vaccine and Moderna COVID-19 Vaccine pages of the COVID-19 Real-Time Learning Network.  

Q: What is the durability of immune response to COVID-19 vaccination? How long are people expected to be protected?  

A: In both the Pfizer-BioNTech COVID-19 vaccine Phase 2/3 trial and the Moderna COVID-19 vaccine Phase 3 trial, participants have not been followed long enough to make firm conclusions on the durability of the immune response; these data are being collected in the trials and will be reported over time. As participants in the Pfizer-BioNTech clinical trial received a second dose 3 weeks after the first dose, there are currently no data of protection lasting longer than a few weeks after the first dose. In a Phase 1 open-label dose escalation trial of the Moderna COVID-19 vaccine, immunogenicity data 119 days after the first vaccination (90 days after the second vaccination) (Jackson, November 2020) and at the 100-μg dose, mRNA-1273 produced high levels of binding and neutralizing antibodies that declined slightly over time.  

Q: What information is available on emerging SARS-CoV-2 variants? Will the mRNA vaccines’ efficacy be impacted by these variants?   

A: Viruses mutate over time; therefore, new variants of viruses tend to emerge. The majority of such mutations do not produce relevant changes to viruses, but occasionally mutations occur that may benefit the virus.   

In November 2020, reports of new variants circulating in the U.K., U.S., Canada, South Africa and other countries emerged (Rambaut, November 2020; Tegally, December 2020; Davies, December 2020; Greany, January 2021). One strain, referred to as 20B/501Y.V1, VOC 202012/01 or B.1.1.7 lineage, appears to have been circulating in the U.K. as of September 2020 and has a large number of mutations. Laboratory data have suggested this strain may be more easily transmitted than the strain of SARS-CoV-2 that originated in Wuhan (CDC, January 2021), and epidemiologic data suggest it may be over 50% more transmissible (Davies, December 2020). Further, recent data suggests that this variant may be more deadly than the original strain. This variant has since been detected in numerous countries around the world, including the United States and Canada. In addition, other variants have emerged in the U.S.  

In South Africa, another strain called 20C/501Y.V2, or B.1.351 lineage, also may be associated with increased transmissibility (Tegally, December 2020). Cases attributed to this variant have been detected outside of South Africa, including in the United States. This variant shares some mutations with the B.1.1.7 lineage, most notably the N501Y substitution, which is located in the SARS-CoV-2 spike protein.   

CDC has begun tracking and publicly reporting variant COVID-19 case counts in the United States. Currently there is no clear evidence this variant, or any other, is associated with more severe disease or different clinical outcomes. Scientists are also working to better understand the impact of these variants on COVID-19 vaccine responses. In a recent non-peer-reviewed in-vitro study, scientists generated isogenic N501 and Y501 SARS-CoV-2 (Xie, January 2021). They then obtained the sera of 20 patients who had participated in the Pfizer-BioNTech COVID-19 Phase 1 and 2/3 vaccine trials and tested it for neutralization of N501 and Y501 viruses. The authors found equivalent neutralization of the viruses, implying no difference in effectiveness of the antibodies generated by the vaccine. This small study has multiple limitations, including the fact that the mutated viruses used did not contain all the mutations found in the B.1.1.7 or B.1.351 lineage viruses. No conclusions regarding the effectiveness of the Pfizer-BioNTech COVID-19 vaccine can be made. Additional efforts are underway to characterize the cross neutralization of antibodies generated by vaccines and test these variants in animal models. It is important to note that the correlates of protection of the currently available COVID-19 vaccines are not known, and it is believed that the protection does not solely rely on generation of antibodies, but on the presence of cellular immunity (i.e., T-cells) as well.  

Q: What do we know about the ability of the mRNA COVID-19 vaccines to prevent viral transmission (i.e., spread)?  

A: It is currently unknown whether vaccinated individuals can develop asymptomatic disease and transmit SARS-CoV-2 to others. Therefore, it important to continue practicing other infection prevention measures, such as wearing a face mask and physically distancing. In the Pfizer-BioNTech and Moderna trials, the primary efficacy endpoint of both studies was clinical disease; asymptomatic infection was not reported in the published interim analysis of the Pfizer-BioNTech COVID-19 vaccine trial, but serology was collected during the trial and that data will be published in the future. As baseline serostatus was known, if a person converted from negative to positive serology during the trial it would imply asymptomatic infection.  

Moderna’s protocol-specified analysis on the efficacy against asymptomatic infection was not available at the time of the EUA submission. However, Moderna did collect pre-dose 1 and pre-dose 2 nasopharyngeal swabs for SARS-CoV-2 virus and performed a descriptive study comparing the number of positive swabs at the pre-dose 2 time point in baseline seronegative participants. Amongst baseline negative participants, 14 participants in the vaccine group and 38 participants in the placebo group had evidence of SARS-CoV-2 infection at the second dose without evidence of COVID-19 symptoms. There were approximately two-thirds fewer swabs that were positive in the vaccine group as compared to the placebo group at the pre-dose 2 time point, suggesting that some asymptomatic infections start to be prevented after the first dose. More complete data are needed to draw conclusions and are forthcoming.   

Q: What is the estimated time frame until likely immunity is achieved from symptomatic disease for either mRNA vaccine after the second dose? 

A: Our current knowledge regarding when vaccinated persons can expect to achieve a high level of protection from developing symptomatic COVID-19 is derived from the Moderna and Pfizer-BioNTech COVID-19 vaccine clinical trial data. In a secondary analysis in the Moderna COVID-19 vaccine study, 95% efficacy for prevention of symptomatic COVID-19 was seen at 14 days after receiving the second dose. In the Pfizer-BioNTech COVID-19 vaccine trial, 95% efficacy for the prevention of symptomatic disease was seen as early as 7 days after receiving the second dose. 

Q: Are the mRNA vaccines more efficacious than Ad26.CoV2.S? How does the single dose of the Janssen vaccine compare to two doses of Pfizer or Moderna in terms of efficacy?

A: The point estimates of vaccine efficacy for the mRNA vaccines (mRNA-1273 and BNT162b2) and Ad26.COV2.S cannot be directly compared. 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 - for example, in the phase III study of Ad26.COV2.S, the investigators measured the incidence of moderate to severe/critical COVID-19 at least 14 and 28 days after vaccination; in contrast in the phase III study of mRNA-1273, the investigators measured the incidence of symptomatic COVID-19 at least 14 days after the second dose of the vaccine. All of these vaccines met the criteria pre-specified by the FDA for emergency use authorization. 

Q: Was there difference in efficacy between young and older group of vaccine recipients in the Janssen COVID-19 vaccine trial in individuals less than 65 years compared to those greater than 65 years?

A: When stratified by age, the vaccine efficacy was 66.1% (95% CI: 53.3- 75.8) for participants 18 to <60 years of age and 66.2% (95% CI: 36.7-83.0) for participants ≥60 years of age at least 28 days after vaccination.

Q: How effective is the Janssen COVID-19 vaccine against SARS-CoV-2 variants?

A: The data submitted to FDA as part of the EUA application did not directly address vaccine efficacy against emerging SARS-CoV-2 variants. However, vaccine efficacy estimates were computed for each participating country where the proportion of circulating variants was different based on strain sequencing data that was collected as part of the study. For example, as of February 12, 2021, in the United States, 73.5% of cases had been sequenced, of which 96.4% were identified as SARS-CoV-2 Wuhan-H1 variant D614G. In contrast, in South Africa, 66.9% of cases had been sequenced, of which 94.5% were identified as 20H/501Y.V2 variant (B.1.351). In subgroup analyses of vaccine efficacy against moderate to severe/critical COVID-19 starting at least 28 days after vaccination, vaccine efficacy was lower in South Africa (vaccine efficacy of 64.0%; 95%CI 41.2-78.7) compared to the United States (vaccine efficacy of 72.0%; 95%CI 58.2-81.7), but the confidence intervals were overlapping.

 

Safety of COVID-19 Vaccines

Q: How was safety measured in the Pfizer-BioNTech and Moderna vaccine trials?  

A: The trials assessed for solicited local reactions, systemic events and antipyretic/pain medication usage within 7 days of each dose, as well as for unsolicited adverse events for an additional 6 months (Pfizer-BioNTech) or until the end of the study (Moderna). More information on the efficacy of these vaccines is available on the Pfizer-BioNTech COVID-19 Vaccine and Moderna COVID-19 Vaccine pages of the COVID-19 Real-Time Learning Network.  

Q: How high were fevers seen after vaccination?  

A: In the Pfizer-BioNTech vaccine study, two participants each in the vaccine and placebo groups reported temperatures above 40.0 C. In the Moderna study, temperatures above 40.0 C were reported by four vaccine recipients after dose 1 and 11 vaccine recipients after dose 2.  

Q: What were the “serious reactions” in the Pfizer-BioNTech trial?  

A: In the Pfizer-BioNTech trial, serious adverse events were uncommon and similar between the vaccinated and placebo groups (0.6% and 0.5%, respectively). Among the 21,621 people in the trial who received BNT162b2, four related serious adverse events were reported: shoulder injury related to vaccine administration, right axillary, paroxysmal ventricular arrhythmia and right leg paresthesia.  

Four participants in the clinical trial who received the vaccine later developed Bell’s palsy. These cases occurred at 3, 9, 37 and 48 days after vaccination. The observed frequency of reported Bell’s palsy in the vaccine group is consistent with the expected background rate in the general population. 

Q: Is there any information/correlation on developing Guillain-Barre after vaccine administration?  

A: There have been no cases of Guillain-Barre syndrome reported following vaccination among participants in either of the mRNA COVID-19 vaccine clinical trials. Individuals who have previously had GBS may receive an mRNA COVID-19 vaccine unless they have another contraindication to vaccination. With few exceptions, the CDC Advisory Committee on Immunization Practices’ general best practice guidelines for immunization do not include history of GBS as a contraindication or precaution to vaccination. Any occurrence of GBS following mRNA COVID-19 vaccination should be reported to the Vaccine Adverse Event Reporting System.  

Q: In the Pfizer-BioNTech clinical trial there were a few cases of Bell’s palsy in the vaccine group and none in the placebo group. Did these cases of Bell’s palsy resolve? Is there any further information on these cases?  

A: Bell’s palsy is one of the conditions that is monitored for in all vaccine trials. Persons with a history of Bell’s palsy may receive an mRNA COVID-19 vaccine unless they have a contraindication to vaccination. Any occurrence of Bell’s palsy following mRNA COVID-19 vaccination should be reported to VAERS.   

The incidence of Bell’s palsy in both of the mRNA COVID-19 vaccine clinical trials was similar to the expected incidence of Bell’s palsy in the general population. There have been four reported cases of Bell’s palsy among Moderna’s COVID-19 vaccine (among more than 30,000 clinical trial participants). Of the four cases, three occurred in persons who received the vaccine, and 1 occurred in the placebo group.  

Pfizer-BioNTech’s trial had four reported cases of Bell’s palsy among 43,000 participants; all four participants had received the vaccine. These cases occurred at 3, 9, 37 and 48 days after vaccination.  

Q: Is there concern about transverse myelitis?  

A: There have not been any reports of transverse myelitis with the mRNA vaccines.  

Q: Is there concern regarding antibody dependent enhancement?  

A: In the clinical trials of both COVID-19 mRNA vaccines (both including more than 30,000 patients each), no participants have developed antibody dependent enhancement.  

Q: Was there difference in efficacy between young and older group of vaccine recipients in the Janssen COVID-19 vaccine trial in individuals less than 65 years compared to those greater than 65 years?

A: When stratified by age, the vaccine efficacy was 66.1% (95% CI: 53.3- 75.8) for participants 18 to <60 years of age and 66.2% (95% CI: 36.7-83.0) for participants ≥60 years of age at least 28 days after vaccination.

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

A: In the phase III 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.

Q: What are the long-term safety implications of the vaccine?  

A: In both the Moderna and Pfizer-BioNTech vaccine trials, the rate of serious adverse events was low. Additional data on long-term safety will be available with more time and as more individuals get vaccinated. Adverse events that occur in an individual following COVID-19 vaccination will be reported to the Vaccine Adverse Event Reporting System. Further, CDC has developed a new, voluntary smartphone-based tool, v-safe, which uses text messaging and web surveys to provide near real-time health check-ins after patients receive COVID-19 vaccination, which uses text messaging and web surveys to provide near real-time health check-ins after patients receive COVID-19 vaccination.   

As of Jan. 20, 2021, 997,042 and 1,083,174 registrants have completed at least one v-safe health check-in for the Pfizer-BioNTech and Moderna vaccines, respectively. The most common local and systemic reactions reported 0-7 days post-vaccination included pain (70.7%), fatigue (33.4%) and headache (29.4%).  

Nine integrated health care organizations, with access to data on >12 million persons per year, are participating in monitoring for 21 vaccine-mediated enhanced disease events and reporting these to the vaccine safety datalink database. There have been no signals of VMEDs as of Jan. 16, 2021.  

Q: Can mRNA vaccines make an individual infertile? 

A: There is no evidence linking either the Pfizer-BioNTech or Moderna mRNA vaccines to infertility. Since FDA authorization of these vaccines, misinformation has circulated on the internet that the antigen created by the vaccine (the SARS-CoV-2 spike protein) is similar to another protein that is important for placental attachment (syncytin-1) and that vaccination results in antibodies that target syncytin-1. Neither COVID-19 mRNA vaccine contains syncytin-1, nor does the mRNA used in the vaccines encode for syncytin-1. In addition, the spike protein formed as a result of vaccination with either COVID-19 mRNA vaccine and syncytin-1 are structurally very dissimilar. No data indicate the antibodies formed as a result of COVID-19 mRNA vaccination target syncytin-1. 

In the Pfizer-BioNTech COVID-19 vaccine study, 23 individuals became pregnant during the trial. Twelve individuals received the vaccine, and 11 received placebo. No unsolicited adverse pregnancy-related events occurred. In the Moderna COVID-19 vaccine study, 13 pregnancies were reported through Dec. 2, 2020; six participants received the vaccine, and seven the placebo. Two pregnancy-related adverse events occurred, both in the placebo group: one was an elective abortion, and one was a spontaneous abortion. 

Trials of both mRNA vaccines including pregnant people are planned, and both trials are collecting data on people who become pregnant during existing trials. 

Q: Regarding allergies, what are the components of the vaccine that an individual should be concerned about?  

A: Individuals who have a known severe allergy to any component of either mRNA vaccine should not take them. The Pfizer-BioNTech COVID-19 vaccine includes the following ingredients: mRNA, lipids ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate), 2 [(polyethylene glycol)-2000]-N,N-ditetradecylacetamide, 1,2-distearoyl-sn-glycero-3-phosphocholine and cholesterol), potassium chloride, monobasic potassium phosphate, sodium chloride, dibasic sodium phosphate dihydrate and sucrose. The Moderna vaccine contains lipids (polyethylene glycol, dimyristoyl glycerol, cholesterol and 1,2-distearoyl-sn-glycero-3-phosphocholine); tromethamine; tromethamine hydrochloride; acetic acid; sodium acetate; and sucrose.   

Q: Do we know the exact chemistry of the lipid in the Pfizer-BioNTech lipid nanoparticle? And how does it compare with the one used by Moderna?  

A: Both the Moderna and Pfizer-BioNTech vaccines contain polyethylene glycol within the lipid nanoparticle.   

Q: Does the vaccine contain any preservatives or adjuvants?  

A: The vaccine does not contain any preservatives or adjuvants.  

 

COVID-19 Vaccination by Patient Population

Q: For Asians and other racial/ethnic populations who were less well represented in the mRNA COVID-19 vaccine studies, how do we know if the vaccine is equally safe and efficacious?  

A: The Pfizer-BioNTech COVID-19 vaccine was 94.6% effective in preventing COVID-19 in the study population, which included 1,630 participants who were Asian or of Asian origin — 815 received the vaccine and 815 received a placebo. While the study was not powered to estimate vaccine efficacy in subgroups, the authors reported efficacy by race and ethnicity was consistent with the vaccine efficacy in the total population. In the Moderna study, 36.5% of participants represented communities of color, with 9.7% African American, 4.7% Asian and <3% from other racial groups; 20% were Hispanic/Latinx.  

Q: What is the efficacy of the vaccine in those that are obese and have diabetes?  

A: Pfizer-BioNTech reports that their vaccine is 95.4% effective in patients with obesity; they did not report efficacy data for patients with diabetes. However, Pfizer-BioNTech noted that similar effectiveness was found in those with controlled pre-existing conditions, such as diabetes. Moderna reports that their vaccine is 91.2% and 100% effective in patients with severe obesity (BMI>=40 kg/m2) and diabetes, respectively.  

Q: Is the vaccine safe for transplant patients?  

A: Immunocompromised people may be at risk for severe COVID-19; therefore, CDC states these groups may receive the vaccine if there are no contraindications. Transplant recipients should be counseled that the effectiveness and safety profile of these vaccines for them are not currently known. However, as these are not live virus vaccines, it is unlikely that these vaccines would pose a safety risk. It is important for there to be intact host immunity in individuals receiving the vaccine for there to be optimal protective immunity post-vaccination, especially with respect to antigen presentation, B and T cell activation and plasma B cell antibody generation. Therefore, individuals lacking functional adaptive immune cells may be unable to generate a fully protective immune response to the SARS-CoV-2 vaccine. Therefore, transplant recipients should be advised regarding the importance of maintaining all current guidance to protect themselves even after vaccination. Additionally, caregivers and household contacts should be strongly encouraged to get vaccinated when vaccine is available in an effort to protect the patient.  

Q: Are there any considerations regarding COVID vaccination in oncology patients, many of whom are immunocompromised either by virtue of their disease of cancer or their treatment, e.g., chemotherapy, radiation, stem cell transplant? Do we think it will it be safe and efficacious in this group?  

A: Persons with HIV infection or other immunocompromising conditions, or who take immunosuppressive medications or therapies, might be at increased risk for severe COVID-19. Data are not currently available to establish vaccine safety and efficacy in these groups. Persons with stable HIV infection were included in mRNA COVID-19 vaccine clinical trials, though data remain limited. Immunocompromised individuals may receive COVID-19 vaccination if they have no contraindications to vaccination. However, they should be counseled about the unknown vaccine safety profile and effectiveness in immunocompromised populations, as well as the potential for reduced immune responses and the need to continue to follow all current guidance to protect themselves against COVID-19.   

Oncology patients should be counseled that the effectiveness and safety profile of these vaccines for them are limited. As these are not live virus vaccines, it is unlikely that these vaccines would pose a safety risk. It is important for there to be intact host immunity in individuals receiving the vaccine for there to be optimal protective immunity post-vaccination, especially with respect to antigen presentation, B and T cell activation and plasma B cell antibody generation. Therefore, individuals lacking functional adaptive immune cells may be unable to generate a fully protective immune response to the SARS-CoV-2 vaccine. Therefore, patients with cancer should be advised regarding the importance of maintaining all current guidance to protect themselves even after vaccination. Additionally, caregivers and household contacts should be strongly encouraged to get vaccinated when vaccine is available in an effort to protect the patient.  

Q: Can patients with autoimmune diseases receive the vaccines? Is there concern for triggering autoimmune diseases/responses in susceptible individuals?  

A: Autoimmune disease is not a contraindication for the mRNA vaccines. The study populations for both mRNA vaccine trials included participants with autoimmune disease. No imbalances were observed in the occurrence of symptoms consistent with autoimmune conditions or inflammatory disorders in clinical trial participants who received an mRNA COVID-19 vaccine compared to placebo.   

Q: Are there any plans to do Phase 4 studies in immunocompromised hosts — people with transplants, people chronically immunosuppressed for autoimmune disorders, people living with HIV?  

A: The FDA EUA recommends that immunocompromised individuals and other subpopulations with specific comorbidities be studied in post-authorization observational studies. People living with HIV were included in both the Pfizer-BioNTech and Moderna trials, although their numbers were low.  

Q: Can the vaccine be administered to asplenic patients — either those with functional asplenia or post splenectomy?  

A: For both mRNA vaccines, CDC recommends that groups at high risk for severe illness (including those with sickle cell disease who have functional asplenia) may still receive the vaccine if there are no contraindications. It is important for there to be intact host immunity in individuals receiving the vaccine for there to be optimal protective immunity post-vaccination, especially with respect to antigen presentation, B and T cell activation and plasma B cell antibody generation. Therefore, individuals lacking functional adaptive immune cells, such as those who are asplenic, may be unable to generate a fully protective immune response to the SARS-CoV-2 vaccine. Therefore, they should be advised regarding the importance of maintaining all current guidance to protect themselves even after vaccination. Additionally, caregivers and household contacts should be strongly encouraged to get vaccinated when vaccine is available in an effort to protect the patient.  

Q: In patients with HIV, are there any recommendations for getting the vaccine in patients based on CD4 count and viral suppression?   

A: Individuals with well-controlled HIV disease were included in the mRNA vaccine trials; however, the number was small. Therefore, there are insufficient data to establish efficacy and safety in this group. Because people living with HIV may be at risk for severe COVID-19, CDC recommends this group may still receive the vaccine if there are no contraindications. People with HIV, particularly those with low CD4 counts or who are not on HAART, should be counseled that they may have a weakened immune response when compared to the general population, and thus should be advised regarding the importance of maintaining all current guidance to protect themselves even after vaccination. Additionally, caregivers and household contacts should be strongly encouraged to get vaccinated when the vaccine is available in an effort to protect the patient.   

 

Q: In the Janssen COVID-19 vaccine trial, what was the vaccine efficacy in HIV patients? What are the implications?

A: The phase III trial of Ad26.COV2.S included 1218 individuals living with HIV, which constituted 2.8% of the total study population. There were too few outcomes among this subgroup to draw any meaningful conclusions about vaccine efficacy. Specifically, there were 5 cases of moderate to severe/critical COVID-19 in both the vaccine and placebo group starting at least 14 days after vaccination, and 2 cases in the vaccine group and 4 in the placebo group starting at least 28 days after vaccination. Safety and immunogenicity studies in “immunocompromised individuals” are planned, but details of these studies are not yet available.

Q: Are there any concurrent medications that are uniquely contraindicated in recipients of mRNA vaccines? Will patients need to stop any medications prior to vaccination?  

A: There are currently no medications that are contraindicated in individuals receiving mRNA vaccines. Due to lack of data on safety and efficacy of the vaccine administered simultaneously with other vaccines, mRNA COVID-19 vaccines should be administered alone with a minimum interval of 14 days before or after administration of any other vaccines.  

Based on the estimated half-life of monoclonal antibodies or convalescent plasma as well as evidence suggesting that reinfection is uncommon in the 90 days after initial infection, vaccination should be deferred for at least 90 days as a precautionary measure until additional information becomes available, to avoid interference of the antibody treatment with vaccine-induced immune responses.  

Q: What concomitant medications or diseases may inhibit or prevent the vaccine from inducing immune response?  

A: According to the American Society of Hematology and the American Society for Transplantation and Cellular Therapy, the following immunocompromised patient populations could have attenuated or absent response to SARS-CoV-2 vaccines (this list is not comprehensive):  

  • “Primary and secondary immunodeficiencies involving adaptive immunity;  
  • Splenectomy or functional asplenia (e.g., sickle cell disease);  
  • B cell directed therapies (e.g., blocking monoclonal antibodies against CD20 or CD22, bispecific agents like blinatumomab, CD19 or CD22-directed CAR-T cell therapies, BTK inhibitors);  
  • T cell directed therapies (e.g., calcineurin inhibitors, antithymocyte globulin, alemtuzumab);  
  • Many chemotherapy regimens;  
  • High-dose corticosteroids (20 mg per dose or >2 mg/kg/day daily prednisone or equivalent);  
  • Hematopoietic cell transplantation, especially within the first 3-6 months after autologous HCT and often longer after allogeneic HCT;  
  • Underlying aberrant immunity (e.g., graft-vs.-host disease, graft rejection, absent or incomplete immune reconstitution, neutropenia, lymphopenia).”  

Q: What are the recommendations for administering the COVID-19 vaccine in pregnant or lactating individuals?  

A: The Pfizer-BioNTech and Moderna vaccine EUAs do not exclude pregnant or lactating people. Per CDC, people who are pregnant or breastfeeding may choose to be vaccinated. Safety data are being collected in pregnant individuals using v-safe, with 227 pregnancies enrolled as of Jan. 22, 2021. 

Observational data have suggested pregnant people may be at risk for more severe illness and worse outcomes from COVID-19. Additionally, they may be at an increased risk of adverse pregnancy outcomes, such as preterm labor. 

Data are currently limited on the safety of COVID-19 vaccines, including mRNA vaccines, in pregnant people. Limited data are currently available from animal developmental and reproductive toxicity studies. No safety concerns were demonstrated in rats that received Moderna COVID-19 vaccine prior to or during gestation in terms of female reproduction, fetal/embryonal development or postnatal development. Studies in pregnant people are planned, and the vaccine manufacturers are following outcomes in people in the clinical trials who became pregnant. Based on current knowledge, experts believe that mRNA vaccines are unlikely to pose a risk to the pregnant person or the fetus because mRNA vaccines are not live vaccines. The mRNA in the vaccine is degraded quickly by normal cellular processes and does not enter the nucleus of the cell. However, the potential risks of mRNA vaccines to the pregnant person and the fetus are unknown because these vaccines have not been studied in pregnant people.  

If pregnant people are part of a group that is recommended to receive a COVID-19 vaccine (e.g., health care personnel), they may choose to be vaccinated. A conversation between the patient and their clinical team may assist with decisions regarding the use of a mRNA COVID-19 vaccine, though a conversation with a health care provider is not required prior to vaccination. When making a decision, pregnant people and their health care providers should consider the level of COVID-19 community transmission, the patient’s personal risk of contracting COVID-19, the risks of COVID-19 to the patient and potential risks to the fetus, the efficacy of the vaccine, the side effects of the vaccine and the lack of data about the vaccine during pregnancy.  

Side effects can occur with COVID-19 vaccine use in pregnant people, similar to those expected among non-pregnant people. Pregnant people who experience fever following vaccination may be counseled to take acetaminophen, as fever has been associated with adverse pregnancy outcomes. Acetaminophen may be offered as an option for pregnant people experiencing other post-vaccination symptoms as well. 

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 mRNA COVID-19 vaccination.  

Of note, the American College of Obstetricians and Gynecologists recommends that COVID-19 vaccines not be withheld from pregnant individuals who meet criteria for vaccination based on ACIP-recommended priority groups. Additionally, the Society for Maternal-Fetal Medicine has stated that the safety risk of mRNA vaccination for pregnant or lactating people appears low, recommended pregnant people be offered vaccination and noted the decision to receive the vaccine should be guided by an individual’s risk of contracting COVID-19 and other individual factors.  

Q: Are there any additional requirements when offering the vaccine to pregnant individuals? Is a consent form required for that population?  

A: There are no additional requirements other than pregnant individuals who experience fever following vaccination should be counseled to take acetaminophen, as fever has been associated with adverse pregnancy outcomes. A consent form is not required.  

Q: I've heard that the immune response to the spike protein antigen that develops after vaccination could cross-react with the syncytin-1 protein on the placenta, resulting in preeclampsia, abruptio placenta, preterm labor or miscarriages. Is this true?  

A: There is no evidence linking either the Pfizer-BioNTech or Moderna mRNA vaccines to adverse pregnancy outcomes. Since FDA authorization of these vaccines, misinformation has circulated on the internet that the antigen created by the vaccine (the SARS-CoV-2 spike protein) is similar to another protein that is important for placental attachment (syncytin-1), and that vaccination results in antibodies that target syncytin-1. Neither COVID-19 mRNA vaccine contains syncytin-1, nor does the mRNA used in the vaccines encode for syncytin-1. In addition, the spike protein formed as a result of vaccination with either COVID-19 mRNA vaccine and syncytin-1 are structurally very dissimilar. No data indicate the antibodies formed as a result of COVID-19 mRNA vaccination target syncytin-1. 

In the Pfizer-BioNTech COVID-19 vaccine study, 23 individuals became pregnant during the trial. Twelve individuals received the vaccine, and 11 received placebo. No unsolicited adverse pregnancy-related events occurred. In the Moderna COVID-19 vaccine study, 13 pregnancies were reported through Dec. 2, 2020; six participants received the vaccine, and seven the placebo. Two pregnancy-related adverse events occurred, both in the placebo group: one was an elective abortion, and one was a spontaneous abortion. 

Trials of both mRNA vaccines including pregnant people are planned, and both trials are collecting data on people who become pregnant during existing trials.  

Q: What do we know about the use of the Janssen COVID-19 Vaccine in pregnant individuals?

A: The phase III 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. The study is collecting outcomes for all reported pregnancies among study participants. Eight pregnancies were reported through January 22, 2021 (4 vaccine, 4 placebo). Unsolicited AEs related to pregnancy include a case of spontaneous abortion (1 vaccine, 0 placebo), incomplete abortion (0 vaccine, 2 placebo), elective abortion (0 vaccine, 2 placebo), and ectopic pregnancy (1 vaccine, 0 placebo). Two pregnancies in the vaccine group are ongoing with outcomes otherwise unknown at this time. A clinical trial of Ad26.COV2.S in pregnant individuals is planned to start in 2021..  

Q: What advantage does getting vaccinated provide if masks are beneficial in decreasing transmission?  

A: Vaccination is intended to prevent illness by providing immunity to the SARS-CoV-2 virus, while masks are intended to reduce transmission but do not provide immunity. However, we still do not know whether the vaccine prevents an individual from carrying SARS-CoV-2 and spreading it to others, so it is still important to wear a face mask and physically distance even after being vaccinated. The CDC recommends that those that have received both doses of the Moderna or Pfizer-BioNTech vaccines do not need to quarantine if exposed to an individual that has possible or confirmed COVID-19 infection if: 1) it has been at least 2 weeks since the final vaccine dose; 2) it has been within 3 months or 90-days from the final vaccine dose; AND 3) they do not have any COVID-19 symptoms. 

 

COVID-19 Vaccine Administration

Q: Is an informed consent form needed prior to vaccinating individuals?  

A: FDA has issued an EUA for both mRNA vaccines. A vaccine received under this authorization mechanism does not require the same informed consent as one received through a clinical trial. However, before vaccination and regardless of occupation, vaccine administrators must complete the following:  

  1. Communicate to the recipient or their caregiver information consistent with the Fact Sheet for Recipients and Caregivers (and provide a copy or direct the individual to the online fact sheet). 
  2. "Counsel on the following:  
    • FDA has authorized the emergency use of the vaccine, which is not an FDA-approved vaccine. 
    • The recipient or their caregiver has the option to accept or refuse COVID-19 vaccine. 
    • The significant known and potential risks and benefits of vaccine, and the extent to which such risks and benefits are unknown, including expected systemic and local reactogenicity and any special population-specific considerations (e.g., pregnant or lactating women, immunosuppressed persons). 
    • Information about available alternative vaccines and the risks and benefits of those alternatives."
  3. Provide a vaccination card to the recipient or their caregiver with the date when the recipient needs to return for the second dose of COVID-19 vaccine.  
  4. Log the vaccination information in the state/local jurisdiction’s Immunization Information System or other designated system.  

Q: Is there any evidence base to avoid NSAIDs and preferentially use acetaminophen to treat vaccine associated local or systemic adverse effects?  

A: Per CDC, acetaminophen or non-steroidal anti-inflammatory drugs may be taken for the treatment of post-vaccination local or systemic symptoms. In those that are pregnant, acetaminophen is preferred.  

Q: Should patients receiving the vaccine be pre-medicated with acetaminophen or an NSAID?   

A: Routine prophylactic administration of these medications for the purpose of preventing post-vaccination symptoms is not currently recommended, as information on the impact of this on both the immune response to the vaccine and on post-vaccine symptoms is not currently available.  

Q: Since coadministration with other vaccines is not recommended, how long after an individual has received another vaccine (e.g., Shingrix, influenza) should the COVID vaccine be administered?  

A: Per CDC, given the lack of data on the safety and efficacy of mRNA COVID-19 vaccines when administered simultaneously with other vaccines, these vaccines should be administered alone, with a minimum interval of 14 days before or after administration with any other vaccine. The exception is if the benefits of vaccination are deemed to outweigh the potential unknown risks of vaccine coadministration (such as tetanus toxoid during wound management), or if not coadministering would result in delays/barriers to receiving a COVID-19 vaccine. If mRNA COVID-19 vaccines are inadvertently administered within 14 days of another vaccine, doses do not need to be repeated for either vaccine.   

Q: Any special considerations for patients who report being on an anticoagulant or with coagulopathy?  

A: Patients should inform their vaccination provider if they have a bleeding disorder or are on a blood thinner, as they may have more bleeding after receiving an injection. Otherwise, there are no special considerations for this group.  

Q: Should an individual receiving a COVID-19 vaccination abstain from steroid use, and if so, for how long?  

A: Per the American Society of Hematology and the American Society for Transplantation and Cellular Therapy, high-dose corticosteroids (20 mg per dose or >2 mg/kg/day daily prednisone or equivalent) may attenuate the immune response in individuals receiving the vaccine if they are already immunosuppressed. Doses lower than this are unlikely to significantly affect the immune response to a COVID-19 vaccine.  

Q: What is the new smartphone-based tool called v-safe? 

A: When someone receives a vaccine, they should also receive a v-safe information sheet telling them how to enroll in v-safe. If the participant enrolls, they will receive regular text messages directing them to surveys where they can report any problems or adverse reactions after receiving a COVID-19 vaccine. 

Q: When does CDC plan to issue information on the v-safe app? When will the v-safe app be available for download? 

A: The v-safe app is now available for download, and information is available on the CDC website. When someone receives a vaccine, they should also receive a v-safe information sheet telling them how to enroll in v-safe. If the participant enrolls, they will receive regular text messages directing them to surveys where they can report any problems or adverse reactions after receiving a COVID-19 vaccine.  

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

A: Antibody testing is not recommended to assess for immunity to COVID-19 following vaccination with either mRNA COVID-19 vaccine.   

Q: Is repeating the initial dose recommended if the recipient is beyond the recommended window for the second dose?  

A: If the recommended window has passed, there is no need to repeat the series. The second dose should be scheduled at the earliest opportunity.  

Q: Would it be recommended to hold back doses to ensure availability of the second dose for all individuals?  

A: Overall vaccine efficacy after one dose has not been studied. While there were patients in Phase 3 trials who received one dose and vaccine efficacy was reported in these patients (the Moderna trial reported an efficacy of 80.2%, and the Pfizer-BioNTech trial 52.4%), the overall number of such patients was small and they were only followed for a short time period. The duration and degree of their immune responses to the single dose of the vaccine is not known; until such data are available and the efficacy of one dose has been studied, FDA recommends that all COVID-19 vaccine recipients receive two doses of vaccine.  

Q: Why is it necessary to vaccinate people who have had COVID-19?  

A: Given that we do not know how long immunity after COVID-19 infection lasts (notably, reinfection cases have happened 3 months following COVID-19 infection), and given people have variable immune responses after having COVID-19 (some data suggest people with mild cases may have a less robust immune response than those with severe disease), CDC recommends offering vaccination to individuals regardless of history of prior symptomatic or asymptomatic SARS-CoV-2 infection. Viral testing to assess for acute SARS-CoV-2 infection or serologic testing to assess for prior infection solely for the purpose of vaccine decision-making is not recommended. Vaccination of individuals with known current SARS-CoV-2 infection should be deferred until they have recovered from the acute illness (if they had symptoms) and criteria have been met for them to discontinue isolation.  

Q: Should those who have had COVID-19 within the past 90 days not receive the vaccine? What about beyond 90 days?  

A: While there is otherwise no recommended minimum interval between infection and vaccination, current evidence suggests that reinfection is uncommon in the 90 days after initial infection. Thus, persons with documented acute SARS-CoV-2 infection in the preceding 90 days may delay vaccination until near the end of this period, if desired.  

Q: Are there any data concerning vaccine administration during PCR- and/or symptom-diagnosed infection?  

A: Vaccination of persons with known current SARS-CoV-2 infection should be deferred until they have recovered from the acute illness (if they had symptoms) and criteria have been met for them to discontinue isolation. This recommendation applies to persons who develop SARS-CoV-2 infection before receiving any vaccine doses as well as those who develop SARS-CoV-2 infection after the first dose but before receipt of the second dose. For vaccinated persons who subsequently develop COVID-19, prior receipt of an mRNA COVID-19 vaccine should not affect treatment decisions (including use of monoclonal antibodies, convalescent plasma, antiviral treatment or corticosteroid administration) or timing of such treatments.  

Q: If someone has a history of COVID, are they more likely to experience a side effect to the vaccine?  

A: Large-scale data on side effects in this particular group are not yet available. In the Moderna COVID-19 and Pfizer-BioNTech vaccine studies, the percentage of participants who had serologic evidence of prior infection at study enrollment was 2.2% and 3%, respectively. Data on these patients showed the vaccines are safe in persons who have had COVID-19.  

Q: Is there a period of time recommended between receipt of monoclonal antibodies and the vaccine to ensure adequate immune response?  

A: Currently, there are no data on the safety and efficacy of mRNA COVID-19 vaccines in persons who received monoclonal antibodies or convalescent plasma as part of COVID-19 treatment. Based on the estimated half-life of such therapies as well as evidence suggesting that reinfection is uncommon in the 90 days after initial infection, vaccination should be deferred for at least 90 days as a precautionary measure until additional information becomes available, to avoid interference of the antibody treatment with vaccine-induced immune responses.   

No recommendation on minimum interval has been provided on administration of mRNA vaccines with antibody-containing treatment that is not specific to COVID-19 therapy, such as i Q: What is the appropriate time frame to get the second vaccine dose in a patient who was given the first vaccine dose and was infected with COVID-19 shortly after and received monoclonal antibodies? Should a second dose be given, or should the series be restarted?  

A: Per CDC guidance, if someone develops symptomatic COVID-19, they can receive COVID-19 vaccination as soon as they have recovered from their symptoms and have met criteria to discontinue isolation. This applies to persons who have not been vaccinated and to persons who have received one dose of the vaccine. Because reinfection is uncommon in the first 90 days post infection, people can choose to delay their vaccination until the end of this period, but it is not required. There is no need to repeat doses of the vaccine, even if the administration of the second dose is delayed; providers should finish the series. 

Data are not available on the efficacy and safety of mRNA COVID-19 vaccines in persons who have received convalescent plasma or monoclonal antibody therapy; it is possible such therapies may interfere with vaccine-induced immune responses. Therefore, until more data are available, CDC recommends persons who have received these therapies for COVID-19 defer vaccination until at least 90 days; this is based on the half-life of the therapies, and the fact that reinfection within 90 days post an initial infection appears to be uncommon. 

Q: Is there any impact on the false positive rate of PCR or antigen testing following vaccination with the mRNA vaccines?  

No, receiving a COVID-19 mRNA vaccine will not result in a false positive PCR or antigen COVID-19 test. The vaccine only contains mRNA that encodes for the SARS-CoV-2 spike protein, which is not a molecular target of either PCR or antigen COVID-19 tests. The vaccines also do not contain any SARS-CoV-2 proteins.   

 

Resources

Multimedia

Sign up for IDSA's Newsletter
Stay informed with daily resources, media and news.

This website uses cookies

We use cookies to ensure that we give you the best experience on our website. Cookies facilitate the functioning of this site including a member login and personalized experience. Cookies are also used to generate analytics to improve this site as well as enable social media functionality.