COVID-19 Clinical Presentation and Management

Basic Information

• Pathogen: SARS-CoV-2

• Disease: Coronavirus disease 2019 (COVID-19)

  • (+) ssRNA, large, enveloped beta-coronavirus
  • Zoonotic origin with mammalian sources including the bat, pangolin, or snake
  • SARS-CoV-2 spike (S) protein binds the ACE2 receptor and requires TMPRSS2 and furin proteases to facilitate host cell entry
  • viral particle entry via respiratory droplets

Pathogenesis

TLDR; SEE PATHOPHYSIOLOGY 1 PAGER HERE

Great resource: https://www.cell.com/immunity/fulltext/S1074-7613(20)30183-7

Overview

1. Infection of type II pneumocytes in the lung by SARS-CoV-2 particles
2. Impaired interferon response and cytolysis results in increased levels of inflammatory cytokines and chemokines in the circulation (IL-6, IL-8, TNF)
3. Vasodilation and increased vascular permeability
4. Edema and compression of alveoli
5. Decreased production of lung surfactant, reduced gas exchange → Acute Respiratory Distress Syndrome (ARDS)

ACE-2 Receptor See graphic here

• SARS-CoV-2 enters cells through the ACE2 receptor
  • Negative regulator of the renin-angiotensin-aldosterone system (RAAS)
  • Promotes vasodilation via conversion of ATII to angiotensin 1-7
  • Ubiquitously expressed by multiple organ tissues, with local regulatory function
    • Lung
    • Heart and vasculature
    • Kidney
    • Intestines
    • Liver
    • Brain
    • Heart and vasculature
    • ACE2 is also described to modulate β-cell activity in the pancreas.
• SARS-CoV-2 binds the ACE2 receptor, disabling the ACE2 signaling axis may explain
  • potential gendered differences in the mortality and susceptibility of male and female cases.
  • range of COVID-19 symptoms at onset, including headache, diarrhea, hepatic dysfunction, stroke, and hypertension.
  • major COVID-19-associated complications, where ACE2 is vital in its niches, including cardiac injury, gastrointestinal symptoms, endocrinopathy, and meningitis.

Immune Dysregulation in COVID-19

See Graphic on Hypercoagulation HERE

Great resource: https://www.cell.com/immunity/fulltext/S1074-7613(20)30183-7

Epidemiology

• R0 (no. of infections from 1 case) = 2.5-2.9
• Attack rate = 0.25%
• CFR (case fatality rate) = 1.3% (influenza CFR = 0.1%)
• Incubation time = 5.2 days (to 14 days)

Affected populations

• Pediatric patients (multisystem inflammatory syndrome in children [MIS-C]):
  • Kawasaki-like syndrome with fever, hypotension, GI symptoms, rash, myocarditis; respiratory symptoms may be absent
• Pregnant women
  • complications of the maternal/placental vasculature (e.g., microthrombi formation), preeclampsia
• Elderly patients
  • mortality in pts > 75 is 75x rate among 18-44-year-olds

Prevention

Control Strategies (WHO)

• Social distancing / quarantine
• Use of face masks
• Contact tracing and screening

Recommended Precautions

• Hand hygiene
  • soap/water for 20 sec when visibly soiled, before eating, and after restroom use
  • otherwise, alcohol-based hand rub and gloves
• Airborne precautions for aerosolizing procedures (intubation, suction, NIPPV)
• Droplet precautions (all else)

Symptoms

• Cough (76%), fever (98%), dyspnea (50%), myalgias or fatigue (44%), GI (10%)
• Presentation rates:
  • asymptomatic (1.2%)
  • mild to medium (80.9%)
  • severe (13.8%)
  • critical (4.7%) -- death (2.3%)

Differential Diagnosis

Source

Laboratory Assessment

Inflammatory Markers

• ↑ CRP, ferritin, D-dimer, PCT, LDH
• ↑ IL-6, IL-10, TNF-α

Liver Function Tests (LFTS)

• ↑ AST/ALT
• ↑ Total bilirubin

Basic metabolic panel (BMP)

• ↑ BUN / Cr

Complete blood count (CBC)

• ↓ lympho-/leukocytes
• ↑ neutrophil count & neutrophil-to-lymphocyte ratio

Imaging

CXR/CT

• Bilateral, multilobar involvement
• Ground glass opacities and consolidation
• CT should only be used when impacting management → CT is sensitive, but not specific

POCUS (Point-of-care ultrasound)

• B-lines, pleural lines, air bronchograms

Prognosis

Risk factors

• Age
• Cardiovascular, endocrine, liver and pulmonary disease
• CKD
• Obesity
• Cancer
• Residence in nursing homes/long-term care facilities

Independent Predictors of Clinical Severity

Great resource: https://www.medrxiv.org/content/10.1101/2020.05.28.20115758v1

• ↑ CRP, LDH, lymphocyte count, IL-6, TNF-α, D-dimer
• ↑ Neutrophil: lymphocyte ratio

Complications

• ARDS
• Sepsis
• AKI
• Transaminitis
• Venous thromboembolic events
• Cardiac (cardiomyopathy, HF, MI, arrhythmias)
• Empyema

COVID-19 calculators

• https://www.mdcalc.com/covid-19 includes calculators that:
  • Predict risk of critical illness in hospitalized patients
  • Need for intubation
  • Likelihood of coagulopathy

Management Strategy

Testing

• RT-PCR (order early - can take days; see testing criteria)
  • 66-80% sensitive; i.e. 20-34% false negative rate

Basic care

• Lung protective ventilation, proning, restrictive fluid management and management of organ failures
• SpO2 target ≥ 93%
• Oxygenation – HFNC, face mask, or non-invasive ventilation
• Systemic anticoagulation (see pathway INSERT LINK TO ANTICOAG PAGE HERE)

Mechanical ventilation

• Indicated by SaO2 < 93-96% + acute lung injury
• 7 P’s: PEEP, Paralysis, Prone positioning, Prostacyclins, Pleural evacuation, Peeing (diuresis), Peripheral oxygenation (ECMO)

Drugs / vaccines

• Remdesivir is the only FDA-approved drug (nucleotide analog, inhibits RNA-dependent RNA polymerase)