key: cord-0902304-mhbkuimg authors: Zhang, Xiaoyu; Wang, Biyan; Geng, Tao; Liu, Di; Tian, Qiuyue; Meng, Xiaoni; Zhang, Qiaoyun; Jiang, Mengyang; Zhang, Yiqiang; Song, Manshu; Wang, Wei; Wang, Youxin; Wang, Baoguo title: Causal associations between COVID-19 and Atrial Fibrillation: A bidirectional Mendelian randomization study date: 2021-11-20 journal: Nutr Metab Cardiovasc Dis DOI: 10.1016/j.numecd.2021.11.010 sha: 441421d5f9c31a5d4834987c032327f3f6521970 doc_id: 902304 cord_uid: mhbkuimg Background and aims Observational studies showed that coronavirus disease 2019 (COVID-19) attacks universally and its most menacing progression uniquely endangers the elderly with cardiovascular disease (CVD). The causal association between COVID-19 infection or its severity and susceptibility of atrial fibrillation (AF) remains unknown. Methods and results The bidirectional causal relations of COVID-19 (including COVID-19, hospitalized COVID-19 compared with not hospitalized COVID-19, hospitalized COVID-19 compared with population, and severe COVID-19) and AF are determined by using two-sample Mendelian randomization (MR) analysis. Genetically predicted severe COVID-19 was not significantly associated with risk of AF [odds ratio (OR), 1.037; 95% confidence interval (CI), 1.005-1.071; P = 0. 023, q = 0.115]. In addition, genetically predicted AF was also not causally associated with severe COVID-19 (OR, 0.993; 95% CI, 0.888-1.111; P = 0.905, q = 0.905). There was no evidence to support association between of genetically determined COVID-19 and risk of AF (OR, 1.111; 95% CI, 0.971-1.272; P = 0.127, q = 0.318), and vice versa (OR, 1.016; 95% CI, 0.976-1.058; P = 0.430, q = 0.851). Besides, no significant association was observed for hospitalized COVID-19 with AF. MR-Egger indicated no evidence of directional pleiotropy. Conclusion Overall, this MR study provides no clear support that COVID-19 is causally associated with the risk of AF. finances and healthcare systems severely [1] . The virus attacks universally and is 52 vulnerable to the elderly, especially those with cardiovascular comorbidities such as 53 diabetes mellitus, hypertension, heart failure, and coronary heart disease [2, 3]. Atrial 54 fibrillation (AF) is the most common cardiac arrhythmia worldwide, and its prevalence 55 is higher in patients with other comorbidities [4] . 56 COVID-19 may cause adverse impact on the heart and cardiovascular system. AF is a 57 frequent clinical manifestation in hospitalized COVID -19 patients who require 58 admission to an intensive care unit [ were delineated into four potential parts. Figure 1 showed an overview of the 135 bidirectional MR study to investigate these explanations. If the P value was less than 136 0.05 only in forward MR for Explanation 1, there was significant association of 137 genetically instrumented COVID-19 with higher AF risk. Then we conducted the 138 reverse MR analysis assessing whether AF affected COVID-19. This reverse causal 139 association was existed if P value was less than 0.05 in Explanation 2. The Explanation 140 3 showed there were bidirectional causality between COVID-19 and AF (P  0.05). 141 There was no any causal association in forward and reverse MR (P  0.05) as showed 142 in Explanation 4. 143 data sets including information on SNPs, alleles, effect sizes, standard errors, P values, 147 and effect allele frequencies for selected exposure instruments. 148 The summary genetic association data were reported in the Supplement The results of leave-one-out sensitivity analyses showed that the causal associations 165 between genetically instrumented COVID-19 phenotypes and AF were not 166 D presented the causal effect of the phenotypes of COVID-19 on AF, in which the 168 regression slopes of the lines corresponded to causal estimates using each of the four 169 different methods. 170 The summary genetic association data of AF were reported in the Supplement Table 1 . 172 As shown in Table 2 are inconsistent with the above mechanism hypothesis. Further research is required to 219 clarify these results using animal models in the laboratory. 220 In our analysis, we did not find any associations between AF and COVID-19. However, 221 it is not clear whether AF would contribute to increasing the risk for worse prognosis, 222 or even higher mortality of COVID-19. 223 Our MR study has several strengths. First, MR analysis is a genetic epidemiology 224 method that uses genetic determinants of the exposure (COVID-19) to understand the 225 effect of the exposure on the outcome (AF), which can control the potential bias. An interactive web-based dashboard to track COVID-19 258 in real time. The Lancet Infectious diseases COVID-19 Illness and Heart Failure: A Missing Link? 260 JACC Heart failure A close-up on COVID-19 and cardiovascular diseases. Nutrition, 262 metabolism, and cardiovascular diseases : NMCD 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed 265 in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS) Atrial Arrhythmias in COVID-19 Patients COVID-271 19 and cardiac arrhythmias COVID-19 and heart failure: from infection to inflammation and angiotensin II 275 stimulation. Searching for evidence from a new disease Electrocardiographic features of patients with COVID-19 pneumonia Mendelian Randomization as an 279 Approach to Assess Causality Using Observational Data usage for SARS-CoV-2 and other lineage B betacoronaviruses Mendelian 341 randomization: using genes as instruments for making causal inferences in 342 epidemiology AF: Atrial fibrillation; MR: mendelian randomization; SNP Circles indicate marginal genetic associations with severe COVID-19 and risk of AF 378 for each variant. Error bars indicate 95% CIs. COVID-19: Coronavirus disease AF: Atrial fibrillation; MR: mendelian randomization; SNP