Extrapulmonary Clinical Manifestations in COVID-19 Patients

Abstract

COVID-19 manifestations in symptomatic patients can be in the form of pneumonia, acute respiratory syndrome, and multiple organ dysfunction as well. Renal complications, gastrointestinal dysfunctions, endocrine system disorders, myocardial dysfunction and arrhythmia, neurological dysfunctions, dermatological symptoms, hematological manifestations, and thromboinflammation are among the reported extrapulmonary complications. Moreover, the presence of coagulopathy, excessive and dysregulated immune responses, and autoimmunity by COVID-19 patients is considerable. The pathogenesis of infection entails the entry of the virus via receptors on cells, principally angiotensin-converting enzyme 2 receptors. Direct virus damage coupled with indirect effects of viral infection including thromboinflammation, dysfunction of the immune system, and dysregulation of the renin-angiotensin system leads to multiple organ failure. This review outlines the extrapulmonary organ-specific complications and their pathophysiology and epidemiology.

Figure 1.

Angiotensin-converting enzyme 2 (ACE2) expressing cells of various organs. These data are provided from genotype-tissue expression (GTEx) project, as preprocessed values; these GTEx values are directly used in the below formula in lieu of the number of mapped reads and gene length. ACTB = beta-actin; TPM = transcripts per million.

Figure 2.

Extrapulmonary manifestations of SARS-CoV-2. Although COVID-19 is principally a respiratory disease, according to the studies, SARS-CoV-2 can infect different body sites through targeting angiotensin-converting enzyme 2 receptors, so the various infected organs manifest individual symptoms.

Figure 3.

Mechanism of liver injury caused by COVID-19. SARS-CoV-2 infection may lead to liver injury through different mechanisms including direct viral toxicity, SARS-CoV-2–induced cytokine storm SIRS and increased right atrial pressure and impeding venous return effect which result in liver damage. These liver injuries can be detected by abnormal levels of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, and free fatty acids according to serum analysis.

Figure 4.

Endocrinological manifestations of SARS-CoV-2. Endocrine disorders such as acute diabetes, type 2 diabetes hyperglycemia, thyrotoxicosis and secondary adrenal insufficiency, and acute adrenal insufficiency are accounted for COVID-19 manifestations.