Severe Acute Respiratory Syndrome—Coronavirus 2019 (SARS-CoV-2)

Essentials of Diagnosis

• Wide spectrum of symptoms

  • Asymptomatic in at least 20–35% of adults

  • Adults have upper respiratory tract illness with fever and cough most often when symptomatic

  • The clinical triad of cough, fever, and dyspnea is infrequent (< 15%)

  • Advanced pulmonary complications (pneumonia, acute respiratory distress syndrome [ARDS]) with fulminant disease

  • Mortality of 1–21% (varied by geographic area and strain)

• High predilection for the elderly, the immunocompromised, those with chronic diseases, those living in crowded conditions

General Considerations

• SARS-CoV-2 shows a higher rate of person-to-person spread than the 2003 SARS-CoV-1 virus

• Some COVID-19 strains from Western Europe have enhanced transmissibility as a function of a modified Spike protein

• Transmission

  • R₀ is the basic reproductive number signifying the number of persons infected by an infected individual

  • Calculations of R₀ for SARS-CoV-2 have varied but the true R₀ likely lies somewhere between 2 and 3

  • Presymptomatic spread probably accounts for a large number of cases, since the viral load is highest in the presymptomatic phase

  • The principal mode of transmission is likely respiratory droplets

• The incubation period for SARS-CoV-2 ranges from 2 to 24 days with an average of about 5 days

• A clinical risk score calculator to predict critical illness in hospitalized patients with COVID-19 called COVID-GRAM has been validated (http://118.126.104.170/)

• SARS-CoV-2 infection is particularly serious in the

  • Elderly

  • Those with comorbid conditions of immunocompromise (including post-organ transplant)

  • Those with chronic diseases (diabetes; obesity; hypertension; chronic heart, lung, or kidney disease; and prior stroke)

Symptoms and Signs

• Most infected individuals are asymptomatic

• Cough

• Fever

• Chills/rigors

• Myalgias

• Dyspnea (more common in severe cases)

• Less common symptoms include

  • Rhinitis

  • Pharyngitis

  • Abdominal symptoms, including nausea and diarrhea

  • Headaches

  • Anosmia

  • Ageusia

• Symptomatic disease in children is more likely to present with gastrointestinal symptoms and less likely to present with respiratory symptoms

• Severe COVID-19 likely occurs because of an intense and/or prolonged inflammatory reaction, often called a "cytokine storm"

Differential Diagnosis

• Seasonal influenza

• Pneumonia

Laboratory Findings

• Diagnosis is established using nucleic acid testing

• Hematologic findings include neutrophilia, absolute lymphopenia, and an increased neutrophil to lymphocyte ratio

• As disease advances, blood chemistry findings often include elevated liver biochemical tests, and total bilirubin

• Serum markers of systemic inflammation are increased in most patients with severe infection, including

  • Lactate dehydrogenase level

  • Ferritin

  • C-reactive protein

  • Procalcitonin

  • Interleukin 6 (IL-6)

• Coagulopathy

  • Identified by elevated von Willebrand factor (VWF) antigen, elevated D-dimer, and fibrin/fibrinogen degradation products

  • Prothrombin time, partial thromboplastin time, and platelet counts are usually unaffected initially

Imaging

• Chest radiographs and chest CT scans may be normal; nonspecific findings overlap with those of many other viral infections

• Later in the disease course, nonspecific diffuse ground glass opacities and multilobular infiltrates (which often progress to consolidation) become more common

• Chest ultrasonography, MRI, and PET/CT findings tend to confirm the CT findings of an evolving organizing pneumonia

• The WHO (https://www.who.int/publications-detail/clinical-management-of-covid-19), the NIH (https://www.covid19treatmentguidelines.nih.gov/whats-new/), and IDSA (https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/) have released guidance for the management of COVID-19 patients from screening to discharge

• The Pediatric Infectious Diseases Society has also published guidelines for management of SARS-CoV-2 infections in children (https://academic.oup.com/jpids/article/doi/10.1093/jpids/piaa045/5823622)

• VTE prophylaxis guidelines published by the American Society of Hematology are available at https://www.hematology.org/covid-19/covid-19-and-vte-anticoagulation

Complications

• Multiorgan failure

• ARDS

• Coagulopathy (eg, pulmonary emboli, thrombosis of renal vessels used for continuous renal replacement therapy)

• Acute kidney injury

• Fulminant myocarditis

• Neurologic complications: headaches; seizures; strokes; and more often, a loss of taste and smell (ageusia and anosmia)

• Acute musculoskeletal pain is reported in nearly 20%

• A hyperinflammatory syndrome akin to atypical Kawasaki disease, called multisystem inflammatory syndrome in children (MIS-C) in the United States and paediatric inflammatory multisystem syndrome-temporally associated with SARS-CoV-2 (PIMS-TS) in Europe

  • Noted in children (see Kawasaki syndrome)

  • Leading systems involved are gastrointestinal, cardiovascular, hematologic, mucocutaneous, and pulmonary

  • Central and peripheral nervous system findings are reported in children with this syndrome even in the absence of pulmonary disease, and such findings show a predilection for the corpus callosum

Prevention

• Frequent handwashing with soap and water for at least 20 seconds

• Avoiding touching the face

• Wearing a face covering

• Isolating cases (ie, removing infected patients from long-term living/care facilities, such as nursing homes, and transportation structures, such as cruise ships)

• Physical distancing is also an important practice for control of the disease

• Vaccines are under development

Prognosis

• Cardiac causes were responsible for most of the excess deaths in the New York outbreak

• Mortality among hospitalized SARS-CoV-2–infected patients correlates with levels of VWF antigen as well as levels of soluble thrombomodulin, suggesting that an endotheliopathy occurs in critically ill patients

When to Admit

• Progression to respiratory failure and ARDS can be rapid

• Any patient in a high-risk category for complications should be admitted for observation and placed under intensive care based on respiratory parameters