The Curbsiders podcast

#304 COVID Updates: The Outpatient Edition

November 8, 2021 | By

Who gets a COVID booster? Can we mix and match COVID vaccines?  What are monoclonal antibodies and when should we use them? What is molnupiravir and does it work? Shots for kids? Ready yourself to answer these questions and more with our guest, Dr. Monica Gandhi @MonicaGandhi9.

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  • Producer and Writer: Isabel Valdez PA, Molly Heublein MD
  • Infographic: Edison Jyang
  • Cover Art:  Edison Jyang,  Isabel Valdez, PA
  • Hosts: Molly Heublein MD, Chris Chui MD, Isabel Valdez PA
  • Reviewer: Emi Okamoto MD
  • Editor: Matthew Watto MD (written materials); Clair Morgan of
  • Guest: Monica Gandhi, MD

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Show Segments

  • Intro, disclaimer, guest bio
  • Guest one-liner, Picks of the Week*
  • Case from Kashlak
  • Covid Boosters
  • Pfizer data
  • Moderna Data
  • DNA vaccines
  • Pediatric Vaccines
  • Monoclonal Antibodies
  • Molnupiravir
  • Dr Gandhi’s crystal ball
  • Outro

COVID-19 Vaccine Updates and Outpatient Treatment Pearls

  1. Patients over 65 and those with immunosuppression should receive an extra COVID vaccine.  Younger patients with comorbidities or risk of exposure are at lower risk, but may choose to get a booster.  
  2. It is safe and effective to mix and match vaccines, ie two-dose Pfizer series and one Moderna booster (half dose or 50 mcg), or the one-dose J&J series and one Pfizer booster (full dose or 30 mcg).
  3. J&J vaccines are much more effective when boosted with a single shot of an mRNA vaccine. 
  4. Getting a two-shot series is still extremely effective at preventing serious illness from COVID-19 for most people.
  5. Monoclonal antibodies reduce hospitalization and death in unvaccinated or high-risk patients with early SARS-CoV-2 infection.
  6. Molnupiravir, an oral antiviral, may receive EUA soon for the treatment of early COVID to reduce hospitalization and serious illness.

COVID Updates: The Outpatient Edition with Dr. Monica Gandhi

COVID Vaccine Updates

Who needs boosters:

CDC and FDA state patients over age 65 and those with other risk factors may get a COVID vaccine booster, since these populations are at higher risk of breakthrough cases.  Immunocompromised patients should receive a third shot to complete their primary vaccine series.  Dr. Gandhi’s expert opinion is that the 2-dose series is sufficient protection for people who are less than 65 and not immunocompromised.  She suggests patients with other underlying medical problems that increased the risk for unvaccinated severe COVID-19 are not at clearly increased risk for developing severe breakthrough infections, so that should be an individualized discussion with their medical provider.

FDA Emergency Use Authorization allows for a COVID booster dose for select groups at 6 months or more after their initial series mRNA, which aligns with CDC recommendations:

  • individuals 65 years of age and older;
  • individuals 18 through 64 years of age at high risk of severe COVID-19; and 
  • individuals 18 through 64 years of age whose frequent institutional or occupational exposure to SARS-CoV-2 puts them at high risk of serious complications of COVID-19 including severe COVID-19.

FDA EUA allows for and CDC recommends a booster shot for all individuals 18 and older who received the primary dose of J&J two or more months earlier. 

Data behind ongoing immunity from vaccine

We have strong evidence that the initial series of vaccines is very effective at preventing serious illness from COVID for most people.  NYC data show that vaccine efficacy is maintained in both preventing cases (reducing spread) and an 89% reduction in hospitalizations due to COVID.  Recent CDC publication on Sept 24 cites 93% efficacy for Moderna to reduce serious infection across age ranges, 88% for Pfizer, and 71% for Johnson & Johnson (Self 2021).  

Waning antibody levels are not clearly a sign of loss of vaccine efficacy.  The vaccine triggers memory T-cells and B-cells which will produce more antibodies if exposed to the virus.  Biopsy of lymph nodes have shown persistent strong B cell and T cell immunity even with waning antibody levels (Turner 2021).

CDC breakthrough data– in fully immunized Americans, those who have breakthrough COVID case deaths 85% are over age 65, and 67% of hospitalizations are in people over age 65.   If you are less than age 65 years, regardless of underlying medical conditions, severe breakthrough cases are rare.

Dr. Gandhi highlights that the use of boosters may have come too quickly, as the White House (Health and Human Services/NIH) encouraged boosters before a full review of data by the FDA/CDC.  There was some dissent among the FDA and CDC, with some FDA vaccine officials co-authoring an article in Lancet outlining why the booster may not even be needed just days before approval of the EUA (Krause 2021).

Third Dose Vs. Boosters

Dr. Gandhi explains that the “third dose” as used in the context of vaccine terminology means this shot is part of the initial series.   A booster shot  is given to strengthen immunity after an initial series, particularly when there are high rates of circulating virus and the dominant Delta variant among unvaccinated populations in the US.  

Differences between the mRNA vaccines

Spacing of vaccines is important– the Pfizer vaccine was studied initially with a 3-week interval between doses.  As such, the FDA and CDC recommendations recommend a 2-dose series separated by 21 days (FDA, CDC).  However, there is growing data around improved immunity with longer spacing intervals between first and second doses (Bruton 2021).   In Canada, they spaced out vaccines to allow for more first doses and showed this actually improved immune response.  For example, the Institut national de santé publique du Québec published data showing when only 3 weeks were waited between Pfizer doses, health care workers had 82% protection from severe COVID, and spacing 7 weeks or longer provided 92% protection against severe disease.  A recent Cell paper showed extending spacing of Pfizer dosing to 6 weeks increases both antibody and T cell immunity (Payne 2021). 

The initial dose of Moderna is 100mcg mRNA with the FDA authorized booster of a smaller 50mcg dose.  The Pfizer vaccine has a smaller 30mcg initial and booster dose.  A JAMA paper showed a higher immune (antibody level) response after the Moderna vaccine (Steensels 2021).  Dr. Gandhi feels that this higher dose and the longer initial spacing (4 weeks for Moderna, instead of Pfizer’s 3) is leading to better lasting COVID protection (expert opinion).

Dr Gandhi’s expert recommendation: If you got your Pfizer shot just 3 weeks apart and you are at increased risk, it’s reasonable to go get a booster.   Patients who received Moderna probably have higher immunity (Naranbhai 2021).

Heterologous (Mix and Match) Vaccination 

It is safe and allowable to mix and match different vaccines (FDA, CDC).  This may improve accessibility and is possibly more effective.  

Dr. Gandhi recommends that patients who previously received J&J one-dose vaccine should get a one-dose booster of any mRNA vaccine, as this provides more antibody response than homologous boosting (Atmar 2021).  The FDA/CDC recommend an additional shot of any authorized COVID vaccine for all patients age 18+ who received the J&J vaccine.  

Dr. Gandhi recommends heterologous boosting if a patient received AstraZeneca or Sputnik V- these and J&J are all adenovirus vector with DNA coding for the SARS-CoV-2 spike protein.  These have not been shown to be as effective in preventing symptomatic COVID as mRNA vaccines, and finishing the series with one dose of an mRNA vaccine improves immunity (Nordstrom 2021).  

Antibody Testing

Antibody testing is not generally helpful in patients with average risk.  In immunocompromised patients, testing for an antibody level shortly after the second dose can show that a patient did not respond well to the vaccine, which may be helpful information.  But for healthy people who responded to the vaccine, it is normal for antibody levels to wane.  These patients have memory B and T cells so will still mount an appropriate response.  One study did show that patients 57 days from vaccination with neutralizing antibody titer levels over 100 had over 90% vaccine efficacy, though vaccine efficacy was still over 50% for those with undetectable titers (Gilbert 2021).  

Pediatric Vaccines

Since May, EUA has been given for Pfizer (full dose- 30mcg) given to children 12-15.  Pfizer has submitted an EUA request for a 10mcg dose, which may be safer with a lower risk of myocarditis. Update since recording: FDA advisors voted in favor for 10mcg dose for children ages 5-11 and upcoming decision on EUA is likely in the coming days (NPR).  No major adverse effects and good immune response seen in the phase 2/3 trial for children age 5-11 per the Pfizer statement.  Dr. Gandhi is personally planning to space out her child’s vaccine by 6 weeks instead of the recommended 3 because she believes it increases immunogenicity based on above data.

Encourage your unvaccinated patients to get their first shots!

CDC data shows unvaccinated individuals are 11 times more likely to die of COVID than those vaccinated.  LA County data showed unvaccinated people were 22.9 times more likely to be hospitalized with COVID than vaccinated people.  Dr Gandhi stresses, “this is as lifesaving as it gets.”  Pregnant women should be vaccinated (ACOG, CDC).

Outpatient COVID treatment

Monoclonal antibodies 

Monoclonal antibodies have FDA EUA for high-risk patients (immunosuppressed patients, unvaccinated patients, or at risk for severe COVID like multiple comorbidities) to be given at the early stage of infection to reduce hospitalization. Options are bamlanivimab and etesevimab (FDA), casirivimab and imdevimab (FDA), or sotrovimab (FDA).  The viral load rises for the first 5 days of infection, so this is the key time to allow the monoclonal antibodies to be beneficial.  It is not appropriate for use in patients who need hospitalization or when patients are hypoxemic. 

Monoclonal antibodies are given via IV infusion for an hour or four subcutaneous injections.  Patients need to be monitored for at least an  hour by an RN or above with availability of emergency support after because of the potential risk for allergic reactions or episodes of hypotension.   These treatments are expensive and in short supply, so we have prioritized highest risk patients.  This is currently only authorized for patients over 40kg (so not kids typically).  There are several options for this which are all the same mechanism- they are manufactured in a lab and usually a combination of two are given to prevent resistance developing.  They bind to different parts of the spike protein.  These do not stimulate the immune system in any way, they just block the virus (UTD COVID-19 Outpatient).

Monoclonal antibodies also have EUA for post-exposure prophylaxis.  These can be given to a high risk patient with a known close exposure before a positive test to prevent serious illness. The current options are bamlanivimab and etesevimab (FDA) or casirivimab and imdevimab (FDA). 

The CDC recommends patients to wait 90 days after monoclonal antibodies to receive a vaccine.  Dr. Gandhi suggests it is probably safe and effective to get the vaccine sooner (2-4 weeks) after monoclonal antibodies though this is off label.  In younger patients, it may be better to wait on the vaccine as there were more side effects seen when vaccines were given shortly after COVID infection.  


Molnupiravir is currently seeking EUA.  This is an oral antiviral directed against the RNA polymerase of SARS-COV2 given at a dose of 800mg PO BID.  This reduces viral load if given within 5 days of infection (Fischer 2021).  MOVe-OUT study showed a 50% reduction in hospitalization and no deaths in the treatment group (Merck Press Release).  

Remdesivir is another antiviral which is given by IV infusion for hospitalized patients, and has shown benefit in severely ill hospitalized patients (NIH).  Dr Gandhi doesn’t have an explanation as to why this would work because this is really past the window we think of for active viral replication.

Take home points:

Get a booster/extra shot if you are over age 65, immunocompromised, or having received J&J initially.  

Get monoclonal antibodies if you are immunosuppressed or unvaccinated and have a COVID-19 exposure or early illness.

Keep an eye out for pediatric vaccines and molnupiravir.


  1. Monica’s Wellness Tip: Reading out loud to your children:  JD Salinger’s books and F Scott Fitzgerald’s The Great Gatsby
  2. The AAP, American Academy of Child and Adolescent Psychiatry (AACAP) and Children’s Hospital Association have declared a national emergency in children’s mental health.  Dr Gandhi encourages strategies to keep our children in school.


Listeners will understand updates to outpatient COVID-19 prevention and treatment.

Learning objectives

After listening to this episode listeners will…

  1. List the patient populations who should receive a 3rd COVID vaccine
  2. Describe some of the rationale for 3rd COVID immunizations in different populations
  3. List options for treatment of early SARS-CoV-2 infection as an outpatient
  4. Be able to counsel patients around use of monoclonal antibody therapies for outpatient treatment for SARS-CoV-2 infection
  5. Identify patients who are high risk who should receive post-exposure prophylaxis with monoclonal antibodies
  6. Describe the current state of pediatric COVID vaccine options


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


Valdez I, Heublein M, Chris C, Gandhi M “#304 COVID Updates: The Outpatient Edition”. The Curbsiders Internal Medicine Podcast. November 8, 2021.

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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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