Diagnosis

COVID-19

Etiology

Cause

• ß-coronavirus (SARS-CoV-2)

Pathophysiology [avt][okt]

1. SARS-CoV 2 replicates mainly in the respiratory tract and the GI tract

2. Viral RNA can be present in peripheral blood in severely ill patients

3. Transmission occurs mainly through respiratory droplets and aerosols

4. May also be spread by touching a surface with the virus on it and then touching one’s mouth, nose, or eyes, but this is less common

5. Can be transmitted by asymptomatic infected individuals

6. Incubation period: Median 5.7 d, 99% of infections within 2–14 d

7. ~90% of infections are uncomplicated, oligosymptomatic or with moderate symptoms not leading to hospitalization

8. Early phase of the infection: viral replication results in direct virus-mediated tissue damage (pulmonary endotheliitis, perivascular inflammation, thrombi)

9. May also affect GI (diarrhea, nausea, vomiting, abdominal pain), liver injury, myocarditis, renal failure, and CNS

10. Late phase: the infected host cells trigger an immune response by recruiting T lymphocytes, monocytes, and neutrophils. Cytokines (TNF α, GM-CSF, IL-1, IL-6, IL-1β, IL-8, IL-12 and IFN-γ) are released

11. Severe COVID-19: cytokine storm is seen (over-activation of the immune system) --> Systemic inflammatory response.

Risk factors for severe disease [okt]

• Higher age ≥60, hypertension, obesity, diabetes, cardiovascular disease, cerebrovascular disease, chronic kidney disease, diabetes, chronic lung disease (asthma, COPD, interstitial lung disease, pulmonary embolism, pulmonary hypertension), cirrhosis, smoking, cancer, immunosuppression, pregnancy

Complications [avt][okt]

• Rates of hospitalization: 4-7%

• 25% of hospitalized patients require intensive care with a high rate of organ replacement therapy (75% invasive ventilation, 25% renal replacement therapy)

• COVID-19 was the 3rd leading cause of death in the USA in 2020 with ~375,000 deaths

• Long COVID [vee]

  • unable to fully recover and suffer persistent symptoms

Epidemiology

Incidence per 100.000 [avt]

Approach

• Nasopharyngeal swab for SARS-CoV-2 nucleic acid using a real-time PCR assay [okt]

  • specificity nearly 100%

• SARS-CoV-2 antigen tests: less sensitive but have a faster turnaround time than PCR

  • limitations in specificity and sensitivity

  • diagnosing SARS-CoV-2 infection with serologic testing is not recommended

• Blood test: complete blood count, renal and liver function testing, coagulation panel, SR, CRP, ferritin, lactate dehydrogenase, D-dimer, and procalcitonin

• Chest x-ray: bilateral multifocal alveolar opacities

• Lung ultrasound: pleural effusion

• CT: multifocal bilateral ground glass opacities with consolidation changes

Treatment

1. Supportive treatment: [okt][vee]

   • Oxygen: high-flow nasal cannula, noninvasive mechanical ventilation, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO)

   • Anticoagulation

2. Early phase: replication of the virus --> virus-mediated tissue damage

   • Antiviral medications to halt viral replication: Remdesivir, Ritonavir-boosted nirmatrelvir, molnupiravir, Tixagevimab 300 mg plus cilgavimab 300 mg

3. Late phase: dysregulated immune response --> systemic tissue damage

   • Immunomodulators in the later phase

   • Dexamethasone 6 mg IV or oral once daily for up to 10 days

   • Baricitinib (JAK Inhibitor) or tocilizumab (IL-6 Inhibitor)

   • Tofacitinib (po) and sarilumab (IV)

   • T Cell Therapy

   • Mesenchymal Stem Cell Therapy

4. Prophylaxis:

   • Tixagevimab 300 mg + cilgavimab 300 mg (anti-spike neutralizing antibodies)

   • Vaccination: mRNA vaccine (Pfizer-BioNTech, Moderna), Recombinant spike protein with matrix-M1 adjuvant vaccine NVX-CoV2373 (Novavax)

5. Long COVID: [vee]

   • symptomatic treatment, psychological support, occupational therapy, and physiotherapy

Differential diagnoses

Acute respiratory distress syndrome, Influenza, Myocardial infarction, Myocarditis, Pneumocystis jiroveci pneumonia, Pneumonia, Pulmonary embolism, Tuberculosis