Profiling the dysregulated immune response in sepsis: overcoming challenges to achieve the goal of precision medicine

The Lancet Respiratory Medicine, Journal Year: 2023, Volume and Issue: 12(4), P. 305 - 322

Published: Dec. 21, 2023

Language: Английский

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SARS-CoV-2 shedding and evolution in patients who were immunocompromised during the omicron period: a multicentre, prospective analysis

The Lancet Microbe, Journal Year: 2024, Volume and Issue: 5(3), P. e235 - e246

Published: Jan. 26, 2024

BackgroundProlonged SARS-CoV-2 infections in people who are immunocompromised might predict or source the emergence of highly mutated variants. The types immunosuppression placing patients at highest risk for prolonged infection have not been systematically investigated. We aimed to assess factors and associated intrahost evolution.MethodsIn this multicentre, prospective analysis, participants were enrolled five US medical centres. Eligible aged 18 years older, SARS-CoV-2-positive previous 14 days, had a moderately severely immunocompromising condition treatment. Nasal specimens tested by real-time RT-PCR every 2–4 weeks until negative consecutive specimens. Positive underwent viral culture whole genome sequencing. A Cox proportional hazards model was used with duration infection.FindingsFrom April 11, 2022, Oct 1, 156 began enrolment process, whom 150 included analyses. Participants B-cell malignancy anti-B-cell therapy (n=18), solid organ transplantation haematopoietic stem-cell (HSCT; n=59), AIDS (n=5), non-B-cell (n=23), autoimmune autoinflammatory conditions (n=45). 38 (25%) RT-PCR-positive 12 (8%) culture-positive 21 days longer after initial detection illness onset. Compared group conditions, dysfunction (adjusted hazard ratio 0·32 [95% CI 0·15–0·64]), HSCT (0·60 [0·38–0·94]), (0·28 [0·08–1·00]) infection, defined as time last positive test. There no significant difference (0·58 [0·31–1·09]). Consensus de novo spike mutations identified individuals than 56 days; (61%) 23 receptor-binding domain. Mutations shared multiple rare (<5%) global circulation.InterpretationIn cohort, replication-competent omicron uncommon. Within-host evolutionary rates similar across patients, but lasting accumulated mutations, which distinct from those seen globally. Populations high should be targeted repeated testing treatment monitored antiviral resistance.FundingUS Centers Disease Control Prevention.

Language: Английский

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An intranasal live-attenuated SARS-CoV-2 vaccine limits virus transmission

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 2, 2024

Abstract The development of effective SARS-CoV-2 vaccines has been essential to control COVID-19, but significant challenges remain. One problem is intramuscular administration, which does not induce robust mucosal immune responses in the upper airways—the primary site infection and virus shedding. Here we compare efficacy a mucosal, replication-competent yet fully attenuated vaccine, sCPD9-ΔFCS, monovalent mRNA vaccine BNT162b2 preventing transmission variants B.1 Omicron BA.5 two scenarios. Firstly, assessed protective by exposing vaccinated male Syrian hamsters infected counterparts. Secondly, evaluated challenge from subsequently challenged naïve contacts. Our findings demonstrate that live-attenuated (LAV) sCPD9-ΔFCS significantly outperformed both results provide evidence for advantages locally administered LAVs over intramuscularly reducing transmission.

Language: Английский

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An intranasal combination vaccine induces systemic and mucosal immunity against COVID-19 and influenza

npj Vaccines, Journal Year: 2024, Volume and Issue: 9(1)

Published: March 21, 2024

Abstract Despite prolonged surveillance and interventions, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) influenza viruses continue to pose a global health burden. Thus, we developed chimpanzee adenovirus-based combination vaccine, AdC68-HATRBD, with dual specificity against SARS-CoV-2 virus. When used as standalone intranasal immunization AdC68-HATRBD induced comprehensive potent immune responses consisting of immunoglobin (Ig) G, mucosal IgA, neutralizing antibodies, memory T cells, which protected mice from BA.5.2 pandemic H1N1 infections. heterologous booster, markedly improved protective response licensed or vaccine. Therefore, whether administered intranasally booster this vaccine is valuable strategy enhance overall efficacy by inducing robust systemic responses, thereby conferring lines immunological defenses for these two viruses.

Language: Английский

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Localised wastewater SARS-CoV-2 levels linked to COVID-19 cases: A long-term multisite study in England

The Science of The Total Environment, Journal Year: 2025, Volume and Issue: 962, P. 178455 - 178455

Published: Jan. 1, 2025

Wastewater-based surveillance (WBS) can monitor for the presence of human health pathogens in population. During COVID-19, WBS was widely used to determine wastewater SARS-CoV-2 RNA concentration (concentrations) providing information on community COVID-19 cases (cases). However, studies examining relationship between concentrations and tend be localised or focussed small-scale institutional settings. Few have examined this multiple settings, over long periods, with large sample numbers, nor attempted quantify detail how catchment characteristics affected these. This 18-month study (07/20-12/21) explored correlation quantitative using censored regression. Our analysis >94,000 samples collected from 452 diverse sampling sites (259 Sewage Treatment Works (STW) 193 Sewer Network Sites (SNS)) covering ~65 % English Wastewater were linked ~6 million diagnostically confirmed cases. High coefficients found (STW: median r = 0.66, IQR: 0.57-0.74; SNS: 0.65, 0.54-0.74). The (regression coefficient) variable catchments. Catchment (e.g. size population grab vs automated sampling) had significant but small effects regression coefficients. last six months reduced became highly coincided a shift towards younger cases, vaccinated rapid emergence variant Omicron. programme rapidly introduced at scale during COVID-19. Laboratory methods evolved catchments characteristics. Despite diversity, findings indicate that provides an effective proxy establishing dynamics across wide variety communities. While there is potential predicting concentration, may more smaller scales.

Language: Английский

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Variants and vaccines impact nasal immunity over three waves of SARS-CoV-2

Nature Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 20, 2025

Language: Английский

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Modeling suggests SARS-CoV-2 rebound after nirmatrelvir-ritonavir treatment is driven by target cell preservation coupled with incomplete viral clearance

Journal of Virology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 4, 2025

ABSTRACT In a subset of SARS-CoV-2-infected individuals treated with the antiviral nirmatrelvir-ritonavir, virus rebounds following treatment. The mechanisms driving this rebound are not well understood. We used mathematical model to describe longitudinal viral load dynamics 51 20 whom rebounded. Target cell preservation, either by robust innate immune response or initiation N-R near time symptom onset, coupled incomplete clearance, appears be main factor leading rebound. Moreover, occurrence is likely influenced treatment relative progression infection, earlier treatments higher chance A comparison an untreated cohort suggests that early nirmatrelvir-ritonavir may associated delay in onset adaptive response. Nevertheless, our demonstrates extending course 10-day regimen greatly diminish people mild-to-moderate COVID-19 and who at high risk severe disease. Altogether, results suggest some individuals, standard 5-day starting around completely eliminate virus. Thus, after ends, can if effective has fully developed. These findings on role target preservation clearance also offer possible explanation for other SARS-CoV-2. IMPORTANCE Nirmatrelvir-ritonavir initial reduction followed once stopped. show timing influence stops growth preserves cells but lead full adequately developed, remaining Our provide insights into help develop better strategies minimize possibility.

Language: Английский

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Rapid review and meta-analysis of serial intervals for SARS-CoV-2 Delta and Omicron variants

BMC Infectious Diseases, Journal Year: 2023, Volume and Issue: 23(1)

Published: June 26, 2023

The serial interval is the period of time between symptom onset in primary case and secondary case. Understanding important for determining transmission dynamics infectious diseases like COVID-19, including reproduction number attack rates, which could influence control measures. Early meta-analyses COVID-19 reported intervals 5.2 days (95% CI: 4.9-5.5) original wild-type variant 4.87-5.47) Alpha variant. has been shown to decrease over course an epidemic other respiratory diseases, may be due accumulating viral mutations implementation more effective nonpharmaceutical interventions. We therefore aggregated literature estimate Delta Omicron variants.

Language: Английский

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Assessing changes in incubation period, serial interval, and generation time of SARS-CoV-2 variants of concern: a systematic review and meta-analysis

BMC Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: Sept. 29, 2023

Abstract Background After the first COVID-19 wave caused by ancestral lineage, pandemic has been fueled from continuous emergence of new SARS-CoV-2 variants. Understanding key time-to-event periods for each emerging variant concern is critical as it can provide insights into future trajectory virus and help inform outbreak preparedness response planning. Here, we aim to examine how incubation period, serial interval, generation time have changed lineage different variants concern. Methods We conducted a systematic review meta-analysis that synthesized estimates (both realized intrinsic) Alpha, Beta, Omicron SARS-CoV-2. Results Our study included 280 records obtained 147 household studies, contact tracing or studies where epidemiological links were known. With variant, found progressive shortening analyzed periods, although did not find statistically significant differences between subvariants. BA.1 had shortest pooled period (3.49 days, 95% CI: 3.13–4.86 days), BA.5 interval (2.37 1.71–3.04 (2.99 2.48–3.49 days). Only one estimate intrinsic was available subvariants: 6.84 days (95% CrI: 5.72–8.60 days) BA.1. The highest investigated period. also observed shorter compared across lineages. When pooling lineages, considerable heterogeneities ( I 2 > 80%; refers percentage total variation due heterogeneity rather than chance), possibly resulting populations (e.g., deployed interventions, social behavior, demographic characteristics). Conclusions supports importance conducting investigations monitor changes in transmission patterns. findings highlight time, which lead epidemics spread faster, with larger peak incidence, harder control. consistently suggesting feature potential pre-symptomatic transmission. These observations are instrumental plan waves.

Language: Английский

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Drug treatment of COVID-19 infection

Current Opinion in Pulmonary Medicine, Journal Year: 2023, Volume and Issue: 29(3), P. 174 - 183

Published: March 14, 2023

COVID-19 pandemic has caused more than 6.6 million deaths globally. Tremendous efforts have been committed for the development of new and repurposed drugs treatment COVID-19. Although different international national guidelines share consensus in management disease with levels severity, challenges emerged, steering need ongoing research advancing clinical

Language: Английский

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