Respiratory virus infection among hospitalized adult patients with or without clinically apparent respiratory infection: a prospective cohort study

To, Kelvin Kai-Wang; Chan, Kwok‐Hung; Ho, John; Peng, Ping; Ho, Deborah Tip Yin; Chang, Arthur; Seng, Claudia Win May; Yip, Cyril Chik-Yan; Cheng, Vincent Chi-Chung; Hung, Ivan Fan-Ngai; Yuen, Kwok‐Yung

doi:10.1016/j.cmi.2019.04.012

Cited by 29 publications

(26 citation statements)

References 29 publications

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“…Our network pathway enrichment analysis showed that steroid-related pathways are enriched. RV is more likely to be associated with acute exacerbation of asthma than influenza virus infection (To et al, 2019). A previous study has shown that RV infection leads to steroid-resistance in airway epithelium (Papi et al, 2013).…”

Section: Discussionmentioning

confidence: 96%

Comparative Transcriptomic Analysis of Rhinovirus and Influenza Virus Infection

et al. 2020

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Section: Discussionmentioning

confidence: 96%

Comparative Transcriptomic Analysis of Rhinovirus and Influenza Virus Infection

et al. 2020

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“…This baseline is important as reliance on case counts alone can overlook subclinical infections, which are common for SARS-CoV-2 and other respiratory viruses. 30 In addition to monitoring the prevalence of subclinical infections, continuous monitoring of seroprevalence will help to establish the level of herd immunity in the population.…”

Section: Discussionmentioning

confidence: 99%

Seroprevalence of SARS-CoV-2 in Hong Kong and in residents evacuated from Hubei province, China: a multicohort study

Cheng

Cai³

et al. 2020

The Lancet Microbe

100

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Background The role of subclinical severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in perpetuating the COVID-19 pandemic is unknown because population seroprevalence data are absent. We aimed to establish the sensitivity and specificity of our enzyme immunoassay and microneutralisation assay, and the seroprevalence of SARS-CoV-2 in Hong Kong before and after the pandemic, as well as in Hong Kong residents evacuated from Hubei province, China. Methods We did a multicohort study in a hospital and university in Hong Kong. We evaluated the sensitivity of our enzyme immunoassay and microneutralisation assay with RT-PCR data from patients positive for SARS-CoV-2 and the specificity of our enzyme immunoassay and microneutralisation assay with archived serum samples collected before 2019. We compared the seropositivity of the general population of Hong Kong before and after the pandemic had begun, and determined the seropositivity of Hong Kong residents evacuated from Hubei province, China, in March, 2020. Findings Between Feb 26 and March 18, 2020, we assessed RT-PCR samples from 45 patients who had recovered from COVID-19 to establish the sensitivity of our enzyme immunoassay and microneutralisation assay. To establish the specificity of these assays, we retrieved archived serum. The sensitivity was 91·1% (41 of 45 [95% CI 78·8–97·5]) for the microneutralisation assay, 57·8% (26 of 45 [42·2–72·3]) for anti-nucleoprotein IgG, 66·7% (30 of 45 [51·1–80·0]) for anti-spike protein receptor binding domain (RBD) IgG, and 73·3% (33 of 45 [58·1–85·4]) for enzyme immunoassay (either positive for anti-nucleoprotein or anti-RBD IgG). The specificity was 100% (152 of 152 [95% CI 97·6–100·0]) for both the enzyme immunoassay and microneutralisation assay. Among the Hong Kong general population, 53 (2·7%) of 1938 were enzyme immunoassay positive, but of those who were positive, all 53 were microneutralisation negative, and no significant increase was seen in the seroprevalence between April 12, 2018, and Feb 13, 2020. Among asymptomatic Hubei returnees, 17 (4%) of 452 were seropositive with the enzyme immunoassay or the microneutralisation assay, with 15 (88%) of 17 seropositive with the microneutralisation assay, and two familial clusters were identified. Interpretation Our serological data suggest that SARS-CoV-2 is a new emerging virus. The seropositivity rate in Hubei returnees indicates that RT-PCR-confirmed patients only represent a small proportion of the total number of cases. The low seroprevalence suggests that most of the Hong Kong and Hubei population remain susceptible to COVID-19. Future waves of the outbreak are inevitable without a vaccine or antiviral prophylaxis. The role of age-related cross reactive non-neutralising antibodies in the pathogenesis of COVID-19 warrants further investigation. Funding Richard and Carol Yu, May Tam Mak Mei Yin, Shaw Foundation (Hong...

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“…If patients were intubated, we obtained endotracheal aspirate instead of posterior oropharynx saliva. 6,[9][10][11] Our initial experience showed that such saliva samples are promising in viral load monitoring in patients with COVID-19. 6 We also retrieved serum remnant from blood samples taken for routine bio chemical testing, and refrigerated these samples at -20°C until antibody testing could be done.…”

Section: Methodsmentioning

confidence: 99%

Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study

Tsang²,

Leung³

et al. 2020

The Lancet Infectious Diseases

3,050

207

3,427

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Background Coronavirus disease 2019 (COVID-19) causes severe community and nosocomial outbreaks. Comprehensive data for serial respiratory viral load and serum antibody responses from patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not yet available. Nasopharyngeal and throat swabs are usually obtained for serial viral load monitoring of respiratory infections but gathering these specimens can cause discomfort for patients and put health-care workers at risk. We aimed to ascertain the serial respiratory viral load of SARS-CoV-2 in posterior oropharyngeal (deep throat) saliva samples from patients with COVID-19, and serum antibody responses.Methods We did a cohort study at two hospitals in Hong Kong. We included patients with laboratory-confirmed COVID-19. We obtained samples of blood, urine, posterior oropharyngeal saliva, and rectal swabs. Serial viral load was ascertained by reverse transcriptase quantitative PCR (RT-qPCR). Antibody levels against the SARS-CoV-2 internal nucleoprotein (NP) and surface spike protein receptor binding domain (RBD) were measured using EIA. Whole-genome sequencing was done to identify possible mutations arising during infection.Findings Between Jan 22, 2020, and Feb 12, 2020, 30 patients were screened for inclusion, of whom 23 were included (median age 62 years [range 37-75]). The median viral load in posterior oropharyngeal saliva or other respiratory specimens at presentation was 5·2 log 10 copies per mL (IQR 4·1-7·0). Salivary viral load was highest during the first week after symptom onset and subsequently declined with time (slope -0·15, 95% CI -0·19 to -0·11; R²=0·71). In one patient, viral RNA was detected 25 days after symptom onset. Older age was correlated with higher viral load (Spearman's ρ=0·48, 95% CI 0·074-0·75; p=0·020). For 16 patients with serum samples available 14 days or longer after symptom onset, rates of seropositivity were 94% for anti-NP IgG (n=15), 88% for anti-NP IgM (n=14), 100% for anti-RBD IgG (n=16), and 94% for anti-RBD IgM (n=15). Anti-SARS-CoV-2-NP or anti-SARS-CoV-2-RBD IgG levels correlated with virus neutralisation titre (R²>0·9). No genome mutations were detected on serial samples.Interpretation Posterior oropharyngeal saliva samples are a non-invasive specimen more acceptable to patients and health-care workers. Unlike severe acute respiratory syndrome, patients with COVID-19 had the highest viral load near presentation, which could account for the fast-spreading nature of this epidemic. This finding emphasises the importance of stringent infection control and early use of potent antiviral agents, alone or in combination, for highrisk individuals. Serological assay can complement RT-qPCR for diagnosis.

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Respiratory virus infection among hospitalized adult patients with or without clinically apparent respiratory infection: a prospective cohort study

Cited by 29 publications

References 29 publications

Comparative Transcriptomic Analysis of Rhinovirus and Influenza Virus Infection

Comparative Transcriptomic Analysis of Rhinovirus and Influenza Virus Infection

Seroprevalence of SARS-CoV-2 in Hong Kong and in residents evacuated from Hubei province, China: a multicohort study

Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study

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