key: cord-0741393-j80k2v21
authors: Chen, Liping; Huang, Shaoping; Yang, Jingmao; Cheng, Xin; Shang, Zhiyin; Lu, Hongzhou; Cheng, Jilin
title: Clinical characteristics in patients with SARS‐CoV‐2/HBV co‐infection
date: 2020-07-15
journal: J Viral Hepat
DOI: 10.1111/jvh.13362
sha: d3c75bea12e22508e0c6a9f841e951d5e87b6d00
doc_id: 741393
cord_uid: j80k2v21

COVID‐19 has become a global pandemic and garnered international attention. Although the clinical features of COVID‐19 related liver injury have been investigated, there have been no reports and studies on the clinical characteristics of COVID‐19 patients co‐infected with Hepatitis B Virus (HBV). This study aimed to evaluate whether SARS‐CoV‐2/HBV co‐infection could influence liver function and the disease outcome. All 326 confirmed COVID‐19 cases in Shanghai Public Health Clinical Center (The COVID‐19 designated hospital in Shanghai, China) from January 20, 2020 to February 24, 2020 were enrolled and followed up until February 29 in this study. The clinical, laboratory data and the length of stay were collected and analyzed retrospectively. 20 patients with HBV co‐infection (6.1%) and 306 patients (93.9%) without HBV infection showed no differences in the level of liver function parameters. However, compared with HBsAg‐ patients [145.4 mg/L (103.9‐179.2)], HBsAg+ patients had a lower level of prealbumin [(102.3 mg/L (76.22‐160.2), P=.0367]. There were also no significant differences for the discharge rate and the length of stay between two groups. Taken together, we found no evidence that SARS‐CoV‐2/HBV co‐infection could aggravate liver injury or extend duration of hospitalization.

Since the first COVID-19 case was reported in Wuhan, Hubei Province, China in December 2019, coronavirus pneumonia caused by SARS-CoV-2 infection has become prevalent globally 1 . So far, there have been almost 2 million patients infected by SARS-CoV-2 2 , becoming a huge threat to global health. In addition to fever, dry cough, weakness, and breathing difficulty, abnormal liver function may occur in considerable proportion of SARS-CoV-2 infected patients (14.8%-76.3%) [3] [4] [5] [6] [7] . Although the exact mechanism of COVID-19 related liver damage is still unknown, the abnormal liver function was associated with severe disease and mortality risk in COVID-19 patients [5] [6] [7] . Hepatitis B virus (HBV) has a worldwide distribution and remains a leading public health problem, with a high prevalence of HBsAg at about 6.0% in China 8 . Huang reported SARS patients with HBV infection were more prone to develop higher degree of liver injury and severe hepatitis, however, the data of the prevalence of SARS-CoV-2/HBV co-infection in COVID-19 patients is still absent 9 . In our previous study 7 (138 cases), there were only 9 (6.1%) cases (too small) with underlying liver diseases, so no further analysis was made Accepted Article over the clinical features of COVID-19 patients with HBV infection. In view of the current pandemic of SARS-CoV-2, the clinical characteristics of SARS-CoV-2 coinfection with HBV should be identified. In this retrospective study, we expanded the sample size and aimed to evaluate the influence of SARS-CoV-2/HBV co-infection on the clinical characteristics including liver function and disease outcome.

This is a retrospective, single-center study. A total of 326 patients with SARS-CoV-2-positive results, admitted to Shanghai Public Health Clinical Center (SHPHC) from January 20, 2020 to February 24, 2020 were included and followed up until February 29. The clinical criteria of diagnosis and di scharge refer to the standards for "Diagnosis and Treatment Scheme of New Coronavirus Infected Pneumonia" (trial version 6).

This study was approved by the Ethics Committee of the Shanghai Public Health Clinical Center (2019-S047-02, Review date: Jan 13, 2020) and was exempted from the need for informed consent from patients.

The basic information and clinical characteristics of patients, including demographic, clinical, laboratory data and the length of stay were collected by electronic medical records.

The continuous data were presented as the mean ± standard deviation (SD), median and interquartile range (IQR), as appropriate. The independent sample t test or Mann-Whitney U test were used to compare the differences between two groups; The categorical variables were expressed by frequency and percentage, and compared by the chi-square test or Fisher exact test. P < 0.05 was determined as with statistically significant differences. Statistical analysis software Graphpad prism 6 was used for all analyses in this study.

Of the 326 patients, 20 cases (6.1%) were HBV infected (HBsAg-positive, HBeAg-negative with undetectable HBV viral load (VL<100 IU/ml; iCycler device, Bio-Rad, USA; lower limit of quantification: 100 IU/mL). As shown in Table 1 , 20 patients with HBV co-infection (6.1%) and 306 patients (93.9%) without HBV infection didn't show any differences regarding age and gender distribution (P>.05). There were also no differences in the level of liver function In HBsAg-patients, 245 cases (80%) were discharged with the median hospital stays of 14 days (11) (12) (13) (14) (15) (16) (17) (18) (19) . Neither the discharge rate nor length of stay show any difference between the two groups. 

infection, there is still a presumption that several cell types in other humoral organs can be attacked by SARS-CoV-2. As for liver, the abundant protein levels of ACE-2, a functional receptor of SARS-CoV-2, in bile ducts have been observed 10 . In addition, a recent study based on the analysis of online single cell RNA sequencing date from healthy liver tissues also confirmed that the level of ACE-2 mRNA in bile duct cells is comparable to ATII cells, but not in hepatocytes. These results suggest that abnormal liver function may be caused by SARS-CoV-2 preferentially binding to cholangiocytes. However, according to recent reports, the bile duct injury related specific index, such as ALP, was not frequently elevated in COVID-19 patients 1 . In general, whether SARS-CoV-2 can directly infect liver cells and leads to the abnormal liver function is a controversial issue due to the absence of histological evidence of COVID-19 patients.

This article is protected by copyright. All rights reserved According to our recent study 7 , we found elevated ALT, AST were more common in COVID-19 patients with abnormal liver function and liver damage can also occur in mild COVID-19 patients without any related medications before hospitalization. There's reason to believe SARS-CoV-2 may attack the liver.

Taken into consideration that viral co-infection can exacerbate liver injury thus have a big impact on disease progression and outcome 11, 12 , we investigated the prevalence of HBV infection in COVID-19 patients and found that there was a comparable rate of SARS-CoV-2/HBV co-infection to that of general population (6.1% vs 6%). These observations suggested that SARS-CoV-2/HBV co-infection is common in COVID-19 patients, although we couldn't assess whether existence of HBV infection increases susceptibility to SARS-CoV-2 infection.

As for liver function parameters, there were no significant differences in related indices, except for the prealbumin, which is frequently measured as indicators of liver reserve and more sensitive than other indicators. The level of prealbumin was lower in patients with co-infection than that in the control group, which indicates that the liver reserve capacity was weak in COVID-19 patients with HBV co-infection. So in our study, no evidence showed coexistence of HBV infection increases the liver injury in COVID-19 patients.

The outcomes of COVID-19 patients with/without HBV infection were also compared in our current study，and SARS-CoV-2/HBV co-infection had no effect on the course and prognosis of COVID-19, including the rates of severe/critically ill, mortality and discharged and hospital stays.

However, previous study 12 

This article is protected by copyright. All rights reserved

Although this study is a single-center, retrospective study, it is convincing as this center is the only designated hospital for COVID-19 treatment in Shanghai, China and a cohort of more than 300 cases were analyzed. Moreover, the positive rate of HBsAg in COVID-19 patients were also close to the that in the general population.

Taken together, our study is the first to elaborate on the clinical characteristics of SARS-CoV-2/HBV co-infection patients and demonstrate that the coinfection with HBV slightly affect liver function, showing no impact on the COVID-19 outcome.

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Accepted Article