Cluster analysis of post-COVID-19 physical and mental health outcomes 3-6 months after SARS-CoV-2 infection: results of the French Prospective ALCOVID Cohort Study

Objectives
This study aims to characterise the diversity of post-COVID-19 physical and mental health outcomes, known as the post-COVID-19 condition (PCC), and the determining factors 3–6 months after acute SARS-CoV-2 infection.

Design
This is a prospective cohort study.

Setting
This study took place at the European Hospital of Marseille, France.

Participants
Participants include patients with acute COVID-19 treated as inpatients or outpatients.

Interventions
Interventions include face-to-face assessment of physical and mental health symptoms.

Main outcome measures
Main outcome measures include symptom scores and scales, as well as paraclinical elements (thoracic CT scan, pulmonary functional tests). Multiple component analysis was used to identify clinical phenotypic clusters of PCC patients, as well as their initial comorbidity groups. A multinomial regression model was used to evaluate the association between the initial comorbidities and disease severity with PCC phenotype.

Results
A total of 210 patients agreed to participate, of which 157 (75%) reported at least one symptom at the 3–6 months visit; mostly asthenia, dyspnoea, psychiatric disorders such as anxiety, depression, post-traumatic stress disorder and cognitive disorders. Four PCC clusters were recognised: (1) paucisymptomatic PCC (n=82, 39%); (2) physical sequelae PCC (n=39, 18.6%), (3) pre-existing pulmonary comorbidities PCC (n=29, 13.8%); and (4) functional somatic and/or mental symptoms PCC (n=60, 28.6%). In addition to their PCC symptoms, the patients in these clusters differed in terms of their demographic characteristics (sex), comorbidities and severity of COVID-19.

Conclusions
The four identified PCC clusters corresponded to distinct and coherent clinical and paraclinical entities, making it possible to consider adapted and personalised prognosis and therapeutic interventions.

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Febbraio 2025

Human Papillomavirus, Human Immunodeficiency Virus, and Oral Microbiota Interplay in Nigerian Youth (HOMINY): A Prospective Cohort Study Protocol

Introduction
Persistent oral infections with high-risk human papillomavirus (HR-HPV) are a potential cause of most oropharyngeal cancers (OPCs). Oral HR-HPV infection and persistence are significantly higher in people living with HIV (PLWH). Most data on oral HR-HPV in PLWH come from developed countries or adult cohorts. This study aims to investigate oral HR-HPV susceptibility and persistence among children and adolescents living with HIV (CALHIV) and to understand the roles of perinatal HIV exposure, infection, antiretroviral treatment, and the oral microbiome.

Methods and analysis
This prospective cohort study is ongoing at the University of Benin Teaching Hospital (UBTH), Nigeria, involving mother-child pairs followed at 6-month intervals for 2 years. Participants include children aged 9–18 and their mothers aged 18 and above. The study targets 690 adolescents in three groups: 230 CALHIV, 230 HIV-exposed but uninfected and 230 HIV-unexposed and uninfected. Oral rinse, saliva, buccal swabs and supragingival plaque samples are collected at each visit. Blood samples are tested for HIV, Hepatitis B virus (HBV) and Hepatitis C virus (HCV), with CD4, CD8 and full blood counts performed. Oral HPV is assessed for incidence, persistence, and clearance. Statistical analyses to look for associations between cohort baseline characteristics and findings will be conducted using univariable and multivariable models for repeated data and high-dimensional microbiome data. All statistical tests will be two-sided; a p value

Leggi
Febbraio 2025

Establishment of enterically transmitted hepatitis virus animal models using lipid nanoparticle-based full-length viral genome RNA delivery system

Background
Enterically transmitted hepatitis viruses, such as hepatitis A virus (HAV) and hepatitis E virus (HEV), remain notable threats to public health. However, stable and reliable animal models of HAV and HEV infection are lacking.

Objective
This study aimed to establish HAV and HEV infections in multiple small animals by intravenously injecting lipid nanoparticle (LNP)-encapsulated full-length viral RNAs (LNP-vRNA).

Design
In vitro transcribed and capped full-length HAV RNA was encapsulated into LNP and was intravenously inoculated to Ifnar–/– mice, and HEV RNA to rabbits and gerbils. Virological parameters were determined by RT-qPCR, ELISA and immunohistochemistry. Liver histopathological changes were analysed by H&E staining. Antiviral drug and vaccine efficacy were further evaluated by using the LNP-vRNA-based animal model.

Results
On intravenous injection of LNP-vRNA, stable viral shedding was detected in the faeces and infectious HAV or HEV was recovered from the livers of the inoculated animals. Liver damage was observed in LNP-vRNA (HAV)-injected mice and LNP-vRNA (HEV)-injected rabbits. Mongolian gerbils were also susceptible to LNP-vRNA (HEV) injections. Finally, the antiviral countermeasures and in vivo function of HEV genome deletions were validated in the LNP-vRNA-based animal model.

Conclusion
This stable and standardised LNP-vRNA-based animal model provides a powerful platform to investigate the pathogenesis and evaluate countermeasures for enterically transmitted hepatitis viruses and can be further expanded to other viruses that are not easily cultured in vitro or in vivo.

Leggi
Febbraio 2025

Deaths in children in England from SARS-CoV-2 infection during the first 2 years of the pandemic: a cohort study

Objective
The aim of this analysis was to describe the epidemiology, demographics and characteristics of children and young people (CYP) who died of SARS-CoV-2 infection in England during the first 2 years of the pandemic.

Design
The cohort investigated in this study is all CYP, born alive at, or after, 22 weeks of gestation, who died before their 18th birthday between 1 February 2020 and 31 March 2022 in England. All cases were reviewed to identify if SARS-CoV-2 probably, or possibly, contributed to death. Mortality rates were calculated, assuming a Poisson distribution, for the whole population, and split by demographics and patient characteristics.

Setting
England.

Participants
6389 CYP deaths in England reported to the National Child Mortality Database (NCMD).

Main outcome
Risk of death.

Results
88 of the 6389 deaths of CYP were identified as deaths probably due to COVID-19. Thus, COVID-19 was responsible for 1.4% of all deaths of CYP in this 26-month period. Overall mortality rate due to COVID-19 in CYP was 3.59 (2.88–4.42) per 1 000 000 person years, being highest in the youngest (< 5 years; 4.68 (3.16–6.68)) and oldest (16/17 years; 4.83 (2.57–8.26)) CYP. Asian and Black CYP had higher mortality than those from white backgrounds (p

Leggi
Febbraio 2025

[Viewpoint] Occult hepatitis B virus infection: risk for a blood supply, but how about individuals’ health?

The implementation of effective blood donation screening for hepatitis B virus (HBV) anti-core antibodies with highly sensitive molecular HBV DNA detection in low-endemic countries like the United Kingdom has improved blood safety. However, the linkage to care and management for blood donors with occult HBV infection (OBI) is a complex dilemma involving virological, clinical, methodological, and social issues. Limited evidence suggests that OBI may accelerate the progression of liver disease and cancer.

Leggi
Febbraio 2025

Determining the incidence, risk factors and biological drivers of irritable bowel syndrome (IBS) as part of the constellation of postacute sequelae of SARS-CoV-2 infection (PASC) outcomes in the Arizona CoVHORT-GI: a longitudinal cohort study

Introduction
Postacute sequelae of SARS-CoV-2 infection (PASC) are extensive. Also known as long COVID, primary outcomes reported are neurologic, cardiac and respiratory in nature. However, several studies have also reported an increase in gastrointestinal (GI) symptoms and syndromes following COVID-19. This study of PASC will include extensive analyses of GI symptoms, determine if people with pre-existing irritable bowel syndrome (IBS) are at higher risk of developing PASC generally or PASC-GI, and which biomarkers are impacted and to what degree. This R01 study is being funded by the National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK135483-01) from 2023 to 2028.

Methods and analyses
This study combines a longitudinal epidemiologic cohort study and in-depth, novel biologic analyses. In collaboration with a pre-existing study, the Arizona CoVID-19 Cohort (CoVHORT)-GI will recruit participants based on the history of COVID infection(s), new or ongoing GI symptoms 3–6 months postinfection, and pre-existing or incident IBS diagnosis to represent five study groups for comparison and analyses. A subset (n=1000) of those recruited will submit both stool and blood samples. Both samples will undergo a novel method to quantitate humoral and mucosal immune responses to host-derived faecal communities in conjunction with magnetic bead-based separation and high-depth shotgun microbial sequencing. Stool samples will also undergo traditional microbiome analyses (diversity and abundance) and faecal calprotectin assays. Additional serum analyses will aim to determine if a proteomics-based signature exists that differentiates a unique biomarker compositional signature discriminating PASC-GI versus no PASC. All laboratory data will be linked with in-depth epidemiologic data on demographics, symptoms and chronic conditions.

Ethics and dissemination
This study involves human participants and was approved by the University of Arizona Institutional Review Board (IRB (#00002332) and has been deemed minimal risk. Participants gave informed consent to participate in the study before taking part. All publications from the study will be shared back to participants along with alternative lay summaries and webinars to communicate key findings. The data management plan has been published and is publicly available online, including protocols for data requests.

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Gennaio 2025