Post-COVID-19 irritable bowel syndrome

We read with interest the article by Marasco et al evaluating the prevalence of gastrointestinal (GI) symptoms and post-COVID-19 disorders of gut–brain interaction after hospitalisation for SARS-CoV-2 infection.1 The author found that COVID-19 is associated with a modest increased risk of irritable bowel syndrome (IBS). Postinfectious IBS (PI-IBS) is a common disease in which GI symptoms begin after an episode of infective gastroenteritis. Acute gastroenteritis following infection with bacterial or viral pathogens is an important risk factor for IBS. Our previous study also confirmed that the odds of developing IBS are increased after acute GI infection.2 The first formal description of PI-IBS was published Chaudhary and Truelove.3 SARS-CoV-2 could also lead to GI symptoms, which involve abdominal pains, diarrhoea, nausea and vomiting. Our previous meta-analysis including 31 studies with 4682 COVID-19 patients found that SARS-CoV-2 infection was associated with diarrhoea, anorexia, abdominal pain…

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CDC Eases Isolation Guidance for Respiratory Viruses

New guidance from the US Centers for Disease Control and Prevention (CDC) provides updated measures to combat respiratory viruses such as SARS-CoV-2, influenza, and respiratory syncytial virus. The recommendations come at a time when deaths and hospitalizations from COVID-19 have decreased from the peak of the pandemic and the availability of tools to fight respiratory viruses is greater than ever, the agency noted.

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Prevalence and impact of SARS-CoV-2 infection among patients with acute ischaemic stroke: a nationwide register-based cohort study in Denmark

Objectives
An increased risk of stroke has been reported among patients with COVID-19 caused by SARS-CoV-2. We aimed to investigate the nationwide prevalence of SARS-CoV-2 among patients with acute ischaemic stroke and to study the impact on stroke severity, quality of care and mortality on an individual patient level.

Design
This was a nationwide register-based cohort study.

Setting
We used data from several Danish registers which were linked at an individual patient level using the unique civil registration number assigned to all Danish citizens. Patients were identified from the Danish Stroke Registry and information on SARS-CoV-2 infection status was collected from the Danish National COVID-19 Registry. Concurrent SARS-CoV-2 infection was defined as a positive PCR test within 31 days prior to, and 1 day after, stroke admission. Information on comorbidity was collected from the Danish National Patient Registry and information on vital status was collected from the Danish Civil Registration System.

Participants
A total of 11 502 patients admitted with acute ischaemic stroke from 10 March 2020 to 31 May 2021 were included in the study.

Results
Among the included patients, the majority (84.6%) were tested for SARS-CoV-2, but only 68 had a positive test. These patients were more prone to have atrial fibrillation and were more often treated with reperfusion therapy. They had a significantly increased risk of severe stroke (adjusted relative risk (aRR) 1.93, 95% CI: 1.22 to 3.04) and a significantly increased 30-day mortality risk (aRR 2.29, 95% CI: 1.19 to 4.39). There was no difference in the proportion of patients fulfilling relevant performance measures on quality of care.

Conclusion
In this nationwide study, only 0.6% of patients with acute ischaemic stroke were tested positive for a concurrent SARS-CoV-2 infection. The patients with SARS-CoV-2 presented with more severe strokes.

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Virus-Induced Acute Respiratory Distress Syndrome Causes Cardiomyopathy Through Eliciting Inflammatory Responses in the Heart

Circulation, Ahead of Print. BACKGROUND:Viral infections can cause acute respiratory distress syndrome (ARDS), systemic inflammation, and secondary cardiovascular complications. Lung macrophage subsets change during ARDS, but the role of heart macrophages in cardiac injury during viral ARDS remains unknown. Here we investigate how immune signals typical for viral ARDS affect cardiac macrophage subsets, cardiovascular health, and systemic inflammation.METHODS:We assessed cardiac macrophage subsets using immunofluorescence histology of autopsy specimens from 21 patients with COVID-19 with SARS-CoV-2–associated ARDS and 33 patients who died from other causes. In mice, we compared cardiac immune cell dynamics after SARS-CoV-2 infection with ARDS induced by intratracheal instillation of Toll-like receptor ligands and an ACE2 (angiotensin-converting enzyme 2) inhibitor.RESULTS:In humans, SARS-CoV-2 increased total cardiac macrophage counts and led to a higher proportion of CCR2+(C-C chemokine receptor type 2 positive) macrophages. In mice, SARS-CoV-2 and virus-free lung injury triggered profound remodeling of cardiac resident macrophages, recapitulating the clinical expansion of CCR2+macrophages. Treating mice exposed to virus-like ARDS with a tumor necrosis factor α–neutralizing antibody reduced cardiac monocytes and inflammatory MHCIIloCCR2+macrophages while also preserving cardiac function. Virus-like ARDS elevated mortality in mice with pre-existing heart failure.CONCLUSIONS:Our data suggest that viral ARDS promotes cardiac inflammation by expanding the CCR2+macrophage subset, and the associated cardiac phenotypes in mice can be elicited by activating the host immune system even without viral presence in the heart.

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CDC Tracking BA.2.87.1, New Omicron Subvariant With Potential to Evade Immunity

Experts detected a strain of SARS-CoV-2 with more than 30 changes in its spike protein compared with Omicron subvariant XBB.1.5, the US Centers for Disease Control and Prevention (CDC) announced. The newer Omicron subvariant, known as BA.2.87.1, has infected at least 9 people in South Africa since September 2023. No cases have been reported in the US or outside South Africa, the CDC noted in its update.

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Multicentre, randomised, double-blind, placebo-controlled, proof of concept study of LSALT peptide as prevention of acute respiratory distress syndrome and acute kidney injury in patients infected with SARS-CoV-2 (COVID-19)

Objective
Dipeptidase-1 (DPEP-1) is a recently discovered leucocyte adhesion receptor for neutrophils and monocytes in the lungs and kidneys and serves as a potential therapeutic target to attenuate inflammation in moderate-to-severe COVID-19. We aimed to evaluate the safety and efficacy of the DPEP-1 inhibitor, LSALT peptide, to prevent specific organ dysfunction in patients hospitalised with COVID-19.

Design
Phase 2a randomised, placebo-controlled, double-blinded, trial.

Setting
Hospitals in Canada, Turkey and the USA.

Participants
A total of 61 subjects with moderate-to-severe COVID-19.

Interventions
Randomisation to LSALT peptide 5 mg intravenously daily or placebo for up to 14 days.

Primary and secondary outcome measures
The primary endpoint was the proportion of subjects alive and free of respiratory failure and/or the need for renal replacement therapy (RRT). Numerous secondary and exploratory endpoints were assessed including ventilation-free days, and changes in kidney function or serum biomarkers.

Results
At 28 days, 27 (90.3%) and 28 (93.3%) of subjects in the placebo and LSALT groups were free of respiratory failure and the need for RRT (p=0.86). On days 14 and 28, the number of patients still requiring more intensive respiratory support (O2 ≥6 L/minute, non-invasive or invasive mechanical ventilation or extracorporeal membrane oxygenation) was 6 (19.4%) and 3 (9.7%) in the placebo group versus 2 (6.7%) and 2 (6.7%) in the LSALT group, respectively (p=0.14; p=0.67). Unadjusted analysis of ventilation-free days demonstrated 22.8 days for the LSALT group compared with 20.9 in the placebo group (p=0.4). LSALT-treated subjects had a significant reduction in the fold expression from baseline to end of treatment of serum CXCL10 compared with placebo (p=0.02). Treatment-emergent adverse events were similar between groups.

Conclusion
In a Phase 2 study, LSALT peptide was demonstrated to be safe and tolerated in patients hospitalised with moderate-to-severe COVID-19.

Trial registration number
NCT04402957.

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Inhaled Nitric Oxide ReDuce postoperatIve pulmoNAry complicaTions in patiEnts with recent COVID-19 infection (INORDINATE): protocol for a randomised controlled trial

Background
A history of SARS-CoV-2 infection has been reported to be associated with an increased risk of postoperative pulmonary complications (PPCs). Even mild PPCs can elevate the rates of early postoperative mortality, intensive care unit (ICU) admission and prolong the length of ICU and/or hospital stays. Consequently, it is crucial to develop perioperative management strategies that can mitigate these increased risks in surgical patients who have recently been infected with SARS-CoV-2. Accumulating evidence suggests that nitric oxide (NO) inhalation might be effective in treating COVID-19. NO functions in COVID-19 by promoting vasodilation, anticoagulation, anti-inflammatory and antiviral effects. Therefore, our study hypothesises that the perioperative use of NO can effectively reduce PPCs in patients with recent SARS-CoV-2 infection.

Method and analysis
A prospective, double-blind, single-centre, randomised controlled trial is proposed. The trial aims to include participants who are planning to undergo surgery with general anaesthesia and have been recently infected with SARS-CoV-2 (within 7 weeks). Stratified allocation of eligible patients will be performed at a 1:1 ratio based on the predicted risk of PPCs using the Assess Respiratory Risk in Surgical Patients in Catalonia risk index and the time interval between infection and surgery.
The primary outcome of the study will be the presence of PPCs within the first 7 days following surgery, including respiratory infection, respiratory failure, pleural effusion, atelectasis, pneumothorax, bronchospasm and aspiration pneumonitis. The primary outcome will be reported as counts (percentage) and will be compared using a two-proportion 2 test. The common effect across all primary components will be estimated using a multiple generalised linear model.

Ethics and dissemination
The trial is approved by the Institutional Review Board of Xijing Hospital (KY20232058-F1). The findings, including positive, negative and inconclusive results, will be published in scientific journals with peer-review processes.

Trial registration number
NCT05721144.

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Subphenotypes of self-reported symptoms and outcomes in long COVID: a prospective cohort study with latent class analysis

Objective
To characterise subphenotypes of self-reported symptoms and outcomes (SRSOs) in postacute sequelae of COVID-19 (PASC).

Design
Prospective, observational cohort study of subjects with PASC.

Setting
Academic tertiary centre from five clinical referral sources.

Participants
Adults with COVID-19 ≥20 days before enrolment and presence of any new self-reported symptoms following COVID-19.

Exposures
We collected data on clinical variables and SRSOs via structured telephone interviews and performed standardised assessments with validated clinical numerical scales to capture psychological symptoms, neurocognitive functioning and cardiopulmonary function. We collected saliva and stool samples for quantification of SARS-CoV-2 RNA via quantitative PCR.

Outcomes measures
Description of PASC SRSOs burden and duration, derivation of distinct PASC subphenotypes via latent class analysis (LCA) and relationship with viral load.

Results
We analysed baseline data for 214 individuals with a study visit at a median of 197.5 days after COVID-19 diagnosis. Participants reported ever having a median of 9/16 symptoms (IQR 6–11) after acute COVID-19, with muscle-aches, dyspnoea and headache being the most common. Fatigue, cognitive impairment and dyspnoea were experienced for a longer time. Participants had a lower burden of active symptoms (median 3 (1–6)) than those ever experienced (p

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Virtual Group Exercise Program Improved Long COVID Symptoms

A group exercise program delivered online in combination with psychological support sessions improved the health-related quality of life for people living with post–COVID-19 condition, also known as long COVID, compared with the usual care of 1 online support session. The results are based on randomized clinical trial data from 585 adults in England and Wales with ongoing physical and mental health symptoms after being hospitalized with SARS-CoV-2.

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Robust SARS-CoV-2 antibody and T cell immunity following three COVID-19 vaccine doses in inflammatory bowel disease patients receiving anti-TNF or alternative treatments

We read Kennedy et al1’s findings with interest, and report in-depth analyses of antibody and T cell responses in patients with inflammatory bowel disease (IBD) to COVID-19 vaccination. We prospectively recruited 100 SARS-CoV-2-uninfected patients with IBD on varying treatments at the Royal Melbourne Hospital (HREC/74403/MH-2021). Healthcare workers who did not have IBD and were not on immunosuppressive medication were enrolled as controls with approvals from Melbourne Health (HREC/68355/MH-2020) and University of Melbourne (HREC 22268, 21626). Participant characteristics are outlined in table 1. IBD medication regimens needed to be stable for at least 8 weeks prior to enrolment. Only one participant was on concomitant low-dose systemic corticosteroids with anti-TNF combination therapy. Eighty-nine patients received BNT162b2 (Pfizer–BioNTech), and 11 received ChAdOx1 nCoV-19 (Oxford–AstraZeneca). No participants had a clinical history of SARS-CoV-2 infection at enrolment. Anti-S1/2 and anti-RBD SARS-CoV-2-specific antibodies were measured at baseline and at five time…

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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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SARS-CoV-2 and the liver: clinical and immunological features in chronic liver disease

Luxenburger H, Thimme R. SARS-CoV-2 and the liver: clinical and immunological features in chronic liver disease. Gut 2023;72:1783-94
The correct legend for figure 4 should be:
Effect of booster vaccination on the adaptive immune response in LTR and AIH patients (A) Booster vaccination significantly improves the SARS-CoV- 2-specific antibody response in AIH, while the frequency of T cells remains stable. (B) Booster vaccination significantly improves the SARS-CoV-2- specific antibody response in LTR, while the frequency of T cells remains stable. (C) After two RNA vaccine doses, the CD4+T cell subset distribution is altered in LTR with lower frequencies of TFH cells, however, the frequencies increase after booster infection. AIH, autoimmune hepatitis; LTR, liver transplant recipients; TFH cells: T follicular helper cells.

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