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Vaccines FAQ

Last Updated: January 21, 2021

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Overview

Vaccination to prevent disease was first conceptualized in the late 18th century, and by the early 20th century vaccines for diseases including tuberculosis, yellow fever, and influenza had been developed (Plotkin, 2014). By 1980, vaccination had been used to eradicate smallpox globally — one of only two infectious diseases to date to be eliminated from the environment. Numerous vaccines are responsible for preventing millions of illnesses annually (Pardi, 2018).

Conventional vaccine types include the following:

  • Live-attenuated vaccines, such as the measles-mumps-rubella vaccine, contain attenuated (weakened) forms of an organism that causes a disease. This attenuated organism acts as an antigen and stimulates the body to create a robust antibody response.
  • Inactivated vaccines, including most influenza vaccines, contain a killed version of an organism that causes a disease. This killed form acts as an antigen and stimulates the body to create an antibody response.
  • Subunit, recombinant, polysaccharide and conjugate vaccines, such as pneumococcal vaccines, contain components of an organism which act as antigens and stimulate an antibody response. They do not contain the organism itself.
  • Toxoid vaccines, such as tetanus vaccine, contain a toxin made by an organism that causes a disease. The toxin acts as an antigen and stimulates an antibody response to specific parts of the organism, rather than the whole organism.

While conventional vaccines are critical in controlling disease, limitations include the time and materials required for production, difficulty with large-scale deployment and a reliance on the adaptive instead of innate immune response (which some infections may evade) (Pardi, 2018).

mRNA Vaccines

mRNA vaccines contain messenger RNA (mRNA), a single-stranded RNA molecule that complements DNA. It 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. Translation of the mRNA results in the development of a protein antigen that triggers an immune response (Schlake, 2012). mRNA vaccines deliver mRNA directly to the cytoplasm, where it is transcribed by ribosomes. 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 (Walsh, 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.

The concept of mRNA vaccines was first developed in the early 1990s (Schlake, 2012). However, due to difficulty with the instability of mRNA, delivery challenges and other factors, the field did not make significant strides until the past decade, when technological advances and investment lead to significant development. Prior to the COVID-19 pandemic, mRNA vaccines targeting infectious diseases including HIV-1, rabies, Zika, and influenza were already in clinical trials, as were mRNA vaccines targeting multiple hematologic and solid organ malignancies (Pardi, 2018). 

Soon after the COVID-19 pandemic emerged, Pfizer and BioNTech began to develop a mRNA vaccine against SARS-CoV-2, as did Moderna—the latter in partnership with the National Institute of Allergy and Infectious Diseases.

  • The Pfizer-BioNTech vaccine, BNT162b2, uses mRNA to create the receptor binding domain of the spike protein of SARS-CoV-2 (Mulligan, August 2020). The spike protein is what SARS-CoV-2 uses to attach to host cells and enter them.
  • The Moderna vaccine, mRNA-1273, uses mRNA to create the SARS-CoV-2 spike protein stabilized in its prefusion conformation (Jackson, 2020). Both vaccines are part of Operation Warp Speed, which allowed for rapid investment in the vaccines and their trials. Studies of these vaccines have shown them to be highly effective in preventing symptomatic COVID-19, and safe after several months of follow-up. 

For additional information, refer to our Pfizer-BioNTech COVID-19 Vaccine and Moderna COVID-19 Vaccine pages.

 

Vectored Vaccines 

Vectored vaccines utilize either non-pathogenic organisms or plasmids (the vector) (Vrba, Nov 2020). Genes of a pathogen—most often proteins that code for specific antigens—are inserted into the genome of the vector. The vaccine delivers the vector, which infects host cells and then travels to the nucleus; there the genes of the pathogen are expressed, resulting in the creation of the antigen. The antigen is then expressed on the host cell surface, resulting in the induction of an immune response. This is both cellular (T cell) and humoral (B cell) response.  

Vectored vaccines can be replicating or non-replicating:  

  • Replicating viral vectored vaccines infect cells, resulting in the production of the vaccine antigen. The viral vector is also produced and is then able to infect new cells, which then create more viral antigen 
  • Non-replicating viral vectored vaccines infect cells, resulting in the production of the vaccine antigen, but the viral vector cannot be reproduced (Riel, July 2020). 

Soon after the COVID-19 pandemic emerged, AstraZeneca and Oxford University partnered to develop a viral vectored vaccine utilizing a modified replication-deficient chimp adenovirus vector, ChAdOx1. It contains a gene that encodes for the SARS-CoV-2 spike protein. The vaccine is part of HHS’s Operation Warp Speedand is also funded by the U.K. Ministry of Health and the Biomedical Advanced Research and Development Authority. Studies have shown it effective in preventing symptomatic COVID-19 and safe after several months of follow-up.  

Multiple viral vectored vaccines utilizing poxviruses, adenoviruses, and vesicular stomatitis virus are also in clinical trials for human use; the only FDA-approved viral vectored vaccine is the Ebola vaccine ERVEBO (Vrba, November 2020). 

FAQ

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

Molecular Features of mRNA Vaccines 

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

A: mRNA vaccines contain messenger RNA (mRNA), a single-stranded RNA molecule that complements DNA. It 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. Translation of the mRNA results in the development of a protein antigen that triggers an immune response (Schlake, 2012). mRNA vaccines deliver mRNA directly to the cytoplasm, where it is transcribed by ribosomes. 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 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 is likely 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 (MHC) 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 would last the same amount time as other proteins made by the body. The protein will be taken up by other cells and processed again. The exact time is not known, but the estimated time is a few weeks.  

Q: Can mRNA alter cellular DNA? 

A: In order for 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, mRNA does not have the nuclear access signals that would allow it to enter. Put quite simply, mRNA vaccines 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, the mRNA vaccines also don’t contain an enzyme called integrase, which is needed to allow mRNA to insert itself into the DNA.  

In short, the mRNA vaccines lack all of the basic requirements necessary to alter DNA. They remain in the cell cytoplasm for just a few days before they are destroyed. One other thing to remember: There are more than 200,000 cellular mRNAs/cell 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 mRNA does not alter the cell or body. It is delivered to the cytoplasm and translated by ribosomes, which then make the SARS-CoV-2 spike protein. This stimulates the body to make an immune response to SARS-CoV-2.   

Q: Is this mRNA self-amplifying? 

A: No, mRNA is not self-amplifying. 

Q: Does the vaccine induce cellular immunity? 

A: Both the Pfizer-BioNTech COVID-19 vaccine and the Moderna COVID-19 vaccine stimulate T cell responses (Sahin, July 2020Anderson, December 2020). 

Q: What do we know about the development of memory cytotoxic cells (memory T8+ cells)? 

A: In Pfizer-BioNTech’s Phase 1/2 data, two doses of 1–50 μg of BNT162b1 elicited robust CD4+ and CD8+ T cell responses and strong antibody responses, with receptor binding domain-binding IgG concentrations above those seen in serum from a cohort of individuals who had recovered from COVID-19. 

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.  

mRNA Vaccine Efficacy & Safety  

mRNA Vaccine Efficacy

Q: 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 trialsMore 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 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 are still able to have asymptomatic disease and transmit the virus. Therefore, it important to continue practicing other preventative measures such as wearing a facemask 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 separately 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 summary comparing the number of positive swabs at the pre-dose 2 timepoint in baseline seronegative participants to get an early idea of the possibility of prevention of asymptomatic infection. 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 2/3 fewer swabs that were positive in the vaccine group as compared to the placebo group at the pre-dose 2 timepoint, suggesting that some asymptomatic infections start to be prevented after the first dose. More complete data are needed to draw conclusions.   

Q: What is the durability of immune response to COVID-19 vaccination, meaning 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; this data is 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 dose escalation trial of the Moderna COVID-19 vaccine, immunogenicity data 119 days after the first vaccination (90 days after the second vaccination) were evaluated from the Phase 1 dose escalation, open-label trial (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 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 disease 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 disease 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: 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, and as a result 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 UKUS, Canada, South Africa, and other countries emerged (Rambaut, November 2020Tegally December 2020Davies, December 2020Greany, January 2021). One strain, 20B/501Y.V1, VOC 202012/01, or B.1.1.7 lineage, appears to have been circulating in the UK 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 suggests it may be over 50% more transmissible (Davies, December 2020). 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. 

CDC has begun tracking and publicly reporting variant COVID-19 case counts in the United States. There is no evidence this variant, or any other, are associated with more severe disease or different clinical outcomes, nor is there any evidence that they may be associated with reduced vaccine efficacy.    

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. 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.   
 
Scientists are working to learn more about these variants and their clinical impact. 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 vaccinees and test these variants in animal models. It is important to note that the correlates of protection of EUA vaccines are currently not known and it is believed that the protection does not solely rely on generation of antibodies but the presence of cellular immunity as well. 

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, information 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 vaccines contain 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 vaccines and syncytin-1 are structurally very dissimilar. No data indicates the antibodies formed as a result of COVID-19 mRNA vaccination target syncytin-1.

In the Pfizer-BioNTech COVID-19 vaccine study, 23 women 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 December 2, 2020; 6 participants received the vaccine, and 7 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 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 obesity and 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: 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 disease in the study population, which included 1,630 Asian participants  815 received the vaccine and 815 received a placebo. According to Pollack et al, although the study was not powered to definitively assess efficacy by subgroup, the point estimates of efficacy for subgroups based on age, sex, race, ethnicity, body-mass index or the presence of an underlying condition associated with a high risk of COVID-19 complications are also high. In the Moderna study36.5% of participants represented communities of color, with 9.7% African American, 4.7% Asian and <3% from other racial groups; 20% were Hispanic/Latino.  

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

A: Vaccination is intended primarily 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. 

mRNA Vaccine Safety

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 eventsfor 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: What were the serious reactions in the Pfizer-BioNTech trial?  

A: In the Pfizer-BioNTech trial, serious adverse events, while uncommon (<1.0%), represented medical events that occur in the general population at similar frequency to that observed in the study. Three serious adverse events in the BNT162b2 group were considered by the investigator, but not the sponsor, as related to study vaccination: shoulder injury (n=1), ventricular arrhythmia in a participant with known cardiac conditions (n=1) and lymphadenopathy temporally related following vaccination (n=1).  

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

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

Q: 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. In the absence of such evidence, 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.  

There have been four reported cases of Bell’s palsy among Moderna’s COVID-19 vaccine in more than 30,000 clinical trial participants. Three of the participants who got Bell’s palsy also received the vaccine instead of a placebo shot. Two of the Bell’s palsy cases among Moderna’s vaccine group have since resolved, while one was still ongoing at the time of the report, FDA stated. Vaccinated participants experienced paralysis between 22 days and 32 days after inoculation. FDA plans to recommend ongoing monitoring for Bells palsy once widespread vaccination begins.  

Pfizer-BioNTech’s trial similarly had four reported cases of Bell’s palsy out of some 43,000 participants. All four Bell’s palsy cases in Pfizer-BioNTech’s trial got the vaccine and not the placebo. These cases occurred at 3, 9, 37 and 48 days after vaccination. One case (onset at 3 days post-vaccination) was reported as resolved with sequelae within 3 days after onset, and the other 3 were reported as continuing or resolving as of the Nov14, 2020 data cutoff. FDA has recommended surveillance for cases of Bell’s palsy with deployment of the vaccine into larger populations. 

Q: Is there concern about transverse myelitis? 

A: There have not been any reports of transverse myelitis with the mRNA vaccine to date.  

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 ADE. Early studies were performed to look at immune responses and found that no definitive role for ADE in SARS-CoV-2 has been established. 

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 (VAERS). 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. 

Dosing & Administration 

Q: How should the vaccine be thawed? How long can a dose be held (refrigerated) in a syringe before being administered?  

A: Vials from Pfizer-BioNTech may be thawed in the refrigerator (2 C to 8 [35 F to 46 F]) or at room temperature (up to 25 [77 F]). If thawed in a refrigerator, vials can be stored in the refrigerator for up to 5 days. Vials thawed at room temperature must be used within 30 minutes.  

Vials from Moderna may be thawed in refrigerated conditions between 2 to 8 C (36 to 46 F) for 2 hours and 30 minutes. After thawing, the vials should stand at room temperature for 15 minutes before administering. Alternatively, the vials can be thawed at room temperature between 15 to 25 C (59 to 77 F) for 1 hour.  

There is no guidance for both vaccines regarding information on refrigerating the dose in a syringe.  

Q: Is the Pfizer vaccine a saline dilution? How big is the administered dose in mL 

A: Vial contents are diluted using 1.8 mL of 0.9% sodium chloride injection, USP (not provided) to form the Pfizer-BioNTech COVID-19 Vaccine. ONLY use 0.9% sodium chloride injection, USP as the diluent. This diluent is not packaged with the vaccine and must be sourced separately. Do not use bacteriostatic 0.9% sodium chloride injection or any other diluent. Once diluted, the vials must be used within 6 hours. The final dosing volume is 0.3 mL.  

Q: Is a reconstituted vaccine in a syringe inactivated by adsorption to the inner surface of the syringe when the syringe is held at refrigerator temperature? 

A: There is currently no information from FDA or Pfizer-BioNTech on the appropriate way to store a syringe in the refrigerator. In regard to vaccine storage, please visit the FDA guidance document. 

Q: Any concerns about multi-dose vial use? 

A: The FDA Pfizer-BioNTech Vaccine Fact Sheet gives instructions on how to use the multi-dose vial:  

  • Record the date and time of dilution on the Pfizer-BioNTech COVID-19 vaccine vial label. 
  • Store between 2 C to 25 C (35 F to 77 F).  
  • Discard any unused vaccine 6 hours after dilution. 

For more details, refer to the FDA Pfizer-BioNTech Vaccine Fact Sheet.  

The FDA Moderna Vaccine Fact Sheet provides instructions how to use the multi-dose vial: 

  • Remove the required number of vial(s) from storage and thaw each vial before use. 
  • Thaw in refrigerated conditions between 2 to 8 C (36 to 46 F) for 2 hours and 30 minutes. After thawing, let vial stand at room temperature for 15 minutes before administering. 
  • Alternatively, thaw at room temperature between 15 to 25 C (59 to 77 F) for 1 hour. 
  • After thawing, do not refreeze. 
  • Swirl vial gently after thawing and between each withdrawal. 

For more details, refer to the FDA Moderna COVID-19 Vaccine Fact Sheet. 

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 jurisdictions Immunization Information System or other designated system.  

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: This is not recommended, as it has not been studied. Both trials reported vaccine efficacy after one dose (the Moderna trial reported an efficacy of 80.2%, and the Pfizer-BioNTech trial 52.4%), but the numbers of patients in both of these analyses were small. In addition, the trials were not designed to assess if one dose lead to prolonged efficacy in terms of preventing clinical disease. Two doses of both vaccines results in a high efficacy of >90%.  

Overall vaccine efficacy after one dose has not been studied. While there were patients in phase 3 trialwho received one dose and vaccine efficacy was reported in these patients, 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 is available and the efficacy of one dose has been studied, FDA recommends that all COVID-19 vaccine recipients receive two doses of vaccine. 

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

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

Concurrent Medications  

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

A: CDC recommends that given the lack of data on the safety and efficacy of mRNA COVID-19 vaccines administered simultaneously with other vaccines, the vaccine series should be administered alone, with a minimum interval of 14 days before or after administration with any other 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: Are there any concurrent medications that are uniquely contraindicated in recipients of mRNA vaccinesWill patients need to stop any medications prior to vaccination? 

A: There are currently no medications that have been listed as being 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.  

Additionally, based on the estimated half-life of monoclonal antibodies or convalescent plasma as part 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: 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. 

For persons receiving antibody therapies not specific to COVID-19 treatment (e.g., intravenous immunoglobulin, RhoGAM), administration of mRNA COVID-19 vaccines either simultaneously with or at any interval before or after receipt of an antibody-containing product is unlikely to substantially impair development of a protective antibody response. Thus, there is no recommended minimum interval between other antibody therapies (i.e., those that are not specific to COVID-19 treatment) and mRNA COVID-19 vaccination.   

Q: How long should one wait to administer vaccine before or after IVIG infusions for patients with IgG deficiency?

A: There are no data regarding the optimal time to provide COVID-19 vaccination to someone who is receiving IVIG infusions for an immune deficiency. However, someone with IgG deficiency may have an absent or attenuated vaccine response

It is not likely that antibody therapies which are not COVID-19 specific, such as IVIG, would impair vaccine-induced immune responses. Therefore, CDC states there is no minimum interval one should wait between administering an antibody therapy and an mRNA COVID-19 vaccine.

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

A: Patients on an anticoagulant or with coagulopathy were not excluded from the clinical studies. You should inform your vaccination provider that you have a bleeding disorder or are on a blood thinner, as if you are taking a blood thinner such as warfarin, or a new anticoagulant, the bleeding may take a little longer to stop and you may get more bruising on your upper arm. The immunization of patients with bleeding disorders differs from that of the normal population with respect to the risk of haematoma formation at the vaccination site and the unusual infective risks associated with potential, and past, exposure to blood products.  

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

A: There is no specific guidance to date, but 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, per the American Society of Hematology and the American Society for Transplantation and Cellular Therapy.  

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: When is the appropriate time frame to get the second vaccine dose if patient was given first vaccine dose but also was infected with COVID-19 shortly after and was given antibodies? Is it 90 days? Do you give 2nd dose or repeat the 2 doses of vaccine?

A: Per CDC guidance, if someone develops symptomatic COVID-19 disease 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 is 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.

Side Effects & Allergic Reactions  

Side Effects

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

A: CDC recommends that 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: 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 4 vaccine recipients after dose 1 and 11 vaccine recipients after dose 2. 

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

A:  Data from clinical trials indicate that mRNA COVID-19 vaccines are safe in people with evidence of a prior SARS-CoV-2 infection. In the Pfizer-BioNTech and Moderna COVID-19 vaccine studies, the percentage of participants who had serologic evidence of prior infection at study enrollment was 2.2% and 3%, respectively. 

Q: I have heard conflicting recommendations as to whether acetaminophen or ibuprofen given for vaccine side effects (fever/arm pain etc.) decrease the vaccine's efficacy and should be avoided when possible. Is that true?

A: If a patient receives an mRNA COVID-19 vaccine and develops local or systemic symptoms that would benefit from acetaminophen or non-steroidal anti-inflammatory drugs, they may be given. However, 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. 

Allergic Reactions

Q: Should patients with history of anaphylaxis to non-medications/food allergies (e.g., shellfish, nuts, eggs), avoid the vaccine?  

A: CDC recommends that people with a history of severe allergic reactions not related to vaccines or injectable medications  such as allergies to food, pet, venom, environmental or latex  may still get vaccinated. People with a history of allergies to oral medications or a family history of severe allergic reactions, or who might have a milder allergy to vaccines (no anaphylaxis), may also still get vaccinated.  Of note, recommendations in the United Kingdom are not the same as those in the United States. 

Q: In the U.K., it is recommended that people with serious allergy history not take the vaccine. What is considered a serious allergy and to what? 

A: An anaphylactic reaction is considered a severe allergy history. For both mRNA vaccines, a severe allergic reaction is referring to any component of the vaccine. Of note, recommendations in the United Kingdom are not the same as those in the United States. CDC recommends that persons with a history of anaphylaxis to any other vaccine or injectable therapy can still receive either mRNA COVID-19 vaccines, but should be counseled about the unknown risks of developing a severe allergic reaction.   

Q: What are the components of the vaccine that an individual should be concerned about regarding allergy? 

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: They appear to be similar. 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. 

Q: In terms of acute allergic reactions, what is the recommended length of time to monitor an individual post-vaccination? 

A: For both mRNA vaccines people with no history of anaphylaxis should be monitored for 15 minutes after vaccination; people with a history of anaphylaxis should be monitored for 30 minutes.  

Q: Are there data on whether patients with asthma are more prone to hypersensitivity or anaphylaxis adverse events? 

A: The risk factors associated with rare hypersensitivity or anaphylaxis adverse events are not clearly outlined at this time. A previous severe reaction (anaphylaxis) to the COVID vaccine is a contraindication to further doses of COVID vaccine. A severe reaction (anaphylaxis) to any other vaccine or injectable therapy (e.g., intramuscular, intravenous or subcutaneous) is a precaution but not a contradiction to vaccination with the COVID vaccine.   

Allocation & Distribution 

Q: How is the vaccine being prioritized among healthcare personnel? 

A: CDC defines healthcare personnel as paid and unpaid people serving in healthcare settings who have the potential for direct or indirect exposure to patients or infectious materials, including bodily substances; contaminated medical supplies, devices and equipment; contaminated environmental surfaces; or contaminated air. However, it is expected that demand for a COVID-19 vaccine will exceed supply during the first months of the national vaccination program. As such, ACIP has set the following additional goals for recommending which groups should receive COVID-19 vaccines when supply is limited: 

  1. Decrease death and serious disease as much as possible; 
  2. Preserve functioning of society; 
  3. Reduce the extra burden the disease is having on people already facing disparities; 
  4. Increase the chance for everyone to enjoy health and well-being. 

States and localities may vary in their specific dissemination strategies. You can view your states COVID-19 vaccination plan here.

Q: Does Phase 1a include healthcare personnel working in behavioral health settings such as residential settings, psychiatric or chemical dependency hospitals (which are not considered acute care hospitals, subacute or long-term care facilities), substance use and mental health sites (as these are not considered hospitals, long-term care facilities, outpatient clinics, home healthcare, pharmacies, emergency medical services or public health facilities)?  

A: Health care workers in behavioral health settings are included under ACIPs recommendations for Phase 1a rollout. CDC defines healthcare settings as places where healthcare is delivered and includes, but is not limited to, acute care facilities, long term acute care facilities, inpatient rehabilitation facilities, nursing homes and assisted living facilities, home healthcare, vehicles where healthcare is delivered (e.g., mobile clinics) and outpatient facilities, such as dialysis centers, physician offices and others. However, it is expected that demand for a COVID-19 vaccine will exceed supply during the first months of the national vaccination program. As such, ACIP has set the following additional goals for recommending which sub-groups should receive COVID-19 vaccines when supply is limited:  

  1. Decrease death and serious disease as much as possible; 
  2. Preserve functioning of society; 
  3. Reduce the extra burden the disease is having on people already facing disparities; 
  4. Increase the chance for everyone to enjoy health and well-being. 

States and localities may vary in their specific dissemination strategies. You can view your states COVID-19 vaccination plan here. 

Q: Where do public health workers who work at a health department and are not frontline workers fall in the allocation sequence?  

A: Public health workers who do not have clinical duties and do not work in a frontline capacity may be considered for vaccination in Phase 1a if they fall within CDCs broad definition for healthcare personnel. CDC defines healthcare personnel as paid and unpaid people serving in healthcare settings who have the potential for direct or indirect exposure to patients or infectious materials, including bodily substances; contaminated medical supplies, devices and equipment; contaminated environmental surfaces; or contaminated air. However, it is expected that demand for a COVID-19 vaccine will exceed supply during the first months of the national vaccination program. As such, ACIP has set the following additional goals for recommending which groups should receive COVID-19 vaccines when supply is limited:  

  1. Decrease death and serious disease as much as possible; 
  2. Preserve functioning of society; 
  3. Reduce the extra burden the disease is having on people already facing disparities; 
  4. Increase the chance for everyone to enjoy health and well-being.  

It is reasonable to assume vaccines may be prioritized for healthcare personnel who have the most direct exposure to COVID-19 based on current job functions. States and localities may vary in their specific dissemination strategies. You can view your states COVID-19 vaccination plan here.

Q: Are medical students in their clerkship years to be part of Phase 1a for vaccination?  

A: Possibly. Students and trainees are included in CDCs broad definition of healthcare personnel who are prioritized for vaccination in Phase 1a. However, it is expected that demand for a COVID-19 vaccine will exceed supply during the first months of the national vaccination program. As such, ACIP has set the following additional goals for recommending which groups should receive COVID-19 vaccines when supply is limited:  

  1. Decrease death and serious disease as much as possible; 
  2. Preserve functioning of society; 
  3. Reduce the extra burden the disease is having on people already facing disparities; 
  4. Increase the chance for everyone to enjoy health and well-being. 

It is reasonable to assume vaccines may be prioritized for healthcare personnel who have the most direct exposure to COVID-19 based on current job functions. States and localities may vary in their specific dissemination strategies. You can view your states COVID-19 vaccination plan here.

Q: Are staff included with long-term care facility residents for the first allocation?  

A: Yes. Staff other than licensed medical professionals working in LTCF is included in CDCs broad definition of healthcare personnel recommended for vaccination in Phase 1a. CDC includes persons who are not directly involved in patient care, but who could be exposed to infectious agents that can be transmitted in the healthcare setting (e.g., clerical, dietary, environmental services, laundry, security, engineering and facilities management, administrative, billing and volunteer personnel).  

Q: Who will be prioritized for COVID-19 vaccination after Phase 1a? 

A: The Advisory Committee on Immunization Practices recommendations for allocation of COVID-19 vaccine state that in Phase 1b, COVID-19 vaccine should be offered to persons aged ≥75 years and non-healthcare frontline essential workers, and in Phase 1c, to persons aged 65–74 years, persons aged 16–64 years with high-risk medical conditions and essential workers not included in Phase 1b. CDC is routinely updating its list of high-risk medical conditions as new data become available. 

Q: How much will state plans for allocation and prioritization differ from the CDC/ACIP recommendations?  

A: States and localities may vary in their specific dissemination strategies. You can view your states COVID-19 vaccination plan here, including at what phase the vaccine is expected to be available for certain populations.

Q: Will vaccines be allowed to be administered through “drive-thru” facilities, as is done for testing? 

A: Yes, although feasibility of drive-thru vaccine clinics largely depends on local resources, including ability to store, handle and prepare equipment. The Pfizer-BioNTech vaccine can be stored for up to 5 days at standard refrigerator temperatures once ready for use, but very cold temperatures are required for shipping and longer storage. It is expected that as more vaccines are brought to market under EUAs, vaccination sites can be expanded beyond those with the ability to maintain the cold chain. CDC has put together guidance for facilities planning curbside or drive-thru vaccination clinics (not COVID-19 specific).   

Special Patient Populations & Settings 

Vaccination in Previously or Currently Infected Individuals

Q: Why is it necessary to vaccinate people who had COVID? In other infections, vaccine is not superior to disease itself in terms of immunization.  

A: Given 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 suggests 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 purposes of vaccine decision-making is not recommended. Vaccination of individuals with known current SARS-CoV-2 infection should be deferred until the person has recovered from the acute illness (if the person 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 the person has recovered from the acute illness (if the person 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. 

Vaccination in People Who Are Pregnant or Breastfeeding

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

A: The Pfizer-BioNTech and Moderna vaccine EUAs do not exclude pregnant or lactating people. People who are pregnant or breastfeeding may choose to be vaccinated, according to CDC.

Observational data demonstrate that while the absolute risk is low, pregnant people with COVID-19 have an increased risk of severe illness, including illness resulting in intensive care admission, mechanical ventilation, or death. Additionally, they might be at an increased risk of adverse pregnancy outcomes, such as preterm birth. There are currently few data 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., healthcare 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 healthcare provider is not required prior to vaccination. When making a decision, pregnant people and their healthcare 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. 

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 womenIs a consent form required for that population? 

A: There are no additional requirements other than pregnant women 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: Is the vaccine safe for women who are trying to get pregnant? Is there a concern that the immune response tthe spike protein could cross-react with the syncytin 1 protein on the placenta, resulting in preeclampsia, abruptio placenta, preterm labor or miscarriages? Why or why not? 

A: There are currently few data 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. If pregnant people are part of a group that is recommended to receive a COVID-19 vaccine (e.g., healthcare 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 healthcare provider is not required prior to vaccination. When making a decision, pregnant people and their healthcare 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.  

Further, the American College of Obstetricians and Gynecologists recommends vaccination of individuals who are actively trying to become pregnant or are contemplating pregnancy and meet the criteria for vaccination based on ACIP prioritization recommendations. Additionally, it is not necessary to delay pregnancy after completing both doses of the COVID-19 vaccine. The spike protein and syncytin are similar only in one very small region, and there is no reason to believe antibodies that can grab onto spike proteins would cross-react with syncytin. The human body generates its own supply of spike antibodies when it fights off the coronavirus, and there is currently no signal that these antibodies attack the placenta. 

Vaccination in Immunocompromised Patients

Q: Is the vaccine safe for transplant patients?  

A: For both mRNA vaccines, because immunocompromised people may be at risk for severe COVID-19, CDC recommends these groups may still 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. 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. It is possible that transplant recipients 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 vaccine is available in an effort to protect the patient.  

Q: 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. It is possible that cancer patients 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 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. It is possible that asplenic patients 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 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?   

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 these groups may still receive the vaccine if there are no contraindications. People living 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: 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.  

Vaccination in Children

Q: If we vaccinate children with Pfizer-BioNTech, could we give half a dose first and half a dose 4 weeks later? 

A: There are currently no data and recommendations for vaccinating children with the Pfizer-BioNTech COVID-19 vaccine. Adolescents aged 16–17 years are included among persons eligible to receive the Pfizer-BioNTech COVID-19 vaccine under the EUA. While vaccine safety and efficacy data in this age group are limited, there are no biologically plausible reasons for safety and efficacy profiles to be different than those observed in persons 18 years of age and older. Adolescents aged 16–17 years who are part of a group recommended to receive a COVID-19 vaccine may be vaccinated with the Pfizer-BioNTech COVID-19 vaccine with appropriate assent. Children and adolescents younger than 16 years of age are not authorized to receive the Pfizer-BioNTech COVID-19 vaccine at this time. Children and adolescents younger than 18 years of age are not authorized to receive the Moderna COVID-19 vaccine at this time. In September, Pfizer-BioNTech began clinical trials in their vaccine on children as young as 12.  Moderna has started trials for 12- to 17-year-olds.  

Q: Are there biological differences between those aged 16 and 17 years versus 18 years in receiving the vaccine? 

A: While vaccine safety and efficacy data in this age group are limited, there are no biologically plausible reasons for safety and efficacy profiles to be different than those observed in persons 18 years of age and older. The Advisory Committee on Immunization Practices guidance states that adolescents aged 16 years or older who are part of a group recommended to receive a COVID-19 vaccine may be vaccinated with the Pfizer-BioNTech vaccine, and those 18 years or older may be vaccinated using the Moderna vaccine. Differences in age requirements relate to the study population used in each vaccine trial and the age groups for which FDA has issued an emergency use authorization for the use of each vaccine. 

Vaccination in Older Persons

Q: Are there any special considerations (restrictions) in people older than 65 years old?  

A: There are no special restrictions in those older than 65 years old that have been noted for either mRNA vaccine. 

Post-Market Safety Monitoring 

Q: Will pharmacies be required to collect follow-up data on vaccinated people?  

A: Vaccination providers administering the mRNA vaccines must report the following information associated with the administration of the vaccines of which they become aware to VAERS in accordance with the fact sheet for healthcare providers: 

  • Vaccine administration errors whether or not associated with an adverse event; 
  • Serious adverse events (irrespective of attribution to vaccination); 
  • Cases of multisystem inflammatory syndrome in children and adults; 
  • Cases of COVID-19 that result in hospitalization or death. 

Complete and submit reports to VAERS online or by calling 1-800-822-7967.  

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: Text messaging and web surveys will exclude many of the most at-risk populations; what is being done to mitigate that gap? 

A: Persons who have received a vaccine, do not have access to the v-safe app, are experiencing an adverse reaction to the vaccine and would like to report the adverse event are able to report directly to VAERS by calling call 1-800-822-7967. Additional reporting options, including an online portal and PDF fillable form, are available on the VAERS website. 

 

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