Viral emissions into the air and environment after SARS-CoV-2 human challenge: a phase 1, open label, first-in-human study

Zhou, Jie; Goonawardane, Niluka; Moshe, Maya; Sweeney, Fiachra; Sukhova, Ksenia; Killingley, Ben; Kalinova, Mariya; Mann, Alexander; Catchpole, Andrew; Barer, Michael R.; Ferguson, Neil M.; Chiu, Christopher; Barclay, Wendy S.

doi:10.1016/s2666-5247(23)00101-5

Cited by 40 publications

(33 citation statements)

References 31 publications

(39 reference statements)

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“…The samples were obtained at variable time points during the course of illness, and only nine studies reported Ct values from the stool specimens at the time of initial attempts at culture. Of the studies that reported Ct values from the faecal and other samples, all the 6 samples found to have presumptive evidence of culturable virus had Ct values reported as ≤ 30, which is in the range where a high likelihood of culturable virus may be found [22], [32], [33]. Considering only the cohort studies, there was a 1.2% (3/256 samples) positive frequency for those specimens.…”

Section: Resultsmentioning

confidence: 99%

Oro-faecal transmission of SARS-CoV-2: A systematic review of studies employing viral culture from gastrointestinal and other potential sources

Gandini,

Conly,

Spencer

et al. 2024

Preprint

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BackgroundThe extent to which the oro-faecal route contributes to the transmission of SARS-CoV-2 is not established.MethodsWe systematically reviewed the evidence on the presence of infectious SARS-CoV-2 in faeces and other gastrointestinal sources by examining studies that used viral culture to investigate the presence of replication-competent virus in these samples. We conducted searches in the WHO Covid-19 Database, LitCovid, medRxiv, and Google Scholar for SARS-CoV-2 using keywords and associated synonyms, with a search date up to 28th of November 2023.ResultsWe included 13 studies involving 328 COVID-19 subjects - providing 314 faecal or rectal swab SARS-CoV2 positive samples tested also with viral culture. The methods used for viral culture across the studies were heterogeneous. Three studies (2 cohorts and 1 case-series) reported observing replication-competent SARS-CoV-2 confirmed by quantitative RT-PCR (qPCR) and whole genome sequencing, and qPCR including appropriate cycle threshold changes. Overall, six (1.9%) of 314 faecal samples subjected to cell culture showed replication-competent virus. One study found replication competent samples from one immunocompromised patient. No studies were identified demonstrating direct evidence of oro-faecal transmission to humans.ConclusionsOur review found a relatively low frequency of replication-competent SARS-CoV-2 in faecal and other gastrointestinal sources. Although it is biologically plausible, more research is needed, using standardized cell culture methods, control groups, adequate follow-up and robust epidemiologic methods, including whether secondary infections occurred, to determine the role of the oro-faecal route in the transmission of SARS-CoV-2.

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Section: Resultsmentioning

confidence: 99%

Oro-faecal transmission of SARS-CoV-2: A systematic review of studies employing viral culture from gastrointestinal and other potential sources

Gandini,

Conly,

Spencer

et al. 2024

Preprint

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“…Unfortunately, no serological data were available for the HLA-B*15:01 carriers in the US prospective and the CHGE cohorts. We tested the hypothesis that the lack of association in our study was due to an absence of prior infection with OC43-CoV or HKU1-CoV by examining the data for the SARS-CoV-2 Human Challenge Characterisation Study (ClinicalTrials.gov identifier NCT04865237; funder, UK Vaccine Taskforce), in which 34 participants seronegative to spike protein were challenged with D614G-containing pre-Alpha SARS-CoV-2, of whom 33 consented for genetic analysis 17 . Serological data, history of prior infections with other coronaviruses and genetic data were available, together with infection status and data concerning the recorded symptoms.…”

Section: Resultsmentioning

confidence: 99%

“…34 participants seronegative to spike protein were challenged with D614G-containing pre-Alpha SARS-CoV-2, of whom 33 consented for genetic analysis. Additional details on the study design and participants were previously published 17 . Ethics approval was obtained from the UK Health Research Authority Ad Hoc Specialist Ethics Committee (reference: 20/UK/0002).…”

Section: Methodsmentioning

confidence: 99%

Lack of association between HLA and asymptomatic SARS-CoV-2 infection

Marchal,

Cirulli,

Neveux

et al. 2023

Preprint

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Human genetic studies of critical COVID-19 pneumonia have revealed the essential role of type I interferon-dependent innate immunity to SARS-CoV-2 infection. Conversely, an association between the HLA-B*15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals was recently reported, suggesting a contribution of pre-existing T cell-dependent adaptive immunity. We report a lack of association of classical HLA alleles, including HLA-B*15:01, with pre-omicron asymptomatic SARS-CoV-2 infection in unvaccinated participants in a prospective population-based study in the US (191 asymptomatic vs. 945 symptomatic COVID-19 cases). Moreover, we found no such association in the international COVID Human Genetic Effort cohort (206 asymptomatic vs. 574 mild or moderate COVID-19 cases and 1,625 severe or critical COVID-19 cases). Finally, in the Human Challenge Characterisation study, the three HLA-B*15:01 individuals infected with SARS-CoV-2 developed symptoms. As with other acute primary infections, no classical HLA alleles favoring an asymptomatic course of SARS-CoV-2 infection were identified. These findings suggest that memory T-cell immunity to seasonal coronaviruses does not strongly influence the outcome of SARS-CoV-2 infection in unvaccinated individuals.

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“…We found two studies comparing URT viral load to exhaled breath condensate (EBC) viral load [47, 143], but only one [47] found a correlation. Three studies [35, 48, 144] investigated whether more severe symptoms were associated with increased EBC viral load. All found a positive correlation, but in two [35, 144] the findings were not significant.…”

Section: Biological Evidencementioning

confidence: 99%

“…few studies have attempted to determine whether increased URT viral load is associated with increased viral load in exhaled breath condensate (EBC) (and therefore with the inoculant dose in those infected); the results so far have been inconclusive. In a human challenge study, Zhou et al[48] found that both nose and throat viral load significantly correlated with facemask sample viral load and Johnson et al[47] found a positive correlation between EBC and URT viral load (r = 0.5). However, Malik et al[143] found no correlation (correlation coefficient R 2 < 0.01).…”

mentioning

confidence: 99%

Symptom propagation in respiratory pathogens of public health concern: a review of the evidence

Asplin,

Mancy,

Finnie

et al. 2024

Preprint

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Symptom propagation occurs when the symptom set an individual experiences is correlated with the symptom set of the individual who infected them. Symptom propagation may dramatically affect epidemiological outcomes, potentially causing clusters of severe disease. Conversely, it could result in chains of mild infection, generating widespread immunity with minimal cost to public health.Despite accumulating evidence that symptom propagation occurs for many respiratory pathogens, the underlying mechanisms are not well understood. Here we conducted a scoping literature review for 14 respiratory pathogens to ascertain the extent of evidence for symptom propagation by two mechanisms: dose-severity relationships and route-severity relationships.We identify considerable heterogeneity between pathogens in the relative importance of the two mechanisms, highlighting the importance of pathogen-specific investigations. For almost all pathogens, including influenza and SARS-CoV-2, we found support for at least one of the two mechanisms. For some pathogens, including influenza, we found convincing evidence that both mechanisms contribute to symptom propagation.Furthermore, infectious disease models traditionally do not include symptom propagation. We summarise the present state of modelling advancements to address the methodological gap. We then investigate a simplified disease outbreak scenario, finding that under strong symptom propagation, quarantining mildly infected individuals can have negative epidemiological implications.

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Viral emissions into the air and environment after SARS-CoV-2 human challenge: a phase 1, open label, first-in-human study

Cited by 40 publications

References 31 publications

Oro-faecal transmission of SARS-CoV-2: A systematic review of studies employing viral culture from gastrointestinal and other potential sources

Oro-faecal transmission of SARS-CoV-2: A systematic review of studies employing viral culture from gastrointestinal and other potential sources

Lack of association between HLA and asymptomatic SARS-CoV-2 infection

Symptom propagation in respiratory pathogens of public health concern: a review of the evidence

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