SARS-CoV-2

Background

Microbiology

• Coronavirus related to SARS-CoV
• Virion consists of:
  • Spike glycoprotein (S), which appears to be an important virulence factor
    • Vaccines may target either the full protein or only its distal receptor binding domain
  • Membrane protein (M)
  • Nucleocapsid protein (N)
  • Hemagglutinin esterase (He)
  • Envelope protein (E)

Epidemiology

• Transmitted mostly by respiratory droplets, with some amount transmission via aerosols and little to no transmission via contact
• First cases detected Dec 2019 related to likely exposure in wet market in Wuhan, Hubei, China, and declared a pandemic in 2020
• Secondary household attack rate of 12-17%
• Possibility of animal reservoirs, including cats (possibly), dogs (unlikely), deer (probably)
  • Difficult to prove transmission to humans
  • Unlikely to contribute to household transmission, since human-to-human transmission is far more likely

Risk Factors for Mortality

• Greater age
• Male sex
• COPD
• Dyslipidemia
• Diabetes

Clinical Manifestations

• Incubation period 4 to 5 days (range 2 to 11 days), possibly as long as 14 days in some cases
• Main presenting symptoms were fever and cough, followed by myalgia, fatigue, headache, dyspnea
• Other symptoms include dyspnea, rhinorrhea, vomiting, diarrhea, anosmia/hyposmia
• Lymphopenia is common, as is hypoalbuminemia, elevated D-dimer, CRP, LDH, AST/ALT
• Viral load detectable before symptom onset and peaks around the time of symptom onset

Pregnancy

• Please refer to a living systematic review on the topic
• Slightly less reported fever and myalgias
• Slightly more ICU admissions and mechanical ventilation
  • Risk factors included age, obesity, hypertension, and diabetes
• With regards to the fetus, there were more preterm deliveries (6%) and more needed NICU admission (25%)

Severity

• Mild: no oxygen
• Moderate: supplemental oxygen
• Severe: non-invasive mechanical ventilation
• Critical: invasive mechanical ventilation

Bacterial Coinfection

• True coinfection is rare, detected in about 5% of patients1
  • See https://www.tarrn.org/covid for a living systematic review
• Most commonly Mycoplasma pneumonia, Pseudomonas aeruginosa, and Haemophilus influenzae
• May be at risk of post-infectious or secondary bacterial infections
• Also possibly need to consider Aspergillus fumigatus and even Pneumocystis jirovecii

Complications

• In critically ill patients:
  • ARDS (75%)
  • AKI (40%)
  • Thrombosis (10%)

Investigations

• CT chest imaging may show:2
  • Typical appearance:, classic for COVID-19
    • Peripheral, bilateral ground-glass opacity with out without consolidation or visible intralobular lines (crazy paving)
    • Multifocal rounded GGO with or without consolidation or crazy paving
    • Reverse halo sign or other findings of organizing pneumonia (later finding)
  • Indeterminate appearance:
    • Multifocal, diffuse, perihilar, or unilateral GGO with or without consolidation lacking a specific distribution and are non-rounded or non-peripheral
    • Few very small GGO with a non-rounded and non-peripheral distribution
  • Atypical appearance, which suggests unlikely to be COVID-19:
    • Isolated lobar or segmental consolidation without GGO
    • Discrete small nodules (centrilobular, tree-in-bud)
    • Lung cavitation
    • Smooth interlobular septal thickening with pleural effusion

Diagnosis

• PCR from NP swab
  • Highest sensitivity within 5 days of symptom onset, with decreasing sensitivity as the disease enters the immune-mediated phase
  • May be positive long after no longer infectious
• Diagnostic accuracy of PCR by sample site (below) has a lot of heterogeneity among the studies

	Sensitivity	Specificity
Upper Respiratory Samples
Oral	56	99
Nasal	76	100
NP	97	100
Nasal	95	100
Saliva	85	100
Mid-turbinate	100	100
Upper Versus Lower Tract
Upper respiratory tract	57	100
Lower respiratory tract	81	100
Single Versus Repeat Testing
Single test	71	100
Repeat testing	100	100

• Serology (IgM and IgG)
  • Total antibodies have poor sensitivity (51%) in first week, and increases to about 90% by week 3

Management

• For patients no requiring supplemental oxygen, the focus is on supportive care
  • Remdesivir 200 mg IV once followed by 100 mg IV daily for 2 more days may be used within 7 days of symptom onset who have at least one risk factor for disease progression (age ≥60 years, obesity, or other medical conditions)3
  • Consideration of monoclonal antibodies such as casirivimab-imdevimab (Regeneron), depending on the variant
    • Use in patients who are anti-spike protein seronegative and within 9 days of symptom onset
    • May reduce hospitalization of high risk patients (hypertension, diabetes, chronic lung disease, congestive heart failure, of immunodeficiency) with ARR of 2 to 3%
  • Paxlovid may be considered for patients at high risk of progressing to severe disease, within 5 days of symptom onset
    • Management of drug-drug interactions is available here
• For patients requiring supplemental oxygen or with oxygen saturation less than 94%:
  • Dexamethasone 6 mg PO/IV daily for 10 days, which has a mortality benefit
  • Remdesivir 200 mg IV once on day one followed by 100 mg PO daily for 5-10 days, which has not been shown to have a mortality benefit
  • Tocilizumab indicated if progressing despite dexamethasone, still requiring oxygen and CRP ≥75 mg/L, per RECOVERY trial
    • ARR for 28-day mortality of about 4%
    • If tocilizumab is unavailable, then baricitinib 4 mg p.o. daily for 14 days or until hospital discharge
  • If unvaccinated/no prior infection, declining clinically, and within 9 days of symptom onset, casirivimab-imdevimab (Regeneron) 8000 mg IV once
• Avoid hydroxychloroquine/chloroquine, lopinavir-ritonavir

Anticoagulation

• A multiplatform RCT combined ATTACC, REMAP-CAP, and ACTIV-4a looked at therapeutic anticoagulation (compared to prophylactic)
  • Therapeutic anticoagulation with heparin derivatives, using the LMWH typical for the hospital at DVT/PE treatment doses
  • Duration 14 days, or until discharge if before 14 days
  • Helpful in moderately ill patients, regardless of D-dimer value
  • Potentially harmful in severely or critically ill patients

Strongyloidiasis

• Patients should be screened per CATMAT guidelines and treated if appropriate
• For steroid exposure, 10 days of dexamethasone +/- tocilizumab is considered substantial risk
• See also Ivermectin treatment for Strongyloides infection in patients with COVID-19 from the CCDR
  

Prevention

Infection Prevention and Control

Healthcare Workers

• Awaiting results
  • If symptomatic, HCWs should be off work
  • If asymptomatic, HCWs may return to work while awaiting results, depending on the reason for testing and the staffing needs
• Positive but asymptomatic: in exceptional circumstances, may return to work early

Clearance

• Non-test based (preferred)
  • Asymptomatic: isolate for 10 days from swab
  • Mild to moderate symptoms in immunocompetent person: 10 days from onset of symptoms, as long as afebrile (without antipyretics) and clinically improving
  • Severe (i.e. ICU-level care) or immunocompromised: 20 days from onset of symptoms, as long as afebrile (without antipyretics) and clinically improving
    • Immunocompromise includes chemotherapy, untreated HIV with CD4 <200, primary immunodeficiency, prednisone 20 mg/day for 14 days, and other immunosuppressing medication
• Test based (alternative): 2 negative swabs at least 24 hours apart (if still positive, repeat in 3 to 4 days), as long as afebrile and clinically improving

Further Reading

• Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review. JAMA. doi: 10.1001/jama.2020.12839

Canadian Guidelines

• Ontario Science Table Clinical Practice Guideline Summary: Recommended Drugs and Biologics in Adult Patients with COVID-19
• BC COVID-19 Therapeutics Committee (CTC) and COVID-19 Therapeutics Review and Advisory Working Group (CTRAWG) Clinical Practice Guidance