NIH COVID-19 Treatment Guidelines

NOTE: The FDA has addressed the use of bebtelovimab among nonhospitalized patients in light of an increase in subvariants. Due to resistance, bebtelovimab is not currently authorized for emergency use in any US region. Information and guidelines may change rapidly. Check in with listed reference in ‘Learn More – Primary Sources’ to best keep up to date.


NIH has released guidance on the diagnosis, management and treatment of COVID-19. A Panel was convened to develop recommendations, with the understanding that there is still much that is unknown and the guidelines will be updated as additional data become available

Critical Care Treatment

Infection Control When Caring for Patients with COVID-19

  • Aerosol-generating procedures
    • Use fit-tested respirators (N-95 respirators) or powered air-purifying respirators rather than surgical masks
    • The above masks should be used in addition to other PPE (gloves, gown, and eye protection such as a face shield or safety goggles)
  • Endotracheal intubation
    • Should be done by healthcare professionals “with extensive airway management experience, if possible”
    • Intubation should be done with video laryngoscopy, if possible

Hemodynamic Support

  • First-choice vasopressor: Norepinephrine
  • To assess fluid responsiveness
    • Use dynamic parameters, skin temperature, capillary refilling time, and/or lactate levels vs static parameters
  • Acute resuscitation of adults with COVID-19 and shock
    • Use buffered/balanced crystalloids over unbalanced crystalloids
    • Panel recommends against initial use of albumin
  • Septic shock and steroids
    • IV hydrocortisone 200 mg per day administered either as an infusion or in intermittent doses
    • Duration of hydrocortisone is typically a clinical decision
    • Patients who are receiving corticosteroids for COVID-19 are receiving sufficient replacement therapy such that they do not require additional hydrocortisone

Ventilatory Support for Patients with COVID-19

  • Oxygen saturation (SpO2) target
    • Optimal goal is uncertain
    • A target SpO2 of 92% to 96% “seems logical”
    • Experience suggests that SpO2 <92% or >96% may be harmful
  • Prone position
    • Appropriate candidate for awake prone positioning: Patients who can adjust their own position independently and tolerate lying prone
    • Awake proning should not be used as a substitute for intubation and invasive mechanical ventilation in patients with refractory hypoxemia who otherwise meet the indications for these interventions
    • Pregnancy: Acceptable and can be done in left lateral decubitus or fully prone
  • Refractory hypoxemia in patients who otherwise require intubation and mechanical ventilation
    • Panel recommends against using awake prone positioning as a rescue therapy to avoid intubation 
  • Acute hypoxemic respiratory failure despite conventional oxygen therapy
    • Options for providing enhanced respiratory support include high-flow nasal cannula (HFNC), NIPPV, intubation and invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO)
    • Use HFNC oxygen rather than noninvasive positive pressure ventilation (NIPPV)
    • If HFNC is unavailable and there is no indication of intubation: Use a closely monitored trial of NIPPV
  • For patients on supplemental oxygen
    • Monitor closely for worsening of respiratory status
    • If respiratory status worsens, the Panel recommends early intubation by an experienced practitioner in a controlled setting
  • For patients mechanically ventilated with ARDS
    • Use low tidal volume (VT) ventilation (VT 4 to 8 mL/kg of predicted body weight) vs higher tidal volumes (VT >8 mL/kg)
    • If refractory hypoxemia despite optimized ventilation, the Panel recommends prone ventilation for 12 to 16 hours per day over no prone ventilation
    • In the setting of hypoxemia and severe ARDS despite optimized ventilation and other rescue strategies, a trial of inhaled pulmonary vasodilators is recommended as a rescue therapy| Taper if there is no rapid improvement in oxygenation

Inpatient Pharmacologic Management

Note: For patients who are hospitalized for reasons other than COVID-19 and who are found to have mild to moderate COVID-19 and a high risk of disease progression, the Panel recommends following its recommendations for treating nonhospitalized patients with COVID-19 (section below)

The following applies to individuals admitted for the treatment of COVID-19

Therapeutic Management of Hospitalized Adults With COVID-19 Based on Disease Severity


  • Recommended for use in hospitalized patients who require supplemental oxygen
    • 200 mg IV once, then RDV 100 mg IV once daily for 4 days or until hospital discharge
    • If the patient progresses to more severe illness, complete course


  • Found to improve survival in hospitalized patients who require supplemental oxygen
    • Greatest effect observed in patients who require mechanical ventilation
    • The Panel recommends against using dexamethasone among patients who do not require supplemental oxygen
  • Dose
    • 6 mg IV or PO once daily for up to 10 days or until hospital discharge
    • If dexamethasone is not available, an equivalent dose of another corticosteroid may be used


  • Humanized monoclonal antibody against the interleukin-6 receptor (IL-6R)
    • FDA approved to treat inflammatory diseases
  • Dose
    • 8 mg/kg actual body weight (up to 800 mg) administered as a single IV dose
    • In clinical trials, a third of the participants received a second dose of tocilizumab 8 hours after the first dose if no clinical improvement was observed
  • Avoid tocilizumab for the following
    • Significant immunosuppression | Alanine transaminase >5 times the upper limit of normal | High risk for gastrointestinal perforation | Uncontrolled, serious bacterial, fungal, or non-SARS-CoV-2 viral infection | Absolute neutrophil count <500 cells/µL | Platelet count <50,000 cells/µL


  • Oral Janus kinase (JAK) inhibitor that is selective for JAK1 and JAK2
    • FDA approved to treat rheumatoid arthritis
  • Dose
    • Baricitinib dose is dependent on eGFR; duration of therapy is up to 14 days or until hospital discharge
    • eGFR ≥60 mL/min/1.73 m2: Baricitinib 4 mg PO once daily
    • eGFR 30 to <60 mL/min/1.73 m2: Baricitinib 2 mg PO once daily
    • eGFR 15 to <30 mL/min/1.73 m2: Baricitinib 1 mg PO once daily
    • eGFR <15 mL/min/1.73 m2: Baricitinib is not recommended


  • Oral Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis
  • Dose
    • 10 mg PO twice daily for up to 14 days or until hospital discharge
    • Use as an alternative immunomodulatory drug if baricitinib is not available or not feasible to use (BIIa)
    • eGFR <60 mL/min/1.73 m2: Tofacitinib 5 mg PO twice daily


  • Humanized monoclonal antibody against the interleukin-6 receptor (IL-6R)
    • FDA approved to treat rheumatoid arthritis
  • Dose
    • Use the single-dose, prefilled syringe (not the prefilled pen) for SQ injection
    • Reconstitute sarilumab 400 mg in 100 cc 0.9% NaCl and administer as an IV infusion over 1 hour
    • Use as an alternative immunomodulatory drug if tocilizumab is not available or not feasible to use

Therapeutic Management of Nonhospitalized Adults With COVID-19

NIH refers to the CDC guidance to determine at increased risk for progression | See ‘Learn More – Primary Care’ for reference

In Order of Preference

  • Paxlovid (for more information, see ‘oral antivirals below’)
    • Orally twice daily for 5 days, initiated as soon as possible and within 5 days of symptom onset in those aged ≥12 years and weighing ≥40 kg
  • Remdesivir
    • 200 mg IV on Day 1, followed by remdesivir 100 mg IV daily on Days 2 and 3, initiated as soon as possible and within 7 days of symptom onset in those aged ≥12 years and weighing ≥40 kg 

Alternative Therapies to be used ONLY if none of the preferred therapies are available, feasible to deliver, or clinically appropriate (listed in alphabetical order)


800 mg orally twice daily for 5 days, initiated as soon as possible and within 5 days of symptom onset in those aged ≥18 years ONLY when none of the above options can be used

Note: BQ.1 and BQ.1.1 subvariants appear to be resistant to bebtelovimab and as of 11/30/2022, bebtelovimab is not currently authorized for emergency use in any US region | The Panel continues to recommend Paxlovid, followed by remdesivir for treatment of mild to moderate COVID-19 in nonhospitalized adults who are at high risk for progression

More on Oral Antivirals

  • Ritonavir-Boosted Nirmatrelvir (Paxlovid)
    • Nirmatrelvir
      • Orally bioavailable protease inhibitor
      • Works by inhibiting viral protease MPRO (protease that plays an essential role in viral replication)
      • Active against all coronaviruses known to infect humans
    • Packaged with ritonavir (as Paxlovid)
      • Ritonavir is a cytochrome P450 (CYP) 3A4 inhibitor and pharmacokinetic boosting agent
      • Boosts nirmatrelvir concentrations to the target therapeutic ranges

Note: Review other medications to assess drug interactions including OTCs and herbal supplements | University of Liverpool has a site with COVID-19 Drug Interactions (included in the NIH Panel guidelines – see “Learn More – Primary Resources’ below)

  • Molnupiravir
    • Oral prodrug of beta-D-N4-hydroxycytidine (NHC)
    • NHC is a ribonucleoside with antiviral activity against RNA viruses
    • NHC uptake by viral RNA-dependent RNA-polymerases results in viral mutations and lethal mutagenesis

Note: Pregnancy and COVID-19 Oral Antivirals

  • Paxlovid
    • SMFM supports the use of Paxlovid in pregnancy as indicated (see ‘Primary Sources – Learn More’ below)
  • Molnupiravir
    • Although FDA concluded that there is a low risk for genotoxicity, due to concern regarding mutagenesis, the FDA EUA recommends against use during pregnancy
    • The NIH Panel states “However, when other therapies are not available, pregnant people with COVID-19 who are at high risk of progressing to severe disease may reasonably choose molnupiravir therapy after being fully informed of the risks, particularly those who are beyond the time of embryogenesis (i.e., >10 weeks’ gestation). The prescribing clinician should document that a discussion of the risks and benefits occurred and that the patient chose this therapy”


Serologic or Antibody Testing for Diagnosis of SARS-CoV-2 Infection

The Panel does not recommend using serologic testing as the sole basis for diagnosing acute SARS-CoV-2 infection 

  • Serologic or antibody tests can detect recent or prior SARS-CoV-2 infection
  • It may take ≥21 days after symptoms for seroconversion to occur (i.e., IgM and/or IgG antibodies to SARS-CoV-2)
  • NAATs and antigen tests for SARS-CoV-2 occasionally yield false negative results
    • Serologic tests have been used in some settings as an additional diagnostic test for patients who are strongly suspected to have SARS-CoV-2 infection
    • Using a serologic test in combination with a NAAT to detect IgG or total antibodies 3 to 4 weeks after symptom onset maximizes the sensitivity and specificity to detect past infection

Concomitant Medications in Patients with COVID-19

Angiotensin-Converting Enzyme (ACE) Inhibitors and Angiotensin Receptor Blockers (ARBs) and Statins (HMG-CoA Reductase Inhibitors)

  • Continue taking these medications as prescribed
  • The Panel recommends against the use of ACE inhibitors or ARBs for the treatment of COVID-19 outside of the setting of a clinical trial

Chronic Corticosteroids

  • For patients on oral corticosteroid therapy used prior to COVID-19 diagnosis for another underlying condition (e.g., rheumatological diseases)
    • Corticosteroids should not be discontinued
    • Supplemental or stress-dose steroids: Determine use on a case-by-case basis
  • Asthma and chronic obstructive pulmonary disease for control of airway inflammation (daily use)
    • Should not be discontinued

Pregnancy Considerations

  • Betamethasone and dexamethasone cross the placenta and are therefore used for fetal benefit to decrease the risk of RDS in the setting or threatened preterm delivery
  • The Panel recommends “using dexamethasone in pregnant women with COVID-19 who are mechanically ventilated or who require supplemental oxygen but who are not mechanically ventilated”

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

  • Continue taking NSAIDs for a co-morbid condition as previously directed by physician
  • “The Panel recommends that there be no difference in the use of antipyretic strategies (e.g., with acetaminophen or NSAIDs) between patients with or without COVID-19”

Coagulopathy Considerations

Antithrombotic Therapy for Nonhospitalized Patients without VTE

  • The Panel recommends against the use of anticoagulants and antiplatelet therapy (aspirin or P2Y12 inhibitors) for the prevention of VTE or arterial thrombosis unless the patient has other indications for the therapy or is participating in a clinical trial
  • The Panel recommends against routinely continuing VTE prophylaxis for patients with COVID-19 after hospital discharge, except in a clinical trial 
  • For patients who are at high risk for VTE and low risk for bleeding, there is insufficient evidence to recommend either for or against continuing anticoagulation after hospital discharge unless another indication for VTE prophylaxis exists

General Considerations for Hospitalized Patients

  • The Panel recommends against using anticoagulant or antiplatelet therapy to prevent arterial thrombosis outside of the usual standard of care for patients without COVID-19 
  • In hospitalized patients, low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) is preferred over oral anticoagulants, because these 2 types of heparin have shorter half-lives and the effect can be reversed quickly, can be administered intravenously or subcutaneously, and have fewer drug-drug interactions 
  • When heparin is used, LMWH is preferred over UFH

Hospitalized, Nonpregnant Adults Who Require Low-Flow Oxygen and Are Not Receiving Intensive Care Unit Level of Care

  • Use therapeutic-dose heparin for patients who have a D-dimer above the upper limit of normal and have no increased bleeding risk
  • LMWH is preferred over unfractionated heparin
  • Contraindications for therapeutic anticoagulation for COVID-19 due to an increased bleeding risk
    • Platelet count <50 x 109/L
    • Hemoglobin <8 g/dL
    • Need for dual antiplatelet therapy
    • Known bleeding within the last 30 days requiring an emergency room visit or hospitalization
    • Known history of a bleeding disorder
    • Inherited or active acquired bleeding disorder
  • If no VTE
    • Continue therapeutic treatment for 14 days or until hospital discharge, whichever comes first
  • The Panel recommends using prophylactic-dose heparin (LMWH or unfractionated heparin) for patients who are not administered therapeutic heparin unless a contraindication exists 

Note: Oral anticoagulants for VTE prophylaxis or prevention of COVID-19 progression are not recommended for hospitalized patients, except in a clinical trial 

Hospitalized, Nonpregnant Adults Who Are Receiving ICU Level of Care (Including Patients Who Are Receiving High-Flow Oxygen)

  • Use prophylactic-dose heparin as VTE prophylaxis unless a contraindication exists 
  • The Panel recommends against the following except in a clinical trial
    • Use of intermediate-dose (e.g., enoxaparin 1 mg/kg daily)
    • Therapeutic-dose anticoagulation for VTE prophylaxis
  • For patients who start on therapeutic-dose heparin while on low-flow oxygen due to COVID-19 and then transfer to the ICU
    • Switch from therapeutic to prophylactic-dose heparin unless a VTE is confirmed 
  • There is insufficient evidence for the Panel to recommend either for or against antiplatelet therapy in critically ill patients with COVID-19

Pregnant Adults

  • The Panel recommends that pregnant patients who are receiving anticoagulant or antiplatelet therapies for underlying conditions continue these medications after they receive a diagnosis of COVID-19
  • Use prophylactic-dose anticoagulation for pregnant patients hospitalized for manifestations of COVID-19 unless otherwise contraindicated
  • Because pregnant patients have not been included in most clinical trials evaluating therapeutic anticoagulation in the setting of COVID-19, there is currently insufficient evidence to recommend either for or against therapeutic anticoagulation for pregnant patients with COVID-19 in the absence of a known VTE

Influenza and COVID-19

Vaccine Considerations

  • It is important to ensure that vaccination programs to protect against influenza continue during the pandemic
  • Patients with COVID-19 can receive inactivated influenza vaccine
  • Moderately or Severely Ill with SARS-CoV-2
    • Consider deferring influenza vaccination until the patients have completed the COVID-19 isolation period and are no longer moderately or severely ill
  • Asymptomatic or not moderately or severely ill with SARS-CoV-2
    • Influenza vaccination can be given when infected individual no longer require isolation
    • Vaccinate sooner if they are in a health care setting for other reasons

Note: Influenza vaccine and a COVID-19 vaccine may be administered concurrently at different injection sites

Testing for Influenza

  • Test for both viruses in all hospitalized patients with acute respiratory illness 
  • The Panel recommends influenza testing in addition to SARS-CoV-2 testing in outpatients with acute respiratory illness if
    • Results will change the clinical management strategy for the patient such as initiating antiviral treatment for influenza 
  • Consider testing patients for other pathogens based on their specific clinical circumstances
    • Additional testing is especially important for patients with influenza who have a high risk of acquiring bacterial superinfections

Treatment for Influenza

  • Antiviral treatment of influenza is the same in all patients with or without SARS-CoV-2 coinfection 
  • Hospitalized patients with suspected influenza
    • Start on empiric treatment for influenza with oseltamivir as soon as possible 
    • Do not wait for influenza test results 
    • Stop antiviral treatment for influenza when influenza has been ruled out by nucleic acid detection assay
      • Nonintubated: Negative report for upper respiratory tract specimens
      • Intubated: Negative report for both upper and lower respiratory tract specimens

Learn More – Primary Sources:

NIH: Coronavirus Disease 2019 (COVID-19) Treatment Guidelines

Underlying Medical Conditions Associated with Higher Risk for Severe COVID-19: Information for Healthcare Providers (

Liverpool COVID-19 Interactions (

SMFM: FDA Issues EUA for the Treatment of Mild-to-Moderate COVID-19 (Paxlovid)

mRNA-Based COVID-19 Vaccines Induce Robust, Persistent Immune Responses in Humans


  • The mRNA-based COVID-19 vaccines are 95% effective at preventing COVID-19, but immune system dynamics induced by the vaccines are not clear 
  • Turner et al. (Nature, 2021) examined antigen-specific B cell responses in peripheral blood and lymph nodes in individuals who received 2 doses of the Pfizer vaccine 


  • Observational study 
  • Participants 
    • Healthy US adults who received both doses of Pfizer’s COVID-19 vaccine 
  • Study design 
    • Blood samples were collected at baseline (before first dose), and at weeks 3 (pre-second dose), 4, 5, 7, and 15 
    • Fine needle aspirates of the draining axillary lymph nodes were also collected from some participants 
    • An enzyme linked immune absorbent spot assay was used to measure antibody-secreting plasmablasts (cells that differentiate into non-dividing plasma cells [aka antibody-secreting cells]) 


  • 41 adults 
    • Evidence of previous SARS-CoV-2 infection: 8 participants 
    • Aspirates collected from lymph nodes: 14 participants 
  • Circulating IgG- and IgA-secreting plasmablasts peaked one week after the second dose and then declined | Undetectable 3 weeks later 
    • Plasmablasts exhibited neutralizing activity against the early circulating SARS-CoV-2 strain and emerging variants 
    • Previously infected participants had the most robust serological response 
  • Aspirates from the draining axillary lymph nodes identified germinal center B cells that bound the SARS-CoV-2 spike protein in all participants who had received first dose 
    • The draining lymph nodes sustained high levels of spike-binding germinal center B cells and plasmablasts for at least 12 weeks after the second dose 
  • Spike-binding monoclonal antibodies derived from germinal center B cells mostly targeted the receptor-binding domain of the spike protein  
    • Fewer clones did cross-react and bind to the N-terminal domain or to epitopes shared with the spike proteins of human betacoronaviruses 
    • These cross-reactive clones had higher levels of somatic hypermutation vs those specific to SARS-CoV-2 spike protein, suggesting a memory B cell origin 


  • mRNA-based COVID-19 vaccines induce a persistent germinal center B cell response, which leads to robust humoral immunity 
  • The authors state 

To our knowledge, this is the first study to provide direct evidence for the induction of a persistent antigen-specific germinal centre B cell response after vaccination in humans 

Elicitation of high affinity and durable protective antibody responses is a hallmark of a successful humoral immune response to vaccination 

By inducing robust germinal centre reactions, SARS-CoV-2 mRNA-based vaccines are on track for achieving this outcome 

Learn More – Primary Sources: 

SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses 

AstraZeneca and Pfizer Side Effects and Efficacy: Real World Data from the UK


  • In phase 3 clinical trials of the Pfizer-BioNTech vaccine, injection-site pain (71 to 83%), fatigue (34 to 47%), and headache (25 to 42%) were commonly seen
  • Menni et al. (The Lancet Infectious Diseases, 2021) investigate the safety and effectiveness of the Pfizer and AstraZeneca vaccines in a UK community setting


  • Prospective observational study
  • Data source
    • COVID Symptom Study app data
    • Between Dec 8 through March 10, 2021
  • Population
    • General UK population 
  • Exposure
    • One or two doses of the Pfizer -BioNTech vaccine
    • One dose of the AstraZeneca vaccine
    • Unvaccinated controls
  • Study design
    • All analyses were adjusted by
      • Age (≤55 years vs >55 years)
      • Sex
      • Health-care worker status (binary variable)
      • Obesity (BMI <30 kg/m2 vs ≥30 kg/m2)
      • Comorbidities (binary variable, with or without comorbidities)
  • Primary outcome
    • Proportion and probability of self-reported systemic and local side effects within 8 days of vaccination
  • Secondary outcome
    • SARS-CoV-2 infection rates in vaccinated individuals


  • 627,383 vaccinated individuals
    • At least one dose of Pfizer-BioNTech: 282,103 individuals | Two doses of Pfizer-BioNTech: 28,207 individuals
    • One dose of AstraZeneca: 345,280 individuals

Systemic Side Effects

  • Report rates of systemic side effects after vaccination
    • After first dose of Pfizer-BioNTech: 13.5% | After second dose of Pfizer-BioNTech: 22.0%
    • After first dose of AstraZeneca: 33.7%
  • Most common systemic side effects
    • Fatigue and headache
    • Usually within first 24 hours after vaccination | Lasted a mean of 1.01 days
  • Systemic side effects were more common among those with a history of previous SARS-CoV-2 infection
    • After first dose of Pfizer-BioNTech: 2.9 times more likely
    • After first dose of AstraZeneca: 1.6 times more likely
  • Adverse systemic events were more common in
    • Women vs men: 16.2% vs 9.3% after first dose of Pfizer-BioNTech (OR 1.89 [95% CI, 1.85 to 1.94]; p<0·0001) and similarly after first dose of AstraZeneca
    • ≤55 years vs >55 years: 20.7% vs 10.6% after first dose of Pfizer-BioNTech (OR 2.19 [95% CI, 2.14 to 2.24]; p<0.0001) and similarly after first dose of AstraZeneca
    • Similar pattern in women and younger individuals were also noted for local side effects

Local Side Effects

  • Most common local side effects
    • Tenderness and local pain around the injection site
    • Usually on the day after injection | Lasted a mean of 1.02 days
  • Local side effects after vaccination
    • After first dose of Pfizer-BioNTech: 71.9% | After second dose of Pfizer-BioNTech: 68.5%
    • After first dose of AstraZeneca: 58.7%
  • Local side effects were also higher in individuals previously infected with SARS-CoV-2
    • After first dose of Pfizer-BioNTech: 1.2 times more likely to experience side effects
    • After first dose of AstraZeneca: 1.4 times more likely

Vaccine Effectiveness

  • SARS-CoV-2 positive tests
    • Vaccinated: 3% (3106 infections per 103,622 vaccinated)
    • Unvaccinated: 11% (50,340 infections per 464,356 unvaccinated)
  • Significant reductions in infection risk were seen starting at 12 days after the first dose and increased over time
    • At 21 to 44 days
      • Pfizer-BioNTech: 69% (95% CI 66 to 72)
      • AstraZeneca: 60% (95% CI 49 to 68)
    • At 45 to 59 days
      • Pfizer-BioNTech: 72% (95% CI 63 to 79)


  • Systematic and local side effects with Pfizer and AstraZeneca COVID-19 vaccination were more common in women, individuals ≤55 years, and those with previous COVID-19 infection
  • A reduction in infection risk was observed starting 12 days after the first dose for both vaccines
  • The authors conclude

Localised and systemic side effects after vaccination are less common in a real-world community setting than reported in phase 3 trials, mostly minor in severity, and self-limiting

Our data will enable prediction of side-effects based on age, sex, and past COVID-19 status to help update guidance to health professionals to reassure the population about the safety of vaccines

Learn More – Primary Sources:

Vaccine side-effects and SARS-CoV-2 infection after vaccination in users of the COVID Symptom Study app in the UK: a prospective observational study

The Value of Vaccination for Those Previously Infected with SARS-CoV-2


  • BNT162b2 (Pfizer/BioNTech) COVID-19 vaccine was shown to be 95% effective at preventing COVID-19
  • Several COVID-19 variants have been detected in recent months
    • South Africa variant: B.1.351
    • UK variant: B.1.1.7
    • Brazil variant: P.1
  • Lustig et al. (NEJM Correspondence, 2021) investigated whether one dose of the BNT162b2 vaccine would increase neutralizing activity against the B.1.1.7, B.1.351, and P.1 variants in people previously infected with SARS-CoV-2


  • Microneutralization assay
  • Population
    • Healthcare workers
    • Previously infected with the original SARS-CoV-2
  • Study design
    • All participants were given a single dose of the BNT162b2 vaccine
    • Serum samples were obtained
      • 1 to 12 weeks after natural infection
      • Immediately before vaccination
      • 1 to 2 weeks after vaccination


  • 18 serum samples from 6 healthcare workers
  • The sample obtained at the first time point (1 to 12 weeks after infection)
    • Had neutralizing activity against
      • The original virus: geometric mean titer 456
      • B.1.1.7 (UK): 256
      • P.1 (Brazil): 71
    • Had no neutralizing activity against
      • B.1.351 (South Africa): geometric mean titer 8
  • Immediately before BNT162b2 vaccination, titers were lower against all virus variants
    • Original virus: geometric mean titer 81
    • B.1.1.7 (UK): 40
    • P.1 (Brazil): 36
    • B.1.351 (South Africa): 7
  • 1 to 2 weeks after vaccination, titers were high against all virus variants
    • Original virus: geometric mean titer 9195
    • B.1.1.7 (UK): 8192
    • P.1 (Brazil): 2896
    • B.1.351 (South Africa): 1625


  • After one dose of the BNT162b2, people who had previously been infected with the original SARS-CoV-2 showed high neutralizing activity against the UK, South Africa and Brazil variants
  • The authors conclude

This highlights the importance of vaccination even in previously infected patients, given the added benefit of an increased antibody response to the variants tested

Learn More – Primary Sources:

Neutralizing Response against Variants after SARS-CoV-2 Infection and One Dose of BNT162b2

Can High Dose Nitric Oxide Improve Respiratory Function in Pregnant Women with Severe COVID-19?


  • There is limited data on how best to manage respiratory failure in pregnant women with COVID-19
  • Safaee Fakhr et al. sought to determine if administering high concentrations of nitric oxide could improve the clinical course of pregnant women with respiratory failure  


  • Case series (April to June 2020)
  • 6 pregnant patients admitted with severe or critical COVID-19
  • Patients received high-dose (160–200 ppm) nitric oxide by mask twice daily
    • Treatment sessions lasted 30 minutes to 1 hour
    • For those patients requiring mechanical ventilation, the high dose regimen was stopped and restarted after extubation | During intubation, the patients received continuous low dose nitric oxide through the ventilator


  • Total of 39 treatments
  • Cardiopulmonary function improved with administration of nitric oxide
    • Systemic oxygenation: Improved following each administration session in hypoxemic patients
    • Tachypnea: Reduced among all patients each session
  • 3 deliveries while in hospital
    • 4 neonates
    • 28-day follow-up: All mothers and infants in good condition at home
  • 3 remaining patients:
    • Discharged home and still pregnant at time of publication  
  • There were no adverse events documented


  • While acknowledging the small cohort size, the authors also conclude that

Nitric oxide at 160–200 ppm is easy to use, appears to be well tolerated, and might be of benefit in pregnant patients with COVID-19 with hypoxic respiratory failure

Learn More – Primary Sources:

High Concentrations of Nitric Oxide Inhalation Therapy in Pregnant Patients With Severe Coronavirus Disease 2019 (COVID-19)

Pregnant Women with COVID-19 at Time of Delivery: NYC Cohort Characteristics and Outcomes


  • Khoury et al. (Obstetrics & Gynecology, 2020) characterized clinical features and disease course among the initial cohort of pregnant women during the COVID-19 pandemic in New York City admitted for delivery


  • Prospective cohort study (March 13 to April 12, 2020 with follow-up completed April 20, 2020)
  • Setting
    • Five New York City medical centers
  • Participants
    • Pregnant women admitted for delivery
    • Confirmed COVID-19  
  • Study design
    • Data collected: Demographics | Presentation | Comorbidities | Maternal and Neonatal outcomes | COVID-19 clinical course
  • COVID-19 cases were defined as
    • Asymptomatic
    • Mild: no additional oxygen supplementation required
    • Severe: Dyspnea | Respiratory rate ≥30 breaths | Oxygen saturation ≤93% | Pneumonia
    • Critical: Respiratory failure | Septic shock | Multiple organ dysfunction or failure


  • 241 women included
    • Asymptomatic on admission: 61.4% | 69% remained asymptomatic
  • Clinical status at time of hospitalization for delivery
    • Mild: 26.5%
    • Severe: 26.1%
    • Critical: 5%
  • Singleton preterm birth rate: 14.6%
  • Critical outcomes
    • ICU admission: 7.1% of women (17 women)
    • Intubation during delivery: 3.7% (9 women)
    • Maternal deaths: 0 women
  • BMI ≥30 associated with COVID-19 severity (P=0.001)
  • Cesarean delivery rates
    • Severe COVID-19: 52.4%
    • Critical COVID-19: 91.7%
    • Linear trend across COVID-19 severity groups for cesarean risk (P<.001)
  • 245 liveborn neonates
    • Resuscitation at delivery beyond normal requirements: 30%
    • NICU admission: 25.7% | Hospitalization <2 days in 62.4%
  • Newborn outcomes
    • Prematurity and low birth weight: 8.7% (most common complications)
    • RDS: 5.8%
    • No complications: 79.3%
  • 97.5% of newborns tested negative for SARS-CoV-2 at 24 to 96 hours  
  • IUFD: 2 cases
    • Case 1: 38 weeks without fetal movement | Symptoms of COVID-19 pneumonia including chest imaging | No supplemental oxygen required | Patient declined autopsy and further work up for COVID-19 | No abnormalities were seen on placental pathology
    • Case 2: 29 weeks of gestation | FGR <1%tile | HELLP syndrome | Severe COVID-19 pneumonia


  • Majority of pregnant women admitted for delivery were asymptomatic for COVID-19  
    • Approximately 1/3 remained asymptomatic
  • Obesity was associated with COVID-19 severity
  • For women with COVID-19 (particularly severe and critical) there is an increased risk for cesarean and preterm birth

Learn More – Primary Sources:

Characteristics and Outcomes of 241 Births to Women With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection at Five New York City Medical Centers

Does Hydroxychloroquine Provide Benefit in Nonhospitalized Patients with Early COVID-19 Infection?


  • Skipper et al. (Annals of Internal Medicine, 2020) sought to determine if hydroxychloroquine is of benefit to individuals with COVID-19 early in their clinical course  


  • Multisite, international, randomized, double-blind, placebo-controlled trial (March 22 through May 20, with final hospital outcomes available June 15, 2020)  
    • 40 states (US) | 3 provinces (Canada)
    • Researchers collected self-reported survey data using the Research Electronic Data Capture (REDCap) system | Outreach traditional and through social media
  • Participants
    • Nonhospitalized | ≤4 days of symptoms with
      • Laboratory-confirmed COVID-19 or COVID-19–compatible symptoms and in contact with COVID-19 positive individual
    • Symptomatic health care workers with high-risk exposure but whose contact had PCR results pending were also included
  • Randomized 1:1 to the following
    • Oral hydroxychloroquine: 800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 more days
    • Masked placebo
  • Measurements
    • Symptoms and severity at baseline and then at days 3, 5, 10, and 14
    • Assessed using a 10-point visual analogue scale
  • Outcomes
    • The primary end point was changed to an overall symptom severity score over the course of 14 days


  • 423 contributed primary end point data (out of 491 randomized)
    • Median age: 40 years | 56% women | Identified as Black or African American were underrepresented (3%)  
    • Enrolled within 1 day of onset of symptoms: 56% (236 of 423)
  • Change in symptom severity over 14 days did not differ between groups
    • Absolute difference in symptom severity: −0.27 points (95% CI, −0.61 to 0.07 points; P=0.117)
  • There was no difference in proportion of patients with ongoing symptoms at 14 days (P=0.21)
    • Hydroxychloroquine: 24%
    • Placebo: 30%
  • Medication adverse effects were more frequent with hydroxychloroquine (P < 0.001)
    • Hydroxychloroquine: 43%
    • Placebo: 22%
  • There was no significant difference in hospitalization or death (P = 0.29)
    • Hydroxychloroquine: 4 hospitalizations occurred | 1 nonhospitalized death
    • Placebo: 10 hospitalizations (2 non–COVID-19–related) | 1 hospitalized death


  • The authors note that the population was relatively young, with few comorbid conditions and therefore these outcomes may not be generalizable to all population groups | A substantial proportion of patients were enrolled based on symptoms and not SARS-CoV-2 testing (due to limited availability)
  • The authors conclude that

Hydroxychloroquine did not substantially reduce symptom severity in outpatients with early, mild COVID-19

Learn More – Primary Sources:

Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19

Universal Masking and COVID-19 Infection Rates in Healthcare Personnel


  • Wang et al. (JAMA, 2020) assessed whether a program of universal masking in a large healthcare system was associated with the SARS-CoV-2 infection rate among healthcare personnel


  • Retrospective cohort study
    • Mass General Brigham (MGB) |12 hospitals 75 000 employees
  • Hospital system initiated a COVID-19 infection reduction strategy that included
    • Systematic SARS-CoV-2 testing of symptomatic healthcare personnel
    •  Universal masking of all healthcare personnel and patients (surgical masks)
  • 3 phases
    • Preintervention period before universal masking: March 1 to 24, 2020
    • Transition period until implementation of universal masking of patients: March 25 to April 5, 2020
      • Lag period to allow for manifestations of symptoms: April 6 to 10, 2020
    • Intervention period; April 11 to 30, 2020
  • Positivity rate
    • Numerator: First positive test result for all healthcare personnel
    • Denominator: Healthcare personnel who never tested positive plus those who tested positive that day
  • Statistical analysis
    • Mean trends calculated based on overall slope of each period was calculated using linear regression
    • Change in overall slope compared between the preintervention vs intervention periods


  • 9850 Healthcare Personnel underwent testing
    • Positive results: 12.9% | Median age, 39 years
      • 73% female | 7.4% physicians or trainees | 26.5% nurses or PAs | 17.8% technologists or nursing support | 48.3% other
    • Preintervention period: SARS-CoV-2 positivity rate increased exponentially from 0% to 21.32% | Weighted mean increase of 1.16% per day | Case doubling time of 3.6 days (95% CI, 3.0 to 4.5 days)
    • Intervention period: SARS-CoV-2 positivity rate decreased linearly from 14.65% to 11.46% | Weighted mean decline of 0.49% per day
    • Net slope change: 1.65% more decline per day compared with the preintervention period (95% CI, 1.13% to 2.15%; P < .001)


  • Universal masking was associated with a decrease in SARS-CoV-2 infection rates among healthcare personnel
  • The authors acknowledge the possibility of confounding due to other transmission prevention measures such as social distancing
  • The authors state that

Randomized trials of universal masking of HCWs during a pandemic are likely not feasible

Nonetheless, these results support universal masking as part of a multipronged infection reduction strategy in health care settings

Learn More – Primary Sources:

Association Between Universal Masking in a Health Care System and SARS-CoV-2 Positivity Among Health Care Workers

Mode of Delivery in the Setting of COVID-19


  • Ferrazzi et al. (BJOG, 2020) report on the mode of delivery and immediate neonatal outcomes in women infected with COVID-19 in Lombardy, Italy


  • Retrospective study
  • Setting
    • 12 hospitals in northern Italy
  • Participants
    • Confirmed COVID-19 prior to or within 36 hours after delivery
    • Delivered from March 1 to March 20, 2020
    • All consecutive cases admitted to maternity ward for delivery
  • Study design
    • Data derived from clinical records
      • General maternal characteristics | Medical or obstetric co-morbidity | Course of pregnancy | Clinical signs and symptoms | Treatment of COVID 19 infection | Mode of delivery | Neonatal data and breastfeeding
  • Primary outcome
    • Mode of delivery
    • Neonatal outcome


  • Total 42 women with COVID-19
    • Mean maternal age: 32.9 years (range 21 to 44 years)
  • COVID-19 diagnosis
    • Known before admission: 19 cases
    • On hospital admission: 10 cases
    • Delivery room: 27 cases
    • Within 36 hours of delivery: 5 cases (patients still admitted)
  • Maternal clinical features
    • Most common symptoms: Fever, cough and mild dyspnoea (80%)
    • Pneumonia: 45.2%
      • Oxygen support: 36.8%
      • Critical care unit: 21.1%
  • Mode of delivery
    • Vaginal: 57.1%
    • Elective cesarean: 42.9% (18 women)
      • COVID-19 indication (e.g. worsening dyspnea): 10 cases
      • Unrelated to COVID-19: 8 cases
  • Neonatal outcomes
    • Spontaneous term: 30 cases (71.4%)
    • Spontaneous preterm birth: 5 cases
    • Elective cesarean: 6 cases
    • Two women breastfed without a mask because COVID-19 infection was diagnosed in the postpartum period
      • Their newborns tested positive for COVID-19 (days 1 and 3)
    • In one case, a newborn had a positive test after a vaginal operative delivery | Mother did not breastfeed
      • Symptoms day 3 | Recovered after 1 day of mechanical ventilation


  • Authors acknowledge that vertical transmission risk with vaginal delivery cannot be excluded
  • However, results from this study would suggest that vaginal delivery is associated with a low risk of COVID-19 transmission
  • In addition, the author conclude that

Vaginal delivery is appropriate in mild cases and caesarean section should be reserved for women with severe respiratory problems, where delivering the baby will allow improved ventilation

Learn More – Primary Sources:

Vaginal delivery in SARS-CoV-2-infected pregnant women in Northern Italy: a retrospective analysis

COVID-19 and Risk for Stillbirth and Preterm Birth


  • Khalil et al. (JAMA, 2020) analyzed the association between COVID-19 and risk for stillbirth and preterm delivery        


  • Retrospective cohort study
    • St George’s University Hospital, London (UK)
  • Compared 2 time periods
    • Prepandemic: October 1, 2019, to January 31, 2020
    • Pandemic (following first reported cases in UK of COVID-19): February 1, 2020, to June 14, 2020
  • Outcomes
    • Stillbirth | Preterm birth | Cesarean delivery | NICU admission
    • Repeat analysis performed with exclusion of terminations for fetal anomalies (IN UK, stillbirth includes late termination ≥24 weeks)


  • Prepandemic
    • 1681 births | 1631 singletons | 22 twins | 2 triplets
  • Pandemic period
    • 1718 births: 1666 singleton | 26 twins
  • Nulliparity was less common during the pandemic period (P < .001)
    • Prepandemic: 52.2%
    • Pandemic: 45.6%
  • Fewer pregnancies were complicated by hypertension during the pandemic period (P = .005)
    • Prepandemic: 5.7%
    • Pandemic period: 3.7%
  • Stillbirth incidence was increased during the pandemic period
    • Prepandemic: 2.38 per 1000 births (n=4)
    • Pandemic: 9.31 per 1000 births (n=16)
    • Difference: 6.93 per 1000 births (95% CI, 1.83-12.0; P = .01)
  • Stillbirth incidence remained elevated after exclusion of terminations for anomalies
    • Prepandemic: 1.19 per 1000 births
    • Pandemic: 6.98 per 1000 births
    • Difference: 5.79 (95% CI, 1.54-10.1; P = .01)
  • There were no significant differences identified for the following outcomes
    • Preterm deliveries (<37 weeks)
    • NICU admission
  • No cases of stillbirth were associated with COVID-19
    • None of the mothers had symptoms associated with COVID-19
    • No placental or postmortem exams suggested of COVID-19
    • Note: Universal testing for SARS-CoV-2 only began May 28, 2020


  • Stillbirth rates were increased during the pandemic vs prepandemic period
    • One important limitation noted by authors is lack of data on cause of the stillbirth
  • Possible reasons for increase in stillbirth rate
    • Increase may still be due to SARS-CoV-2 infection in asymptomatic women (who would not have been tested)
    • Women may have deferred care due to COVID-19 concerns (e.g. delaying care to avoid infection)
    • Possible change in practice resulting in fewer antenatal visits or ultrasound assessments
    • Chance: Study time frame was short | If study was longer, difference perhaps would resolve
    • Hospital may have received more referrals 

Learn More – Primary Sources:

Change in the Incidence of Stillbirth and Preterm Delivery During the COVID-19 Pandemic

CDC Reports on Pregnancy and COVID-19 Outcomes

NOTE: Information and guidelines may change rapidly. Check in with listed references in ‘Learn More – Primary Sources’ to best keep up to date


The CDC now includes a separate page on COVID-19 and pregnancy data (see ‘Learn More – Primary Sources’). The initial dataset is based on the MMWR review (June 26, 2020) and the page will be updates as new data becomes available

Summary of MMWR study


  • CDC receives reports of COVID-19 cases through
    • Electronic standardized case report form or The National Notifiable Diseases Surveillance System
    • Data updated by health departments
    • Case reports for this study: January 22 to June 7 and updated as of June 17, 2020
  • Participants
    • Women aged 15 to 44 years (reproductive age) from 50 states, the District of Columbia, and New York City
    • Lab confirmed SARS-CoV-2 infection
  • Data collected included
    • Demographics | Pregnancy status | Underlying medical conditions | Clinical course | Outcomes (maternal)
  • Missing data
    • To avoid overestimating the risk for adverse outcomes, “Outcomes with missing data were assumed not to have occurred (i.e., if data were missing on hospitalization, women were assumed to not have been hospitalized)”
  • Statistical analysis
    • Outcomes: Logistic regression, using crude and adjusted risk ratios and 95% CIs
    • Risk ratios (RR) adjusted for
      • Age | Presence of underlying chronic conditions | Race/ethnicity


  • Women of reproductive age and positive for SARS-CoV-2: 326,335
  • Pregnancy status
    • 28% (91,412) of all reproductive age women had pregnancy status available | Among those women with pregnancy information, 9% (8,207) were reported as pregnant
  • Symptoms
    • Cough: Similar between pregnant and nonpregnant women (>50%)
    • Shortness of breath: Similar between pregnant and non-pregnant (30%)
    • Pregnant women less frequently reported
      • Headache | Muscle aches | Fever | Chills | Diarrhea
  • Comorbidities
    • More frequently reported in pregnant women
      • Chronic lung disease | Diabetes mellitus | CVD
  • Hospitalization
    • Significantly higher in pregnant women (adjusted)
    • Pregnant: 31.5% | Nonpregnant: 5.8%
    • aRR: 5.4 (95% CI, 5.1 to 5.6)
  • ICU admission
    • Significantly higher in pregnant women (adjusted)
    • Pregnant: 1.5% | Nonpregnant: 0.9%
    • aRR: 1.5 (95% CI, 1.2 to 1.8)
  • Mechanical ventilation
    • Significantly higher in pregnant women (adjusted)
    • Pregnant: 0.5% | Nonpregnant 0.3%
    • aRR: 1.7 (95% CI, 1.2 to 2.4)
  • Maternal mortality
    • There was no difference between groups
    • Pregnant : 0.2% (16 patients) | Nonpregnant: 0.2% (208 patients)
    • aRR: 0.9 (95% CI, 0.5 to 1.5)


  • Limitations include
    • Pregnancy status was missing for approximately 75% of women of reproductive age
    • Data on race/ethnicity, symptoms, underlying conditions, and outcomes were missing “for a large proportion of cases”
    • Data not available for the following
      • Trimester at time of infection was not available
      • Whether hospitalization was related to COVID-19
    • Current routine case surveillance does not capture pregnancy or birth outcomes
  • CDC concludes that

These findings suggest that among women of reproductive age with COVID-19, pregnant women are more likely to be hospitalized and at increased risk for ICU admission and receipt of mechanical ventilation compared with nonpregnant women, but their risk for death is similar

Learn More – Primary Sources:

CDC (MMWR): Characteristics of Women of Reproductive Age with Laboratory-Confirmed SARS-CoV-2 Infection by Pregnancy Status — United States, January 22–June 7, 2020

CDC: Data on COVID-19 During Pregnancy

CDC Who Needs Extra Precautions: People of Any Age with Underlying Medical Conditions

ACOG: Novel Coronavirus 2019 (COVID-19)