COVID-19 Clinical Resources and Pertinent Research
A regularly updated list of the most useful COVID-19 clinical resources, the most significant research publications, and reliable news. To contribute, click the plus button on the left. Short URL: bit.ly/C19Res

Knowns and Unknowns

COVID-19: Knowns

Epidemiology
  • Symptomatic infection fatality rate (IFR-S) in the U.S. is 0.8–1.5% and the case fatality rate (CFR) is ~6%.
  • CFR for patients requiring invasive mechanical ventilation is ~45%.
  • Seroprevalence of SARS-CoV-2–specific antibodies among adults remains very low at ~10%.
  • Greater than 75% of Americans are at risk of severe COVID-19 based on the prevalence of known comorbidities.
  • Outbreak clusters have been traced to flights, parties, nightclubs, bars, karaoke bars, and gyms.
  • Universal face mask use, including the use of cloth masks, significantly reduces viral transmission, hospitalizations, and death.
  • Effects of introducing and relaxing non-pharmaceutical interventions on SARS-CoV-2 transmission are delayed by 1–3 weeks.
  • Testing of wastewater is useful in monitoring and predicting infection rates.
  • Symptom screening and temperature checks fail to identify most children with COVID-19.
Viral Transmission
  • Presymptomatic, and to a lesser extent asymptomatic, transmission play a substantial role in community spread.
  • 10–20% of individuals may be responsible for 80% of transmission.
  • Short range aerosol and droplet are the primary routes of spread.
  • Longer-range aerosol transmission can occur in closed, poorly-ventilated spaces.
  • Infected persons shed SARS-CoV-2 during respiration, toileting, and fomite contact.
  • SARS-CoV-2 can remain viable and infectious in aerosols for hours and viable on surfaces for days.
  • Climate and temperature do not affect transmission.
  • Infected domestic cats shed infectious virus for up to 5 days, while dogs do not appear to shed virus.
  • Biting insects do not pose a transmission risk to humans or animals.
Immunology
  • Mean SAR-CoV-2 incubation period is 5.7 days
  • Peak viral load occurs 4-6 days after symptom onset.
  • Viral load appears to be correlated with disease severity.
  • Antibody responses are be short-lived, particularly in mild or asymptomatic infections.
  • Magnitude of the neutralizing antibody response appears to depend on disease severity.
  • IgM and IgG appear at approximately the same time.
  • Type I interferon responses play a critical role during early infection.
  • Prior infection with human coronaviruses appears to induce lasting cross-reactive T cell immunity that neutralizes SARS-CoV-2.
  • Reinfection is possible but appears to be exceedingly rare at this time.
Virology
  • Dominant strain of SARS-CoV-2 is the G614 strain that began spreading in Europe and the U.S. East Coast in Feb-Mar 2020.
  • G614 is a result of a change of the amino acid at position 614, from aspartic acid [D] to glycine [G], thus the “D614G” mutation.
  • D614G marks the evolution of the initial D614 (Wuhan) strain to the now dominant and likely more virulent G614 strain.
  • A now extinct and less severe Δ382 strain began spreading in East Asia in Jan-Feb 2020.
  • A potentially immunovasive N439K strain has been identified in 12 counties and has emerged independently at least twice.
  • SARS-CoV-2 is not a purposefully manipulated virus and it’s lineage has been circulating in bats for decades.
Treatment and Management
  • As with other viral upper respiratory infections, there is no outpatient treatment regimen other than supportive care.
  • Corticosteroids appear to marginally reduce mortality in hospitalized patients requiring mechanical ventilation.
  • Delaying intubation and using non-invasive ventilation can reduce complications and possibly avoid clinical deterioration.
  • Proning may improve oxygenation in select patients.
  • Convalescent plasma does not appear to reduce mortality or progression to severe disease
  • Remdesivir, hydroxychloroquine, tocilizumab, lopinavir–ritonavir, and interferon have little or no effect on hospitalized patients.
  • Little data exists on the efficacy of vitamin D, favipiravir, famotidine, ivermectin, and almitrine for the treatment of COVID-19.
  • Systemic anticoagulation appears to lower mortality in hospitalized patients; risks/benefits should be considered case by case.
  • Early superinfections are rare but late infections, including invasive pulmonary aspergillosis, are a risk in critically ill patients.
  • Cardiopulmonary resuscitation is ineffective in hospitalized COVID-19 patients in cardiac arrest.
Clinical
  • Age, sex, and comorbidities, especially obesity, have a major impact on disease severity and mortality.
  • Inflammatory vascular and thromboembolic complications are frequently encountered in severe infections.
  • Venous thromboembolism occurs in approximately 8% of non-ICU patients and 23% of ICU patients.
  • Pulmonary embolism occurs in approximately 4% of non-ICU patients and 14% of ICU patients.
  • Biomarkers, including IL-6 and TNF-α, can predict disease progression and complications.
  • Severe disease with respiratory failure is associated with a robust type 2 proinflammatory immune response (cytokine storm).
  • Acute myocardial injury occurs in ~30% of hospitalized COVID-19 patients.
  • Acute kidney injury occurs in 26% of hospitalized patients and is associated with a 3-fold increase in mortality.
  • Anosmia, dysgeusia/aguesia, gastrointestinal symptoms, and cutaneous lesions are all associated with COVID-19.
  • Conjunctivitis may also be a presenting symptom, especially in pediatric patients.
  • Use of ACEI, ARB, or NSAIDs is not contraindicated in COVID-19.
  • There is little evidence of direct neurological involvement aside from anosmia.
  • Pregnant women appear to be at higher risk of severe infection and increased need for mechanical ventilation.
  • Natural passive immunity without vertical transmission has been observed postpartum.
  • Children have generally mild illness but rarely can develop an immune-mediated Multisystem Inflammatory Syndrome (MIS-C).
  • Adults with previous infection can develop a similar Multisystem Inflammatory Syndrome in Adults (MIS-A).
Testing
  • Nucleic acid amplification tests to detect viral RNA are recommended for diagnosis.
  • Detection of viral RNA via PCR does not necessarily indicate infectiousness following symptom resolution.
  • Sensitivity of diagnostic tests can depend on specimen and assay type and is time-dependent.
Personal Protective Equipment
  • Health care workers are at risk but can be protected by appropriate PPE.
  • Masks with exhalation valves or vents are completely ineffective.
  • Face shields are not a substitute for masks and are used for eye protection.
  • Masks do not affect gas exchange , including in older persons, and do not decrease oxygen or increase carbon dioxide levels.
  • Wearing gloves does not protect against SARS-CoV-2 infection.


COVID-19: Unknowns

Epidemiology
  • How can superspreader events be avoided?
  • Is temperature screening at all effective as a control strategy given the prevalence of presymptomatic transmission?
  • Why do infection rates and severity vary so widely among individuals and countries?
  • Why are global COVID-19 mortality rates falling?
Immunology
  • What are the correlates and durability of protective immunity?
  • Does low-level viral exposure lead to protective immunity?
  • What role do T and B cells play in long term protective immunity?
  • What type of T cell response elicited by vaccines will be the best predictor of protective immunity?
  • Will memory T cells in the upper respiratory tract provide durable protection from lower pulmonary disease upon reinfection?
  • What is the impact of prior exposure to endemic seasonal coronaviruses?
Virology
  • Does viral diversity influence illness severity?
Clinical
  • What are late complications and how can they be managed and/or prevented?
Treatment
  • What is the treatment for mild disease?
  • How does the timing of intubation affect mortality?
  • What is the role and optimal dosing of anticoagulant therapy?
  • Are vitamin D, famotidine, favipiravir, ivermectin, almitrineor, or interferon effective in the treatment of COVID-19?
  • What is the role of monoclonal antibodies in the treatment of COVID-19?
  • When should antifungal prophylaxis be considered?
  • Is there a role for immunomodulatory agents in addition to corticosteroids?
  • How should the timing of immunomodulatory interventions be optimized?
  • Why does convalescent plasma seem to provide little or no benefit?
Testing
  • What is the accuracy of antigen compared to viral RNA testing?
Prevention
  • Can vaccines, especially mRNA vaccines, induce long term protective immunity?
  • In those infected following vaccination, how do vaccines affect disease severity and asymptomatic spread?
  • Can upgrading ventilation systems in businesses and schools facilitate reopening?

Inspired by Fang FC, et al. COVID-19—Lessons Learned and Questions Remaining. Clin Infect Dis. Oct 2020.

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