In the late December of 2019, the Wuhan City of China experienced an unprecedented outbreak of a cluster of pneumonia cases having mysterious aetiology (6,7). Since then, it has rapidly spread across China and to many other countries across the globe. Recent researches on COVID-19 mainly emphasized on lungs as the main organ affected in the disease, whileas less data is reported regarding the involvement of other organs like liver and kidneys. The involvement of multiple organs including the liver, gastrointestinal tract, and kidney have been previously reported in patients with COVID-19 (8).
Our study is perhaps unique in reporting the impact of severity of covid 19 disease on the liver and renal functioning of the COVID-19 patients with no prior underlying liver or renal impairments. Recent studies have described distinctive levels of elevated liver enzymes in COVID-19 cases, mostly exhibiting higher alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels accompanied by mildly elevated total bilirubin (TB) levels (9,10). We have found similar kind of results, wherein, the patients with elevated liver enzymes accompanied by moderate to highly elevated direct bilirubin depicted severe illness compared to those who had normal to very mildly elevated results. A similar kind of results were also reported in a study done by Qingxian Cai et al., (11), where high levels of AST was seen in 62% (8 of 13) of patients who were critically ill and shifted to the intensive care unit (ICU) compared to 25% (7 of 28) of patients who were mildly ill having normal to mildly raised levels of liver enzymes and hence corroborating with our current findings. Furthermore, some of the asymptomatic COVID-19 patients in this study also showed normal or mildly elevated liver enzymes, suggesting that liver damage is more predominant in severe cases compared to mild cases of COVID-19 as also reported in a similar study done by Zhang C et al., (12). However, the reason for the elevation of liver enzymes or liver injury still remains unclear as to whether it is caused by the virus itself or due to a severe inflammatory reaction produced in response to the infection (13). In this connection, a recent study by Hamming et al., has revealed that the novel coronavirus might directly infect the liver cells as the docking receptor of the virus, angiotensin‐converting enzyme 2 (ACE2), is released by the cells of both liver and bile-duct, where the virus replicates and consequently invades the cells of the upper respiratory tract and lung tissue and hence the patients develop the clinical symptoms(14). Moreover, a recent pilot study has proposed that an enhanced expression of ACE2 receptor is developed in cholangiocytes (15) signifying that the novel coronavirus may bind directly to the ACE2-positive cholangiocytes and impair the normal liver functions. Additionally, cytokine storm and pneumonia-related hypoxia, might add to the liver damage leading to complete or partial liver failure in severely ill COVID-19 patients.
In addition to liver damage, an increased incidence of acute renal injury in COVID-19 patients has also been previously reported. (16). Covid-19 has been shown to impair renal function in several ways, ranging from poor blood flow to the formation of tiny blood clots which can clog the kidneys and prevent urine formation. The current clinical study revealed that the patients suffering with severe cases of COVID-19 are also showing signs of kidney damage, even though they had no history of kidney ailments prior to the infection with the novel coronavirus.
We found the patients who were categorized as severely ill had altered kidney function tests, characterized by elevated serum creatinine, urea and blood urea nitrogen levels as also been reported by Fan C et al. [17]. The altered kidney function can be attributed to the variations in angiotensin-converting enzyme 2 (ACE2) receptor expression leading to kidney dysfunction. ACE2, which is expressed on the brush border apical membrane of the proximal tubules of kidneys, as well as in podocytes at low level (18). Therefore, it is plausible that the virus could enter the podocytes first, infects them, and then binds to ACE2 to enter the kidney tubular cells, that leads to the impaired renal function, as has been reported by Batlle D et al., (19)
Furthermore, we also observed hypernatremia and hyperchloremia in our severely ill COVID − 19 patients, which has not been reported previously. We attribute the elevation of Na and Cl to severe water loss due to pyrexia, use of diuretics and high respiration rate. Additionally, there are fair chances of hypernatremia and hyperchloremia in COVID-19 patients due to abnormally low levels of oxygen in the blood, caused by the pneumonia which is common in severe cases of this disease. The large influx of cytokines known as cytokine storm leads to severe inflammation, which can damage the healthy tissues, including that of the kidneys, and therefore we propose an association between the metabolic acidosis (hypernatraemic and hyperchloremia) and the cytokine storm. we further suggest that severity of pneumonia could be an important factor in development of AKI in patients with COVID-19.
The current study has certain limitations, which includes limited number of patients, the patient duration in the hospital was not enough to predict the possibilities of remission of liver and renal damage. We were not able to detect the presence of SARS-CoV-2 in urine samples and hence could not evaluate the correlations between urine virus and kidney complications. Therefore, we recommend repeated and meticulous observation of liver and renal functions in patients with COVID-19 that can help in achieving the optimum mode of treatment and reduce the number of deaths due to organ failure.