key: cord-0931954-u5q5ghrc
authors: Monto, Arnold S; DeJonge, Peter; Callear, Amy P; Bazzi, Latifa A; Capriola, Skylar; Malosh, Ryan E; Martin, Emily T; Petrie, Joshua G
title: Coronavirus occurrence and transmission over 8 years in the HIVE cohort of households in Michigan
date: 2020-04-04
journal: J Infect Dis
DOI: 10.1093/infdis/jiaa161
sha: d5ac016c92e3b02870f7761d52e80824c9ed0b14
doc_id: 931954
cord_uid: u5q5ghrc

BACKGROUND: As part of the Household Influenza Vaccine Evaluation (HIVE) study, acute respiratory infections (ARI) have been identified in children and adults over 8 years. METHODS: Annually, 890 to 1441 individuals were followed and contacted weekly to report ARIs. Specimens collected during illness were tested for human coronaviruses (HCoV) types OC43, 229E, HKU1, and NL63. RESULTS: In total, 993 HCoV infections were identified over 8 years, with OC43 most commonly seen and 229E the least. HCoVs were detected in a limited time period, between December and April/May, and peaked in January/February. Highest infection frequency was in children <5 years (18 per 100 person-years), with little variation in older age groups (range: 7 to 11 per 100 person-years). Overall, 9% of adult cases and 20% of cases in children were associated with medical consultation. Of the 993 infections, 260 were acquired from an infected household contact. The serial interval between index and household-acquired cases ranged from 3.2 to 3.6 days and the secondary infection risk ranged from 7.2% to 12.6% by type. CONCLUSIONS: Coronaviruses are sharply seasonal. They appear, based on serial interval and secondary infection risk, to have similar transmission potential to influenza A(H3N2) in the same population.

secondary infection risk, to have similar transmission potential to influenza A(H3N2) in 23 the same population. 24 A c c e p t e d M a n u s c r i p t Coronaviruses, long known to infect a wide variety of species, have been recognized as 25 human respiratory pathogens for more than 60 years. [1] [2] [3] While animal coronaviruses 26 have been associated with severe disease in their respective hosts, human 27 coronaviruses (HCoV) were historically detected in mild respiratory illnesses. 4-6 28 Therefore, the identification of Severe Acute Respiratory Syndrome (SARS) as caused 29 by a coronavirus of animal origin in 2002 was a surprise because of its epidemic 30 behavior as well as its severity. 7, 8 Also a surprise was ultimate interruption of SARS 31 transmission by public health measures. 9 In 2012, another novel coronavirus of animal 32 origin emerged as the causative agent of Middle East Respiratory Syndrome (MERS). 10 

Unlike SARS, human-to-human transmission of MERS has been limited and sporadic 34 cases have continued to occur primarily in Saudi Arabia among those with contact with 35 camels. 11 The current outbreak of a novel coronavirus (SARS-CoV-2) has focused 36 attention back to this often forgotten and unstudied group of pathogens. 12 

HCoVs were first recognized when specimens from individuals ill with respiratory 38 illnesses were inoculated into organ cultures. One of these viruses is now known as OC 39 (organ culture) 43. 13 Another virus, 229E was first grown in primary human kidney 40 culture. 14 Because of the difficulties in isolating them, much of the initial work in 41 understanding their occurrence in was done by serology. 15, 16 Following renewed interest 42 after the SARS epidemic, two additional coronaviruses, HKU1 and NL63, were identified 43 in the 2000's, first from persons with severe respiratory illnesses. 17-20 44 Availability of reverse-transcriptase polymerase chain reaction (RT-PCR) has now made 45 it possible to detect infection easily for each of the 4 known human coronaviruses. 46 However, as data from population-based studies using molecular methods have A c c e p t e d M a n u s c r i p t accumulated, minimal attention has been paid to these viruses, perhaps because there HCoV type involved in coincident detection was also included in type-specific analyses.

Type-specific coronavirus incidence and corresponding 95% confidence intervals were 103 calculated by age group (<5, 6-11, 12-17, 18-49, and ≥50 years) and by study year. Age-adjusted multinomial logistic regression models were then used to compare the 128 odds of being assigned to each latent class between the four HCoV types.

Characteristics of the study population 131 The number of individuals under study ranged from 895 to 1441, and the number of 132 households ranged from 209 to 340 over the 8 years (Table 1) 

The number of ARIs reported also varied from year to year, mainly related to the 139 number of individuals on report but also the differential occurrence of influenza and 140 other respiratory viruses (Table 1) person-years was relatively low and did not vary by age, the incidence was consistently 166 highest among children less than 5 years (Figure 3 ). Among those older than 5 years, 167 incidence was relatively flat with little consistent variation with increase in age. a n u s c r i p t illnesses in children less than 5 years and adults older than 50 years were most likely to 180 be classified as severe. In age-adjusted multinomial regression models (Table 2) (Table 3) . has most frequently infected adults to date. 30 Whether the relative sparing of children 236 has largely been driven by contact and exposure patterns or other factors remains 237 unclear. However, the frequency of infection in adults suggests that there is likely little 238 cross-protective immunity from prior seasonal HCoV infection.

The MERS coronavirus is limited in its potential for human to human transmission 240 except in the nosocomial setting. 11 Although the SARS coronavirus more effectively 241 transmitted human to human, transmission was interrupted by public health 242 interventions. 31 The seasonal HCoV viruses are clearly different in their transmission 243 characteristics given their continued seasonal circulation year after year. The serial 244 interval between cases and the secondary infection risk in the HIVE cohort was similar 245 to that previously found for A(H3N2). 32 Our secondary attack rates may reflect the 246 smaller household structure found in our region. A longitudinal study in Kenya found 247 M a n u s c r i p t overall attack rates as high as 34.0% over one season in a study of households of sizes 248 ranging to 37 members. 33 

The transition from pandemic to seasonal circulation is well established for influenza, 250 wherein, following an influenza pandemic, the novel virus becomes the new seasonal 251 virus, replacing the previous A subtype. 34 The four current HCoVs have been circulating 252 for decades, and it is unclear how they initially emerged or whether they replaced 253 previously circulating viruses. 35 

Cultivation of a Novel Type of Common-cold Virus in Organ Cultures

A new virus isolated from the human respiratory tract

Recovery in tracheal organ cultures of novel viruses from patients with respiratory disease

CORONAVIRUS 229E INFECTIONS DURING SIX YEARS OF SURVEILLANCE

Animal coronaviruses : what can they teach us about the severe acute respiratory syndrome?

Identification of a novel coronavirus in patients with severe acute respiratory syndrome

Coronavirus as a possible cause of severe acute respiratory syndrome

SARS : how a global epidemic was stopped

Manila : WHO Regional Office for the Western Pacific

Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia

Middle East respiratory syndrome coronavirus: risk factors and determinants of primary, household, and nosocomial transmission

A Novel Coronavirus from Patients with Pneumonia in China

The adaptation of two human coronavirus strains (OC38 and OC43) to growth in cell monolayers

Growth and Intracellular Development of a New Respiratory Virus

Community-wide Outbreak of Infection with a 229E-like Coronavirus in Tecumseh, Michigan

The Tecumseh Study of Respiratory Illness. VI. Frequency of and Relationship between Outbreaks of Coronavims Infection

Isolation and Characterization of Viruses Related to the SARS Coronavirus from Animals in Southern China

Characterization and Complete Genome Sequence of a Novel Coronavirus, Coronavirus HKU1, from Patients with Pneumonia

Data resource profile: Household Influenza Vaccine Evaluation (HIVE) Study

Comparison of fast-track diagnostics respiratory pathogens multiplex real-time RT-PCR assay with in-house singleplex assays for comprehensive detection of human respiratory viruses

SEROEPIDEMIOLOGIC SURVEY OF CORONAVIRUS (STRAIN 229E) INFECTIONS IN A POPULATION OF CHILDREN

Coronavirus Infections in Working Adults

OC43 strain-related coronavirus antibodies in different age groups

Human Coronavirus in Hospitalized Children With Respiratory Tract Infections: A 9-Year Population-Based Study From Norway

Epidemiology of viral respiratory tract infections in a prospective cohort of infants and toddlers attending daycare

Investigation of the second wave (phase 2) of severe acute respiratory syndrome (SARS) in Toronto, Canada. What happened?

Frequency of Acute Respiratory Illnesses and Circulation of Respiratory Viruses in Households With Children Over 3 Surveillance Seasons

Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia

Transmission Dynamics and Control of Severe Acute Respiratory Syndrome

Influenza transmission in a cohort of households with children

Continuous Invasion by Respiratory Viruses Observed in Rural Households During a Respiratory Syncytial Virus Seasonal Outbreak in Coastal Kenya

Lessons from Influenza Pandemics of the last 100 Years

The Pediatric Burden of Human Coronaviruses Evaluated for Twenty Years

Table 1: Characteristics of the study population and counts of human coronavirus infections by study year: Household Influenza Vaccine Evaluation (HIVE) cohort

a Individual types sum to more than all types because coinfections were counted in each type, but only included as single cases in counts of all types. Abbreviation: HCoV

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