key: cord-0690636-uhfq7241
authors: Li, Pengfei; Ikram, Aqsa; Peppelenbosch, Maikel P; Ma, Zhongren; Pan, Qiuwei
title: Systematically mapping clinical features of infections with classical endemic human coronaviruses
date: 2020-09-14
journal: Clin Infect Dis
DOI: 10.1093/cid/ciaa1386
sha: 2f9f101b965b4f3f884a67cb3a63bdac7b3420b9
doc_id: 690636
cord_uid: uhfq7241

nan

A c c e p t e d M a n u s c r i p t Dear editor,

The classical endemic human coronaviruses including HKU1, OC43, NL63 and 229E are widely circulating among the global population. However, research on these coronaviruses has been largely neglected, until the recent outbreak of SARS-CoV-2 that caused COVID-19 pandemic. Emerging evidence indicates cross-reactive immunity towards SARS-CoV-2 by pre-exposure of endemic coronaviruses, which may induce possible protective effects but could also interfere with serological diagnosis of COVID-19 [1] . Therefore, several recent studies have investigated the prevalence of these endemic coronaviruses [2] [3] [4] . In line with these studies, Cummings et al [5] found that 8% of healthcare personnel were infected with endemic coronavirus, and they further investigated risk factors of the infection. However, little efforts have been dedicated to understand their clinical features. Such knowledge is essentially required for assessing the burden of endemic coronavirus infection per se, but also for better understanding the implications in COVID-19 pandemic.

In this study, we performed a systematic review and meta-analysis to comprehensively characterize the epidemiology and clinical features of endemic coronavirus infection (supplementary data). From 3225 searched records, we identified 157 eligible studies originated from 44 countries/territories across six continents.

Among the reported 282162 outpatient clinic or hospitalized patients with respiratory symptoms, OC43 was estimated as the most prevalent genotype (2.40%, 95% CI 2.15-2.66%, I 2 =95%), followed by NL63 (1.60%, 95% CI 1.39-1.82%, I 2 = 95%), HKU1

(1.04%, 95% CI 0.85-1.25%, I 2 = 94%) and 229E (0.97%, 95% CI 0.82-1.15%, I 2 = 95%) ( Figure 1A, supplementary data) . Interestingly, the young children group with 0-9 years A c c e p t e d M a n u s c r i p t old has the highest infection rate of 4.71% (95% CI 3.89-5.60%; I 2 =94%), as compared to 0.94% and 2.35% in two older age groups ( Figure 1B, supplementary data ). This appears in line with the findings of Cummings et al [5] that younger healthcare personnel, those who saw pediatric patients and those with household members under the age of five are at increased risk of infection.

In total, 18 types of clinical symptoms and features have been identified among endemic coronavirus confirmed patients by pooling all the studies irrespective of the genotypes or possible co-infection with multiple genotypes. Fever, cough, rhinorrhea, sore throat and headache commonly occurred in over half of the confirmed patients.

Diarrhea was reported in about 5% of patients. Unexpectedly, over 25% patients developed pneumonia potentially resulting in serious complications, although the severity of pneumonia was not specified in these studies ( Figure 1C) . We further stratified patients with mono-infection of 229E, HKU1, NL63 or OC43, and characterized their clinical symptoms and features respectively ( Figure 1D ). Strikingly, pneumonia was reported in over 40% patients with NL63 or OC43 infection, although the included patient number is small (supplementary data). M a n u s c r i p t A c c e p t e d M a n u s c r i p t 

Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals

Estimating Global Epidemiology of Low-Pathogenic Human Coronaviruses in Relation to the COVID-19 Context

Epidemiology of Seasonal Coronaviruses: Establishing the Context for the Emergence of Coronavirus Disease

Coronavirus Occurrence and Transmission Over 8 Years in the HIVE Cohort of Households in Michigan

Risk Factors for Healthcare Personnel Infection with Endemic Coronaviruses (HKU1, OC43, NL63, 229E): Results from the Respiratory Protection Effectiveness Clinical Trial

We greatly thank Wichor M. Bramer from the Medical Library, Erasmus MC-University Medical Center for conducting literature search. 

All the authors declare that they have no conflict of interest.

A c c e p t e d M a n u s c r i p t