by Editorial Board last updated 2020-05-29 13:48:57.867286-04:00 © Antimicrobial Therapy, Inc.
Coronavirus, SARS CoV-2, COVID-19

Clinical Setting

  • SARS-CoV-2 (2019-nCoV) is a respiratory coronavirus that causes the disease COVID-19.
  • Origins of the virus: SARS-CoV-2 emerged in late 2019 from live animal markets in Wuhan, China.  Bats are the reservoir species and an animal intermediate host is thought to have transmitted the virus to humans (


  • Transmission:
  • Mean incubation time is estimated to be ~5 days after exposure (range 4.1 - 7.0 days, but as short as 36 hours. Transmission can occur from an infected person who is asymptomatic (prior to onset of symptoms; see above)
  • Viral shedding:


  • Prevention measures
    • Frequent handwashing (alcohol-based sanitizer and/or soap and water)
    • Sanitize common surfaces
    • Social distancing (at least 6 feet / 1.8 meter)
      • AVOID CROWDS AND/OR CONGESTED PLACES. Limit the amount of time spent in congregate places as much as possible.
      • WEAR A FACE MASK WHEN IN THE PRESENCE OF OTHERS: Primarily protects others by preventing generation of of nasal/respiratory droplets 
      • Respiratory hygiene, i.e., cover nose and mouth when sneezing or coughing
      • Avoid touching eyes, nose, mouth
    • Consult Federal, State and local guidance for reopening measures in specific situations
  • Personal protective equipment (PPE) when caring for a patient with COVID-19
    • Patients not undergoing aerosol generating procedures: N95 respirator preferred, surgical mask acceptable; face shield, gown, gloves
    • Patient undergoing nasopharyngeal swab, aerosol generating procedures: N95 respirator or PAPR, face shield, gown, gloves

Clinical Manifestations

  • Mean incubation time is estimated to be ~5 days after exposure (range 4.1 - 7.0 days), but as short as 36 hours.
  • 25-50% of cases may be asymptomatic or minimally symptomatic (Euro Surveill. 2020 Mar;25(10). doi: 10.2807/1560-7917.ES.2020.25.10.2000180).
  • Presentation / symptoms:
    • Common presenting signs and symptoms: headache, arthralgias, myalgias, fatigue, fever, cough, shortness of breath, loss of taste and/or smell, nausea, vomiting, diarrhea, sore throat. See CDC listing of symptoms
    • One week to 10 days prodrome which may  progress to difficulty breathing at any time, often in the second week.
    • Average 8 days to development of dyspnea and average 9 days to onset of pneumonia/pneumonitis.
    • Key presentation vitals (at triage): temp > 38ºC (30.7%), O2 sat < 90% (20.4%), heart rate > 100 beats/min (43.1%)
    • Approximately 15% of patients will develop severe disease with 5% requiring mechanical ventilation.   Fatality rates in confirmed cases ~ 5-10%, overall mortality probably 0.5%. JAMA online 04/20/2020
  • Associated co-morbidities / risk factors
    • Most common: hypertension (56.6%), obesity (41.7%), diabetes (33.8%)
    • Risk factors
  • Other manifestations, often associated with severe disease: myocarditis, heart failure, myocardial infarction; stroke; thromboembolic events; acute kidney injury; ARDS, multiple organ failure
  • Multisystem Inflammatory Syndrome in Children (MIS-C)(CDC HAN No, 432, 05/14/20)
    • Age <21 years, fever, lab evidence of inflammation, hospitalized severe illness, multi-organ involvement: cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic or neurological + no alternate diagnosis + current / recent positive test for SARS CoV-2 or COVID-19 exposure within 4 weeks of symptom onset.

Testing / Diagnostics

  • Testing Priorities for nucleic acid amplification or antigen tests (see below and
    • High Priority
      • Patients with symptoms requiring hospitalization
      • Healthcare facility workers, workers in congregate living settings, and first responders with symptoms
      • Residents in long-term care facilities or other congregate living settings, including prisons and shelters with symptoms
      • Workers exposed to an active case in high-risk facilities such as meat processing plants
    • Priority
      • Persons with symptoms of potential COVID-19 infection, including: fever, cough, shortness of breath, chills, muscle pain, new loss of taste or smell, vomiting or diarrhea, and/or sore throat
      • Persons without symptoms who are prioritized by health departments or clinicians, for any reason, including, but limited to: public health monitoring, sentinel surveillance, or screening or other asymptomatic individuals according to state and local plans
  • Nucleic acid amplification tests
  • Antigen tests
    • The FDA issued the first emergency use authorization (EUA) to Quidel Corporation for the Sofia 2 SARS Antigen FIA for diagnosis of active COVID-19 infection.  Antigen tests detect viral protein fragments of proteins from samples collected from the nasal cavity using swabs. 
    • The utility of this approach compared to PCR-based testing in diagnosis of COVID-19, its advantages and disadvantages, are a work in progress.
  • Viral dynamics
    • Study 9 patients without medical co-morbidities and relatively mild disease (Nature, April 1, 2020): Virus was readily cultured from nasopharyngeal swabs, throat and lung specimens, but not stool; no virus was isolated from urine or serum. No live virus was isolated from any specimen after 8 days. Viral RNA loads were highest in the early symptomatic period, declining slowly and remained detectable into the second or third week after onset of illness, despite resolution of symptoms.
    • Study of RT-PCR for viral RNA (Clin Infect Dis, April 19, 2020, ahead of print) in respiratory samples of 56 patients with mild to moderate COVID-19: 66% converted to negative by the 4th week, 95% by the 5th week, 100% by the 6th week
  • Serological testing
    • Variety of tests available of varying reliability (see CDC Interim Guidelines for COVID-19 Antibody Testing); exact role of these tests in manage of COVID patients and determining protective immunity is evolving.
    • Mt Sinai study or 624 NYC patients with mild disease found that IgG antibodies develop over a  period of 7 to 50 days from symptom onset and 5 to 49 from symptom resolution, with a median of 24 days from symptom onset to higher antibody titers, and a median of 15 days from symptom resolution to higher antibody titers. All but 3 (0.5%) subjects with PCR-confirmed infections seroconverted; optimal time frame for widespread antibody testing is at least three to four weeks after symptom onset and at least two weeks after symptom resolution. 


Primary Regimens

  • See also Critical Care Considerations, below
  • Patients with hypoxia
    • Remdesivir (U.S. FDA Emergency Use Authorization 05/01/2020) (See Comments and provider Fact Sheet).
      • Adult dosing (wt > 40 kg): 200 mg IV loading dose on day 1, then 100 mg IV daily maintenance dose
        • Infuse each dose over 30-120 min
        • 5 day course if not on ventilation/ECMO. If no clinical improvement at 5 days, extend to 10 days
        • 10 day course for patients on mechanical ventilation/ECMO (see Comments)
      • Pediatric dosing (wt 3.5 - 40 kg): 5 mg/kg loading dose on day 1, then 2.5 mg/kg maintenance dose
        • 5 day course if not on ventilation/ECMO. If no clinical improvement at 5 days, extend to 10 days
        • 10 day course for patients on mechanical ventilation/ECMO
    • Enrollment in a randomized clinical trial, if available, is strongly encouraged 
  • Patients without hypoxia
    • Supportive care

Alternative Regimens

  • None

Critical Care Considerations

  • Critical illness, hospitalized in ICU, on mechanical ventilation. Suggested interventions (NIH COVID-19 Treatment Guidelines; Surviving Sepsis Campaign Guidelines, Intens Care Med 46:854, 2020):
    • Fluids: balanced crystaloids
    • Pressors: norepi > vasopression/epi; cardiogenic shock - dobutamine; not dopamine
    • Steroids:
      • Refractory shock: low dose hydrocortisone
      • No ARDS: no steroids
      • ARDS: steroids controversial 
    • Anti-inflammatory: acetaminophen and/or ibuprofen
    • Antiviral therapy for SARS CoV-2: Remdesivir (See Primary Regimens, above)
    • Co-infection. Empiric antimicrobial therapy (data insufficient, but reasonable to consider; if initiated, re-evaluate at 2-3 days and adjust or discontinue antimicrobials, as appropriate, based on clinical status and microbiology):
  • Co-infection: Important to differentiate quickly between viral and bacterial systemic inflammation. Diagnostics should include multiplex PCR for respiratory pathogens other than SARS CoV-2, e.g., bacterial pneumonia (S. aureus, S. pneumoniae, gram negative bacilli), influenza. Use rapid test panels if possible due to potential for rapid progression of pneumonia in severely ill COVID-19 patients.
  • Immune-based and antithrombotic therapy guidance, see NIH Guidelines (rapidly evolving area)
  • References: bacterial co-infections (Lancet Microbe online 24 Apr 2020); recognition and management of respiratory co-infection and bacterial pneumonia (Cleve Clin J Med online May 2020)


  • Remdesivir
    • Superior to placebo in shortening time to recovery in hospitalized adults (N Engl J Med online 22 May 20):
      • Randomized, double-blind, placebo controlled trial of 1059 patients (NCT04280705) sponsored by NIAID found that patients that remdesivir treated patients had a median time to recovery of 11 days compared to 15 days for patients who received placebo (p<0.001). The odds of clinical improvement, a secondary outcome, were higher in the remdesivir group  at the day 15 visit, than in the placebo group (odds ratio for improvement, 1.50; 95% CI, 1.18 to 1.91; P = 0.001; 844 patients). Results also suggested a survival benefit, with a 14-day mortality rate of 7.1% for the group receiving remdesivir versus 11.9% for the placebo group (hazard ratio for death, 0.70; 95% CI, 0.47 to 1.04; 1059 patients). Rates of adverse events were similar. Subgroup analysis suggested benefit across multiple subgroups with the notable exception of patients receiving mechanical ventilation or ECMO, suggesting a lack of efficacy in those with advanced disease.  
    • Efficacy of 5-day and 10-day courses of Remdesivir similar for patients with severe COVID-19 not requiring mechanical ventilation (N Engl J Med, May 27, 2020, doi: 10.1056/NEJMoa201530).
  • Chloroquine or Hydroxychloroquine ± Azithromycin:
    • Not recommended due to lack of data supporting efficacy and risk of serious, potentially fatal cardiac arrhythmia. See FDA Drug Safety Communication (04/24/2020)
    • Retrospective study of 1,376 hospitalized patients from one medical center in New York study, 811 of whom were treated with hydroxychloroquine and 565 were not: Hydroxychloroquine treatment was not associated with either a greatly lowered or an increased risk of the composite end point of intubation or death in either unadjusted or propensity weighted analyses.
    • A large multinational registry study (Lancet,  published online May 22, 2020) of 96,032 patients, 14,888 of whom were treated with chloroquine or hydroxychloroquine + a macrolide and 81,144 control patients who were not treated with these drugs found significantly higher in-hospital mortality in treated (16.4% to 23.8%) versus control patients (9.3%) after adjustment for potential confounders. Hydroxychloroquine regimens were independently associated with an increased risk of ventricular arrhythmia (6.1% to 8.1%%) compared with the control group (0·3%). 
    • Study from Brazil (JAMA Netw Open. 2020 Apr 24;3(4.23):e208857) comparing 2 dosage regimens of Chloroquine diphosphate, 450 mg bid on day one then 450 mg once daily x 5 days (2.7 gm total dose) compared to 600 mg bid x 10 days (12 gm) for 81 patients with severe COVID-19 illness was terminated early due to toxicity, principally in the higher dose arm: ventricular tachycardia in 2 patients (both higher dose arm), 15% with QTc prolongation > 500 msec (11% in the lower dose group, 18% in the higher dose group).
  • Cytidine nucleoside analogs 
    • EIDD-1931: Broad spectrum antiviral activity against SARS-CoV-2, MERS-CoV, SARS-CoV, and group 2b or 2c Bat-CoVs. Increased potency against CV bearing resistance mutations to remdesivir. Now entering Phase I studies in patients with COVID-19.
    • EIDD-2801: Similar compound as EIDD-1931 except it has an isopropyl ester at the 5' position.  In mice models infected with SARS-CoV and MERS Co-V, this drug reduced virus titers and body weight loss, while improving pulmonary function.  Sci. Transl. Med. 12: 541,  Apr 2020
  • HIV protease inhibitors:
    • Lopinavir/ritonavir
      • RCT showed no benefit and no antiviral effect vs. standard care (N Engl J Med doi: 10.1056/NEJMoa2001282)(03/18/20). Due to the high risk of adverse drug-drug interactions (see University of Liverpool compilation: in critically ill patients, further trial data are needed before lopinavir/ritonavir can be recommended for treatment of COVID-19.
      • Open label, phase 2 randomized controlled trial of a 14-day triple drug combination of lopinavir/ritonavir 400 mg/100 mg + ribavirin 400 mg every 12 h + up to 3 doses of 8 million international units of interferon beta-1b on alternate days (86 subjects) versus 14 days of lopinavir/ritonavir 400 mg/100 mg every 12 h alone (41 subjects) for mild to moderate COVID-19 found that the combination reduced viral load to undetectable more rapidly (7 days vs. 12 days) and shortened time to clinical improvement (4 days vs. 8 days).  There were no deaths in either group.
    • Darunavir: no in vitro activity, no evidence of any effect - do not use (
  • Updates on COVID-19 research here.
  • Other therapeutic options under evaluation:
  • Other Comments: