Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2, COVID-19)

Epidemiology

China 2019-2020 Pandemic (NEJM, 2020) [MEDLINE]

Case Series of 1,099 COVID-19 Laboratory-Confirmed Hospitalized Cases
- 552 Hospitals in 30 Provinces
- Cases Reported Through January 29, 2020
Age
- Median Age: 47 y/o
Sex
- 58.1% of Cases were Male
Smoking History
- Only 14.5% of Cases were Former/Current Smokers
Coexisting Disorders: one of the following was present in only 23.7% of cases
- Cancer
- Cerebrovascular Disease
- Chronic Kidney Disease (CKD) (see Chronic Kidney Disease)
- Chronic Obstructive Pulmonary Disease (COPD) (see Chronic Obstructive Pulmonary Disease)
- Coronary Artery Disease (CAD) (see Coronary Artery Disease)
- Diabetes Mellitus (DM) (see Diabetes Mellitus)
- Hepatitis B Virus (HBV) (see Hepatitis B Virus)
- Hypertension (see Hypertension)
- Immunodeficiency
Contact with Wildlife
- Only 1.9% of Cases Had Contact with Wildlife
Geography
- 43.9% of Cases Lived in Wuhan
- Among Non-Residents of Wuhan, 72.3% of Cases Had Contact with Residents of Wuhan (Including 31.3% Who Had Visited the City)
Incubation Period: 4 days (interquartile range: 2-7 Days)

Washington State 2019-2020 Pandemic (NEJM, 2020) [MEDLINE]

Case Series of 24 Critically Ill Patients Requiring ICU Admission
- Community Transmission was First Detected in Washington State in February, 2020
Age
- Mean Age: 64 ± 18 y/o
Sex
- 63% of Patients were Male
xxxx
- XXXX

Microbiology

COVID019 is a 30 kb Single-Stranded RNA Virus
- XXXX

Diagnosis

Chest X-Ray (CXR) (see Chest X-Ray, [[Chest X-Ray]])

xxx

Chest CT (see Chest Computed Tomography, [[Chest Computed Tomography]])

xxxx

COVID-19 Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR)

xxxx

Clinical Manifestations

General Comments

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Gastrointestinal Manifestations

Diarrhea (see Diarrhea, [[Diarrhea]])
- Epidemiology
  - Diarrhea Occurred in 3.8% of Cases (Chinese 2019-2020 Pandemic: Case Series of 1,099 Hospitalized Patients) (NEJM, 2020) [MEDLINE]
Elevated Liver Function Tests (LFT’s)
- Epidemiology
  - Transaminitis Occurred in Approximately 21-22% of Cases (Chinese 2019-2020 Pandemic: Case Series of 1,099 Hospitalized Patients) (NEJM, 2020) [MEDLINE]
  - Hyperbilirubinemia Occurred in 10.5% of Cases (Chinese 2019-2020 Pandemic: Case Series of 1,099 Hospitalized Patients) (NEJM, 2020) [MEDLINE]
Nausea/Vomiting (see Nausea and Vomiting, [[Nausea and Vomiting]])
- Epidemiology
  - Nausea/Vomiting Occurred in Only 5% of Cases (Chinese 2019-2020 Pandemic: Case Series of 1,099 Hospitalized Patients) (NEJM, 2020) [MEDLINE]

Hematologic Manifestations

Hyperferritinemia (see Hyperferritinemia, [[Hyperferritinemia]])
Increased D-Dimer (see Increased D-Dimer, [[Increased D-Dimer]])
- Epidemiology
  - D-Dimer ≥0.5 mg/L was Observed in 46.4% of Cases (Chinese 2019-2020 Pandemic: Case Series of 1,099 Hospitalized Patients) (NEJM, 2020) [MEDLINE]
Leukopenia/Lymphocytopenia (see Leukopenia, [[Leukopenia]])
- Epidemiology
  - Lymphocytopenia was Present in 83.2% of Patients at Time of Admission (Chinese 2019-2020 Pandemic: Case Series of 1,099 Hospitalized Patients) (NEJM, 2020) [MEDLINE]
Thrombocytopenia (see Thrombocytopenia, [[Thrombocytopenia]])
- Epidemiology
  - Thrombocytopenia (<150k) Occurred in 36.2% of Cases (Chinese 2019-2020 Pandemic: Case Series of 1,099 Hospitalized Patients) (NEJM, 2020) [MEDLINE]

Neurologic Manifestations

Headache (see Headache, [[Headache]])
- Epidemiology
  - Headache Occurred in 13.6% of Cases (Chinese 2019-2020 Pandemic: Case Series of 1,099 Hospitalized Patients) (NEJM, 2020) [MEDLINE]

Pulmonary Manifestations

Upper Respiratory Infection (URI) Symptoms

Clinical
- Nasal Congestion Occurred in 4.8% of Cases (Chinese 2019-2020 Pandemic: Case Series of 1,099 Hospitalized Patients) (NEJM, 2020) [MEDLINE]
- Pharyngitis Congestion Occurred in 13.9% of Cases (Chinese 2019-2020 Pandemic: Case Series of 1,099 Hospitalized Patients) (NEJM, 2020) [MEDLINE]
- Pharyngitis Occurred in 8% of Cases (Seattle 2020 Pandemic: Case Series of 24 Critically Ill Patients Requiring ICU Admission) (NEJM, 2020) [MEDLINE]

Pneumonia/Acute Respiratory Distress Syndrome (ARDS) (see Pneumonia and Acute Respiratory Distress Syndrome)

Epidemiology
- Physician-Diagnosed Pneumonia Occurred in 91.1% of Cases (Chinese 2019-2020 Pandemic: Case Series of 1,099 Hospitalized Patients) (NEJM, 2020) [MEDLINE]
- ARDS Occurred in Only 3.4% of Cases (Chinese 2019-2020 Pandemic: Case Series of 1,099 Hospitalized Patients) (NEJM, 2020) [MEDLINE]
- XXX
Diagnosis
- Chest X-Ray (CXR) (see Chest X-Ray, [[Chest X-Ray]])
- Chest CT (see Chest Computed Tomography, [[Chest Computed Tomography]])
  - Ground Glass Infiltrates were the Most Common Radiologic Finding: Present in 56.4% of Cases (Chinese 2019-2020 Pandemic: Case Series of 1,099 Hospitalized Patients) (NEJM, 2020) [MEDLINE]
  - No Radiographic Abnormality was Found in 17.9% of Non-Severe Disease Cases and 2.9% of Severe Disease Cases (Chinese 2019-2020 Pandemic: Case Series of 1,099 Hospitalized Patients) (NEJM, 2020) [MEDLINE]
  - In a Series of 51 Patients with Chest CT and RT-PCR Assay Performed within the First 3 Days, Sensitivity of CT for COVID-19 Infection was 98%, as Compared to RT-PCR Sensitivity of 71% (p<0.001) (Radiology, 2020) [MEDLINE]
- COVID-19 Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR) (see xxxx, [[xxxx]])
  - In a Series of 51 Patients with Chest CT and RT-PCR Assay Performed within the First 3 Days, Sensitivity of CT for COVID-19 Infection was 98%, as Compared to RT-PCR Sensitivity of 71% (p<0.001) (Radiology, 2020) [MEDLINE]
Clinical
- Onset of Symptoms
  - In Seattle Case Series of 24 Critically Ill Patients Requiring ICU Admission, Symptom Onset Occurred 7 ± 4 Days Prior to Hospital Admission (NEJM, 2020) [MEDLINE]
- Cough (see Cough)
  - Cough Occurred in 67.8% of Cases (Chinese 2019-2020 Pandemic: Case Series of 1,099 Hospitalized Patients) (NEJM, 2020) [MEDLINE]
  - Cough Occurred in 88% of Cases (Seattle 2020 Pandemic: Case Series of 24 Critically Ill Patients Requiring ICU Admission) (NEJM, 2020) [MEDLINE]
- Sputum
  - Sputum Production Occurred in 33.7% of Cases (Chinese 2019-2020 Pandemic: Case Series of 1,099 Hospitalized Patients) (NEJM, 2020) [MEDLINE]
  - Sputum Occurred in 42% of Cases (Seattle 2020 Pandemic: Case Series of 24 Critically Ill Patients Requiring ICU Admission) (NEJM, 2020) [MEDLINE]
- Dyspnea (see Dyspnea)
  - Sputum Occurred in 18.7% of Cases (Chinese 2019-2020 Pandemic: Case Series of 1,099 Hospitalized Patients) (NEJM, 2020) [MEDLINE]
  - Dyspnea Occurred in 88% of Cases (Seattle 2020 Pandemic: Case Series of 24 Critically Ill Patients Requiring ICU Admission) (NEJM, 2020) [MEDLINE]
- Hemoptysis (see Hemoptysis)
  - Hemoptysis Occurred in Only 0.9% of Cases (Chinese 2019-2020 Pandemic: Case Series of 1,099 Hospitalized Patients) (NEJM, 2020) [MEDLINE]
Treatment
- Mechanical Ventilation
  - Invasive Mechanical Ventilation was Required in 2.3% of Cases (Chinese 2019-2020 Pandemic: Case Series of 1,099 Hospitalized Patients) (NEJM, 2020) [MEDLINE]

Renal Manifestations

Acute Kidney Injury (AKI) (see Acute Kidney Injury, [[Acute Kidney Injury]])
- Epidemiology
  - AKI Occurred in Only 0.5% of Cases (Chinese 2019-2020 Pandemic: Case Series of 1,099 Hospitalized Patients) (NEJM, 2020) [MEDLINE]

Rheumatologic Manifestations

Arthralgias/Myalgias
- Epidemiology
  - Arthralgias/Myalgias Occurred in 14.9% of Cases (Chinese 2019-2020 Pandemic: Case Series of 1,099 Hospitalized Patients) (NEJM, 2020) [MEDLINE]
Elevated Creatine Kinase (CK) (see xxxx)
- Epidemiology
  - Elevated Creatine Kinase (≥200 U/L) Occurred in 13.7% of Cases (Chinese 2019-2020 Pandemic: Case Series of 1,099 Hospitalized Patients) (NEJM, 2020) [MEDLINE]

Other Manifestations

Fatigue (see Fatigue)
- Epidemiology
  - Fatigue Occurred in 38.1% of Cases (Chinese 2019-2020 Pandemic: Case Series of 1,099 Hospitalized Patients) (NEJM, 2020) [MEDLINE]
Fever (see Fever, [[Fever]])
- Epidemiology
  - Fever Occurred in 43.8% of Cases at Time Of Admission (Chinese 2019-2020 Pandemic: Case Series of 1,099 Hospitalized Patients) [MEDLINE]
    - Only 21.7% of Fevers were ≥38.1 Degrees C
  - Fever Occurred in 88.7% of Cases During Hospitalization (Chinese 2019-2020 Pandemic: Case Series of 1,099 Hospitalized Patients) [MEDLINE]
    - 57.2% of Fevers were ≥38.1 Degrees C
  - Fever Occurred in XXXX% of Cases (Seattle 2020 Pandemic: Case Series of 24 Critically Ill Patients Requiring ICU Admission) (NEJM, 2020) [MEDLINE]
Chills (see xxxx)
- Epidemiology
  - Chills Occurred in 11.5 % of Cases (Chinese 2019-2020 Pandemic: Case Series of 1,099 Hospitalized Patients) [MEDLINE]
Elevated Procalcitonin (see xxxx)
- Epidemiology
  - Elevated Procalcitonin (≥0.5 ng/mL) Occurred in 5.5 % of Cases (Chinese 2019-2020 Pandemic: Case Series of 1,099 Hospitalized Patients) [MEDLINE]
Increased C-Reactive Protein (CRP) (see Increased C-Reactive Protein, [[Increased C-Reactive Protein]])
Increased IL-6 (see xxxx, [[xxxx]])
Increased Serum Lactate Dehydrogenase (LDH) (see xxxx, [[xxxx]])
Septic Shock (see Septic Shock, [[Septic Shock]])
- Epidemiology
  - Septic Shock Occurred in Only 1.1% of Cases (Chinese 2019-2020 Pandemic: Case Series of 1,099 Hospitalized Patients) (NEJM, 2020) [MEDLINE]

Treatment

Respiratory Support

xxxx

Post-Exposure Prophylaxis

Clinical Efficacy
- XXXX

Pharmacologic Therapy

Remdesivir (XXX) (see Remdesivir, [[Remdesivir]])

Manufactured by Gilead Pharmaceuticals
- Currently in Trials
Administration
- Day 1 Dose: 200 mg IV
- Day 2-10 Dose: 100 mg qday
Clinical Efficacy
- XXXX

Lopinavir–Ritonavir (Kaletra) (see Lopinavir–Ritonavir, [[Lopinavir–Ritonavir]])

History
- Originally Formulated to Treat Human Immunodeficiency Virus (HIV) (see Human Immunodeficiency Virus, [[Human Immunodeficiency Virus]])
Pharmacology
- SARS-CoV-2 Protease Inhibition
Administration
- XXX
Clinical Efficacy
- Randomized Controlled Trial of Lopinavir–Ritonavir in SARS-COV-2 (COVID-19) (NEJM, 2020) [MEDLINE]
  - No Clinical Benefit

Chloroquine Phosphate (see Chloroquine, [[Chloroquine]])

Administration
- XXXX
Contraindications
- Prolonged Q-T Syndrome (see Torsade, [[Torsade]])
Adverse Effects
- Hepatotoxicity
Clinical Efficacy
- Systematic Review of Chloroquine for COVID-19 (J Crit Care, 2020) [MEDLINE]
  - Chloroquine seems to be effective in limiting the replication of SARS-CoV-2 (virus causing COVID-19) in vitro
- In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) (Clin Infect Dis, 2020) [MEDLINE]
  - Hydroxychloroquine was found to be more potent than chloroquine to inhibit SARS-CoV-2 in vitro

Hydroxychloroquine (Plaquenil) (see Hydroxychloroquine, [[Hydroxychloroquine]])

Administration
- XXXX
Contraindications
- Congestive Heart Failure (CHF) (see Congestive Heart Failure, [[Congestive Heart Failure]])
- Prolonged Q-T Syndrome (see Torsade, [[Torsade]])
Adverse Effects
- Cardiotoxicity
Clinical Efficacy
- In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) (Clin Infect Dis, 2020) [MEDLINE]
  - Hydroxychloroquine was found to be more potent than chloroquine to inhibit SARS-CoV-2 in vitro

Teicoplanin (XXX) (see Teicoplanin, [[Teicoplanin]])

Clinical Efficacy
- XXXX

Tocilizumab (Actemra) (see Tocilizumab, [[Tocilizumab]])

Pharmacology
- XXXX
Administration
- XXX
Clinical Efficacy
- XXX

Favipiravir (Avigan) (see Favipiravir, [[Favipiravir]])

Pharmacology
- Inhibition of Viral RNA-Dependent RNA Polymerase
Administration
- XXX
Clinical Efficacy
- XXX

Sarilumab (Kevzara) (see Sarilumab, [[Sarilumab]])

Pharmacology
- XXXX
Administration
- XXX
Clinical Efficacy
- XXX

Corticosteroids (see Corticosteroids, [[Corticosteroids]])

No Efficacy

Intravenous Immunoglobulin (IVIG) (see Intravenous Immunoglobulin, [[Intravenous Immunoglobulin]])

Unclear Efficacy

Avoidance of Nonsteroidal Anti-Inflammatory Drugs (NSAID’s) (see Nonsteroidal Anti-Inflammatory Drugs, [[Nonsteroidal Anti-Inflammatory Drugs]])

xxxx

Avoidance of Angiotensin Converting Enzyme Inhibitors (ACE-I) (see Angiotensin Converting Enzyme Inhibitors, [[Angiotensin Converting Enzyme Inhibitors]])

xxxx

Anticoagulation

xxx

Prognosis

Clinical Features in the 2019-2020 Chinese Pandemic (NEJM, 2020) [MEDLINE]
- Primary Composite Endpoint of Admission to the Intensive Care Unit, Use of Mechanical Ventilation, or Death Occurred in 6.1% of Cases
  - Required ICU Admission: 5% of cases
  - Required Invasive Mechanical: 2.3% of cases
  - Mortality Rate: 1.4%
- Median Hospital Length of Stay: 12 days (Interquartile Range: 10-14 days)

References

Epidemiology

Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): Facts and myths. J Microbiol Immunol Infect. 2020 Mar 4. pii: S1684-1182(20)30040-2. doi: 10.1016/j.jmii.2020.02.012 [MEDLINE]
The COVID-19 epidemic. Trop Med Int Health. 2020 Mar;25(3):278-280. doi: 10.1111/tmi.13383 [MEDLINE]
Understanding of COVID-19 based on current evidence. J Med Virol. 2020 Feb 25. doi: 10.1002/jmv.25722 [MEDLINE]
Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. N Engl J Med. 2020 Mar 26;382(13):1199-1207. doi: 10.1056/NEJMoa2001316 [MEDLINE]

Diagnosis

Sensitivity of Chest CT for COVID-19: Comparison to RT-PCR. Radiology. 2020 Feb 19:200432. doi: 10.1148/radiol.2020200432 [MEDLINE]

Clinical

Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Feb 28. doi: 10.1056/NEJMoa2002032 [MEDLINE]
Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020 Feb 24. doi: 10.1001/jama.2020.2648 [MEDLINE]
Presumed Asymptomatic Carrier Transmission of COVID-19. JAMA. 2020 Feb 21. doi: 10.1001/jama.2020.2565 [MEDLINE]
Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020 Feb 18. pii: S2213-2600(20)30076-X. doi: 10.1016/S2213-2600(20)30076-X [MEDLINE]
Covid-19 in Critically Ill Patients in the Seattle Region – Case Series. N Engl J Med. 2020 Mar 30. doi: 10.1056/NEJMoa2004500 [MEDLINE]
Characteristics and Outcomes of 21 Critically Ill Patients With COVID-19 in Washington State. JAMA. 2020 Mar 19. doi: 10.1001/jama.2020.4326 [MEDLINE]
Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med. 2020 Mar 13. doi: 10.1001/jamainternmed.2020.0994 [MEDLINE]
Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore. JAMA. 2020 Mar 3. doi: 10.1001/jama.2020.3204 [MEDLINE]
Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020 Feb 15;395(10223):507-513. doi: 10.1016/S0140-6736(20)30211-7 [MEDLINE]
Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062. doi: 10.1016/S0140-6736(20)30566-3 [MEDLINE]
WHO COVID-19 Report [LINK]

Treatment

A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020 Mar 18. doi: 10.1056/NEJMoa2001282 [MEDLINE]
Teicoplanin: an alternative drug for the treatment of coronavirus COVID-19? Int J Antimicrob Agents. 2020 Mar 13:105944. doi: 10.1016/j.ijantimicag.2020.105944 [MEDLINE]
A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19. J Crit Care. 2020 Mar 10. pii: S0883-9441(20)30390-7. doi: 10.1016/j.jcrc.2020.03.005 [MEDLINE]
New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19? Int J Antimicrob Agents. 2020 Mar 11:105938. doi: 10.1016/j.ijantimicag.2020.105938 [MEDLINE]
In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020 Mar 9. pii: ciaa237. doi: 10.1093/cid/ciaa237 [MEDLINE]
Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020 Mar;30(3):269-271. doi: 10.1038/s41422-020-0282-0 [MEDLINE]
Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. [MEDLINE]
Of chloroquine and COVID-19. Antiviral Res. 2020 Mar 5;177:104762. doi: 10.1016/j.antiviral.2020.104762 [MEDLINE]
COVID-19: combining antiviral and anti-inflammatory treatments. Lancet Infect Dis. 2020 Feb 27. pii: S1473-3099(20)30132-8. doi: 10.1016/S1473-3099(20)30132-8 [MEDLINE]

Prognosis

Coronavirus covid-19 has killed more people than SARS and MERS combined, despite lower case fatality rate. BMJ. 2020 Feb 18;368:m641. doi: 10.1136/bmj.m641 [MEDLINE]