Estimating Global Epidemiology of Low-Pathogenic
Human Coronaviruses in Relation to the COVID-19
Context
Pengfei Li, Jiaye Liu, Zhongren Ma, Wichor M Bramer, Maikel P Peppelenbosch,
Qiuwei Pan
The Journal of Infectious Diseases
C O R R E S P O N D E N C E
CORRESPONDENCE • jid 2020:222 (15 August) • 695 Estimating Global Epidemiology
of Low-Pathogenic Human Coronaviruses in Relation to the COVID-19 Context
To the Editor—Coronaviruses (CoV) comprise a large family of zoonotic RNA viruses. Among the 7 members known to infect humans, SARS-CoV-2, the causa-tive agent of COVID-19, together with SARS-CoV and MERS-CoV, cause se-vere respiratory syndrome. The other 4 members, including NL63, HKU1, OC43, and 229E, are widely circulating in humans but predominantly cause mild respiratory tract illness [1]. Thus we call these 4 viruses low-pathogenic human CoVs (LPH-CoV). Two recent studies by Nickbakhsh et al and Monto et al in The Journal of Infectious Diseases have reported the prevalence of LPH-CoV as 4.0% in western Scotland and
8.3%–16.3% in Michigan, United States [2, 3]. Interestingly, both studies de-tected the highest frequency of infection in children younger than 5 years. This is the opposite to the COVID-19 pan-demic where children are less commonly affected by SARS-CoV-2 [4]. These in-triguing findings trigger important hy-potheses on whether coinfection with LPH-CoV interferes with SARS-CoV-2 or exposure to LPH-CoV confers cross-protective immunity to some extent.
As COVID-19 is currently affecting the global population and research on LPH-CoV has been largely neglected in the past, we attempted to perform a sys-tematic review and meta-analysis to map the global epidemiology of LPH-CoV. LPH-CoV–related studies from 1990 to March 2020 were systematically searched in Medline, Embase, Web of Science,
Cochrane Central Register of Controlled Trials (CENTRAL), and Google scholar. Studies were included and data extracted only if they reported participants with symptoms of acute respiratory tract in-fections or influenza like illness. A 95% confidence interval (95% CI) was es-timated using Wilson score method. Pooled prevalence (detection rate) was calculated using the DerSimonian-Laird random-effects model with Freeman-Tukey double arcsine transformation.
In total, 128 studies with 205 421 in-dividuals were included, and an overall infection rate was estimated as 5.21% (95% CI, 4.62%–5.83%; I2 = 97%). The
prevalence of LPH-CoV varied sub-stantially among the reported 44 coun-tries, from 0.73% (Philippines; 95% CI, 0.09%–1.84%) to 21.51% (Tunisia; 95% CI, 17.47%–25.83%) (Figure 1A and 1B).
A C B Prevalence 20% 15% 10% 5% 25 20 15 10 5 0 Distrib ution of confir med cases (%) 5.09%5.63% 6.97% 5.63% 0.80%2.41%1.87% 10.45% 13.67%14.20% 13.40% 19.57%
Oct Nov Dec Jan FebMar Apr May Jun Jul Aug Sep
Country Positive patients All patients Proportion (95% Cl) Australia 74 125 30 30 149 1876 9 35 251 68 47 81 7 26 198 175 40 580 21 35 28 30 116 26 230 303 25 367 11 3 5 23 81 6 60 66 1652 48 71 20 131 80 29 18 1231 12 523 514 2277 526 561 6221 70 988 277 739 6064 1041 665 593 244 300 1910 4259 1059 7158 450 417 309 311 2060 1404 2693 3899 407 3910 172 411 114 369 2370 67 972 1528 40 150 686 1166 112 8462 372 2428 369 24 417 205 421 Brazil Cambodia Cemeroon Canada China Egypt Finland Germany Gabon France Greece Ghana India Israel Italy Ivory Coast Japan Jordan Kenya Laos Madagascar Malaysia Multiple countries Mexico Nepal Netherlands Norway Peru Philippines Poland Qatar Senegal Saudi arabia Slovenia South Africa South Korea Spain Sweden Switzer1and Thailand Tunisia Turkey Uganda USA Global prevalence 14.40% (11.49–17.57) 4.65% (3.06–6.53) 5.71% (2.68–9.72) 5.35% (3.63–7.38) 3.50% (2.03–5.33) 4.12% (3.11–5.26) 3.22% (1.36–5.73) 4.68% (3.25–6.35) 5.30% (2.86–8.43) 6.53% (5.11–8.12) 7.07% (5.24–9.15) 13.66% (11.01–16.55) 2.87% (1.08–5.40) 8.67% (5.72–12.14) 10.37% (9.04–11.77) 3.83% (2.65–5.20) 7.93% (5.15–11.23) 5.77% (.00–21.40) 8.39% (5.91–11.26) 9.06% (6.09–12.54) 9.65% (6.59–13.20) 5.63% (4.68–6.67) 1.85% (1.21–2.63) 6.68% (.02–23.21) 6.90% (4.56–9.67) 8.14% (1.11–19.72) 10.15% (7.51–13.13) 6.40% (3.16–10.60) 0.73% (.09–1.84) 4.39% (1.25–9.06) 6.23% (3.97–8.95) 3.28% (2.58–4.05) 8.96% (3.09–17.16) 6.16% (4.72–7.77) 4.21% (3.14–5.43) 3.90% (2.43–5.70) 7.00% (5.20–9.03) 6.04% (4.73–7.49) 17.86% (11.26–25.55) 2.29% (.55–5.10) 21.51% (17.47-25.83) 2.36% (.00–8.06) 4.88% (2.89–7.34) 6.01% (4.15–8.17) 5.21% (4.62–5.83) 3.78% (2.71–5.02) 0 10% 20% Prevalence of LPH-CoV 30% 40%
Figure 1. A, Global prevalence of LPH-CoV. The rate was determined as positive cases in tested populations with respiratory illness or symptoms. B, Forest plot of LPH-CoV prevalence among 44 countries. C, Monthly distribution of confirmed LPH-CoV cases. Abbreviations: CI, confidence interval; LPH-CoV, low-pathogenic human coronavirus.
696 • jid 2020:222 (15 August) • CORRESPONDENCE The number of available studies was very
limited and many studies had small pop-ulation sizes. This likely caused bias in prevalence estimations. Furthermore, similar to the studies of Nickbakhsh et al and Monto et al [2, 3], our included studies only detected LPH-CoV in indi-viduals with respiratory illness or symp-toms. This suggests that the prevalence rate of LPH-CoV in the general popu-lation could be even lower, raising the question of how large the impact could be on COVID-19.
Monto et al have nicely presented the seasonal distribution of the identified cases in Michigan according to the 4 LPH-CoV types [3]. We performed sim-ilar analyses by pooling 5 studies with relevant data, and all these studies were from countries in the northern hemi-sphere. We confirmed their findings that more cases were detected in the winter season (Figure 1C). However, we are cau-tious about the interpretation of these seasonal distribution data (Figure 1C) [3] because they only specified the iden-tified cases and not the rate of infection, as the total number of tested cases in each month was not given. More importantly, whether SARS-CoV-2 will develop into a seasonal and/or endemic virus only time will tell [3].
In summary, we have comprehensively estimated the global prevalence of LPH-CoV among 44 countries and mapped their seasonal distribution. Our results further strengthen the epidemiological findings of Nickbakhsh et al and Monto et al, but also raise cautions about the interpretation of existing data. We agree that continued and enhanced monitoring of circulating HLP-CoV is necessary to understand how they may have an im-pact on the epidemiology and outcome of COVID-19 [5, 6].
Notes
Author contributions. P. L., J. L., and Q. P. designed the project and analyzed the data. P. L. drafted the manuscript. W. M. B. performed database searching.
Z. M. and M. P. P. discussed the project and critically revised the manuscript. All authors reviewed the final version of the manuscript and approved for submission.
Disclaimer. Funding sources had no role in the design and conduct of the study; collection, management, anal-ysis, and interpretation of the data; and preparation, review, or approval of the manuscript.
Financial support. This work was sup-ported by the Netherlands Organization for Scientific Research (grant number 91719300 to Q. P.); and the China Scholarship Council (grant numbers 201808370170 and 201606240079 PhD fellowships to P. L. and J. L.).
Potential conflicts of interest. All au-thors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors con-sider relevant to the content of the manu-script have been disclosed.
Pengfei Li,1 Jiaye Liu,1 Zhongren Ma,2
Wichor M. Bramer,3 Maikel P. Peppelenbosch,1 and
Qiuwei Pan1,2
1Department of Gastroenterology and Hepatology, Erasmus
University Medical Center, Rotterdam, The Netherlands,
2Biomedical Research Center, Northwest Minzu University,
Lanzhou, China, and 3Medical Library, Erasmus University
Medical Center, Rotterdam, The Netherlands References
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3. Monto AS, DeJonge P, Callear AP, et al. Coronavirus occurrence and transmission over 8 years in the HIVE cohort of households in Michigan . J Infect Dis 2020; 222:9–16.
4. Zimmermann P, Curtis N. Coronavirus infections in children including COVID-19: an overview
of the epidemiology, clinical features, diagnosis, treatment and prevention options in children. Pediatr Infect Dis J 2020; 39:355–68.
5. Bedford J, Enria D, Giesecke J, et al; WHO Strategic and Technical Advisory Group for Infectious Hazards. COVID-19: towards con-trolling of a pandemic. Lancet 2020; 395:1015–8.
6. Ji Y, Ma Z, Peppelenbosch MP, Pan Q. Potential association between COVID-19 mortality and health-care resource availability. Lancet Glob Health 2020; 8:e480.
Received 1 May 2020; editorial decision 2 June 2020; ac-cepted 8 June 2020; published online June 4, 2020.
Correspondence: Qiuwei Pan, PhD, Erasmus MC, Wytemaweg 80, NL-3015 CE Rotterdam, The Netherlands (q.pan@erasmusmc.nl).
The Journal of Infectious Diseases® 2020;222:695–6
© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/ by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com DOI: 10.1093/infdis/jiaa321
Reply to Li et al
To the Editor—We read with interest the letter by Li et al [1] reporting on the global prevalence of endemic human coronaviruses. The last decade has wit-nessed an expansion of global surveil-lance efforts in influenza and respiratory syncytial virus infections, leading to an increased recognition of the impor-tance of these viruses, particularly in low- and middle-income settings [2]. However, a paucity of epidemiological research exists for other respiratory vir-uses, as highlighted by the World Health Organization’s Battle Against Respiratory Viruses initiative [3].
Such knowledge is currently hin-dered by the lack of capacity of many diagnostic laboratories, including those
