Clinical Characteristics of COVID-19 Patients With Pre-existing Hepatitis B Virus Infection: A Multicenter Report.

Coronavirus disease 2019 (COVID-19) has become a global challenge since December 2019 (1). Of the 99 patients with COVID-19 in Wuhan, 43 (43.4%) had differing degrees of liver function abnormality (1). Therefore, liver disease in COVID-19 attracted widespread concern (2). There are no data yet focusing on the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with underlying liver disease, such as hepatitis B virus (HBV) infection. To date, 257 million people are living with HBV infection worldwide (3). Thus, it is indispensable to study the clinical characteristics of COVID-19 patients with pre-existing HBV infection.

Data were obtained from a cohort (coronavirus disease 2019-hepatitis B virus-Chinese Portal Hypertension Diagnosis and Monitoring Study Group, COVID-HBV-CHESS) to consecutively monitor COVID-19 patients in 10 designed hospitals of 8 provincial administrative regions in China (Figure 1a). Patients were hospitalized from January 10, 2020, to February 20, 2020, with a final follow-up on April 2, 2020. This study was approved by all ethics commissions, with a waiver of written informed consent. As of April 2, we have collected and analyzed 571 cases diagnosed with laboratory-confirmed SARS-CoV-2 infection by real-time fluorescence polymerase chain reaction. Fifteen (2.63%) of 571 patients had a history of HBV infection that seems to be lower than the incidence of HBV infection in the overall Chinese population (5.7%) (3). There were no cases with cirrhosis diagnosed by either clinical findings and/or liver biopsy in the cohort. Of them, 3 (20.00%) of 15 patients had a history of antiviral treatment (entecavir), and all had suppression of the HBV. The mean age of COVID-19 positive patients with pre-existing HBV infection was 45.80 years (SD, 11.06), and 10 (66.67%) were men. The common symptoms at onset of illness were fever (9 [60.00%]), dry cough (7 [46.67%]), and diarrhea (2 [13.33%]). On admission, 2 (13.33%) and 9 (60.00%) of 15 patients had lymphopenia and leukopenia, respectively. Most patients showed the elevated levels of C-reactive protein (5 [33.33%]), aspartate aminotransferase (5 [33.33%]), and alanine aminotransferase (5 [33.33%]). Chest CT scans showed ground-glass opacity or bilateral patchy shadows in lungs of 14 (93.33%) of 15 patients. Most importantly, compared with 556 (97.37%) of 571 COVID-19 cases without HBV infection, patients with HBV infection were observed to have a lower risk of severe events (a composite endpoint defined as the incidence of intensive care unit admission or death, none [0%] vs 36 [6.47%]; P = 0.309, Figure 1b).

Figure 1.

COVID-19 patients with pre-existing hepatitis B virus infection. (a) The distribution of 10 designed hospitals in 8 provincial administrative regions and the percentage of COVID-19 patients with pre-existing HBV infection. (b) The incidence of ICU admission or death in patients with or without HBV infection. HBV, hepatitis B virus; ICU, intensive care unit.

In the COVID-HBV-CHESS study, we analyzed the clinical characteristics of COVID-19 patients with pre-existing HBV infection for the first time, to our best knowledge; only by multicenter analysis can we follow-up COVID-19 with underlying liver disease, such as HBV infection. We found that patients with pre-existing HBV infection might have a lower incidence of intensive care unit admission or death, and similar findings were reported in severe acute respiratory syndrome (SARS) coronavirus with HBV coinfection during the outbreak of SARS in 2003 (4). Our hypothesis of the mechanism of this protective effect might be mediated by host immune responses (5) on the indirect interplay between HBV and SARS-CoV-2. However, the study was limited with a small sample size of cases with pre-existing HBV infection. A larger longitudinal cohort is needed to demonstrate the impact of HBV infection in patients with COVID-19.

CONFLICTS OF INTEREST

Guarantor of the article: Xiaolong Qi, MD.

Specific author contributions: Qing He, MD, Guo Zhang, MD, Ye Gu, MD, Jitao Wang, MD, Qiyuan Tang, MD, contributed equally to this work. Concept and design: X.Q. Acquisition of data: Q.H., G.Z., Y.G., Q.T., Z.J., C.S., H.Z., Z.C., B.M., D.L., H.H, Y.W., H.L., J.Y., H.P., S.Z., F.L., F.W., W.W., L.L., J.Y., B.X., and X.L. Analysis and interpretation of data: C.L., J.W., G.X., D.X., Y.H., H.Z., and M.L. Drafting of the manuscript: X.Q. and J.W. Critical revision of the manuscript: X.Q. All authors have contributed significantly to the work and fulfill the requirement of authorship.

Financial support: None to report.

Potential competing interests: None to report.