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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Targeted metagenomics reveals association between severity and pathogen co-detection in infants with respiratory syncytial virus

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

Published: March 16, 2024

Abstract Respiratory syncytial virus (RSV) is the leading cause of hospitalisation for respiratory infection in young children. RSV disease severity known to be age-dependent and highest infants, but other correlates severity, particularly presence additional pathogens, are less well understood. In this study, nasopharyngeal swabs were collected from two cohorts RSV-positive infants <12 months Spain, UK, Netherlands during 2017–20. We show, using targeted metagenomic sequencing >100 including all common viruses bacteria, samples 433 that burden (111/433, 26%) only modestly with severity. contrast, there strong evidence both across age groups Haemophilus bacteria (194/433, 45%) associated higher much rates (odds ratio 4.25, 95% CI 2.03–9.31). There no association between detected difference genotypes. Our findings reveal genomic diversity pathogens provide an base future causal investigations impact co-infection on

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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Viral load dynamics and shedding kinetics of mpox infection: a systematic review and meta-analysis

Journal of Travel Medicine, Journal Year: 2023, Volume and Issue: 30(5)

Published: July 1, 2023

Viral load dynamics and shedding kinetics are critical factors for studying infectious diseases. However, evidence on the viral of mpox remains limited inconclusive. Thus, we aimed to provide a comprehensive understanding viability re-emerged virus since 2022.For this systematic review meta-analysis, searched PubMed/MEDLINE, Embase Google Scholar published articles that related up April 2023.From 19 studies, 880 samples 1477 specimens were collected. The pooled median Ct values appeared in following order: skin lesion [Ct value 21.7 (IQR 17.8-25.5)], anorectal [22.3 (16.9-27.6)], saliva [25.9 (22.5-31.1)], oral [29.0 (24.5-32.8)], semen [29.6 (25.9-33.4)], urine [30.5 (24.6-36.4)], pharyngeal [31.9 (26.5-37.3)], urethra [33.0 (28.0-35.0)] blood [33.2 (30.4-36.1)]. People living with human immunodeficiency (HIV) have lower [skin HIV+, 19.2 (18.3-20.0) vs HIV-, 25.4 (21.2-29.0)]. From test day symptom onset, identified temporal trends each specimen type. Changes trend observed at 4 days saliva, 5 blood, 6 skin, 7 anorectal, urine, 8 urethra. We determined optimal cutoff (34.0), (27.7) (33.0) specimens, where above suggests minimal viability. Using these values, derived duration viable isolation specific type (anorectal days, 14 days).Skin lesion, contained highest load. peak manifests within 4-8 after detection was presumed cease 14-19 from onset urethral samples.

Language: Английский

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SARS-CoV-2 Rebound With and Without Use of COVID-19 Oral Antivirals

MMWR Morbidity and Mortality Weekly Report, Journal Year: 2023, Volume and Issue: 72(51), P. 1357 - 1364

Published: Dec. 21, 2023

Early treatment with a first-line therapy (nirmatrelvir/ritonavir [Paxlovid] or remdesivir) second-line (molnupiravir) prevents hospitalization and death among patients mildto-moderate COVID-19 who are at risk for severe disease is recommended by the National Institutes of Health Treatment Guidelines.On May 25, 2023, Food Drug Administration approved nirmatrelvir/ritonavir adults high disease.Although antiviral therapies widely available, they underutilized, possibly because reports SARS-CoV-2 rebound after treatment.To enhance current understanding rebound, CDC reviewed studies published during February 1, 2020-November 29, 2023.Overall, seven 23 that met inclusion criteria, one randomized trial six observational studies, compared persons received did not receive treatment.In four including trial, no statistically significant difference in rates was identified receiving those treatment.Depending on definition used, prevalence varied.No hospitalizations deaths were reported outpatients experienced signs symptoms mild.Persons might be higher host factors treatment-induced viral suppression early course illness.The potential should deter clinicians from prescribing lifesaving treatments when indicated to prevent morbidity mortality COVID-19.* https://covid.cdc.gov/covid-data-tracker/#datatracker-home(Accessed December 15, 2023).Although currently much lower than peak pandemic, continues cause substantial mortality.As 9, approximately 23,000 per week COVID-19, highest aged ≥65 years.Currently, health care providers positioned mitigate safe effective vaccines † diagnosis (1). Antiviral TherapeuticsEarly reduces mild-to-moderate (2-4), https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19vaccines-us.html

Language: Английский

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