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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
  • Primary immunomodulator for all patients who require high-flow nasal canula oxygen, noninvasive ventilation, mechanical ventilation, or ECMO
  • 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)

COVID-19 Testing: CDC Guidance on Virus and Antibody Testing

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 has provided guidance on both viral testing for SARS-CoV-2 as well as the role of antibody testing. Testing for the presence of the virus during the pandemic remains the current diagnostic standard. While antibody testing can play a role for public health teams to understand the spread of the disease, currently its use as a diagnostic test for individuals remains limited. A COVID-19 vaccine will not affect the results of SARS-CoV-2 viral tests.

Viral Testing

Specimen Collection

  • Obtain an upper respiratory specimen for initial diagnostic testing
    • A nasopharyngeal (NP) specimen collected by a healthcare professional  or
    • An oropharyngeal (OP) specimen collected by a healthcare professional  or
    • A nasal mid-turbinate swab collected by a healthcare professional or by a supervised onsite self-collection (using a flocked tapered swab)  or
    • An anterior nares (nasal swab) specimen collected by a healthcare professional or by onsite or home self-collection (using a flocked or spun polyester swab)  or
    • Nasopharyngeal wash/aspirate or nasal wash/aspirate (NW) specimen collected by a healthcare professional
  • Lower respiratory tract specimens
    • Collect and test sputum in patients who develop a productive cough | Induction of sputum is not recommended
    • Under certain clinical circumstances (e.g., those receiving invasive mechanical ventilation), a lower respiratory tract aspirate or bronchoalveolar lavage sample should be collected and tested as a lower respiratory tract specimen

How is SARS-CoV-2 RNA Testing Performed?


  • Usually performed using real-time reverse transcription polymerase chain reaction (RT-PCR)
    • Qualitative detection of RNA
  • Multiple tests on the market that can target various genes
    • Envelope (env) | Nucleocapsid (N) | Spike (S) | RNA-dependent RNA polymerase (RdRp) | ORF1
  • A positive test can only determine presence of SARS-CoV-2 RNA and not whether the virus is intact and capable of infecting others


  • Antigen tests can quickly detect fragments of proteins found on or within the virus by testing samples collected from the nasal cavity using swabs
  • The benefit of antigen testing is speed, with results potentially available within minutes
  • However, antigen tests, while very specific for the virus, are not as sensitive as molecular PCR tests
    • Positive antigen results: Highly accurate but higher chance of false negatives | Negative antigen results may still need PCR confirmation prior to treatment decisions or to prevent inadvertent spread of SARS-CoV-2

Note: Prior receipt of a COVID-19 vaccine should not affect the results of SARS-CoV-2 viral tests (NAAT or antigen)

Breath Sample Analysis

  • FDA has issued an emergency use authorization (EUA) for a diagnostic test that detects chemical compounds in breath samples associated with a SARS-CoV-2 infection
  • Test is performed by a qualified, trained operator under the supervision of a health care provider licensed or authorized by state law to prescribe tests
  • Results available in <3 minutes

Diagnostic Testing

Signs or Symptoms of COVID-19

  • Positive test
    • NAAT: Indicates infection regardless of vaccine status
    • Positive antigen test result may need confirmatory testing if the person has a low likelihood of SARS-CoV-2 infection (e.g., no known exposure to a person with COVID-19 within the last 14 days or is fully vaccinated or has had a SARS-CoV-2 infection in the last 3 months)
    • Isolate if positive test: Discontinue isolation 5 days after symptom onset and at least 24 hours after the resolution of any fever (without the use of fever-reducing medications) | Continue to wear mask around others for 5 additional days
      • Some individuals may require extended isolation and precautions (e.g., severely immunocompromised)
      • Testing is not recommended to determine when infection has resolved
      • Loss of taste and smell may persist for weeks or months after recovery and need not delay the end of isolation​
  • Negative test
    • If symptoms are consistent with COVID-19, may be a false negative | Isolation and further discussion with healthcare professional recommended

Testing to determine resolution of infection

  • May be appropriate for severe illness or immunocompromise
  • “For all others, a test-based strategy is no longer recommended except to discontinue isolation or precautions earlier than would occur under the symptom-based strategy”

Screening Testing

No Symptoms and No Close Contact with Someone Known to Have a COVID-19 Infection

  • Asymptomatic or presymptomatic infection contribute to community SARS-CoV-2 transmission
    • May help with re-opening of businesses, communities, and schools
  • Point-of-care tests (e.g., antigen tests) can be particularly helpful due to short turn-around times
  • Quarantine not required while results are pending
  • Examples of screening programs
    • Testing employees in a workplace setting
    • Testing students, faculty, and staff in a school or university setting
    • Testing a person before or after travel

How Early Will a Test Be Positive and How Long Until Negative?

  • In patient with COVID-19 infection who tested positive using a nasopharyngeal swab
    • Earliest detection: Day 1 of symptoms
    • Peak levels highest within week 1 and therefore probability of detection will be highest during that time
    • Viral load declines by week 3 and therefore virus more likely to be undetectable in to week 4
    • Infection severity: More virus may be present in patients with severe disease and therefore it may take longer to obtain a negative test result vs someone with a mild COVID-19 infection

Performance of RT-PCR Viral Tests

  • RT-PCR specificities are close to 100% because they target specific RNA sequences of the SARS-CoV-2 virus
  • False negative results may be due to
    • Inappropriate timing of collection vs symptom onset
    • Poor sampling technique (need to sample at the back of the nose)
  • False positive results may occur due to lab error or contamination
  • However, even with good analytic performance, PPV and NPV are related to prevalence and therefore can differ between geographic regions
    • In a setting with high COVID-19 prevalence, a negative test does not necessarily rule out the possibility that an individual is infected with SARS-CoV-2

Antibody Testing

General CDC Antibody Guidance

  • According to the CDC

Antibody testing does not replace virologic testing and should not be used to establish the presence or absence of acute SARS-CoV-2 infection

Antibody testing is not currently recommended to assess for immunity to SARS-CoV-2 following COVID-19 vaccination, to assess the need for vaccination in an unvaccinated person, or to determine the need to quarantine after a close contact with someone who has COVID-19

Some antibody tests will not detect the antibodies generated by COVID-19 vaccines

Because these vaccines induce antibodies to specific viral protein targets, post-vaccination antibody test results will be negative in persons without history of previous infection, if the test used does not detect antibodies induced by the vaccine

  • In general, antibodies will be detectable 7 to 14 days after illness onset and will be present in most people by 3 weeks
    • Infectiousness likely decreased by that time
    • Evidence suggests some degree of immunity will have developed
  • IgM and IgG can appear together, usually within 1 to 3 weeks
    • IgG antibodies appear to persist for at least several months
    • Some individuals may be infected but will not develop antibodies
  • Neutralizing antibodies can also be identified and are associated with immunity
  • FDA requires companies providing antibody testing to obtain an EUA

What Are the Different Types of Antibody Tests?

  • Antigenic Targets
    • Spike glycoprotein (S): Present on viral surface and facilitates virus entry
    • Nucleocapsid phosphoprotein (N): Immunodominant and interacts with RNA
    • Protein targeting is important to reduce cross-reactivity (cause of false positives which may occur with other coronaviruses like the common cold) and improve specificity
  • Types of Antibody Testing
    • Binding antibody detection that use purified SARS-CoV-2 (not live virus)
      • Point-of-care (POC) tests
      • Laboratory tests that usually require skilled personnel and specialized equipment
    • Neutralizing antibody detection (none currently FDA authorized)
      • Serum or plasma is incubated with live virus followed by infection and incubation of cells
      • Can take up to 5 days to complete the study

When Can Antibody Testing be Helpful?

Antibody testing may be helpful in the following situations

  • Seroconversion: In a patient who did not receive a positive viral test
    • A positive antibody test at least 7 days following acute illness onset but a previous negative antibody test may indicate new onset SARS-CoV-2 infection
  • To support a diagnosis in the presence of a complex clinical situation, such as patients who present with COVID-19 complications (e.g., multisystem inflammatory syndrome and other post-acute sequelae of COVID-19)
    • Note: Due to antibody persistence, a single positive antibody test result may reflect previous SARS-CoV-2 infection and not a recent illness
  • Clinical, occupational health, and public health purposes, such as serologic surveys

Vaccination and Test Interpretation

  • In a person never vaccinated
    • testing positive for antibody against either N, S, or RBD indicates prior natural infection
  • In a vaccinated person
    • Testing positive for antibody against the vaccine antigen target, such as the S protein, and negative for other antigen: Suggests vaccine-induced antibody and not SARS-CoV-2 infection
    • Testing positive for any antibody other than the vaccine-induced antibody, such as the N protein: Indicates resolving or resolved SARS-CoV-2 infection that could have occurred before or after vaccination
  • The CDC states that

SARS-CoV-2 antibodies, particularly IgG antibodies, might persist for months and possibly years

Therefore, when antibody tests are used to support diagnosis of recent COVID-19, a single positive antibody test result could reflect previous SARS-CoV-2 infection or vaccination rather than the most recent illness

Learn More – Primary Sources:

CDC: Interim Guidelines for Collecting, Handling, and Testing Clinical Specimens from Persons for Coronavirus Disease 2019 (COVID-19)

Interim Guidelines for COVID-19 Antibody Testing in Clinical and Public Health Settings

CDC: Overview of Testing for SARS-CoV-2

CDC: Interim Public Health Recommendations for Fully Vaccinated People

Interpreting SARS-CoV-2 Test Results

The Promise and Peril of Antibody Testing for COVID-19

EUA Authorized Serology Test Performance

CDC Updates and Shortens Recommended Isolation and Quarantine Period for General Population

CDC: Quarantine and Isolation

Coronavirus (COVID-19) Update: FDA Authorizes First COVID-19 Diagnostic Test Using Breath Samples

COVID-19: Category Definitions, Symptoms and Those at Increased Risk

NOTE: Information and guidelines may change rapidly. Check in with listed references in ‘Learn More – Primary Sources’ to best keep up to date. This summary has been updated with the latest CDC guidelines on when to end quarantine.


The novel coronavirus, named SARS-CoV-2, is the pathogen underlying the pandemic (a global outbreak of disease). The disease associated with this virus has been officially named COVID-19. Coronaviruses represent a large family of viruses. They can cause human illness, but many are found in animals and, rarely, animal coronaviruses can evolve and infect people as was the case in previous infectious outbreaks such as MERS and SARS.

COVID-19 Categories (NIH Panel)

  • Asymptomatic or pre-symptomatic infection
    • Test positive for SARS-CoV-2 using a virologic test (i.e., a nucleic acid amplification test [NAAT] or an antigen test)
    • No symptoms that are consistent with COVID-19
  • Mild illness
    • Have any of the various signs and symptoms of COVID-19 (e.g., fever, cough, sore throat, malaise, headache, muscle pain, nausea, vomiting, diarrhea, loss of taste and smell)
    • No shortness of breath, dyspnea, or abnormal chest imaging
  • Moderate illness
    • Evidence of lower respiratory disease during clinical assessment or imaging and oxygen saturation (SpO2) ≥94% on room air at sea level
  • Severe illness
    • SpO2 <94% on room air at sea level, a ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) <300 mm Hg, a respiratory rate >30 breaths/min, or lung infiltrates >50%
  • Critical illness
    • Respiratory failure, septic shock, and/or multiple organ dysfunction

Note: SpO2 is a key parameter for defining the illness categories listed above | Pulse oximetry has important limitations (e.g., skin pigmentation, thickness or temperature) | Clinicians who use SpO2 when assessing a patient must be aware of those limitations and conduct the assessment in the context of that patient’s clinical status

Pregnancy: Oxygen supplementation in pregnancy generally used when SpO2 <95% on room air at sea level to accommodate the physiologic needs of mother and fetus


  • Incubation period
    • Time from exposure to development of symptoms: 2 to 14 days
      • Delta variant studies: Mean incubation period of 4.3 days (see ‘Learn More – Primary Sources Below) which was shorter than initial variants (5.0 days)
      • Omicron variant studies: Median incubation period of 3 to 4 days
  • Signs and Symptoms
    • Fever or chills
    • Cough
    • Shortness of breath or difficulty breathing
    • Fatigue
    • Muscle or body aches
    • Headache
    • New loss of taste or smell
    • Sore throat
    • Congestion or runny nose
    • Nausea or vomiting
    • Diarrhea
  • Additional points regarding presentation
    • Older adults: Especially those with comorbidities may have delayed presentation of fever and respiratory symptoms
    • Fatigue, headache, and muscle aches (myalgia) are among the most commonly reported symptoms in people who are not hospitalized
    • Sore throat and nasal congestion or runny nose (rhinorrhea) also may be prominent symptoms
    • GI symptoms may be relatively common
      • Nausea, vomiting or diarrhea may occur prior to fever and lower respiratory tract signs and symptoms
    • Loss of smell (anosmia) or taste (ageusia) has been commonly reported, especially among women and younger or middle-aged patients

Those at Risk Based on Evidence (CDC)

  • Age
    • The CDC states

Age is the strongest risk factor for severe COVID-19 outcomes. Approximately 54.1 million people aged 65 years or older reside in the United States; in 2020 this age group accounted for 81% of U.S. COVID-19 related deaths, and as of September 2021 the mortality rate in this group was more than 80 times the rate of those aged 18-29

Higher Risk: Meta-analysis or systematic review demonstrates good or strong evidence

  • Asthma
  • Cancer
  • Cerebrovascular disease
  • Chronic kidney disease*
  • Chronic lung diseases limited to
    • Interstitial lung disease
    • Pulmonary embolism
    • Pulmonary hypertension
    • Bronchiectasis
    • COPD (chronic obstructive pulmonary disease)
  • Chronic liver diseases limited to
    • Cirrhosis
    • Non-alcoholic fatty liver disease
    • Alcoholic liver disease
    • Autoimmune hepatitis
  • Cystic fibrosis
  • Diabetes mellitus, type 1 and type 2*‡
  • Disabilities‡
    • Attention-Deficit/Hyperactivity Disorder (ADHD)
    • Cerebral Palsy
    • Congenital Malformations (Birth Defects)
    • Down syndrome
    • Limitations with self-care or activities of daily living
    • Learning Disabilities
    • Spinal Cord Injuries
    • See ‘Learn More – Primary Care’ CDC reference that includes extensive list for included disabilities
  • Heart conditions (such as heart failure, coronary artery disease, or cardiomyopathies)
  • HIV (human immunodeficiency virus)
  • Mental health disorders limited to
    • Mood disorders, including depression
    • Schizophrenia spectrum disorders
  • Neurologic conditions limited to dementia‡
  • Obesity (BMI ≥30 kg/m2 or ≥95th percentile in children)*‡
  • Primary Immunodeficiencies
  • Pregnancy and recent pregnancy
  • Physical inactivity
  • Smoking, current and former
  • Solid organ or hematopoietic cell transplantation
  • Tuberculosis
  • Use of corticosteroids or other immunosuppressive medications

Suggestive Higher Risk: Underlying medical condition or risk factor that neither has a published meta-analysis or systematic review nor completed the CDC systematic review process

  • Children with certain underlying conditions
  • Overweight (BMI ≥25 kg/m2, but <30 kg/m2)
  • Sickle cell disease
  • Substance use disorders

Comorbidities with mostly case series, case reports, or, if other study design, the sample size is small 

  • Overweight (BMI ≥25 kg/m2, but <30 kg/m2)
  • Sickle cell disease
  • Substance use disorders
  • Thalassemia

Mixed Evidence: Meta-analysis or systematic review is inconclusive, either because the aggregated data on the association between an underlying condition and severe COVID-19 outcomes are inconsistent in direction or there are insufficient data

  • Alpha 1 antitrypsin deficiency
  • Bronchopulmonary dysplasia
  • Hepatitis B
  • Hepatitis C
  • Hypertension*
  • Thallassemia


* indicates underlying conditions for which there is evidence for pregnant and non-pregnant people

‡ underlying conditions for which there is evidence in pediatric patients

Learn More – Primary Sources:

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

NIH: Clinical Spectrum | COVID-19 Treatment Guidelines

Impact of SARS-CoV-2 Delta variant on incubation, transmission settings and vaccine effectiveness: Results from a nationwide case-control study in France (Lancet Regional Health, 2022)

CDC: Clinical Presentation | Clinical Care Considerations

CDC Coronavirus Disease 2019: Overview of Testing for SARS-CoV-2

Clinical Questions about COVID-19: Questions and Answers

WHO: Novel coronavirus Information Page

JAMA: Coronavirus Disease 2019

FDA: Coronavirus Disease 2019

BMJ: Coronavirus Updates

Lancet: Coronavirus Hub

NEJM: 2019 Novel Coronavirus

Annals of Internal Medicine: Content Related to Coronavirus in Annals of Internal Medicine

JAMA: What Is a Pandemic?

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