Clinical Review

Atypical Features of COVID-19: A Literature Review




In a report of 138 Chinese patients hospitalized for COVID-19, 36 required ICU admission: 44.4% of these had arrhythmias and 22.2% had developed acute cardiac injury.6 In addition, the cardiac cell injury biomarker troponin I was more likely to be elevated in ICU patients.6 A study of 21 patients admitted to the ICU in Washington State found elevated levels of brain natriuretic peptide.7 These biomarkers reflect the presence of myocardial stress, but do not necessarily indicate direct myocardial infection. Case reports of fulminant myocarditis in those with COVID-19 have begun to surface, however.8,9 An examination of 68 deaths in persons with COVID-19 concluded that 7% were caused by myocarditis with circulatory failure.10

The pathophysiology of myocardial injury in COVID-19 is likely multifactorial. This includes increased inflammatory mediators, hypoxemia, and metabolic changes that can directly damage myocardial tissue. These factors can also exacerbate comorbid conditions, such as coronary artery disease, leading to ischemia and dysfunction of preexisting electrical conduction abnormalities. However, pathologic evidence of myocarditis and the presence of the ACE2 receptor, which may be a mediator of cardiac function, on cardiac muscle cells suggest that SARS-CoV-2 is capable of directly infecting and damaging myocardial cells. Other proposed mechanisms include infection-mediated downregulation of ACE2, causing cardiac dysfunction, or thrombus formation.11 Although respiratory failure is the most common source of advanced illness in COVID-19 patients, myocarditis and arrhythmias can be life-threatening manifestations of the disease.


As noted, ACE2 is expressed in the GI tract. In 73 patients hospitalized for COVID-19, 53.4% tested positive for SARS-CoV-2 RNA in stool, and 23.4% continued to have RNA-positive stool samples even after their respiratory samples tested negative.12 These findings suggest the potential for SARS-CoV-2 to spread through fecal-oral transmission in those who are asymptomatic, pre-symptomatic, or symptomatic. This mode of transmission has yet to be determined conclusively, and more research is needed. However, GI symptoms have been reported in persons with COVID-19. Among 138 hospitalized patients, 10.1% had complaints of diarrhea and nausea and 3.6% reported vomiting.6 Those who reported nausea and diarrhea noted that they developed these symptoms 1 to 2 days before they developed fever.6 Also, among a cohort of 1099 Chinese patients with COVID-19, 3.8% complained of diarrhea.13 Although diarrhea does not occur in a majority of patients, GI complaints, such as nausea, vomiting, or diarrhea, should raise clinical suspicion for COVID-19, and in known areas of active transmission, testing of patients with GI symptoms is likely warranted.


Ocular manifestations of COVID-19 are now being described, and should be taken into consideration when examining a patient. In a study of 38 patients with COVID-19 from Hubei province, China, 31.6% had ocular findings consistent with conjunctivitis, including conjunctival hyperemia, chemosis, epiphora, and increased ocular secretions.14 SARS-CoV-2 was detected in conjunctival and nasopharyngeal samples in 2 patients from this cohort. Conjunctival congestion was reported in a cohort of 1099 patients with COVID-19 treated at multiple centers throughout China, but at a much lower incidence, approximately 0.8%.13 Because SARS-CoV-2 can cause conjunctival disease and has been detected in samples from the external surface of the eye, it appears the virus is transmissible from tears or contact with the eye itself.

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