No Genetically Predicted Association Between Human Papillomavirus and COVID-19: A Mendelian Randomization Analysis in European Ancestry Population

Sha-Sha Tao,1– 3,* Man Ge,1,2,* Yi-Fan Cai,4,* Shu-Zhen Xu,1,2 Yi-Sheng He,1,2 Yi-Qing Xu,1,2 Tian He,1,2 Xiao-Fan Dai,5 Xiao Hu,6 Peng Wang,6 Hai-Feng Pan1,2 1Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, Anhui, People’s Republic of China; 3Preventive Medicine Experimental Teaching Center, School of Public Health, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 4Department of Clinical Medicine, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 5Department of Public Utilities Management, School of Health Service Management, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 6Teaching Center for Preventive Medicine, School of Public Health, Anhui Medical University, Hefei, Anhui, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hai-Feng Pan, Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, People’s Republic of China, Email [email protected]; [email protected] Peng Wang, Teaching Center for Preventive Medicine, School of Public Health, Anhui Medical University, Hefei, Anhui, People’s Republic of China, Email [email protected]: Previous studies reveal that coronavirus disease 2019 (COVID-19) infection accelerates the progression of Human papillomavirus (HPV)-related diseases, but the results remain controversial. We conducted a bidirectional two-sample Mendelian randomization (MR) study to evaluate the causal association between HPV infection and COVID-19 using genome-wide association study (GWAS) summary data from European ancestry populations.Patients and Methods: Genetic summary data of HPV infection and COVID-19 were derived from the public GWAS meta-analysis and the COVID-19 host genetics initiative GWAS, respectively. The causal link between HPV infection and COVID-19 was evaluated by MR analysis with inverse variance weighting (IVW), MR-Egger, and weighted median methods. Additional MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) and MR-Egger regression methods were used to identify the potential pleiotropy of the instrumental variables (IVs). Bonferroni correction was used to account for the issue of multiple comparisons, leading to a statistically significant P-value of less than 0.004 (0.05/2*3*2).Results: There were no significantly causal links of HPV-16 or HPV-18 infection with COVID-19 infection, hospitalized COVID-19, or severe COVID-19 (all P> 0.05). Furthermore, no significant causal effect of all three types of COVID-19 on HPV-16 and HPV-18 was observed in the reverse MR analyses (all P> 0.05). MR-Egger regression and MR-PRESSO global test did not find the presence of horizontal pleiotropy between IVs of HPV infection and COVID-19.Conclusion: This study shows that COVID-19 infection does not affect the risk of HPV-16/18 infection, nor does HPV-16/18 infection increase COVID-19 infection risk. It highlights the need to maintain routine health management and no change to HPV prevention strategies.Keywords: HPV, COVID-19, mendelian randomization, causal relationship, genetic association