The Curbsiders podcast

#253 COVID-19 Vaccines with Dr Monica Gandhi

January 27, 2021 | By

They’re finally here!

Answer all your burning questions (and your patients’ burning questions) about the different COVID-19 vaccines currently authorized in the US. Infectious diseases / HIV expert, Dr Monica Gandhi @MonicaGandhi9 (UCSF) joins us to cover: the Pfizer-BioNTech and Moderna novel mRNA vaccine mechanisms, trial data, and practicalities of who should receive them.  We discuss data around the Oxford-AstraZeneca adenovirus vaccine, which is authorized in the UK and India, and may be available in the US later this year.  Feel confident recommending COVID-19 vaccines to your patients!

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  • Written and Produced by: Molly Heublein, MD
  • Cover Art: Chris Chiu, MD, FACP, FAAP
  • Infographic: Tima Karginov
  • Hosts: Chris Chiu, MD, FACP, FAAP; Molly Heublein, MD; Paul Williams, MD, FACP
  • Editor: Emi Okamoto MD (written materials); Clair Morgan of (audio)
  • Guest: Monica Gandhi, MD, MPH

Sponsor: Panacea Financial

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Sponsor: VCU Health CE

The Curbsiders are partnering with VCU Health Continuing Education to offer FREE continuing education credits for physicians and other healthcare professionals. Visit and search for this episode to claim credit.

Time Stamps

  • Intro, disclaimer, guest bio – 00:00
  •  Guest one-liner, book recommendation – 3:40
  • Authorized vaccines in the US – 8:30
  • AstraZeneca vaccine mechanism- 9:26
  • mRNA vaccine mechanism – 10:30
  • Vaccine distribution issues (cold chain) – 16:05
  • mRNA safety – 18:24
  • mRNA vaccine efficacy/data from phase 3 trials – 19:40
  • How did we get this so quickly – 23:40
  • Vaccine impact on asymptomatic infection – 26:18
  • AstraZeneca trials – 28:20
  • Pregnancy – 35:10
  • Anaphylaxis – 37:10
  • Prior COVID-19 infection – 39:07
  • Side effects – 42:05
  • Pediatric patients – 45:12
  • Phases of role outs in the US -46:50
  • Herd immunity – 48:16
  • Thoughts of how to make this happen – 52:45
  • Preexisting conditions – 53:40
  • How long will immunity last – 57:15
  • Mutant strains – 58:25
  • Future of mRNA vaccines – 1:00:30
  • Take home points and Outro – 1:02:12

COVID-19 Vaccine Pearls

  1. The novel mRNA vaccines inject a sequence of messenger RNA which triggers our cells to replicate coronavirus spike proteins to yield an effective immune response preventing symptomatic COVID-19 infection.
  2. Almost all adults can safely receive the authorized mRNA vaccines, there is very little signal of serious risk associated with these.
  3. The Pfizer-BioNTech vaccine is currently approved for ages 16+ and the Moderna vaccine for ages 18+.
  4. The AstraZeneca-Oxford vaccine is approved in the UK and India, it may be authorized in the US in the coming months pending more trial data

Authorized mRNA Vaccines in the US: Pfizer-BioNTech and Moderna

There are two currently authorized vaccines under Emergency Use Authorization by the FDA in the US (as of this recording 1/2021): Pfizer-BioNTech and Moderna.  

Mechanism of Action:

These use a novel mechanism of messenger RNA (mRNA) coding for the coronavirus spike protein encapsulated in a lipid nanoparticle.  When injected into the body, the lipid nanoparticles allow the mRNA to easily enter our cells.  The genetic coding is picked up by our ribosomes and endoplasmic reticulum, causing our cells to make large amounts of the coronavirus spike proteins which then triggers immune response to activate T cells and create antibodies.  The mRNA quickly degrades and is not incorporated into the nucleus thus does not stay around in the host’s body (Almeh 2020, Sahin 2020).

The Pfizer and Moderna vaccines each require two shots each, typical for many vaccines to stimulate lasting immunity.

As genetic material is unstable, mRNA degrades quickly and needs to be kept extremely cold which impacts the ability to distribute.  For reference, a typical refrigerator is 4℃.  The Pfizer-BioNTech vaccine needs to be kept at -70℃, typical of a research laboratory refrigerator.  The Moderna vaccine can be stored at -20℃ for 6 months and in a typical refrigerator (2-8℃) for 30 days allowing for a little more flexibility with mass distribution (FDA 2020, FDA 2020).

Trial Data: 

The Pfizer-BioNTech and Moderna COVID-19 vaccines phase 3 trials were designed to evaluate rates of symptomatic COVID-19 infection and assess the presence of severe disease.  The trade-off for getting data from these trials as quickly as possible was that asymptomatic disease detection with routine swabbing was not an outcome studied.  Both of the mRNA vaccines showed around a 95% efficacy in preventing symptomatic infection and significantly reduced rates of severe disease.  Unfortunately, we don’t know yet if they stopped asymptomatic spread and we need to wait for the data to be published.  Dr. Gandhi thinks it would make sense, biologically speaking, that it would stop the asymptomatic spread of COVID-19 infection.  These large phase 3 trials showed no sign of serious safety concerns (Baden 2020, Polack 2020).

These vaccines have come to market very quickly by overlapping phases of the vaccine trials, as opposed to being carried in a subsequent manner.  Additionally, the interval of time between the first and second vaccine administrations was shortened to 21 days for the Pfizer-BioNTech and 28 days for Moderna (many other vaccines may be spaced by months).  Dr. Gandhi mentioned it may be efficacious to separate the doses by a wider interval since it helps create greater immunogenicity.  The outcomes were assessed starting just 2 weeks following the second dose (Baden 2020, Polack 2020).

Since these vaccines are so new, we don’t know how long they will offer protection.  Dr. Gandhi is hopeful these vaccines will provide lasting immunity for at least 5 years, from extrapolating existing data.  She says they may require periodic boosters, but will not likely be yearly.

SARS-CoV-2 mutations

A number of mutated strains of coronavirus have spread, including  an earlier D614G, the recent UK Variant B.1.1.7 lineage, and South African variant B.1.351 lineage.  These strains seem more transmissible because of increased viral load.  At this point, research suggests the current vaccines should still be highly effective.  (CDC 2021, Conti 2021)

Who should/should not receive COVID-19 vaccines:

Dr. Gandhi suggests basically everyone should get the vaccine. 

Pregnant and Breastfeeding Patients:

While pregnant and breastfeeding women were excluded from trials, Dr.  Gandhi feels there should not be a scientific reason for vaccination to be unsafe.  The mRNA degrades very quickly and the spike protein is very specific to coronavirus thus there is little risk of autoimmunity.  Current guidance is that we should offer the vaccine to pregnant patients since the risk of COVID-19 infection in pregnancy is serious; women should discuss their concerns with their medical providers and weigh the risks and benefits (Rasmussen 2020, CDC 2021).


Only a small number of patients with HIV or immunosuppression were included in the Pfizer-BioNTech trial.   Dr. Gandhi suggests that vaccination should be safe in immunosuppressed patients though we do not have specific data on this matter.

Anaphylaxis and Allergic Reactions

Out of the 21,000 Pfizer and 16,000 Moderna trial participants, there were no hypersensitivity reactions noted.   Anaphylaxis was seen among healthcare workers who were vaccinated early during the roll out.  The CDC issued a caveat for patients to wait 15 minutes after vaccination and wait for 30 minutes if they have a history of anaphylaxis.  Dr. Gandhi feels this is probably overkill and people who know what to look for with anaphylaxis should likely self monitor for symptoms.  At this point, it seems the reaction may be to PEG (polyethylene glycol).  Someone with a peanut or seafood allergy is likely at very low riskSince our recording, the CDC/MMWR released data that only 21 cases of anaphylaxis have been recorded in the 1.8 million doses of Pfizer-BioNTech vaccine given so far (11 cases per million).

Patients with history of COVID-19 infection

Patients who had COVID-19 infection have immunity, and vaccines should ideally be saved for others when we still have vaccine shortages.  The CDC/ACIP recommend waiting 90 days after COVID-19 infection for vaccination, not because of any risk, but because the risk of reinfection is very low.  A recent NEJM study showed that immunity lasts at least 6 months, so this recommendation may be extended (Lumley 2020).    


The  Pfizer-BioNTech mRNA vaccine is authorized for age 16 and up (FDA 2020).  The Moderna vaccine is only approved for age 18+ (FDA, 2020).  There are active pediatric vaccine trials enrolling for younger children.  Dr Gandhi is hopeful we can achieve herd immunity without needing to vaccinate very young children, but it is likely the vaccines may be available to older children over the coming months.

Side effects:

Dr. Gandhi states the main point to remember is that most of the effects were not too serious. Injection site reactions were reported in over 90% of the participants, with pain being the most common side effect.   A fair amount of people reported fatigue, headaches, and fever; these reactions are a reassuring sign of  an active immune stimulation.  Dr. Gandhi notes those with fever could be managed with antipyretics. Serious side effects were rare, and similar between vaccine and placebo groups (Baden 2020, Polack 2020).

Vaccine Distribution:

The main goals laid out by the CDC are to protect the vulnerable populations and focus on reopening society.  It should be noted that the vaccine distribution groups vary from state to state in the US.

Phase 1a: Health care and nursing home residents and staff (done in Jan)

Phase 1b: Age 75+, teachers, grocery store, transit workers, meat processors, etc (Late Jan-Feb)

Phase 1c: Ages 65-74 or 16+ if you have a pre-existing condition, or others who cannot work from home (CDC timeline said March-June)

Phase 2: Anyone age 16+

Dr Gandhi suggests herd immunity might be at 70% of the population.  She is hopeful we will reach this by the time we complete phase 2 which should be helpful with protecting the pediatric population since there will not be high priority to immunize young children.

University of Oxford-AstraZeneca vaccine:

As of this recording (1/2021), the University of Oxford-AstraZeneca vaccine is only approved in the UK and India.  This vaccine uses an adenovirus from a primate as the vector for DNA that codes for the coronavirus spike protein.  This DNA is taken up within our cells and coded into mRNA which then triggers our cells to create the spike protein.  This primate adenovirus does not reproduce or cause pathology in humans.   This is also a two-dose vaccine. Unlike the mRNA vaccines available, this vaccine can be stored in a regular refrigerator for at least 6 months which allows for more flexibility with mass distribution such as rural settings.  According to trial data, no severe outcomes were found in the vaccine group.

Trial differences 

Unlike the mRNA vaccine trial, the participants in the Oxford-AstraZeneca vaccine trial self-swabbed every week to watch for asymptomatic infection.   Phase 3 data showed a 59% reduction in asymptomatic infection.  There were some irregularities in these study protocols.  Some participants were accidentally given a lower first dose then received the standard dose for the second shot (LD/SD).  The LD/SD arm of the trial was found to be more effective at 90% compared to 62% effectiveness for individuals in the standard dose/standard dose (SD/SD) arm.  Participants in the LD/SD arm were mostly under the age of 55 and received the doses of their vaccines with an interval of 12-weeks, which could explain the higher immunogenicity.  The LD/SD participants  also experienced fewer side effects. The total effectiveness at reducing sympathetic disease was reported to be 70%, with no hospitalizations or COVID-19 deaths seen in the vaccinated arm (Voysey 2020).  As of the time of the recording, the AstraZeneca trial is still ongoing in the US.

Take home points:

  • These mRNA vaccines have amazing effectiveness- 95% reduction in the most important outcome- reducing symptomatic COVID-19 infections.
  • Nothing mechanistically is scary about these mRNA vaccines, and we don’t expect long term side effects.
  • As primary care providers, we should encourage our patients to receive these vaccines. 
  • Even if there is a delay between doses, we should still offer 2 doses to all patients.


  1. The Vanishing Half, novel by Brit Bennett Dr Gandhi’s book recommendation 
  2. “ Nation Can’t Believe They Spent So Long Overlooking Obvious Solution Of mRNA Instructions For Spike Protein Encapsulated In Lipid Nanoparticle” The Onion Article  
  3. Ukaih distributes 850 doses of vaccine in hours when freezer fails

*The Curbsiders participates in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising commissions by linking to Amazon. Simply put, if you click on our links and buy something we earn a (very) small commission, yet you don’t pay any extra.


Listeners will understand the currently available and likely soon to be released COVID-19 vaccines.

Learning objectives

After listening to this episode listeners will…  

  1. Explain the mechanism of action for the authorized mRNA vaccines
  2. Identify patients who should or should not receive a COVID-19 vaccine
  3. Describe common side effects of authorized COVID-19 vaccines
  4. Be aware of vaccines in the pipeline which may soon be approved


Dr Gandhi reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures. 


Heublein M, Gandhi M, Chiu C, Okamoto E, Karginov T, Williams P.  “#253 COVID-19 Vaccines with Dr Monica Gandhi”. The Curbsiders Internal Medicine Podcast. January 27, 2021.


  1. January 27, 2021, 7:28am JOHN EMY writes:

    Thank you for the episode. I'd like to point out animal studies in which primates were vaccinated and then challenged with SARS-CoV2. The next day, virus was not detectable in the nasal passages or BAL fluid (NEJM 10/15/20). It would have been nice if you had addressed whether ITP is a contraindication to vaccination. The only death attributable to the vaccine occurred in a healthy man who developed profound acute ITP (at least according to news reports). I don't know obviously whether molecular mimicry or another mechanism was involved, but what do I tell my patients who have either chronic ITP or a history of acute ITP s/p steroid treatment or splenectomy?

  2. January 27, 2021, 9:08pm Jennifer writes:

    Hello, Thank you for your work tackling the conversation on the current Covid-19 vaccines with Dr. Monica Gandhi. I am a primary care RN and have a couple of questions I’m hoping one of you can answer (or direct me to someone who can): I’ve read in Peter Doshi’s editorial in the BMJ that there were 3,410 participants in the Pfizer trial who were reported to have “suspected but unconfirmed covid-19.” As far as I’m aware, no reason was provided as to why these symptomatic individuals were not swabbed. 1,594 of these people were in the vaccine group. I was surprised Dr. Gandhi didn’t bring this up as a criticism of the trial. Do you know of any explanation for this gap in data? Dr. Gandhi almost discussed the concern of pathogenic priming or antibody-dependent enhancement. I have concerns after this was observed during the animal trials for the SARS and MERS vaccines. Is there any risk of this happening when exposed to the wild spike proteins after covid-19 vaccination? Were animal studies part of the clinical trials for Pfizer and Moderna’s vaccines? I’ve read that they were skipped but then also heard that they were completed but the data not published… please clarify. Dr. Gandhi also briefly discussed side effects but failed to mention the serious adverse reactions that are being reported - ie transverse myelitis during the AstraZeneca trial, Mexican internist who experienced seizures and encephalomyelitis shortly after receiving the Pfizer vaccine, several cases of Bells’ Palsy being reported). Not to mention the deaths that have occurred in otherwise healthy individuals shortly after vaccination (ie OB in Florida whose death has been confirmed to be linked to the vaccine, 13 deaths confirmed to be related to covid-19 vaccination in Norway, deaths of 29 elderly people in NY nursing home after vaccination, 181 deaths (as of Jan 15) that have been reported to VAERS for investigation as possibly linked to Pfizer or Moderna vaccines, more recently the X-Ray technician who died 4 days after his second dose, 41 year old health care worker in Portugal who died 2 days after getting the Pfizer shot… to name a few). I found it slightly insulting that Dr. Gandhi answered the question of possible side effects by reviewing that most trial participants experienced pain at injection site… I understand that we all want this pandemic to end. We’re all desperate to return to some semblance of normalcy. But I believe very strongly that we need to be fully informed (both as patients and health care providers) about this vaccine and have honest dialogue about the unknowns - of which there are many. I would truly appreciate any feedback/guidance/information you can provide to address my above concerns. Sincerely, Jennifer

  3. January 28, 2021, 7:39pm Antonio Viana writes:

    You have a typo in the show notes: "sympathetic* disease was reported to be 70%" Thank you What a great episode!

  4. January 29, 2021, 12:19pm Doug Cifuentes writes:

    Another timely episode that knocked it out of the park !! Pardon the baseball reference

  5. February 2, 2021, 12:44pm Liz B writes:

    Wow. This episode was excellent. Dr. Gandhi's excitement and enthusiasm were palpable and I feel so much more comfortable addressing vaccine concerns.

  6. February 2, 2021, 10:12pm C. Sambrano writes:

    I listened to this episode 3 days ago and have referred dozens of people (practitioners) to it already. Well done, yet again.

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The Curbsiders are partnering with VCU Health Continuing Education to offer FREE continuing education credits for physicians and other healthcare professionals. Visit and search for this episode to claim credit.

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