Interindividual clinical variability in the course of SARS-CoV-2 infection is immense. We report that at least 101 of 987 patients with life-threatening COVID-19 pneumonia had neutralizing IgG auto-Abs against IFN-ω (13 patients), the 13 types of IFN-α (36), or both (52), at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1,227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 were men. A B cell auto-immune phenocopy of inborn errors of type I IFN immunity underlies life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.

Clinical outcome upon infection with SARS-CoV-2 ranges from silent infection to lethal COVID-19. We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern TLR3- and IRF7-dependent type I interferon (IFN) immunity to influenza virus, in 659 patients with life-threatening COVID-19 pneumonia, relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally define LOF variants in 23 patients (3.5%), aged 17 to 77 years, underlying autosomal recessive or dominant deficiencies. We show that human fibroblasts with mutations affecting this pathway are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection.

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We have recently described the discovery of a novel coronavirus, coronavirus HKU1 (CoV-HKU1), associated with community-acquired pneumonia. However, the clinical spectrum of disease and the epidemiology of CoV-HKU1 infections in relation to infections with other respiratory viruses are unknown. In this 12-month prospective study, 4,181 nasopharyngeal aspirates from patients with acute respiratory tract infections were subjected to reverse transcription-PCRs specific for CoV-HKU1 and human coronaviruses NL63 (HCoV-NL63), OC43 (HCoV-OC43), and 229E (HCoV-229E). Coronaviruses were detected in 87 (2.1%) patients, with 13 (0.3%) positive for CoV-HKU1, 17 (0.4%) positive for HCoV-NL63, 53 (1.3%) positive for HCoV-OC43, and 4 (0.1%) positive for HCoV-229E. Of the 13 patients with CoV-HKU1 infections, 11 were children and 8 had underlying diseases. Similar to the case for other coronaviruses, upper respiratory infection was the most common presentation of CoV-HKU1 infections, although pneumonia, acute bronchiolitis, and asthmatic exacerbation also occurred. Despite a shorter duration of fever (mean, 1.7 days) and no difference in maximum temperature in children with CoV-HKU1 infections compared to patients with most other respiratory virus infections, a high incidence of febrile seizures (50%) was noted, which was significantly higher than those for HCoV-OC43 (14%), adenovirus (9%), human parainfluenza virus 1 (0%), and respiratory syncytial virus (8%) infections. CoV-HKU1 and HCoV-OC43 infections peaked in winter, although cases of the former also occurred in spring to early summer. This is in contrast to HCoV-NL63 infections, which mainly occurred in early summer and autumn but were absent in winter. Two genotypes of CoV-HKU1 cocirculated during the study period. Continuous studies over a longer period are warranted to ascertain the seasonal variation and relative importance of the different coronaviruses. Similar studies in other countries are required to better determine the epidemiology and genetic diversity of CoV-HKU1.Since a significant proportion of patients with respiratory tract infections remain undiagnosed (14, 24), research has been conducted to identify novel causative agents. Of the four novel agents identified in the past 3 years, including human metapneumovirus (28), severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) (21), human coronavirus NL63 (HCoV-NL63) (9, 29), and coronavirus HKU1 (CoV-HKU1) (32), three are coronaviruses. Based on serologic and phylogenetic characterization, coronaviruses were divided into three distinct groups, with human coronavirus 229E (HCoV-229E) and HCoV-NL63 being group 1 coronaviruses and human coronavirus OC43 (HCoV-OC43) and CoV-HKU1 being group 2 coronaviruses (12). SARS-CoV, which causes the most severe form of respiratory disease among coronaviruses that infect humans (3, 11, 19-21, 33, 34), represents an early split from group 2 coronaviruses (7,15,23,26) and is believed to have originated from wild animals (10, 13).While HCoV-229E and HCoV-OC43 were kn...

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Although human coronavirus OC43-OC43 (HCoV-OC43Coronaviruses cause infections in a wide variety of animals, resulting in respiratory, enteric, hepatic, and neurological diseases of various levels of severity. Based on genotypic and serological characterization, coronaviruses traditionally were classified into three distinct groups, groups 1, 2, and 3 (4). Recently, the Coronavirus Study Group of the International Committee for Taxonomy of Viruses has renamed the traditional group 1, 2, and 3 coronaviruses as Alphacoronavirus, Betacoronavirus, and Gammacoronavirus, respectively (http: //talk.ictvonline.org/media/p/1230.aspx).The recent severe acute respiratory syndrome (SARS) epidemic due to SARS coronavirus (SARS-CoV) and the identification of SARS-related coronaviruses (SARSr-CoVs) from Himalayan palm civets and horseshoe bats in mainland China have led to a boost in interest in the study of coronaviruses in both humans and animals (5,13,24,26,33,37,55). Before the SARS epidemic in 2003, there were only 19 known coronaviruses, including 2 human, 13 mammalian, and 4 avian coronaviruses. After the SARS epidemic, more than 20 additional novel coronaviruses have been described with complete genome sequences (9, 24-26, 31, 42, 45, 50, 53, 54, 57). These include 3 human coronaviruses, 15 mammalian coronaviruses, and 4 avian coronaviruses. For human coronaviruses, human coronavirus NL63 (HCoV-NL63) (an alphacoronavirus) and human coronavirus HKU1 (HCoV-HKU1) (a betacoronavirus) have been discovered in addition to the two previously known human coronaviruses, human coronavirus 229E (HCoV-229E) (an alphacoronavirus) and human coronavirus OC43 (HCoV-OC43) (a betacoronavirus), as well as SARSCoV (a betacoronavirus) (9,45,53,56). While HCoV-229E and HCoV-OC43 were thought to account for 5 to 30% of human respiratory tract infections, HCoV-NL63 and HCoV-HKU1 often were detected in Ͻ5% of respiratory tract samples (23,29,38). Outbreaks due to HCoV-OC43 also have been reported (3,32,44). Nevertheless, the different HCoVs often cocirculate, with one or two HCoVs being predominant depending on the geographical area and year (8,11,19,23).Coronaviruses are unique in having a high frequency of homologous RNA recombination, which is a result of random

Background Serial cross-sectional data on antibody levels to 2009 pandemic influenza A (H1N1) virus from a population can be used to estimate the infection attack rates and immunity against future infection in the community. Methods Between April and December 2009, we obtained 12,217 serum specimens from blood donors (16–59 yo), 2,520 from hospital outpatients (5–59yo), and 917 from subjects of a community pediatric cohort study (5–14yo). We estimated infection attack rates by comparing the proportions of specimens with antibody titers ≥1:40 by viral microneutralization before and after the first wave of the pandemic. Estimates were validated using paired sera from 324 individuals that spanned the first wave. Combining these estimates with epidemiologic surveillance data, we calculated the proportion of infections that led to hospitalization, intensive care admission, and death. Results We found that 3.3% and 14% of 5–59 yo had antibody titers ≥1:40 before and after the first wave. The overall attack rate was 10.7% with the following age-stratification: 43.4% in 5–14 yo, 15.8% in 15–19 yo, 11.8% in 20–29 yo, and 4–4.6% in 30–59 yo. Case-hospitalization rates were 0.47%–0.87% among 5–59 yo. Case-ICU and case-fatality rates increased from 7.9 and 0.4 per 100,000 infections in 5–14 yo to 75 and 26.5 per 100,000 infections in 50–59 yo. Conclusions Almost half of all school-children in Hong Kong were infected during the first wave. Compared to school-children aged 5–14, older adults aged 50–59 had 9.5 and 66 times higher risk of ICU admission and death if infected.

HBoV was detected in fecal specimens in children with acute gastroenteritis. A single lineage of HBoV was associated with both respiratory tract and enteric infections.