**4. Discussion**

We report here, for the first time, the prevalence, severity and mortality of patients diagnosed with COVID-19 with underlying chronic kidney disease and liver diseases. Our outcomes show that the overall prevalence of CKD and Liver Diseases in COVID-19 are 1% and 3% respectively. We also report a COVID-19 severity of 83.93% (47/56) in patients with CKD and 57.33% (43/75) in patients with liver diseases. The rate of mortality in COVID-19 patients with CKD and Liver diseases was found to be 53.33% (8/15) and 17.65% (6/34) respectively.

The presence of comorbidities is associated with poor prognoses in patients with COVID-19, with higher mortality rates and severity. The most common comorbidities reported so far in severe cases have been hypertension, diabetes, cardiovascular diseases, cerebrovascular diseases and COPD [29]. However, how these diseases contribute to the COVID-19 outcome remains unclear.

Biomarkers of liver injuries have been reported to increase in patients with COVID-19 [25,35,45], although, no virus was found in the liver tissue of patients who died from the disease [54]. This is to be expected, as angiotensin II-converting enzyme (ACE2) receptor, a key player in the "docking" and replication of the SARS-CoV-2 virus, is not expressed in hepatocytes. However, ACE2 expression has been reported in cholangiocytes [55], leading to the suggestion that the binding of SARS-CoV-2 to the epithelial cells of the biliary tree may cause biliary dysfunction [56]. Zhang et al. also suggested that the transient liver injuries observed in COVID-19 patients may be associated with drug toxicity, cytokine storm or hypoxia [56]. While many studies have reported liver dysfunction in COVID-19 [25,35,45], the mechanistic link between the two remains to be established.

Furthermore, CKD have been associated with inflammation and dysregulation of the immune system [57]. This dysregulation of immune function, which may exist in patients with underlying CKD, may explain the increased severity and mortality due to COVID-19. The levels of ACE2 receptor in the kidney have been previously reported to be altered in patients with human kidney diseases [58]. In a recent study by Fan et al., it was reported that ACE2 receptor is overexpressed in the tubular cells of patients with CKD. Alteration in kidney functions, characterised by increased serum creatinine and urea nitrogen, was also reported in patients with COVID-19 [59]. Taken together, the alterations in ACE2 receptor expression may explain the observed kidney dysfunction in COVID-19 and provide the answer to why patients with CKD are vulnerable to the SARS-CoV-2 virus.

This study is limited by several factors. Firstly, some included studies did not report comorbidities. Where comorbidities were specified, the criteria for defining severity were not uniform. Some studies included only patients with primary composite outcomes, while some did not report mortality. Lastly, the aetiology and pathophysiological characteristics of the comorbidities were not documented.

Indeed, this review involved an in-depth literature search followed by a systematic analysis of data involving a total of 5595 patients with confirmed COVID-19. For the first time, we have established the potential risk of COVID-19 in liver disease and CKD patients, which indicates an increased vulnerability of this subpopulation.

The most important clinical implication of this study is that Liver disease and CKD patients are potentially highly vulnerable to COVID-19 and should be considered for remote consultation and the most stringent social isolation to prevent infection. Future studies should investigate how liver diseases and CKD contribute to poor prognoses in COVID-19.
