The causal association between COVID-19 and herpes simplex virus: a Mendelian randomization study

Ming Yan; Li-Yuan Xiao; Martin Gosau; Reinhard E Friedrich; Ralf Smeets; Ling-Ling Fu; Hong-Chao Feng; Simon Burg

doi:10.3389/fimmu.2023.1281292

The causal association between COVID-19 and herpes simplex virus: a Mendelian randomization study

Front Immunol. 2023 Dec 11:14:1281292. doi: 10.3389/fimmu.2023.1281292. eCollection 2023.

Authors

Ming Yan^{1

2}, Li-Yuan Xiao¹, Martin Gosau², Reinhard E Friedrich², Ralf Smeets^{2

3}, Ling-Ling Fu^{1

2}, Hong-Chao Feng¹, Simon Burg²

Affiliations

¹ Department of Oral and Maxillofacial Surgery, Guiyang Hospital of Stomatology, Guiyang, China.
² Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
³ Department of Oral and Maxillofacial Surgery, Division of Regenerative Orofacial Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Abstract

Introduction: The coronavirus disease 2019 (COVID-19) has emerged as a main global public health challenge. Additionally, herpes simplex virus type-1 (HSV-1) and type 2 (HSV-2) are widespread viruses that can cause orolabial herpes and genital herpes. Several clinical case reports have declared a possible association between the two, however, the causal relationship between them has not been clarified.

Methods: This study utilized a Mendelian randomization (MR) approach for causality assessment between COVID-19 infection and HSV infection based on the latest public health data and Genome-Wide Association Study (GWAS) data. Multiple causal estimation methods, such as IVW, weighted median, simple mode, and weighted mode, were employed to validate the causal relation between COVID-19 infection and HSV infection, with COVID-19 infection, COVID-19 hospitalization, and severe COVID-19 as exposures, and HSV1/2 infection as the outcome. A reverse MR analysis was subsequently performed.

Results: MR analysis exhibited that COVID-19 infection was relevant to a reduced risk of HSV1 infection (p=7.603239e-152, OR=0.5690, 95%CI=0.5455-0.5935, IVW). Regarding the effect of COVID-19 infection on HSV2, MR analysis suggested that COVID-19 infection was correlated with an augmented risk of HSV2 infection (p=6.46735e-11, OR=1.1137, 95%CI=1.0782-1.1502, IVW). The reverse MR analysis did not demonstrate a reverse causal relationship between HSV and COVID-19.

Discussion: Altogether, COVID-19 infection might cause a decreased risk of HSV1 infection and an elevated risk of HSV2 infection.

Keywords: COVID-19; Mendelian randomization; association; causal effect; herpes simplex virus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

COVID-19*
Genome-Wide Association Study
Herpes Simplex* / complications
Herpes Simplex* / epidemiology
Herpesvirus 1, Human* / genetics
Humans
Mendelian Randomization Analysis

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by a grant from the Foundation of Guiyang Science and Technology Bureau (No. [2018]1-56). MY was supported by the Merit Scholarship of Hamburg University for International Students (No.7238065). L-LF was supported by the Chinese Government Scholarship (CSC Scholarship) (No.202208520014).