Definitions

• Zoonosis: a disease that spreads from animals to humans
• Ancestral host: the “normal” animal host of a virus, often asymptomatic or minimally symptomatic. In the case of COVID-19, thought to be bats
• Epidemic: an outbreak of disease affecting unusual numbers of people, often confined to a discrete area
• Pandemic: a global epidemic affecting large numbers of people (formal definitions vary)
• PUI: person under investigation; someone for whom COVID-19 is a hypothesized but not a proven diagnosis
• Confirmed case: a person with one or more positive tests
• Quarantine: the separation of a person or group who is thought to potentially be infected with a transmissible infection
• Isolation: the separation of a person who is infected with a transmissible infection
• Social distancing: a community-wide attempt to reduce disease transmission. Social distancing is used as a mitigation strategy. If the assumption is made that every person has a non-zero chance of carrying SARS-CoV-2019, then decreasing person-to-person interactions should reduce the chance that the virus has to transmit in the community
• Shelter-in-Place: a legal measure undertaken by local government requesting that all citizens remain at home except for essential work; one way of mandating social distancing

Overview

SARS-CoV-2 is a novel coronavirus that causes the clinical syndrome COVID-19. The virus emerged in late 2019 and has given rise to a global pandemic. SARS-CoV-2 is closely related to other coronaviruses, including 4 that circulate in humans normally and cause URIs. It is also related to two other zoonotic coronaviruses: MERS-CoV, a zoonosis that passes through camels as intermediate host, SARS-CoV, the cause of SARS outbreak in 2002-2003.

Diagnosis

Who should be tested?

• COVID-19 testing is considered for patients with suspected respiratory illnesses and/or fever
• UCSF clinical guidelines for evaluation of hospitalized patients with suspected respiratory illness can be found here
• Clinical indications vary and continue to evolve based on location and testing availability

Approach to testing

• For initial testing, the CDC recommends testing for SARS-CoV-2 from an upper respiratory specimen, which can be performed according to the UCSF guide for recommended testing. The CDC also recommends testing lower respiratory specimens if available. Testing modalities are rapidly evolving
• We are currently using pooled nasopharyngeal and oropharyngeal samples
• Current testing utilizes PCR. While we do not have sensitivity and specificity of our current testing at this time, we believe that testing is more specific than sensitive – false positives are rare but false negatives are possible

Clinical Manifestations

For the UCSF COVID-19 clinical evaluation guide here and summarized below:

COVID-19 may cause the following symptoms:

Note: lack of symptoms, e.g. fever, do not exclude COVID-19

• Constitutional
  • Fever (occurs over hospital course in >75% cases, but >50% are afebrile on admission)
  • Myalgias
  • Fatigue
• Lower respiratory
  • Cough, dry or productive (>40%)
  • Dyspnea (20-50%)
  • Tachypnea
• Chest tightness
• Upper respiratory (can occur, but not typical, <15%)
  • Rhinorrhea
  • Pharyngitis
  • Sneezing
• Gastrointestinal (can occur, but not typical, <20%)
  • Diarrhea (<25%)
  • Nausea/Vomiting (<10%)
• Anosmia – inability to smell or taste; frequency not known, but if present is suggestive

Laboratory evaluation

• CBC with differential, may have
  • Leukopenia
  • Lymphopenia (~33-85%)
• Basic metabolic panel
  • CRP (may be elevated)
  • Liver function testing (mild transaminitis may be seen)
  • Procalcitonin ≥0.5 argues against COVID-19 however, may be elevated in severe/ICU level patients, thus high procalcitonin cannot exclude COVID-19
• Respiratory viral panel OR rapid flu testing (per clinical suspicion)
  • Co-infection with other viruses makes COVID-19 less likely but does not rule it out
  • Standard respiratory viral panels reporting "coronavirus" are not COVID-19; they refer to the four circulating non-pandemic coronaviruses, which cause seasonal URIs

Imaging

• Imaging with CXR or chest CT should be considered on initial evaluation
• CXR or CT is reportedly abnormal in ~50% of cases on first presentation
• Imaging findings of COVID-19 are consistent with that of viral pneumonia, specifically geographic areas of ground glass opacities, often peripheral, as well as consolidations
• Chest CT
  • Should be used to evaluate and rule in/out alternative diagnoses, such a pulmonary embolus, based on clinical suspicion
  • Is not routinely recommended as a first pass test for ruling in/out COVID-19
  • Is through to be very sensitive for the detection of COVID-19, however less specific
  • If early COVID-19 is suspected (<3-5 days from symptom onset), and preliminary PCR testing is negative, Chest CT can be considered as imaging findings may be present prior to first positive PCR in some cases

Critical Care

The primary indication for ICU admission in COVID-19 is characterized by impaired oxygenation and hypoxemic respiratory failure. The pathophysiology is characteristically acute respiratory distress syndrome (ARDS). Some patients may present with features of a "cytokine storm" or a clinical presentation that mimics bacterial sepsis; various biomarkers such as CRP, procalcitonin, ferritin, D-dimer have been observed as being associated with worse outcomes.

Management

Anti-viral therapy

• There are no current proven medications for the treatment of COVID-19
• Multiple randomized control trials (RCTs) are ongoing for the care of COVID-19 patients, with >300 clinical trials ongoing worldwide
• Whenever possible, patients should be enrolled in RCTs
• Providers should review existing evidence and are encouraged to make individualized decisions about the appropriateness of available medications

Supportive Care

The mainstay of treatment for COVID-19 is standard supportive therapy. Approach to treatment is similar to care in other respiratory viral illnesses that can have severe manifestations. See the most recent UCSF management guidelines here.

Laboratory Evaluation
The following labs are often routinely obtained on admission and may be followed as clinically indicated:

• CBC and differential, BMP, Magnesium, LFTs (AST, ALT, TBili, Alk Phos), procalcitonin (low or normal)
• CRP, LDH, and inflammatory markers (ESR, CRP, ferritin) may be considered given their correlation with disease severity in early literature
• Troponin, CK, BNP, d-dimer, and INR may also be considered to aid in clinical evaluation

Monitoring of vital signs

• Low threshold to call ICU for evaluation for patients with higher oxygen requirements (>6L NC/minute) or rapidly escalating oxygen requirements

Additional diagnostic studies

• See above under clinical manifestations for imaging guides; daily CXR is not recommended
• Order diagnostic studies only when clinically indicated, as supply chain impacts each phase of patient care and each test can increases exposure to additional hospital staff

Discharge Considerations

• When preparing for discharge, providers must consider the patient’s anticipated clinical stability, anticipated course after discharge, laboratory/virologic test guidance, symptom monitoring, and return precautions
• Safety and screening of the patient’s home environment, household contacts, use of congregate resources (e.g. dialysis) and travel precautions should also be reviewed when pertinent

Critical Care

• In addition to the body of evidence for the management of ARDS (summarized in the pulmonology section in ARDSNet Protocol), there are limited case series summarizing approaches that have been used at different centers for managing critically ill COVID-19 positive patients, including a summary of evidence-based approaches to the management of COVID-19 patients by UCSF clinicians here
• Application of ARDS management principles to the care of critically ill COVID-19 patients includes using the high PEEP ladder of the ARDSNet Protocol, early prone ventilation (at P/F ratios <150), conservative fluid strategies (aiming for a net fluid balance of 0.5–1.0 L per day or a CVP <4), and consideration of extracorporeal membrane oxygenation (ECMO) based on EOLIA criteria, among other approaches, are under investigation

References

1. Zhu N, Zhang D, Wang W, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med 2020; 382(8): 727-33.
2. Shi H, Han X, Jiang N, et al. Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. Lancet Infect Dis 2020.
3. Gautret P, Lagier JC, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents 2020: 105949.
4. de Wit E, Feldmann F, Cronin J, et al. Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection. Proc Natl Acad Sci U S A 2020; 117(12): 6771-6.
5. Cao B, Wang Y, Wen D, et al. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med 2020.
6. Russell CD, Millar JE, Baillie JK. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet 2020; 395(10223): 473-5.
7. Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q. Structural basis for the recognition of the SARS-CoV-2 by full-length human ACE2. Science 2020.
8. Fauci AS, Lane HC, Redfield RR. Covid-19 - Navigating the Uncharted. N Engl J Med 2020.
9. Gates B. Responding to Covid-19 - A Once-in-a-Century Pandemic? N Engl J Med 2020.
10. Matthay A, Aldrich M, Gotts J, Treatment for severe acute respiratory distress syndrome from COVID-19. Lancet, March 20, 2020.