GI highlights from the literature

Basic scienceComplement dysregulation in long COVID Cervia-Hasler C, Bruningk S, Hoch T, et al. Persistent complement dysregulation with signs of thromboinflammation in active Long Covid. Science 2024; doi: 10.1126/science.adg7942. There is currently a lack of diagnostic and therapeutic tests for patients affected by long COVID (coronavirus disease). In this multicentre, longitudinal study, a total of 113 SARS-CoV-2-infected patients and 39 healthy controls were prospectively followed up for 1 year with serial serum collected for analysis. A total of >6500 proteins in the serum were measured using the SomaScan (Slow Off-rate Modified Aptamer Scan) platform with top candidate biomarkers being identified using computational tools. Cervia-Hasler et al showed that terminal complement complexes (TCCs) were most differentially expressed in 6-month long COVID patients, compared with healthy controls, patients without long COVID and patients hospitalised for other reasons, confirming the presence of dysregulated complement system. At 6-month follow-up, those with…

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Error in Author Affiliation

In the Research Letter titled “Mortality and Hospitalization Risks in Patients With Cancer and the SARS-CoV-2 Omicron Variant,” published online November 22, 2023, an affiliation was omitted for the fourth author, Adi Turjeman, PhD. Her name has now been added to the affiliation, “Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.” This article has been corrected online.

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Impact and cost-effectiveness of SARS-CoV-2 self-testing strategies in schools: a multicountry modelling analysis

Objectives
To determine the most epidemiologically effective and cost-effective school-based SARS-CoV-2 antigen-detection rapid diagnostic test (Ag-RDT) self-testing strategies among teachers and students.

Design
Mathematical modelling and economic evaluation.

Setting and participants
Simulated school and community populations were parameterised to Brazil, Georgia and Zambia, with SARS-CoV-2 self-testing strategies targeted to teachers and students in primary and secondary schools under varying epidemic conditions.

Interventions
SARS-CoV-2 Ag-RDT self-testing strategies for only teachers or teachers and students—only symptomatically or symptomatically and asymptomatically at 5%, 10%, 40% or 100% of schools at varying frequencies.

Outcome measures
Outcomes were assessed in terms of total infections and symptomatic days among teachers and students, as well as total infections and deaths within the community under the intervention compared with baseline. The incremental cost-effectiveness ratios (ICERs) were calculated for infections prevented among teachers and students.

Results
With respect to both the reduction in infections and total cost, symptomatic testing of all teachers and students appears to be the most cost-effective strategy. Symptomatic testing can prevent up to 69·3%, 64·5% and 75·5% of school infections in Brazil, Georgia and Zambia, respectively, depending on the epidemic conditions, with additional reductions in community infections. ICERs for symptomatic testing range from US$2 to US$19 per additional school infection averted as compared with symptomatic testing of teachers alone.

Conclusions
Symptomatic testing of teachers and students has the potential to cost-effectively reduce a substantial number of school and community infections.

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Viral shedding of SARS-CoV-2 in body fluids associated with sexual activity: a systematic review and meta-analysis

Objective
To identify and summarise the evidence on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA detection and persistence in body fluids associated with sexual activity (saliva, semen, vaginal secretion, urine and faeces/rectal secretion).

Eligibility
All studies that reported detection of SARS-CoV-2 in saliva, semen, vaginal secretion, urine and faeces/rectal swabs.

Information sources
The WHO COVID-19 database from inception to 20 April 2022.

Risk of bias assessment
The National Institutes of Health tools.

Synthesis of results
The proportion of patients with positive results for SARS-CoV-2 and the proportion of patients with a viral duration/persistence of at least 14 days in each fluid was calculated using fixed or random effects models.

Included studies
A total of 182 studies with 10 023 participants.

Results
The combined proportion of individuals with detection of SARS-CoV-2 was 82.6% (95% CI: 68.8% to 91.0%) in saliva, 1.6% (95% CI: 0.9% to 2.6%) in semen, 2.7% (95% CI: 1.8% to 4.0%) in vaginal secretion, 3.8% (95% CI: 1.9% to 7.6%) in urine and 31.8% (95% CI: 26.4% to 37.7%) in faeces/rectal swabs. The maximum viral persistence for faeces/rectal secretions was 210 days, followed by semen 121 days, saliva 112 days, urine 77 days and vaginal secretions 13 days. Culturable SARS-CoV-2 was positive for saliva and faeces.

Limitations
Scarcity of longitudinal studies with follow-up until negative results.

Interpretation
SARS-CoV-2 RNA was detected in all fluids associated with sexual activity but was rare in semen and vaginal secretions. Ongoing droplet precautions and awareness of the potential risk of contact with faecal matter/rectal mucosa are needed.

PROSPERO registration number
CRD42020204741.

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Impact of immunosuppressive therapy on SARS-CoV-2 mRNA vaccine effectiveness in patients with immune-mediated inflammatory diseases: a Danish nationwide cohort study

Objective
Patients receiving immunosuppressives have been excluded from trials for SARS-CoV-2 vaccine efficacy. Investigation of immunosuppressants’ impact on effectiveness of vaccines, particularly in patients with immune-mediated inflammatory diseases (IMID), is therefore required.

Design
We performed a nationwide cohort study to assess the risk of COVID-19 infection in vaccinated patients with IMID exposed to immunosuppressives compared with IMID unexposed to immunosuppressives. Exposure to immunosuppressives in the 120 days before receiving the second SARS-CoV-2 mRNA vaccination was assessed. Patients were followed from date of second vaccination and weighted Cox models were used to estimate the risk of infection associated with immunosuppressives. Secondary outcomes included hospitalisation and death associated with a positive SARS-CoV-2 test. Risk of infection by immunosuppressant drug class was also analysed.

Setting
This study used population-representative data from Danish national health registries in the period from 1 January to 30 November 2021.

Results
Overall, 152 440 patients were followed over 19 341 person years. Immunosuppressants were associated with a significantly increased risk of infection across IMID (HR: 1.4, 95% CI 1.2 to 1.5), in inflammatory bowel disease (IBD) (HR: 1.6, 95% CI 1.4 to 1.9) and arthropathy (HR: 1.3, 95% CI 1.1 to 1.4) but not psoriasis (HR: 1.1, 95% CI 0.9 to 1.4). Immunosuppressants were also associated with an increased risk of hospitalisation across IMID (HR: 1.4, 95% CI 1.1 to 2.0), particularly in IBD (HR: 2.1, 95% CI 1.0 to 4.1). No significantly increased risk of death in immunosuppressant exposed patients was identified. Analyses by immunosuppressant drug class showed increased COVID-19 infection and hospitalisation with anti-tumour necrosis factor (TNF), systemic corticosteroid, and rituximab and other immunosuppressants in vaccinated patients with IMID.

Conclusion
Immunosuppressive therapies reduced effectiveness of mRNA SARS-CoV-2 vaccination against infection and hospitalisation in patients with IMID. Anti-TNF, systemic corticosteroids, and rituximab and other immunosuppressants were particularly associated with these risks.

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Worry perception and its association with work conditions among healthcare workers during the first wave of the COVID-19 pandemic: a web-based multimethod survey at a university hospital in Sweden

Objectives
In this study, we explored healthcare workers’ (HCWs) worry perception and its association with their work situation during the first wave of the COVID-19 pandemic.

Design
A web-based multimethods survey including multiple choice and open-ended questions was used.

Setting
The study was conducted at a university hospital in Sweden.

Participants
All HCWs who were working during the first wave of the COVID-19 pandemic in March–June 2020 were eligible. HCWs (n=6484, response rate=41%) from 69 departments fulfilled the study inclusion criteria and responded to the survey. Of them, we analysed data from the 3532 participants who replied to the open-ended questions (54% of the respondents).

Main outcomes measures
Worry perception and its association with work conditions among HCWs.

Results
29% (n=1822) and 35% (n=2235) of the responding HCWs experienced a daily or more than daily strong worry of being infected or infecting others with SARS-CoV-2. This finding could be further confirmed and explored with themes from the qualitative results: ‘ambiguity of feeling safe and secure’, ‘being obliged to adapt to a new reality’ and ‘into the unknown’. The themes consisted of 6 main categories and 15 subcategories. The findings revealed that the two main drivers of worry perceived by HCWs were lack of personal protective equipment and fear of bringing the virus home to their families and friends.

Conclusions
Worries of getting infected are common among HCWs during crises such as the COVID-19 pandemic. Several factors are raised that plausibly could minimise the negative effects of worry among HCWs. Thus, effective preventive work plans should be created, promoted and communicated in order to minimise the effects of such crises and support HCWs. By focusing on effective communication and preparedness, including access to relevant protective equipment and providing general support to HCWs, the work environment and patient care could be sustained during a crisis such as the COVID-19 pandemic.

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Nudging towards COVID-19 and influenza vaccination uptake in medically at-risk children: EPIC study protocol of randomised controlled trials in Australian paediatric outpatient clinics

Introduction
Children with chronic medical diseases are at an unacceptable risk of hospitalisation and death from influenza and SARS-CoV-2 infections. Over the past two decades, behavioural scientists have learnt how to design non-coercive ‘nudge’ interventions to encourage positive health behaviours. Our study aims to evaluate the impact of multicomponent nudge interventions on the uptake of COVID-19 and influenza vaccines in medically at-risk children.

Methods and analyses
Two separate randomised controlled trials (RCTs), each with 1038 children, will enrol a total of approximately 2076 children with chronic medical conditions who are attending tertiary hospitals in South Australia, Western Australia and Victoria. Participants will be randomly assigned (1:1) to the standard care or intervention group. The nudge intervention in each RCT will consist of three text message reminders with four behavioural nudges including (1) social norm messages, (2) different messengers through links to short educational videos from a paediatrician, medically at-risk child and parent and nurse, (3) a pledge to have their child or themselves vaccinated and (4) information salience through links to the current guidelines and vaccine safety information. The primary outcome is the proportion of medically at-risk children who receive at least one dose of vaccine within 3 months of randomisation. Logistic regression analysis will be performed to determine the effect of the intervention on the probability of vaccination uptake.

Ethics and dissemination
The protocol and study documents have been reviewed and approved by the Women’s and Children’s Health Network Human Research Ethics Committee (HREC/22/WCHN/2022/00082). The results will be published via peer-reviewed journals and presented at scientific meetings and public forums.

Trial registration number
NCT05613751.

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Association of Long COVID with mental health disorders: a retrospective cohort study using real-world data from the USA

Objectives
Mental health disorders (MHD) rank third for US adult hospitalisations. Given the substantial prevalence of ‘Long COVID’ in SARS-CoV-2 survivors, this study aims to assess its association with increased MHD risk using extensive real-world data.

Design
A retrospective cohort study with propensity score matching was conducted. We used the International Classification of Diseases, 10th Revision codes to identify individuals with Long COVID status and COVID-19 histories. Multivariable stratified Cox proportional hazards regression analysis was conducted to determine the association of Long COVID status with MHD.

Setting
Data were sourced from the TriNetX database, spanning records from 1 October 2021 to 16 April 2023.

Participants
Two distinct cohorts were established: one comprising individuals diagnosed with Long COVID and another comprising individuals with no history of Long COVID or COVID-19. At the start of the study, none of the participants had a recorded MHD.

Primary and secondary outcome measures
The main outcome of interest was a composite diagnosis of MHD. Secondary outcomes were individual mental health conditions.

Results
The study included 43 060 control participants without Long COVID and 4306 Long COVID participants, demonstrating well-balanced distribution across all covariates. After adjusting for 4 demographic factors and 10 comorbidities, Long COVID was associated with MHD (adjusted HR, aHR 2.60; 95% CI 2.37 to 2.85). In subgroup analysis, Long COVID was associated with major depression disorder (aHR 3.36; 95% CI 2.82 to 4.00) and generalised anxiety disorder (aHR 3.44; 95% CI 2.99 to 3.96).

Conclusions
In this retrospective large real-world cohort study, Long COVID was associated with an increased risk of incident MHD. The MHD impact is significant considering the vast number of patients with Long COVID. Enhanced MHD screening among COVID-19 survivors should be a priority.

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