Pub Date : 2026-01-01DOI: 10.1016/j.lanmic.2025.101227
Melisa M Shah MD , Glen R Abedi MPH , Scott Lu MBBS , Miguel Garcia-Knight PhD , Jesus Pineda-Ramirez BA , Sarah A Goldberg MAS , Prof Carlos G Grijalva MD , Prof H Keipp Talbot MD MPH , Jonathan Schmitz MD PhD , Karen Lutrick PhD , Katherine D Ellingson PhD , Prof Melissa S Stockwell MD MPH , Ellen Sano DO , Huong Q Nguyen PhD , Suchitra Rao MBBS , Prof Edwin J Asturias MD , Mehul S Suthar PhD , Alexandra M Mellis PhD , Prof Steven G Deeks MD , Prof Jeffrey N Martin MD , Amethyst Zhang
<div><h3>Background</h3><div>The effect of COVID-19 oral antivirals on the duration of SARS-CoV-2 infectious viral shedding and viral rebound remains uncertain. This study aimed to examine the association of oral antivirals with viral dynamics, shedding of infectious virus, and SARS-CoV-2 rebound.</div></div><div><h3>Methods</h3><div>A prospective case-ascertained household study design was used. Participants were non-hospitalised adults older than 18 years with symptomatic SARS-CoV-2 enrolled in one of two prospective household transmission studies (University of California, San Francisco, FindCOVID and Respiratory Virus Transmission Network–Sentinel [RVTN–S]) conducted in the USA across six states at academic institutions from Jan 1, 2022 to June 10, 2023. We excluded those reporting receipt of multiple COVID-19 outpatient medications, treatment with remdesivir, a treatment duration of more than 6 days, and those from whom fewer than five daily anterior nasal swabs were collected during their illness. Participants were considered to be at high risk of severe COVID-19 (and, therefore, eligible for SARS-CoV-2 oral antiviral treatment) if they were aged 50 years or older or were aged 18 years or older and reporting at least one underlying condition. Study procedures included frequent self-collected nasal swabs (daily for 14 days after symptom onset and then every 3 days until day 28 after symptom onset in FindCOVID and two nasal swabs daily for 10 days from enrolment in RVTN-S) and viral testing by quantitative reverse transcriptase PCR (qRT-PCR), at-home antigen testing, and viral culture. Treatment was defined as self-reported receipt of an oral antiviral (nirmatrelvir–ritonavir or molnupiravir). The primary analysis compared viral detection by qRT-PCR, antigen test positivity, and culture positivity and assessed SARS-CoV-2 viral rebound (viral RNA, antigen, culture, and symptom rebound) in untreated and treated participants at high risk of severe outcomes. We used multivariable Poisson regression to assess associations between treatment, duration of test positivity, and the presence of viral culture rebound, adjusting for age, underlying conditions, and recent immunological events.</div></div><div><h3>Findings</h3><div>Between Jan 1, 2022, and June 10, 2023, 160 individuals with symptomatic COVID-19 and at high risk of severe outcomes were included in FindCOVID and RVTN–S. There was no significant difference in the duration of viral detection between treated and untreated participants at high risk of severe COVID-19 by antigen test positivity (6 days [IQR 5–11] <em>vs</em> 8 days [5–10]; adjusted relative risk [RR] 1·07, 95% CI 0·24–4·81) or viral culture (7 days [4–11] <em>vs</em> 6 days [5–9]; 2·21, 0·45–10·79). Among 122 participants without viral RNA rebound, the last day of antigen test positivity and detection of culturable virus post-symptom onset was earlier in treated participants than in untreated participants (5 days [4–8] <em>vs</em
{"title":"SARS-CoV-2 infectious shedding and rebound among adults with and without oral antiviral use: two case-ascertained prospective household studies","authors":"Melisa M Shah MD , Glen R Abedi MPH , Scott Lu MBBS , Miguel Garcia-Knight PhD , Jesus Pineda-Ramirez BA , Sarah A Goldberg MAS , Prof Carlos G Grijalva MD , Prof H Keipp Talbot MD MPH , Jonathan Schmitz MD PhD , Karen Lutrick PhD , Katherine D Ellingson PhD , Prof Melissa S Stockwell MD MPH , Ellen Sano DO , Huong Q Nguyen PhD , Suchitra Rao MBBS , Prof Edwin J Asturias MD , Mehul S Suthar PhD , Alexandra M Mellis PhD , Prof Steven G Deeks MD , Prof Jeffrey N Martin MD , Amethyst Zhang","doi":"10.1016/j.lanmic.2025.101227","DOIUrl":"10.1016/j.lanmic.2025.101227","url":null,"abstract":"<div><h3>Background</h3><div>The effect of COVID-19 oral antivirals on the duration of SARS-CoV-2 infectious viral shedding and viral rebound remains uncertain. This study aimed to examine the association of oral antivirals with viral dynamics, shedding of infectious virus, and SARS-CoV-2 rebound.</div></div><div><h3>Methods</h3><div>A prospective case-ascertained household study design was used. Participants were non-hospitalised adults older than 18 years with symptomatic SARS-CoV-2 enrolled in one of two prospective household transmission studies (University of California, San Francisco, FindCOVID and Respiratory Virus Transmission Network–Sentinel [RVTN–S]) conducted in the USA across six states at academic institutions from Jan 1, 2022 to June 10, 2023. We excluded those reporting receipt of multiple COVID-19 outpatient medications, treatment with remdesivir, a treatment duration of more than 6 days, and those from whom fewer than five daily anterior nasal swabs were collected during their illness. Participants were considered to be at high risk of severe COVID-19 (and, therefore, eligible for SARS-CoV-2 oral antiviral treatment) if they were aged 50 years or older or were aged 18 years or older and reporting at least one underlying condition. Study procedures included frequent self-collected nasal swabs (daily for 14 days after symptom onset and then every 3 days until day 28 after symptom onset in FindCOVID and two nasal swabs daily for 10 days from enrolment in RVTN-S) and viral testing by quantitative reverse transcriptase PCR (qRT-PCR), at-home antigen testing, and viral culture. Treatment was defined as self-reported receipt of an oral antiviral (nirmatrelvir–ritonavir or molnupiravir). The primary analysis compared viral detection by qRT-PCR, antigen test positivity, and culture positivity and assessed SARS-CoV-2 viral rebound (viral RNA, antigen, culture, and symptom rebound) in untreated and treated participants at high risk of severe outcomes. We used multivariable Poisson regression to assess associations between treatment, duration of test positivity, and the presence of viral culture rebound, adjusting for age, underlying conditions, and recent immunological events.</div></div><div><h3>Findings</h3><div>Between Jan 1, 2022, and June 10, 2023, 160 individuals with symptomatic COVID-19 and at high risk of severe outcomes were included in FindCOVID and RVTN–S. There was no significant difference in the duration of viral detection between treated and untreated participants at high risk of severe COVID-19 by antigen test positivity (6 days [IQR 5–11] <em>vs</em> 8 days [5–10]; adjusted relative risk [RR] 1·07, 95% CI 0·24–4·81) or viral culture (7 days [4–11] <em>vs</em> 6 days [5–9]; 2·21, 0·45–10·79). Among 122 participants without viral RNA rebound, the last day of antigen test positivity and detection of culturable virus post-symptom onset was earlier in treated participants than in untreated participants (5 days [4–8] <em>vs</em","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"7 1","pages":"Article 101227"},"PeriodicalIF":20.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145960390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/j.lanmic.2025.101230
Lisa Bauer PhD , Lonneke Leijten BSc , Matteo Iervolino MSc , Varun Chopra MSc , Laura van Dijk MSc , Mark Power MSc , Willemijn Rijnink MSc , Mark Pronk BSc , Monique Spronken MSc , Mathis Funk PhD , Rory D de Vries PhD , Mathilde Richard PhD , Prof Thijs Kuiken PhD DVM , Debby van Riel PhD
<div><h3>Background</h3><div>Highly pathogenic avian influenza H5N1 viruses of the A/Goose/Guangdong/1/1996 lineage pose a global threat to wildlife, domestic animals, and humans. Cross-species transmission events to mammals, including humans, in the past 4 years highlight this threat. For influenza A viruses, crucial determinants of cross-species and intraspecies transmission to and among mammals include attachment to and replication in respiratory airway epithelial cells. Although these determinants have been studied for H5N1 viruses in the past, limited studies for clade 2.3.4.4b viruses exist. Therefore, the aim of this study was to determine the ability of recent clade 2.3.4.4b H5N1 viruses to attach to human respiratory tissues, to replicate in human airway epithelial cells and the associated immune response.</div></div><div><h3>Methods</h3><div>In this in-vitro study, we investigated three H5N1 clade 2.3.4.4b viruses (H5N1<sup>Gull2022</sup>, H5N1<sup>Polecat2022</sup>, and H5N1<sup>Bovine2024</sup>) in comparison with previously studied 2.1.3.2 H5N1 (H5N1<sup>2005</sup>) and a seasonal H3N2 virus. First, we compared virus attachment patterns by virus histochemistry. Second, we investigated the infection and replication efficiency, and innate immune responses in infected human respiratory epithelium in vitro. Third, we measured polymerase complex activity using a minigenome assay.</div></div><div><h3>Findings</h3><div>Clade 2.3.4.4b viruses and H5N1<sup>2005</sup> virus differed by five amino acids located near the receptor binding site of the haemagglutinin. All clade 2.3.4.4b viruses attached more efficiently to cells of the human upper and lower respiratory tract compared with H5N1<sup>2005</sup> virus. All clade 2.3.4.4b viruses replicated in human nasal and tracheobronchial respiratory epithelium cultures. In the tracheobronchial respiratory epithelium cultures, H5N1<sup>Gull20</sup><sup>2</sup><sup>2</sup> virus replicated more efficiently than H5N1<sup>2005</sup> virus (p=0·0050) and reached titres similar to H3N2<sup>2003</sup> virus. Polymerase complex activity of H5N1<sup>Gull2022</sup> virus was not significantly different from that of H5N1<sup>2005</sup> and was significantly lower compared with H3N2<sup>2003</sup> virus (p≤0·0001). Infection with H5N1<sup>Gull2022</sup> virus induced a broader antiviral immune response than H5N1<sup>2005</sup> virus.</div></div><div><h3>Interpretation</h3><div>Clade 2.3.4.4b H5N1 viruses have phenotypic characteristics that are different from a clade 2.1.3.2 H5N1<sup>2005</sup> virus. The ability of clade 2.3.4.4b viruses to attach to and replicate in respiratory epithelium likely contributes to an increased risk for both human infection and virus adaptation to humans.</div></div><div><h3>Funding</h3><div>The EU, the Dutch Research Council, the Netherlands Organization for Health Research and Development, and the Dutch Ministries of Agriculture, Fisheries, Food Security and Nature, and Health,
{"title":"Attachment and replication of clade 2.3.4.4b influenza A (H5N1) viruses in human respiratory epithelium: an in-vitro study","authors":"Lisa Bauer PhD , Lonneke Leijten BSc , Matteo Iervolino MSc , Varun Chopra MSc , Laura van Dijk MSc , Mark Power MSc , Willemijn Rijnink MSc , Mark Pronk BSc , Monique Spronken MSc , Mathis Funk PhD , Rory D de Vries PhD , Mathilde Richard PhD , Prof Thijs Kuiken PhD DVM , Debby van Riel PhD","doi":"10.1016/j.lanmic.2025.101230","DOIUrl":"10.1016/j.lanmic.2025.101230","url":null,"abstract":"<div><h3>Background</h3><div>Highly pathogenic avian influenza H5N1 viruses of the A/Goose/Guangdong/1/1996 lineage pose a global threat to wildlife, domestic animals, and humans. Cross-species transmission events to mammals, including humans, in the past 4 years highlight this threat. For influenza A viruses, crucial determinants of cross-species and intraspecies transmission to and among mammals include attachment to and replication in respiratory airway epithelial cells. Although these determinants have been studied for H5N1 viruses in the past, limited studies for clade 2.3.4.4b viruses exist. Therefore, the aim of this study was to determine the ability of recent clade 2.3.4.4b H5N1 viruses to attach to human respiratory tissues, to replicate in human airway epithelial cells and the associated immune response.</div></div><div><h3>Methods</h3><div>In this in-vitro study, we investigated three H5N1 clade 2.3.4.4b viruses (H5N1<sup>Gull2022</sup>, H5N1<sup>Polecat2022</sup>, and H5N1<sup>Bovine2024</sup>) in comparison with previously studied 2.1.3.2 H5N1 (H5N1<sup>2005</sup>) and a seasonal H3N2 virus. First, we compared virus attachment patterns by virus histochemistry. Second, we investigated the infection and replication efficiency, and innate immune responses in infected human respiratory epithelium in vitro. Third, we measured polymerase complex activity using a minigenome assay.</div></div><div><h3>Findings</h3><div>Clade 2.3.4.4b viruses and H5N1<sup>2005</sup> virus differed by five amino acids located near the receptor binding site of the haemagglutinin. All clade 2.3.4.4b viruses attached more efficiently to cells of the human upper and lower respiratory tract compared with H5N1<sup>2005</sup> virus. All clade 2.3.4.4b viruses replicated in human nasal and tracheobronchial respiratory epithelium cultures. In the tracheobronchial respiratory epithelium cultures, H5N1<sup>Gull20</sup><sup>2</sup><sup>2</sup> virus replicated more efficiently than H5N1<sup>2005</sup> virus (p=0·0050) and reached titres similar to H3N2<sup>2003</sup> virus. Polymerase complex activity of H5N1<sup>Gull2022</sup> virus was not significantly different from that of H5N1<sup>2005</sup> and was significantly lower compared with H3N2<sup>2003</sup> virus (p≤0·0001). Infection with H5N1<sup>Gull2022</sup> virus induced a broader antiviral immune response than H5N1<sup>2005</sup> virus.</div></div><div><h3>Interpretation</h3><div>Clade 2.3.4.4b H5N1 viruses have phenotypic characteristics that are different from a clade 2.1.3.2 H5N1<sup>2005</sup> virus. The ability of clade 2.3.4.4b viruses to attach to and replicate in respiratory epithelium likely contributes to an increased risk for both human infection and virus adaptation to humans.</div></div><div><h3>Funding</h3><div>The EU, the Dutch Research Council, the Netherlands Organization for Health Research and Development, and the Dutch Ministries of Agriculture, Fisheries, Food Security and Nature, and Health,","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"7 1","pages":"Article 101230"},"PeriodicalIF":20.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/j.lanmic.2025.101243
Seshasailam Venkateswaran , Jessica Mitchell , Marieke Emonts , Mark Bradley , Nichola Hawkins , Andrew C Singer
{"title":"Diagnostics at the frontline: using the Public Accounts Committee report to catalyse the UK’s antimicrobial resistance diagnostics strategy","authors":"Seshasailam Venkateswaran , Jessica Mitchell , Marieke Emonts , Mark Bradley , Nichola Hawkins , Andrew C Singer","doi":"10.1016/j.lanmic.2025.101243","DOIUrl":"10.1016/j.lanmic.2025.101243","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"7 1","pages":"Article 101243"},"PeriodicalIF":20.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145114707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/j.lanmic.2025.101336
The Lancet Microbe
{"title":"We have the means to beat malaria, do we have the will?","authors":"The Lancet Microbe","doi":"10.1016/j.lanmic.2025.101336","DOIUrl":"10.1016/j.lanmic.2025.101336","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"7 1","pages":"Article 101336"},"PeriodicalIF":20.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145844235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Editor note to PET-CT-guided characterisation of progressive, preclinical tuberculosis infection and its association with low-level circulating Mycobacterium tuberculosis DNA in household contacts in Leicester, UK: a prospective cohort study","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"7 1","pages":"Article 101310"},"PeriodicalIF":20.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145996546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Staphylococcus aureus bacteraemia presents a substantial clinical burden, with high rates of morbidity and mortality. Despite its severity, therapeutic advancements have been small in the past decade, prompting exploration of adjunctive treatment strategies against S aureus bacteraemia. Among these strategies, P2Y12 inhibitors have gained attention due to their potential antistaphylococcal and platelet-modulating effects. Preclinical studies suggest that ticagrelor enhances platelet-mediated bacterial killing and interferes with S aureus metabolism. Clinical data indicate a potential protective effect of ticagrelor in S aureus bacteraemia, as compared with that of clopidogrel. Nevertheless, clopidogrel itself appears to offer protective effects, when compared with no treatment. However, these findings are based exclusively on non-randomised studies conducted in individuals with cardiovascular disease. Two randomised trials currently in development could provide further evidence on the therapeutic role of P2Y12 inhibitors in S aureus bacteraemia. Future research should also focus on preventive strategies and identifying populations at high risk who could benefit from such interventions.
{"title":"P2Y12 inhibitors in Staphylococcus aureus bacteraemia: current evidence and clinical implications","authors":"Emanuele Rando MD , Luis Eduardo López-Cortés MD PhD , Prof Jesús Rodríguez-Baño","doi":"10.1016/j.lanmic.2025.101255","DOIUrl":"10.1016/j.lanmic.2025.101255","url":null,"abstract":"<div><div><em>Staphylococcus aureus</em> bacteraemia presents a substantial clinical burden, with high rates of morbidity and mortality. Despite its severity, therapeutic advancements have been small in the past decade, prompting exploration of adjunctive treatment strategies against <em>S aureus</em> bacteraemia. Among these strategies, P2Y12 inhibitors have gained attention due to their potential antistaphylococcal and platelet-modulating effects. Preclinical studies suggest that ticagrelor enhances platelet-mediated bacterial killing and interferes with <em>S aureus</em> metabolism. Clinical data indicate a potential protective effect of ticagrelor in <em>S aureus</em> bacteraemia, as compared with that of clopidogrel. Nevertheless, clopidogrel itself appears to offer protective effects, when compared with no treatment. However, these findings are based exclusively on non-randomised studies conducted in individuals with cardiovascular disease. Two randomised trials currently in development could provide further evidence on the therapeutic role of P2Y12 inhibitors in <em>S aureus</em> bacteraemia. Future research should also focus on preventive strategies and identifying populations at high risk who could benefit from such interventions.</div></div>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"7 1","pages":"Article 101255"},"PeriodicalIF":20.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145432532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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