Clinical Review

Atypical Features of COVID-19: A Literature Review




Common reported neurologic symptoms include dizziness, headache, impaired consciousness, ataxia, and cerebrovascular events. In a cohort of 214 patients from Wuhan, China, 36.4% had some form of neurological insult.15 These symptoms were more common in those with severe illness (P = 0.02).15 Two interesting neurologic symptoms that have been described are anosmia (loss of smell) and ageusia (loss of taste), which are being found primarily in tandem. It is still unclear how many people with COVID-19 are experiencing these symptoms, but a report from Italy estimates 19.4% of 320 patients examined had chemosensory dysfunction.16 The aforementioned report from Wuhan, China, found that 5.1% had anosmia and 5.6% had ageusia.15 The presence of anosmia/ageusia in some patients suggests that SARS-CoV-2 may enter the central nervous system (CNS) through a retrograde neuronal route.15 In addition, a case report from Japan described a 24-year-old man who presented with meningitis/encephalitis and had SARS-CoV-2 RNA present in his cerebrospinal fluid, showing that SARS-CoV-2 can penetrate into the CNS.17

SARS-CoV-2 may also have an association with Guillain–Barré syndrome, as this condition was reported in 5 patients from 3 hospitals in Northern Italy.18 The symptoms of Guillain–Barré syndrome presented 5 to 10 days after the typical COVID-19 symptoms, and evolved over 36 hours to 4 days afterwards. Four of the 5 patients experienced flaccid tetraparesis or tetraplegia, and 3 required mechanical ventilation.18

Another possible cause of neurologic injury in COVID-19 is damage to endothelial cells in cerebral blood vessels, causing thrombus formation and possibly increasing the risk of acute ischemic stroke.15,19 Supporting this mechanism of injury, significantly lower platelet counts were noted in patients with CNS symptoms (P = 0.005).15 Other hematological impacts of COVID-19 have been reported, particularly hypercoagulability, as evidenced by elevated D-dimer levels.13,20 This hypercoagulable state is linked to overproduction of proinflammatory cytokines (cytokine storm), leading to dysregulation of coagulation pathways and reduced concentrations of anticoagulants, such as protein C, antithrombin III, and tissue factor pathway inhibitor.21


Cutaneous findings emerging in persons with COVID-19 demonstrate features of small-vessel and capillary occlusion, including erythematous skin eruptions and petechial rash. One report from Italy noted that 20.4% of patients with COVID-19 (n = 88) had a cutaneous finding, with a cutaneous manifestation developing in 8 at the onset of illness and in 10 following hospital admission.22 Fourteen patients had an erythematous rash, primarily on the trunk, with 3 patients having a diffuse urticarial appearing rash, and 1 patient developing vesicles.22 The severity of illness did not appear to correlate with the cutaneous manifestation, and the lesions healed within a few days.

One case report described a patient from Bangkok who was thought to be suffering from dengue fever, but was found to have SARS-CoV-2 infection. He initially presented with skin rash and petechiae, and later developed respiratory disease.23

Other dermatologic findings of COVID-19 resemble chilblains disease, colloquially referred to as “COVID toes.” Two women, 27 and 35 years old, presented to a dermatology clinic in Qatar with a chief complaint of skin rash, described as red-purple papules on the dorsal aspects of the fingers bilaterally.22 Both patients had an unremarkable medical and drug history, but recent travel to the United Kingdom dictated SARS-CoV-2 screening, which was positive.24 An Italian case report describes a 23-year-old man who tested positive for SARS-CoV-2 and had violaceous plaques on an erythematous background on his feet, without any lesions on his hands.25 Since chilblains is less common in the warmer months and these events correspond with the COVID-19 pandemic, SARS-CoV-2 infection is the suspected etiology. The pathophysiology of these lesions is unclear, and more research is needed. As more data become available, we may see cutaneous manifestations in patients with COVID-19 similar to those commonly reported with other viral infectious processes.


Of 138 patients hospitalized in Wuhan, China, for COVID-19, 34.8% presented with myalgia; the presence of myalgia does not appear to be correlated with an increased likelihood of ICU admission.6 Myalgia or arthralgia was also reported in 14.9% among the cohort of 1099 COVID-19 patients in China.13 These musculoskeletal symptoms are described among large muscle groups found in the extremities, trunk, and back, and should raise suspicion in patients who present with other signs and symptoms concerning for COVID-19.


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