The novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was first emerged in December 2019 in Wuhan, China, and has become a pandemic of coronavirus disease (COVID-19), posing a global public health emergency. It has been observed that SARS-CoV-2, after SARS-CoV-1 and the Middle East respiratory syndrome-CoV (MERS-CoV) is the third highly pathogenic betacoronavirus, which has infected over 4,137,190 people and caused about 285,760 deaths globally. Owing to new emergence, the first source of origin, high transmission and mechanisms of severity of SARS-CoV-2 in humans are still debatable, however, recent data has established its close similarity (~96% identity) with bat SARS-like coronaviruses (bat-SL-CoV) RNA sequences. The SARS-CoV-2 genome is a single-strand positive-sense RNA (∼30 kb) with 5′-cap and 3′-poly(A) tail, and includes 12 open-reading frames that translate into various structural, nonstructural and accessory proteins, required for its life cycle and pathogenesis. Among these, the viral structural ‘spike/S’ protein’s C-terminal structural subunit ‘S1’ binds to the human cell-receptor angiotensin converting enzyme-2 (ACE2) whereas the ‘S2’ subunit is needed for cell membrane fusion.

SARS-CoV-2 has the incubation period of 2–14 days and the patient presents with symptoms including fever, cough, headache and breathlessness, resulting in mild pneumonia to severe illness and death. Besides, few patients may also show symptoms like rashes on toes, discoloration of skin, dizziness, fizzing, burning sensation and loss of taste or smell. Evidences suggest that higher mortality can be seen in COVID-19 patients with older age or with pre-existing chronic conditions like respiratory, cardiac, renal and hepatic disorders. 

Evidence based observations have revealed that SARS-CoV-2 is associated with mild-to-moderate liver injury as evaluated by elevated serum aminotransferases (ALT/AST), bilirubin, hypoproteinemia and prothrombin time prolongation, along with liver histopathology. A study showed that single-cell RNA sequencing data from two distinct cohorts of COVID-19 patients showed increased expression of ACE-2 receptor in cholangiocytes (59.7%) in comparison to hepatocytes (2.6%), suggestive of the fact that SARS-CoV-2 might influence intrahepatic bile ducts. Findings showed that few patients with COVID-19 cases exhibited mild derangement of liver function, patients with different periods of symptoms did not reveal that these patients were later related to greater liver function derangement. However, the postmortem liver biopsy in a COVID-19 case showed only microvesicular steatosis. A trial also divulged that COVID-19 patients who had digestive issues before respiratory problems were associated with a higher risk of mortality in contrast to those without digestive symptoms.

Liver dysfunction is reported to be accompanied with greater activation of coagulative and fibrinolytic pathways along with altered platelets, neutrophil and lymphocytes profiles in severe cases of COVID-19. Furthermore, chronic liver disease patients with reduced immunity attributed to classical hepatitis viruses (HBV, HCV, HDV and HEV) or other hepatotropic viruses (HGV, GBV, TTV and SENV) infection or nonalcoholic fatty liver disease/nonalcoholic steatohepatitis are more vulnerable to COVID-19, and often show worse outcomes from acute respiratory distress syndrome in contrast to other critically ill patients.

The main pathogenesis of hepatic pathogenesis involves induced elevations of liver function biomarkers by other respiratory viruses, which are associated with liver inflammation or hepatocytes damage as a result of interaction of cytotoxic T-cells and Kupffer cells. Thus, it has been postulated that SARS-CoV-2 can cause viral hepatitis while inducing a dysregulated innate immune response. SARS-CoV-2-encoded nonstructural and accessory proteins have the potential to modify induction of cellular interferon and cytokines, causing the virus to evade antiviral mechanism of interferon-stimulated genes. Moreover, the host-immune responses through inflammatory and cytotoxic lymphocytes activities are crucial to impede viral replication and dissemination resulting in immune overdrive along with cytolytic effects, which in turn causes severity of disease. 

Source: Parvez MK. COVID-19 and coronaviral hepatitis: evidence of collateral damage. Future Virol. 2020;10.2217/fvl-2020-0065.