• US FDA has authorized COVID-19 vaccines from Pfizer-BioNTech, Moderna, and Janssen under Emergency Use Authorization. Please see above question for US FDA-CDC statement to pause Janssen vaccine

• European Medicines Agency (EMA) has recommended the BioNTech/Pfizer, Moderna, Oxford/AstraZeneca and Janssen (J&J) vaccines under conditional marketing authorization

• WHO has listed Pfizer/BioNTech, Astrazeneca-SK Bio and Serum Institute of India vaccines, and Janssen vaccine for Emergency Use Listing in all countries and for COVAX roll-out

• UK regulatory authority has authorized Pfizer/BioNTech vaccine , Oxford University/AstraZeneca vaccine  and Moderna vaccine under Regulation 174

• Canada has authorized Pfizer and Moderna vaccines

• In addition, Russian health ministry has registered Sputnik V vaccine, and China's National Medical Products Administration has approved (conditional approval?) Sinopharm vaccine for general use (Government Source Link needed)

• India has recommended emergency use authorization of Serum Institute (manufacturing Oxford/AstraZeneca vaccine) and Bharat Biotech COVID-19 vaccines 

You will note that different authorities use different terms - approval, authorization, validation, etc. There are some nuances to appropriate use of these words, but for sake of simplicity one can assume it as recommendation for use 

Last Updated: Mar 18, 2021

• The US FDA has authorized the emergency use of the Pfizer-BioNTech COVID-19 Vaccine to prevent COVID-19 in individuals 12 years of age and older under an Emergency Use Authorization (EUA)

• The US FDA has authorized the emergency use of the Moderna COVID-19 Vaccine to prevent COVID-19 in individuals 18 years of age and older under an Emergency Use Authorization (EUA)

• The US FDA has authorized the emergency use of the Janssen COVID-19 Vaccine to prevent COVID-19 in individuals 18 years of age and older under an Emergency Use Authorization (EUA)

• EU has given conditional marketing approval for COMIRNATY (Pfizer-BioNtech) COVID-19 Vaccine to prevent COVID-19 in people aged 16 years or older

• EU has given conditional marketing approval for JnJ COVID-19 Vaccine to prevent COVID-19 in people aged 18 years or older

• EU has given conditional marketing approval for Moderna COVID-19 Vaccine to prevent COVID-19 in people aged 18 years or older

• EU has given conditional marketing approval for Vaxzevria (AstraZeneca/Oxford COVID-19) Vaccine to prevent COVID-19 in people aged 18 years or older

• In UK MHRA has authorized Oxford-AstraZeneca vaccine for individuals 18 years of age and older* under Regulation 174

Please Note: these vaccines are considered "authorized" under Emergency Use Authorization by USFDA and not considered as "approved"

* Certain countries within EU have put restrictions on age-eligibility for Oxford-AstraZeneca vaccine. Please consult local guidelines

• Pfizer-BioNTech COVID-19 Vaccine: A 2-month median follow-up from one large trial (>43,000 enrolled participants) indicated 95.0% efficacy in preventing symptomatic, laboratory-confirmed COVID-19

• Moderna COVID-19 Vaccine: A 2-month median follow-up from one large trial (~30,000 enrolled participants) indicated 94.1% efficacy in preventing symptomatic, laboratory-confirmed COVID-19

• Oxford/AstraZeneca Vaccine: In pooled analysis of two trials (11,636 participants), the vaccine was 70.4% after two doses, and 52.7% after one dose, with a median follow up of 132 days post-dose 1 and 63 days post-dose 2

• Janssen COVID-19 Vaccine: Analysis of 39,321 participants showed vaccine was approximately 67% effective in preventing moderate to severe/critical COVID-19 occurring at least 14 days after vaccination and 66% effective in preventing moderate to severe/critical COVID-19 occurring at least 28 days after vaccination. Additionally, the vaccine was approximately 77% effective in preventing severe/critical COVID-19 occurring at least 14 days after vaccination and 85% effective in preventing severe/critical COVID-19 occurring at least 28 days after vaccination

• Regulatory bodies like FDA prescribe standards to make sure that the approved products (medicines, vaccines or devices) are safe and effective. These are usually proven through large clinical trials where a sub-group taking the product under test (e.g. COVID-19 vaccine) is compared with the control group who has been given a placebo (which doesn't have the ingredient e.g. could be injectable normal saline). Rate of COVID-19 infection or side-effects in the product sub-group (also called arm) is compared with the control arm to see the benefit as well as safety of the product

• Pfizer-BioNTech, Moderna, Oxford-AstraZeneca and Janssen vaccines showed an efficacy of 95.0%, 94.1%, 70.4% and 67% respectively. The vaccines may cause side-effects like sore muscles, tiredness and mild fever. It's rare but possible to have serious side-effects. Please call your physician, nurse for mild side-effects, and call 911 or go to nearest emergency room for serious side-effects.

US CDC recently presented data on Pfizer and Moderna vaccines side effects

• As of Jan 24, 2021, 21.8MM people had been vaccinated with first dose with either of the vaccine

• 2.1 MM registrants completed check-in on V-safe, while VAERS (Vaccine Adverse Event Reporting System) had 9,096 adverse events reports.

• Most common side effects remain similar to Phase III trials and include pain, fatigue, headache or myalgia

• Reported Anaphylaxis rates were about 5.0 per million doses administered for Pfizer (total doses - 9.94 million), and 2.8 per million doses administered for Moderna vaccine (total doses - 7.58 million doses) as of Jan 18, 2021

• Overall, the safety profiles of COVID-19 vaccines are reassuring and consistent with that observed that observed from the pre authorization clinical trials  

Pfizer-BioNTech COVID-19 Vaccine

• • 84.7% vaccine recipients reported at least one local reaction. Pain at the injection site was most frequent, followed by redness and swelling

  • 77.4% vaccine recipients reported at least one systemic reaction. Frequency and severity of systemic reactions was higher after second dose. Fatigue, headache and new or worsened muscular pain were most common. Vomiting and Diarrhea were exceptions

  • More detailed information can be found at this link

Moderna COVID-19 Vaccine

• • Local reactions were reported by majority of vaccine recipients. Frequency was higher in younger (aged 18-64 years) vs. older (65 years or more) (90.5% vs. 89.3% after Dose 2). Pain at the injection site was most frequent. Axillary swelling (swelling in armpit) or tenderness was the second most frequently reported

  • Frequency of systemic reactions was higher in younger (81.9%) vs. older (71.9%) age groups. Fatigue, headache and muscular pain were most common. Fever was more common after second dose

  • More detailed information can be found at this link 

Oxford/AstraZeneca Vaccine 

• Most frequently reported adverse reactions were injection site tenderness (>60%); followed by injection site pain, headache, fatigue (>50%); followed by myalgia, malaise (>40%). Adverse reactions were generally milder and reported less frequently in older adults (≥ 65 years old)

• More details can be found at this link (Section 4.8)

Janssen (J&J) Vaccine

• In study COV3001, most common local solicited adverse reaction was injection site pain (48.6%), most common systemic adverse reactions were headache (38.9%), fatigue (38.2%), myalgia (33.2%), and nausea (14.2%)

• More details can be found at this link (Section 6) 

Last Updated: May 11, 2021

Oxford/AstraZeneca COVID-19 Vaccine

• EMA found a possible link to very rare cases of unusual blood clots with low platelets. However, EMA confirms overall benefit-risk remains positive. Various EU countries have restricted vaccination recommendations, readers are requested to refer to local guidelines and consult  their health care practitioner for any questions or concerns

• UK JCVI (Joint Commission on Vaccination and Immunisation) has advised that it's preferable for people 39 and below to have a vaccine other than AZ. However, if they have already taken first dose of AZ vaccine without suffering this rare side effect you should complete the course. 

JnJ COVID-19 Vaccine

• EMA found a possible link to very rare cases of unusual blood clots with low platelets. However, EMA confirms overall benefit-risk remains positive.

• US FDA and CDC issued a joint statement lifting the pause in the use of Johnson & Johnson COVID-19 vaccine, underscoring the confidence in vaccine safety and effectiveness; available data suggests potential blood clots are very rare events

• For Background: Of the nearly 7 million doses administered so far in the United States, a small number of  cases of a rare and severe type of blood clot have been reported in people after receiving the J&J/Janssen COVID-19 Vaccine.  All reports occurred among women between the ages of 18 and 48, and symptoms occurred six to 13 days after vaccination. As of April 13, 2021, no cases have been reported among the more than 180 million people who received the Pfizer-BioNTech or Moderna vaccines. 

• Pfizer-BioNTech vaccine is a two dose vaccine, with second dose recommended 3 weeks after the first dose

• Moderna vaccine is a two dose vaccine, with second dose recommended 4 weeks after the first dose

• Oxford/AstraZeneca vaccine is a two dose vaccine, with second dose recommended between 4 - 12 weeks after the first dose

• Janssen (J&S) vaccine is a single dose vaccine

USA CDC Recommendation (Dec 31, 2020)

• As the vaccines availability will be limited in the near-term, CDC has recommended vaccination priority based on three goals

  • Decrease death and serious disease as much as possible

  • Preserve functioning of society

  • Reduce the extra burden COVID-19 is having on people already facing disparities

• With these goals in mind, CDC recommends that the initial supplies should be allocated to Healthcare Personnel and Long-Term Care Facility Residents as Phase 1a on Dec 3, 20220

• On Dec 22, 2020 CDC recommended following groups for Phase 1b and Phase 1c 

  • Phase 1b - Frontline Essential workers & People aged 75 years and older

  • Phase 1c - People aged 65-74 years, People aged 16-64 years with underlying medical conditions, and Other essential workers

• As vaccines availability increases, vaccination recommendations will expand to other groups. 

Please check your state website for local eligibility criteria, and schedule an appointment, if eligible 

UK JVCI Recommendation (Dec 30, 2020)

• Phase 1 objective is "Direct prevention of mortality and supporting the NHS and social care system, in the following order of priority

  • residents in a care home for older adults and their carers

  • all those 80 years of age and over and frontline health and social care workers

  • all those 75 years of age and over

  • all those 70 years of age and over and clinically extremely vulnerable individuals[footnote 1]

  • all those 65 years of age and over

  • all individuals aged 16 years[footnote 2] to 64 years with underlying health conditions which put them at higher risk of serious disease and mortality[footnote 3]

  • all those 60 years of age and over

  • all those 55 years of age and over

  • all those 50 years of age and over

• Phase 2 objective will be further reduction in hospitalization and targeted vaccination of those at high risk of exposure and/or those delivering key public services

Canada NACI provides a similar staged recommendation on prioritization of vaccines for efficient and equitable distribution, and these can be found at this link  

• US FDA evaluated and analyzed vaccines safety data from Pfizer and Moderna vaccines (separately), involving tens of thousands of trial participants. Evaluation included a follow up for a median of 2 months after receiving second dose (in line with the guidance set forth by FDA, and the follow up currently continuing as well.  Further, the regulatory bodies, including FDA continue to monitor the reported adverse events.

• While the approval timelines have been accelerated significantly whereby we have more than one vaccine available for use within almost a year, most of the reduction in timelines were achieved through reduction in administrative tasks, and not short-cuts in clinical trials.

• There is also a concern regarding "newness" of the mRNA technology. Although there is no currently approved preventative vaccine (apart from current COVID-19 vaccines), this technology has been used to develop other vaccines that have been tested in human clinical trials. To quote US FDA "FDA does not have specific safety concerns with a vaccine that utilizes this technology."    

• As of now, none of the regulatory or recommending bodies have given any preference for one vaccine over the other for following reasons

  • No head-to-head trials (i.e. using one company's vaccine in one set of population and another vaccine in second set of population in the same clinical trial with comparable populations on both sides/cohorts) have been conducted to show better efficacy of one vaccine over the other

  • It's not advisable to compare efficacy data from different trials as the protocols, background environment and population criteria aren't matched across trials

  • Vaccines have shown good safety profile

• While vaccines have shown 94%-95% efficacy in 2-month median follow-up period after a two-dose regimen, the vaccines don't offer 100% protection and don't start providing protection immediately after vaccination

• Also, the current studies has demonstrated efficacy against symptomatic, laboratory-confirmed COVID-19 infection. No data were available to assess the efficacy for prevention of asymptomatic SARS-CoV-2 infection. You may still be able to transmit the virus to others

• Hence, routine precautionary measures like social distancing, hand-hygiene, masks, etc. should be continued even after vaccination

• Unfortunately, Yes. The vaccine efficacy rates for currently approved mRNA vaccines are very high at 94%-95%, but it still implies that there may be 5-6% of vaccinated population who won't develop immunity or adequate immunity, and hence continue to have the risk of acquiring infection. Apart from the special underlying medical conditions (see below), it is difficult to estimate who may not develop immunity or adequate immunity

• You may also get COVID-19 infection within a short window (2-3 weeks) post-vaccination, when your body is still building up it's immune responses

• Hence, it is recommended that vaccine recipients should continue to take preventive measures, like social distancing, face masks, hand hygiene, etc. even after taking full course of vaccines

• CDC and ACIP have recommended certain groups to be offered vaccines first due to limited availability of vaccines. If you are pregnant and part of the recommended group, you may choose to be vaccinated

• Both vaccines have not been tested in pregnant and lactating mothers. Please consult your physician to make an informed choice

• Persons with weakened immune systems may be at increased risk for severe illness with the virus. The vaccine may be administered in such populations, however there is limited safety data, and persons with weakened immune system may also have reduced response to the vaccine. They should continue to follow preventive measures for protection. 

• More information can be found at this link

• Anaphylaxis (severe allergic reactions) has been observed in patients, most of these instances have been observed in population with previous history of allergic reactions. Vaccines aren't recommended for people with known allergy to vaccine components

• Second dose isn't recommended for those who experienced severe allergic reactions (like anaphylaxis, generalized urticaria i.e. hives/red itchy welts) to the first dose

• As per CDC, 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, because current evidence suggests reinfection is uncommon during this time.

• There is limited information available at this moment. However, based on the fact that re-infection is uncommon in 90 days after initial infection, and estimated half-life of MABs (monoclonal antibodies e.g. Bamlanivimab by Eli Lilly and Company) or convalescent plasma, vaccinations should be deferred for at least 90 days

FACTS

• • Norway is vaccinating elderly and people in nursing homes, many of them have serious underlying diseases. In Norway, about 400 people die every week in nursing homes and long-term care facilities

  • All adverse reactions, whether related to vaccination or not, are reported if they occurred within few days of vaccination. This process is routinely followed across the globe

  • Norway reported suspected adverse reactions, including 23 deaths, post vaccination in elderly frail population. The total number has since risen to 33 deaths, and total number of people vaccinated is about 40,000 elderly individuals 

  • As per Jan 14th Weekly adverse reaction report, there were a total of 29 adverse reports that week including  21 in 80+ and 4 in 70-79 years old. This included 13 fatal outcomes, however age or disease split is usually not provided for privacy reasons

  • Since these patients are frail, some of common adverse reactions may have worse outcome in these patients. TGA, Australia has reported that the deaths were associated fever, nausea, diarrhoea - relatively common and short-lived vaccine effects 

WHAT WE DON'T KNOW

• The cause of deaths have not been clearly linked with vaccination. Today (Jan 18, 2021), some media outlets have quoted Steiner Madsen, Medical Director at Norwegian Medicines Agency

“All of these patients have had serious underlying illnesses,” Madsen said. “We can’t say that people die from the vaccine. We can say that it may be coincidental. It is difficult to prove that it’s the vaccine which is the direct cause.”

• While remarkable and commendable advances have been made to get more than one vaccine for COVID-19 being made available within one year of first case detection, there is still a lot more that is not known yet. This is also a word of caution to continue practicing preventive measures like social distancing, masks, hand-hygiene, etc. to prevent the spread

• We don't know how long the protective effect of vaccines will last. The ongoing studies and real world experience will help uncover this with time. Based on this, we don't know whether we will need a regular booster (like Tetanus, Pneumococcal vaccines, etc.)

• We don't know what will be the impact of recent mutations (and future mutations) on vaccine efficacy. Currently, experts estimate that the current vaccines will be effective against these two new mutations. 

• We don't know when we will have sufficient doses (and acceptance) to vaccinate whole or large part of population

• We don't know what is the right level of population vaccination rates for herd-immunity. Experts have estimated a range of numbers taking into account people already having been infected or vaccinated, but there is no single consensus number

• Currently, there is no data on interchangeability (i.e. taking first and second dose from different manufacturers) of vaccines, so same vaccine should be used for completing the vaccination series