COVID-19: Virology, Clinical Disease, and Epidemiology

COVID-19: Virology, Clinical Disease, and Epidemiology Theresa Madaline, MD Healthcare Epidemiologist Montefiore Health System June 24, 2020 1

Coronaviruses and COVID-19 

Coronaviruses  Named for the crown-like glycoprotein spikes on their surface  Large genomes (26.4–31.7 kb)  Seven known types range from common cold to severe disease    

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Four common human coronaviruses: 229E, NL63, OC43, and HKU1 Severe Acute Respiratory Syndrome (SARS-CoV) Middle East Respiratory Syndrome (MERS-CoV) COVID-19 (SARS-CoV-2)

SARS-CoV-2 Virology    

Enveloped, +single stranded RNA virus with nucleocapsid Envelope bears club-shaped glycoprotein projections Spike protein binds to ACE2 receptor to enter cells using TMPRSS2 protease 3 ACE2 expressed on human endothelial cells (oral and nasal mucosa, nasopharynx, lung, stomach, small intestine, colon, skin, lymph nodes, thymus, bone marrow, spleen, liver, kidney, and brain, arterial and venous endothelial cells and arterial smooth muscle)  Replicates using viral RNA-dependent RNA polymerase  Released by budding from cell surface

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https://www.physio-pedia.com/Coronavirus_Disease_(COVID-19)#cite_note-1; Hafeez et al. Eurasian J Medicine and Oncology. 2020: 4(2): 116-125; Sohrabi et al. Int J Surg. 2020 Feb 26; Mousavizadeh and Ghasemi J Micro, Imm and Inf. 2020 Mar 31.

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Clinical Symptoms of COVID-19 Nausea or vomiting

Shortness of breath or Difficulty breathing

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Muscle or body aches or fatigue

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3 Cough or Sore throat

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Diarrhea

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Clinical symptoms of COVID-19

Wang et al, JAMA 2020 February 7; https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html;

New loss of taste or smell Congestion or Runny nose

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Headache

Clinical Symptoms of COVID-19  Asymptomatic in up to 80%  Symptomatic  ~80% mild or moderate disease (including without pneumonia and mild pneumonia)  14% severe disease, including acute kidney injury, liver injury  5% critical illness, including rhabdomyolysis, myocarditis, cytokine release syndrome, ARDS, shock

 Some with mild symptoms initially have acute deterioration median 1 week after symptom onset  In those with risk factors for severe disease close monitoring for clinical progression is warranted Wu et al, JAMA 2020 February 24; Huang et al, Lancet 2020;395:497-506; Wu et al, JAMA Intern Med 2020 March 13; Guo et al, JAMA Cardiol 2020 March 27; Bhatraju et al, N Engl J Med, DOI: 10.1056/NEJMoa200500; Mehta et al, Lancet 2020;395:1033;

Clinical Symptoms of COVID-19

Berlin, Gulick, Martinez, N Engl J Med 2020 May 15, DOI: 10.1056/NEJMcp2009575

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Severe Disease Risk Factors Diabetes

Cancer/Transplant AIDS/Immunosuppressives Hypertension

Cardiovascular disease

High Risk Populations

Older age (over 65)

Chronic respiratory & lungs disease Obesity

WHO. Coronavirus disease 2019 (COVID-19): situation report, 51; Huang, et al Lancet 2020; Wu JAMA Intern Med 2020; Zhou. Lancet 2020

Lab and Imaging Abnormalities  In hospitalized patients  Lymphopenia  Elevated D-dimer, lactate dehydrogenase, C-reactive protein, ferritin, fibrinogen, and IL-6  Procalcitonin typically normal

 Associated with poor outcomes  Neutrophilia, lymphopenia, prolonged prothrombin time, and elevated liver enzymes, lactate dehydrogenase, D-dimer, interleukin-6, C-reactive protein, and procalcitonin

 Imaging: typically ground-glass opacifications or consolidation on CXR or ultrasound; CAT Scan discouraged Wang D et al, JAMA 2020 February 7; Zhou et al, Lancet 2020; Bernheim et al, Radiology 2020

Diagnosis  Clinically in high incidence setting and mild illness  SARS-CoV-2 by polymerase-chain-reaction (PCR) of nasopharyngeal (NP) swab  Early after symptom onset, NP PCR sensitivity ~60-80%  False negatives • Repeat testing if consistent symptoms, active community transmission, and especially with moderate-severe disease

 Alternatives  Oropharyngeal PCR  Anterior nares PCR acceptable; may facilitate home-based testing and reduce health care worker exposure  Antigen  Antibody assays FIND. SARS-COV-2 diagnostic pipeline. 2020 (https://www.finddx.org/covid-19/pipeline/. opens in new tab); Babiker A. SARS-CoV-2 testing. Am J Clin Pathol 2020 March 30; CDC. Interim guidelines for collecting, handling, and testing clinical specimens from persons for coronavirus disease 2019. 2020 (https://www.cdc.gov/coronavirus/2019-ncov/lab/guidelines-clinical-specimens.html. opens in new tab). Food and Drug Administration. FAQs on diagnostic testing for SARS-CoV-2. 2020 (https://www.fda.gov/medical-devices/emergency-situations-medical-devices/faqs-diagnostic-testing-sars-cov-2. opens in new tab).

Severity Staging  Moderate  SpO2 >94% on room air, without tachypnea

 Severe  Tachypnea (respiratory rate, ≥30 breaths per minute)  Hypoxemia (SpO2, ≤93%; ratio of partial pressure of arterial oxygen to fraction of inspired oxygen, <300)  Lung infiltrates (>50% of lung field involved)  Need for O2 by nasal cannula, non-rebreather mask, high-flow, non-invasive ventilation

 Critical     

Mechanical ventilation or ECMO Septic shock ARDS Multisystem failure Pressor-dependent

Wu et al, JAMA 2020 February 24.

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Complications  Thrombosis

 Pulmonary emboli and deep vein thromboses  Myocardial infarction (heart attack)  Cerebrovascular accident (stroke)

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Renal failure Arrhythmias and sudden cardiac arrest Neurologic changes and encephalopathy Cytokine storm Pulmonary fibrosis and injury Healthcare-associated conditions due to prolonged ICU care

https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html, TCTMD

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Pediatric Multi-system Inflammatory Syndrome temporally associated with COVID-19 (PMIS-C)  Inflammatory syndrome associated with COVID-19 in children  Distinct from other inflammatory syndromes like Kawasaki disease  Fever PLUS hospitalization PLUS organ dysfunction OR rash, conjunctivitis, GI symptoms or mucous membrane involvement  Inflammatory abnormalities on laboratory testing  Evidence of COVID-19 by approved laboratory test or epidemiologic link to COVID-19  PMIS-C in New York  Predominantly school-aged children  71% ICU, 19% intubation, 3 fatalities (5-18 year old age grouping)  87% positive on any testing for SARS-CoV-2 or antibodies, 14% on both NYSDOH, CBSNews

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COVID-19 Epidemiology

Current Epidemiology: Global Pandemic

https://coronavirus.jhu.edu/map.html

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Estimated Ro • Reproductive value • Early stage calculated 2 and 3.5 • Indicate one patient could transmit 2 to 3 people

• Value higher than SARS & MERS • Infectivity peaks early

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Host of virus • Link to wild animal markets

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• SARS & MERS intermediate host (palm civets & dromedary camels respectively) • SARS-Cov-2 intermediate hosts unclear (pangolins?)

Wang Y, Wang Y, Chen Y, Qin Q. Unique epidemiological and clinical features of the emerging 2019 novel coronavirus pneumonia (COVID‐19) implicate special control measures. Journal of medical virology. 2020 Jun;92(6):568-76.

SARS-CoV-2 Transmission: Human to Human Aerosol transmission

Respiratory droplets

Contact & fomites

Nosocomial transmission Five

Fecal-oral transmission

Zoonotic transmission

Wang Y, Wang Y, Chen Y, Qin Q. Unique epidemiological and clinical features of the emerging 2019 novel coronavirus pneumonia (COVIDâ&#x20AC;?19) implicate special control measures. Journal of medical virology. 2020 Jun;92(6):568-76.

Median incubation period • Exposure to symptoms: 4-5 days • 97.5% of those symptomatic will have symptoms within 11.5 days12

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Case fatality rate

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• Large variation based on case series and severity • 1-3% • 40-80% if mechanically ventilated

Lauer SA, Grantz KH, Bi Q, et al. The incubation period of coronavirus disease 2019 (COVID-19) from publicly reported confirmed cases: estimation and application. Ann Intern Med 2020 March 10 (Epub ahead of print).

SARS-CoV-2 Prevention and Control in the Community Mask wearing Hand hygiene

Isolation

COVID Prevention

Social distancing

Tracing

Testing Nature

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SARS-CoV-2 Prevention and Control in Healthcare Facilities

Early identification

Engineering controls

Transmission based precautions

Isolation

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Barriers to Effective Control  Economic impact of social distancing  Global shortages of PPE and other critical medical supplies in the setting of sharp increases in demand  Autonomy of specific states/regions leading to variation in adherence to public health recommendations  Political pressure  International commerce and travel  Socioeconomic status  Population density and housing 19

Thank You

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