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People living with HIV (PLWH) despite having an appreciable depletion of CD4 + T-cells show a good severe acute respiratory syndrome coronavirus 2 vaccination response. The underlying mechanism(s) are currently not understood. We studied serological and polyfunctional T-cell responses in PLWH receiving anti-retroviral therapy stratified on CD4 + counts as PLWH-high (CD4 ≥ 500 cells/mm 3 ) and PLWH-low (<500 cells/mm 3 ). Responses were assessed longitudinally before the first vaccination (T0), 1-month after the first dose (T1), 3-months (T2), and 6-months (T3) after the second dose. Expectedly, both PLWH-high and -low groups developed similar serological responses after T2, which were also non-significantly different from age and vaccination-matched HIV-negative controls at T3. The immunoglobulin G titers were also protective showing a good correlation with angiotensin-converting enzyme 2-neutralizations (R = 0.628, p = 0.005). While surface and intracellular activation analysis showed no significant difference at T3 between PLWH and controls in activated CD4 + CD154 + and CD4 + memory T-cells, spike-specific CD4 + polyfunctional cytokine expression analysis showed that PLWH preferentially express interleukin (IL)-2 (p < 0.001) and controls, interferon-γ (p = 0.017). CD4 + T-cell counts negatively correlated with IL-2-expressing CD4 + T-cells including CD4 + memory T-cells (Spearman ρ: -0.85 and -0.80, respectively; p < 0.001). Our results suggest that the durable serological and CD4 + T-cell responses developing in vaccinated PLWH are associated with IL-2-mediated CD4 + T-cell activation that likely compensates for CD4 + T-cell depletion in PLWH., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

Background: The risk of barotrauma associated with different types of ventilatory support is unclear in COVID-19 patients. The primary aim of this study was to evaluate the effect of the different respiratory support strategies on barotrauma occurrence; we also sought to determine the frequency of barotrauma and the clinical characteristics of the patients who experienced this complication., Methods: This multicentre retrospective case-control study from 1 March 2020 to 28 February 2021 included COVID-19 patients who experienced barotrauma during hospital stay. They were matched with controls in a 1:1 ratio for the same admission period in the same ward of treatment. Univariable and multivariable logistic regression (OR) were performed to explore which factors were associated with barotrauma and in-hospital death., Results: We included 200 cases and 200 controls. Invasive mechanical ventilation was used in 39.3% of patients in the barotrauma group, and in 20.1% of controls (p<0.001). Receiving non-invasive ventilation (C-PAP/PSV) instead of conventional oxygen therapy (COT) increased the risk of barotrauma (OR 5.04, 95% CI 2.30 - 11.08, p<0.001), similarly for invasive mechanical ventilation (OR 6.24, 95% CI 2.86-13.60, p<0.001). High Flow Nasal Oxygen (HFNO), compared with COT, did not significantly increase the risk of barotrauma. Barotrauma frequency occurred in 1.00% [95% CI 0.88-1.16] of patients; these were older (p=0.022) and more frequently immunosuppressed (p=0.013). Barotrauma was shown to be an independent risk for death (OR 5.32, 95% CI 2.82-10.03, p<0.001)., Conclusions: C-PAP/PSV compared with COT or HFNO increased the risk of barotrauma; otherwise HFNO did not. Barotrauma was recorded in 1.00% of patients, affecting mainly patients with more severe COVID-19 disease. Barotrauma was independently associated with mortality., Trial Registration: this case-control study was prospectively registered in clinicaltrial.gov as NCT04897152 (on 21 May 2021)., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

Objectives: The study aim was to assess predictors of negative antibody response (AbR) in solid organ transplant (SOT) recipients after the first booster of SARS-CoV-2 vaccination., Methods: Solid organ transplant recipients receiving SARS-CoV-2 vaccination were prospectively enrolled (March 2021-January 2022) at six hospitals in Italy and Spain. AbR was assessed at first dose (t 0 ), second dose (t 1 ), 3 ± 1 month (t 2 ), and 1 month after third dose (t 3 ). Negative AbR at t 3 was defined as an anti-receptor binding domain titre <45 BAU/mL. Machine learning models were developed to predict the individual risk of negative (vs. positive) AbR using age, type of transplant, time between transplant and vaccination, immunosuppressive drugs, type of vaccine, and graft function as covariates, subsequently assessed using a validation cohort., Results: Overall, 1615 SOT recipients (1072 [66.3%] males; mean age±standard deviation [SD], 57.85 ± 13.77) were enrolled, and 1211 received three vaccination doses. Negative AbR rate decreased from 93.66% (886/946) to 21.90% (202/923) from t 0 to t 3 . Univariate analysis showed that older patients (mean age, 60.21 ± 11.51 vs. 58.11 ± 13.08), anti-metabolites (57.9% vs. 35.1%), steroids (52.9% vs. 38.5%), recent transplantation (<3 years) (17.8% vs. 2.3%), and kidney, heart, or lung compared with liver transplantation (25%, 31.8%, 30.4% vs. 5.5%) had a higher likelihood of negative AbR. Machine learning (ML) algorithms showing best prediction performance were logistic regression (precision-recall curve-PRAUC mean 0.37 [95%CI 0.36-0.39]) and k-Nearest Neighbours (PRAUC 0.36 [0.35-0.37])., Discussion: Almost a quarter of SOT recipients showed negative AbR after first booster dosage. Unfortunately, clinical information cannot efficiently predict negative AbR even with ML algorithms., (Copyright © 2023. Published by Elsevier Ltd.)

BackgroundThe role of host immunity in emergence of evasive SARS-CoV-2 Spike mutations under therapeutic monoclonal antibody (mAb) pressure remains to be explored.MethodsIn a prospective, observational, monocentric ORCHESTRA cohort study, conducted between March 2021 and November 2022, mild-to-moderately ill COVID-19 patients (n = 204) receiving bamlanivimab, bamlanivimab/etesevimab, casirivimab/imdevimab, or sotrovimab were longitudinally studied over 28 days for viral loads, de novo Spike mutations, mAb kinetics, seroneutralization against infecting variants of concern, and T cell immunity. Additionally, a machine learning-based circulating immune-related biomarker (CIB) profile predictive of evasive Spike mutations was constructed and confirmed in an independent data set (n = 19) that included patients receiving sotrovimab or tixagevimab/cilgavimab.ResultsPatients treated with various mAbs developed evasive Spike mutations with remarkable speed and high specificity to the targeted mAb-binding sites. Immunocompromised patients receiving mAb therapy not only continued to display significantly higher viral loads, but also showed higher likelihood of developing de novo Spike mutations. Development of escape mutants also strongly correlated with neutralizing capacity of the therapeutic mAbs and T cell immunity, suggesting immune pressure as an important driver of escape mutations. Lastly, we showed that an antiinflammatory and healing-promoting host milieu facilitates Spike mutations, where 4 CIBs identified patients at high risk of developing escape mutations against therapeutic mAbs with high accuracy.ConclusionsOur data demonstrate that host-driven immune and nonimmune responses are essential for development of mutant SARS-CoV-2. These data also support point-of-care decision making in reducing the risk of mAb treatment failure and improving mitigation strategies for possible dissemination of escape SARS-CoV-2 mutants.FundingThe ORCHESTRA project/European Union's Horizon 2020 research and innovation program.

Background: Residual symptoms can be detected for several months after COVID-19. To better understand the predictors and impact of symptom persistence we analyzed a prospective cohort of COVID-19 patients., Methods: Patients were followed for 9 months after COVID-19 onset. Duration and predictors of persistence of symptoms, physical health and psychological distress were assessed., Results: 465 patients (54% males, 51% hospitalized) were included; 37% presented with at least 4 symptoms and 42% complained of symptom lasting more than 28 days. At month 9, 20% of patients were still symptomatic, showing mainly fatigue (11%) and breathlessness (8%). Hospitalization and ICU stay vs. non-hospitalized status increased the median duration of fatigue of 8 weeks. Age > 50 years (OR 2.50), ICU stay (OR 2.35), and presentation with 4 or more symptoms (OR 2.04) were independent predictors of persistence of symptoms at month 9. A total of 18% of patients did not return to optimal pre-COVID physical health, while 19% showed psychological distress at month 9. Hospital admission (OR 2.28) and persistence of symptoms at day 28 (OR 2.21) and month 9 (OR 5.16) were independent predictors of suboptimal physical health, while female gender (OR 5.27) and persistence of symptoms at day 28 (OR 2.42) and month 9 (OR 2.48) were risk factors for psychological distress., Conclusions: Patients with advanced age, ICU stay and multiple symptoms at onset were more likely to suffer from long-term symptoms, which had a negative impact on both physical and mental wellbeing. This study contributes to identify the target populations and Long COVID consequences for planning long-term recovery interventions., Competing Interests: Declaration of Competing Interest The authors have no competing interests, (Copyright © 2022. Published by Elsevier Ltd.)

COVID-19 has been associated with having a negative impact on patients' gut microbiome during both active disease and in the post-acute phase. In acute COVID-19, rapid alteration of the gut microbiome composition was observed, showing on one side a reduction in beneficial symbionts (e.g., Roseburia, Lachnospiraceae) and on the other side an increase in opportunistic pathogens such as Enterococcus and Proteobacteria. Alpha diversity tends to decrease, especially initially with symptom onset and hospital admission. Although clinical recovery appears to align with improved gut homeostasis, this process could take several weeks, even in mild infections. Moreover, patients with COVID-19 post-acute syndrome showed changes in gut microbiome composition, with specific signatures associated with decreased respiratory function up to 12 months following acute disease. Potential treatments, especially probiotic-based therapy, are under investigation. Open questions remain on the possibility to use gut microbiome data to predict disease progression and on potential confounders that may impair result interpretation (e.g., concomitant therapies in the acute phase; reinfection, vaccines, and occurrence of novel conditions or diseases in the post-acute syndrome). Understanding the relationships between gut microbiome dynamics and disease progression may contribute to better understanding post-COVID syndrome pathogenesis or inform personalized treatment that can affect specific targets or microbiome markers. [ABSTRACT FROM AUTHOR]

Objective: Several studies showed the substantial use of antibiotics and increased risk of antimicrobial resistant infections in patients with COVID-19. The impact of COVID-19-related treatments and antibiotics on gut dysbiosis has not been clarified. Design: The prospective cohort study included hospitalized COVID-19 patients (April–December 2020). The gut microbiome composition was analysed by 16S sequencing. The gut diversity and changes in opportunistic bacteria (OBs) or symbionts were analysed according to clinical parameters, laboratory markers of disease progression, type of non-antibiotic COVID-19 treatments (NACT) and type, WHO AWaRe group, and duration of antibiotic therapy (AT). Results: A total of 82 patients (mean age 66 ± 13 years, 70% males) were enrolled. The relative abundance of Enterococcus was significantly correlated with duration of hospitalization, intensive care unit stay, O2 needs, and D-dimer, ferritin, and IL-6 blood levels. The presence of Enterococcus showed the highest number of correlations with NACT, AT, and AT + NACT (e.g., hydroxychloroquine ± lopinavir/ritonavir) and increased relative abundance with AWaRe Watch/Reserve antibiotics, AT duration, and combinations. Abundance of Dorea, Agathobacter, Roseburia, and Barnesiella was negatively correlated with AT and corticosteroids use. Patients with increased IL-6, D-dimer, and ferritin levels receiving AT were more likely to show dysbiosis with increased abundance of Enterococcus and Bilophila bacteria and decreased abundance of Roseburia compared with those not receiving AT. Conclusion: Microbiome diversity is affected by COVID-19 severity. In this context, antibiotic treatment may shift the gut microbiome composition towards OBs, particularly Enterococcus. The impact of treatment-driven dysbiosis on OBs infections and long-term consequences needs further study to define the role of gut homeostasis in COVID-19 recovery and inform targeted interventions. [ABSTRACT FROM AUTHOR]

Previous studies assessing the antibody response (AbR) to mRNA COVID-19 vaccines in solid organ transplant (SOT) recipients are limited by short follow-up, hampering the analysis of AbR kinetics. We present the ORCHESTRA SOT recipients cohort assessed for AbR at first dose (t0), second dose (t1), and within 3 ± 1 month (t2) after the first dose. We analyzed 1062 SOT patients (kidney, 63.7%; liver, 17.4%; heart, 16.7%; and lung, 2.5%) and 5045 health care workers (HCWs). The AbR rates in the SOTs and HCWs were 52.3% and 99.4%. The antibody levels were significantly higher in the HCWs than in the SOTs (p < 0.001). The kinetics showed an increase (p < 0.001) in antibody levels up to 76 days and a non-significant decrease after 118 days in the SOT recipients versus a decrease up to 76 days (p = 0.02) and a less pronounced decrease between 76 and 118 days (p = 0.04) in the HCWs. Upon multivariable analysis, liver transplant, ≥3 years from SOT, mRNA-1273, azathioprine, and longer time from t0 were associated with a positive AbR at t2. Older age, other comorbidities, mycophenolate, steroids, and impaired graft function were associated with lower AbR probability. Our results may be useful to optimize strategies of immune monitoring after COVID-19 vaccination and indications regarding timing for booster dosages calibrated on SOT patients' characteristics. [ABSTRACT FROM AUTHOR]

The article discusses research which peer-reviewed web sources specifically addressing the type and amount of physical activity (PA) recommended for home training during the coronavirus disease-2019 (COVID-19) pandemic. Topics covered include the useful features to address for PA during the current pandemic, and government and sport society-related web sources for home exercising and other recommendations during COVID-19-related restrictions on PA.