The Patient: Initial Considerations and Brief Review of Clinical Findings

Although reports vary, the incubation period of COVID-19 averages about 5 days, and nearly all infected patients will exhibit symptoms by day 12.¹ In contrast to previous coronaviruses causing severe diseases such as SARS-CoV-1 (severe acute respiratory syndrome coronavirus 1) and MERS (Middle East respiratory syndrome), the asymptomatic and presymptomatic phases of COVID-19 are associated with the highest viral load.^2,3 Patients are more likely to be contagious in the asymptomatic and presymptomatic phases of COVID-19.^2,3 We propose that COVID-19 progresses from an asymptomatic phase to a symptomatic phase and then to an early pulmonary phase and, finally, to a late pulmonary phase in which symptomatology, laboratory parameters, and severity of the disease can be better understood employing this paradigm (Fig. 5.1). The following section is a brief overview of the clinical presentations of patients with COVID-19. Many of the clinical presentations that involve the cardiac, dermatologic, pulmonary, and gastrointestinal systems will be covered in detail in the ensuing chapters.

Presenting Symptoms

Although proportions of symptoms may differ depending on the geographic location, e.g., gastrointestinal symptoms seem to be more prominent in Western countries, the most common symptoms include fever, fatigue, dry cough, myalgias, chill, anosmia, and ageusia (Table 5.1).^4,5–9 In a small percentage of patients, anosmia and ageusia may be the only presenting symptoms.^10–12 Dyspnea develops in some patients within 5 to 8 days after the onset of symptoms.^4,6 Fever may be absent in 20% of patients; however, if patients require hospitalization, fever occurs in up to 89%.^4,6 In the majority of patients (80%), these symptoms are self-limiting and resolve by 7 to 10 days. Approximately 20% of patients progress to a pulmonary phase characterized by progressive dyspnea and progressive respiratory distress severe enough to require hospitalization; 5% of these patients develop advanced pulmonary phase associated with progressive hypoxemia, thereby increasing supplemental oxygen requirements, severe lung injury/pneumonia/respiratory failure, cytokine storm, and shock requiring intensive care admission.^4,13–15

Other symptoms: Chills, rhinorrhea, hemoptysis, rash

*Represented as proportion of patients will not add up to 100% as many patients have more than one symptom

Physical Examination

Physical findings on examination vary with the severity of disease and systemic involvement. Patients in the early symptomatic disease may present with a relatively benign physical exam such as mild temperature elevation, sore throat, upper respiratory tract symptoms, and normal vital signs.^6,16,17 It is important to note that although major findings are consistent with an upper and lower respiratory tract illness, distal organ system involvement, including cardiac, neurologic, gastrointestinal, and integumentary, is not uncommon.^6,13,17,18 As the disease progresses in severity, patients may present with high-grade fever, tachypnea, tachycardia, hemodynamic instability (hypertension or hypotension), clinical evidence of volume depletion, and evidence of respiratory distress such as wheezing, rales, or decreased breath sounds.^18–20 Patients with myocarditis may present with clinical evidence of congestive heart failure.²¹ The abdominal examination is usually benign despite abdominal pain, a common complaint in patients presenting with COVID-19.⁹ Once hypercapnia and hypoxemia have been excluded, a change in mental status or lethargy may be indicative of COVID-19-associated encephalitis.²² Patients with COVID-19-associated hypercoagulable state can present with deep vein thrombosis, arterial thrombosis, and stroke.^22–25 There are a multitude of skin lesions that may be present such as chilblain lesions on extremities, acral cyanosis, and maculopapular and vesicular rash.^26–28

Laboratory Findings

Several laboratory parameters are correlated with severity and clinical outcome. In contrast to their less severely ill counterparts, typical laboratory parameters of patients hospitalized with COVID-19 demonstrate marked dysfunction in innate immunity and adaptive immunity.^29–31 Understanding this imbalance has therapeutic implications, which will be covered in the ensuing chapters. Elevations in interleukin 6, serum ferritin, and C-reactive protein indicate an unabated innate immune response and hyperinflammation.^29,31,32 The presence of lymphopenia or an elevated neutrophil-to-lymphocyte ratio is indicative of a dysfunctional adaptive immunity mediated by cytokine-induced apoptosis of lymphocytes and possible direct cytopathic effects of viral infection.^30,32–36 Endothelial damage and dysfunction, elevations in fibrinogen and D-dimer, and abnormalities in coagulation parameters are common.^37,38 Approximately 57% of patients with COVID-19 have elevated activated partial thromboplastin time and accompanying thrombocytopenia.^39,40 Despite anticoagulation, up to 20% of patients develop thrombotic and thromboembolic events.^41,42 Recently, there have been COVID-19 case series reporting the presence of antiphospholipid antibodies.^39,42,43 Progressive hypoxemia elevations in alanine aminotransferase, lactate dehydrogenase, and troponin I are early markers of progressive organ dysfunction possibly mediated by unabated inflammation and microvascular thrombosis.^25,39,44