key: cord-331731-c2r0kfaz
authors: Anugwom, Chimaobi M; Aby, Elizabeth S; Debes, Jose D
title: Inverse association between chronic hepatitis B infection and COVID-19: immune-exhaustion or coincidence?
date: 2020-06-05
journal: Clin Infect Dis
DOI: 10.1093/cid/ciaa592
sha: 
doc_id: 331731
cord_uid: c2r0kfaz

nan

M a n u s c r i p t Dear Editor, We read with great interest the report by Zhao et al, regarding a case of delayed immune response to SARS-CoV-2 in a patient with HIV and HCV co-infection [1] . The authors stipulate the previous HIV and HCV infection could confer immune dysfunction providing a differential immune response during COVID-19 development.

This report, as most initial reports, originate in China which has an intermediate-high prevalence of chronic hepatitis B (HBV) infection [2] . We evaluated all peer-reviewed articles, written in the English language, reporting cases of COVID-19 infection and specifically defining rates of HBV infection and hospital admission, since December 1 st , 2019 until March 25 th , 2020 and found a surprisingly low prevalence of chronic HBV in COVID-19 cases admitted to the hospital. Indeed, Of the 2054 cases that were reported with this information, only 28 patients (1.36%) were reported positive for HBV. Several of these studies reported 0% incidence of HBV among individuals infected with COVID-19. We matched the HBV-rates in COVID-19 subjects to age-specific rates of HBV reported in the respective geographic areas of origin ( Table 1 ). The median age of COVID-19 infected individuals in the evaluated studies ranged between 47-51 years, corresponding to HBV rates ranging from 7-11% while the HBV rates of those with COVID-19 remained between 0-1.3%. It is unclear whether this is a simple epidemiological "misconnection" or if being chronically infected with HBV impacts the chances of clinically significant infection with SARS-CoV-2 leading to less hospital admissions, in a similar fashion as that reported by Zhao et al to HIV and HCV. In this regard, research has documented that, chronic HBV infection leads to a reduced or absent virus specific T-cell reactivity (although HBV-specific T cells). This phenomenon, A c c e p t e d M a n u s c r i p t known as "immune exhaustion", is manifested by an impaired ability of T-lymphocytes to produce appropriate cytokines secondary to years of continuous, yet inefficient, immune reaction to the virus [3] . Immune exhaustion is also frequently observed in chronic HCV infection [4] . In this setting, it is plausible that the exhaustion of T-lymphocytes may affect their ability to respond to other viruses and reduce the degree of "cytokine storm" that has been noticed in COVID-19 patients, thus culminating in a less severe disease.

Similar patterns of immune co-interaction with consequences in clinical presentation and prognosis have been reported in individuals infected with HBV and schistosomiasis [5] . A c c e p t e d M a n u s c r i p t

Early virus clearance and delayed antibody response in a case of COVID-19 with a history of co-infection with HIV-1 and HCV

Prevalence of Hepatitis B Virus Infection in

Molecular and transcriptional basis of CD4⁺ T cell dysfunction during chronic infection

The Path to Cancer and Back: Immune Modulation During Hepatitis C Virus Infection, Progression to Fibrosis and Cancer, and Unexpected Roles of New Antivirals

Helminth-Induced Immune Modulation Influences the Outcome of Acute and Chronic Hepatitis B Virus Infection

A comparative study on the clinical features of COVID-19 pneumonia to other pneumonias

Clinical Characteristics of Coronavirus Disease 2019 in China

Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series

Clinical progression of patients with COVID-19 in

Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore

We thank Drs. Lanjuan Li (Wuhan, China) and Barnaby Young (Singapore, Singapore) for providing information from their manuscripts regarding HBV. 

A c c e p t e d M a n u s c r i p t A c c e p t e d M a n u s c r i p t