Skip to content
Publicly Available Published by De Gruyter January 19, 2021

Atrial arrhythmia and its association with COVID-19 outcome: a pooled analysis

Eka Prasetya Budi Mulia, Irma Maghfirah, Dita Aulia Rachmi and Rerdin Julario
From the journal Diagnosis

To the Editor,

The current coronavirus disease 2019 (COVID-19) outbreak has escalated rapidly to a global pandemic. While clinical symptoms are primarily linked to the respiratory system, cardiovascular complications have been identified as well. COVID-19 may have a serious effect on cardiac function and cause heart injury along with increased severity of illness and fatal outcomes [1]. Cardiac arrhythmias were found among these documented cardiac manifestations, with varying estimates between studies and according to severity levels [2], [3].

An overall cardiac arrhythmia prevalence of 17% in patients hospitalized for COVID-19 was indicated from China’s early reports. Furthermore, in COVID-19 patients admitted to the intensive care unit (ICU), a higher arrhythmia incidence (44%) was observed [2]. Since there is an increasing prevalence of arrhythmia in COVID-19 with atrial fibrillation (AF) being the most common form [4] and its possibility to be associated with COVID-19 prognosis, we aimed to evaluate here whether the incidence of atrial arrhythmia was associated with COVID-19 outcome.

A systematic search was performed in three different databases (PubMed, Scopus, and MedRxiv) using keywords “COVID-19” OR “SARS-CoV-2” AND “atrial arrhythmia” OR “atrial fibrillation” AND “mortality” OR “severity” between January 1–November 30, 2020. Reference lists of the included studies were also screened to identify additional relevant studies. We included all observational studies or trials involving adult patients with COVID-19 who had any atrial arrhythmia and COVID-19 outcome data. We excluded any study that had missing required data and not in English literature. Titles and abstracts were screened and assessed before full-text retrieval. The full papers that met the eligibility criteria were included in analysis. The primary endpoint of our meta-analysis was the poor outcome of COVID-19. Poor outcome was defined as in-hospital mortality, severity based on WHO criteria, or use of mechanical ventilation during hospitalization in COVID-19 patients. A pooled analysis was performed using STATA v.16. Meta-analysis of proportions was used to pool the incidence of atrial arrhythmia. Mantel-Haenszel formula was used for dichotomous variables to calculate the pooled odds ratios (ORs). Random effect models were used regardless of heterogeneity. Random-effects meta-regression was performed for age and sex.

Search result in 412 records. After duplicate removal, 384 records remained. Title and abstracts were then screened, and a total of 315 records were removed. Sixty-nine full texts were then assessed for eligibility, and 59 articles were excluded due to incorrect patient population (n=9); unavailability of data on atrial arrhythmia (n=23); no outcome of interest (n=27). Finally, we included 10 eligible studies (5,193 patients) for analysis.

All included studies were retrospective observational. Most studies were conducted in USA (Table 1). The prevalence of atrial arrhythmia in patients with COVID-19 was 9.2% (95% CI: 6.5–12.7%; I2: 92.66, p<0.001). Atrial arrhythmia occurred in 14.8% (95% CI: 10.0–21.4%; I2: 82.99, p<0.001) of patients with poor outcome and 7.0% (95% CI: 4.7–10.5%; I2: 91.90, p<0.001) of patients without poor outcome.

Table 1:

Characteristics of included studies.

No Author Outcome Study design Country Total sample, na Atrial arrhythmia prevalence, n, % Type of atrial arrhythmia Male, % Age, year
1 Peltzer B, 2020 [14] Mortality Retrospective observational USA 1,053 (184 vs. 869) 166 (15.8) AF/Aflut 62.3 62 ± 17
2 Mccullough SA, 2020 [15] Mortality Retrospective observational USA 756 (90 vs. 666) 42 (5.6) AF/Aflut 63.2 63.3 ± 16.0
3 Li L, 2020 [16] Mortality Retrospective observational China 113 (50 vs. 63) 7 (6.2) NR 60.2 67.3 ± 14.1
4 Quisi A, 2020 [17] Mortality Retrospective observational Turkey 349 (38 vs. 311) 16 (4.6) AF 43.8 56 (20–80)
5 Russo V, 2020 [18] Mortality Retrospective observational Italy 414 (107 vs. 307) 71 (17.1) AF 61.1 66.9 ± 15.0
6 Abrams MP, 2020 [19] Mortality Retrospective observational USA 133 (11 vs. 122) 31 (23.3) AF 55.6 81 (70.5–88)
7 Ghio S, 2020 [20] Mortality Retrospective observational Italy 405 (124 vs. 281) 29 (7.2) AF 68.6 69.8 (58.6–78.3)
8 Wang Y, 2020 [21] Severity Retrospective observational China 319 (97 vs. 222) 20 (6.6) AF 47.6 64.97 ± 13.15
9 Elias P, 2020 [22] MV Retrospective observational USA 1,258 (174 vs. 1,101) 108 (13) AF/Aflut, atrial ectopy 54 61.6 ± 18.4
10 Goyal P, 2020 [23] MV Retrospective observational USA 393 (130 vs. 263) 29 (7.4) NR 60.6 62.2 (48.6–73.7)

  1. aData were presented as poor vs. good outcome. AF, atrial fibrillation; Aflut, atrial flutter; NR, not reported; MV, mechanical ventilation.

Patients with COVID-19 experiencing atrial arrhythmia had an increased risk of poor outcome (OR 2.63 [95% CI: 1.57–4.43], p<0.001; I2: 77.64%, p<0.001) (Figure 1). Sensitivity analysis removing the study of Elias et al. showed the statistical robustness with a similar result (OR 2.94 [95% CI: 1.71–5.04], p<0.001; I2: 74.03%, p<0.001). The association between atrial arrhythmia and COVID-19 outcome was not affected by sex (p=0.855), but affected by age (p=0.042).

Figure 1: 
Pooled analysis of atrial arrhythmia and COVID-19 outcome.
Atrial arrhythmia was associated with an increased risk of poor outcome.

Figure 1:

Pooled analysis of atrial arrhythmia and COVID-19 outcome.

Atrial arrhythmia was associated with an increased risk of poor outcome.

Our finding was consistent with the previous meta-analyses showed that arrhythmia was quite prevalent in COVID-19, which was about 19% [3], [5]. This analysis also showed that arrhythmia was associated with poor outcomes. A pooled analysis by Pranata et al. also showed that arrhythmia incidence was higher in COVID-19 with poor outcomes, which might be a predictor of poor prognosis [5]. However, those previous meta-analyses did not specify the type of arrhythmia in COVID-19.

Arrhythmias and disorder of the conduction system are not an early or typical manifestation of COVID-19. Our understanding of arrhythmic complications is still improving in COVID-19. Several reports have been reported with multiple complications of arrhythmia, and the number is still increasing. The literature, however, lacks studies that explicitly directed at atrial arrhythmias in patients with COVID-19.

Cardiac arrhythmias in COVID-19 may be secondary to side effects of treatment, hypoxia and pulmonary disease, the activity of direct oxidized Ca2+/calmodulin-dependent protein kinase II, activated protein kinase C, and myocarditis. Hypoxemia induced by respiratory failure leads the myocardium to get a relatively hypoxic condition. Hypoxia can facilitate the death of cardiomyocytes and affect ion channels’ activity, resulting in alterations in the action prolongation and/or repolarization of the heart, thereby facilitating arrhythmogenesis [6]. Additionally, electrolyte disturbances that may precipitate or worsen heart arrhythmias are often found in these patients [5].

AF was the most frequent cardiac arrhythmia reported in COVID-19 infected patients [4]. Inciardi et al. reported that AF prevalence was 36% in patients with cardiovascular diseases, with more commonly in 42% of patients who did not survive [7]. Similarly, in a study of 115 hospitalized patients (46 admitted to the general ward and 69 ICUs), Colon et al. reported that in 19 patients (16.5%), all of whom were admitted to the ICU (27.5% of ICU patients), new-onset atrial tachyarrhythmia including AF, atrial flutter, and atrial tachycardia were observed [8].

The mechanisms that may induce atrial fibrillation in COVID-19 may be due to systemic infection, direct viral endothelial damage and cardiomyocyte injury, the interaction of CD147 and sialic acid-spike protein, a decrease in the availability of angiotensin-converting enzyme 2 (ACE2) receptors, enhanced inflammatory signaling eventually resulting in an inflammatory cytokine storm, hypoxemia, electrolytes and acid-base balance abnormalities, and patients’ vulnerability was owing to old age and their comorbidities, and inevitably, overactivity of the sympathetic nervous system [9], [10]. A case of new-onset atrial fibrillation and flutter in a COVID-19 patient was also documented by Seecheran et al., further indicating the atrial arrhythmogenicity of COVID-19 infection [11].

Whether AF has contribution in increasing the risk of severe COVID-19 is not yet established. But the possible mechanism of AF in increasing risk of severity in COVID-19 was proposed by Sanchis-Gomar et al. In patient with cardiovascular disease, including atrial fibrillation, the level and activity of ACE2 are deranged. SARS-CoV-2 binds with the ACE2 in the cell surface to penetrate the human cell. It has been previously described that plasma ACE2 activity levels are increased in AF and have been suggested as a better marker of disease severity in human AF. Thus, increasing the risk of developing severe COVID-19 in those population [12].

Notably, the involvement of AF, along with poor rate control, may have a detrimental effect on the prognosis of patients. With a high prevalence of AF in the general population, especially the elderly, and the established correlation between arrhythmic burden and viral disease, AF can affect mortality [13].

In conclusion, our finding showed that atrial arrhythmia was prevalent and associated with poor outcome of COVID-19. Early screening of arrhythmia, especially atrial arrhythmia, may help clinicians differentiate against the arrhythmia’s prognostic importance, facilitating more effective risk stratification.

Corresponding author: Eka Prasetya Budi Mulia, MD, Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Airlangga – Dr. Soetomo General Hospital, Jalan Mayjen Prof. Dr. Moestopo No. 6-8, Surabaya , 60286, Indonesia, Phone: +62 85 627 65365, Fax: +62 31 5031752, E-mail:

  1. Research funding: None declared.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Ethical approval: Not applicable.


1. Wang, Y, Wang, Z, Tse, G, Zhang, L, Wan, EY, Guo, Y, et al.. Cardiac arrhythmias in patients with COVID‐19. J Arrhythmia 2020;36:827–36. in Google Scholar

2. Wang, D, Hu, B, Hu, C, Zhu, F, Liu, X, Zhang, J, et al.. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA, J Am Med Assoc 2020;323:1061–9. in Google Scholar

3. Hamam, O, Goda, A, Eldalal, M, Ussama, A, Fahmy, M, Elyamany, K, et al.. Cardiac arrhythmias in patients with COVID-19: a systematic review and meta-analysis. medRxiv 2020;1–16. in Google Scholar

4. Gopinathannair, R, Merchant, FM, Lakkireddy, DR, Etheridge, SP, Feigofsky, S, Han, JK, et al.. COVID-19 and cardiac arrhythmias: a global perspective on arrhythmia characteristics and management strategies. J Intervent Card Electrophysiol 2020;59:329–36. in Google Scholar

5. Pranata, R, Huang, I, Raharjo, SB. Incidence and impact of cardiac arrhythmias in coronavirus disease 2019 (COVID-19): a systematic review and meta-analysis. Indian Pacing Electrophysiol J 2020;20:193–8. in Google Scholar

6. Babapoor-Farrokhran, S, Rasekhi, RT, Gill, D, Babapoor, S, Amanullah, A. Arrhythmia in COVID-19. SN Compr Clin Med 2020;2:1430–5. in Google Scholar

7. Inciardi, RM, Adamo, M, Lupi, L, Cani, DS, Di Pasquale, M, Tomasoni, D, et al.. Characteristics and outcomes of patients hospitalized for COVID-19 and cardiac disease in Northern Italy. Eur Heart J 2020;41:1821–9. in Google Scholar

8. Colon, CM, Barrios, JG, Chiles, JW, McElwee, SK, Russell, DW, Maddox, WR, et al.. Atrial arrhythmias in COVID-19 patients. JACC Clin Electrophysiol 2020;6:1189–90. in Google Scholar

9. Russo, V, Rago, A, Carbone, A, Bottino, R, Ammendola, E, Della Cioppa, N, et al.. Atrial fibrillation in COVID-19: from epidemiological association to pharmacological implications. J Cardiovasc Pharmacol 2020;76:138–45. in Google Scholar

10. Gawałko, M, Kapłon-Cieślicka, A, Hohl, M, Dobrev, D, Linz, D. COVID-19 associated atrial fibrillation: incidence, putative mechanisms and potential clinical implications. IJC Heart Vasc 2020;30:100631. in Google Scholar

11. Seecheran, R, Narayansingh, R, Giddings, S, Rampaul, M, Furlonge, K, Abdool, K, et al.. Atrial arrhythmias in a patient presenting with coronavirus disease-2019 (COVID-19) infection. J Invest Med High Impact Case Rep 2020;8:1–6. doi: in Google Scholar

12. Sanchis-Gomar, F, Perez-Quilis, C, Lavie, CJ. Should atrial fibrillation be considered a cardiovascular risk factor for a worse prognosis in COVID-19 patients? Eur Heart J 2020;41:3092–3. in Google Scholar

13. Schnaubelt, S, Breyer, M-K, Siller-Matula, J, Domanovits, H. Atrial fibrillation: a risk factor for unfavourable outcome in COVID-19? A case report. Eur Hear J Case Rep 2020;4:1–6. in Google Scholar

14. Peltzer, B, Manocha, KK, Ying, X, Kirzner, J, Ip, JE, Thomas, G, et al.. Outcomes and mortality associated with atrial arrhythmias among patients hospitalized with COVID-19. J Cardiovasc Electrophysiol 2020;31:3077–85. in Google Scholar

15. McCullough, SA, Goyal, P, Krishnan, U, Choi, JJ, Safford, MM, Okin, PM. Electrocardiographic findings in coronavirus disease-19: insights on mortality and underlying myocardial processes. J Card Fail 2020;26:626–32. in Google Scholar

16. Li, L, Zhang, S, He, B, Chen, X, Wang, S, Zhao, Q. Risk factors and electrocardiogram characteristics for mortality in critical inpatients with COVID‐19. Clin Cardiol 2020;43:1624–30. in Google Scholar

17. Quisi, A, Alıcı, G, Harbalıoğlu, H, Genç, Ö, Er, F, Allahverdiyev, S, et al.. The CHA2DS2-VASc score and in-hospital mortality in patients with COVID-19: a multicenter retrospective cohort study. Arch Turk Soc Cardiol 2020;48:656–63. in Google Scholar

18. Russo, V, Di Maio, M, Mottola, FF, Pagnano, G, Attena, E, Verde, N, et al.. Clinical characteristics and prognosis of hospitalized COVID-19 patients with incident sustained tachyarrhythmias: a multicenter observational study. Eur J Clin Invest 2020;50:e13387. in Google Scholar

19. Abrams, MP, Wan, EY, Waase, MP, Morrow, JP, Dizon, JM, Yarmohammadi, H, et al.. Clinical and cardiac characteristics of COVID‐19 mortalities in a diverse New York City Cohort. J Cardiovasc Electrophysiol 2020;31:3086–96. in Google Scholar

20. Ghio, S, Baldi, E, Vicentini, A, Lenti, MV, Di Sabatino, A, Di Matteo, A, et al.. Cardiac involvement at presentation in patients hospitalized with COVID-19 and their outcome in a tertiary referral hospital in Northern Italy. Intern Emerg Med 2020;15:1457–65. in Google Scholar

21. Wang, Y, Chen, L, Wang, J, He, X, Huang, F, Chen, J, et al.. Electrocardiogram analysis of patients with different types of COVID‐19. Ann Noninvasive Electrocardiol 2020;25:e12806. in Google Scholar

22. Elias, P, Poterucha, TJ, Jain, SS, Sayer, G, Raikhelkar, J, Fried, J, et al.. The prognostic value of electrocardiogram at presentation to emergency department in patients with COVID-19. Mayo Clin Proc 2020;95:2099–109. in Google Scholar

23. Goyal, P, Choi, JJ, Pinheiro, LC, Schenck, EJ, Chen, R, Jabri, A, et al.. Clinical characteristics of Covid-19 in New York City. N Engl J Med 2020;382:2372–4. in Google Scholar

Received: 2020-12-05
Accepted: 2021-01-05
Published Online: 2021-01-19
Published in Print: 2021-11-25

© 2021 Walter de Gruyter GmbH, Berlin/Boston