Risk Of Severe COVID-19 Outcomes Research Articles

IMPACT OF INFLAMMATORY RHEUMATIC DISEASES ON THE COURSE AND OUTCOME OF COVID-19

. Literature data on the risk of SARS-CoV-2 coronavirus infection in people with inflammatory rheumatic diseases (RD) are contradictory. According to most studies, the risk of infection and development of severe forms of COVID-19 is higher in patients with RD compared to the general population, but largely depends on the type and activity of RD. Patients with severe RD most often required mechanical ventilation and died more often. This is due to immune dysfunction caused by both the disease itself and antirheumatic therapy using immunomodulatory drugs. The state of immunosuppression, additional comorbid chronic diseases and incomplete vaccination are factors in the need for hospitalization, intensive care, the risk of severe COVID-19 outcomes and reinfection with coronavirus in patients with RD. They retained their significance during the spread of the SARS-CoV-2 Omicron variant. Although there is no complete consensus in the literature regarding the association between the presence of rheumatic diseases and the severity of COVID-19, in general, rheumatic diseases are not considered to be a factor that increases the severity and mortality of COVID-19. Vaccination against SARS-CoV-2 stimulates the antibody response and reduces the incidence and severity of COVID-19. However, people with rheumatic diseases have reduced or absent antibody production in response to even full vaccination and higher rates of breakthrough infection after vaccination. Further research on specific rheumatic diseases and the use of antirheumatic drugs in the context of COVID-19 is needed to reduce the severity of COVID-19 in this population.

Evaluation of Inflammatory Status in COVID-19 Patients with Chronic Kidney Disease: A Comparative Analysis Based on Creatinine Clearance Levels

Background and Objectives: Patients with chronic kidney disease (CKD) are at increased risk of severe COVID-19 outcomes due to their compromised immune systems and chronic inflammatory state. This study aimed to evaluate and compare the inflammatory status of COVID-19 patients with CKD, stratified by creatinine clearance (CrCl) levels: CrCl < 30 mL/min, CrCl 30–60 mL/min, and CrCl > 60 mL/min. Multiple inflammatory scores combining laboratory parameters were assessed, including novel scores and established indices. Methods: In this retrospective cohort study, 223 patients admitted with confirmed COVID-19 were included and divided into three groups based on CrCl levels: CrCl < 30 (n = 41), CrCl 30–60 (n = 78), and CrCl > 60 (n = 104). Laboratory parameters including C-reactive protein (CRP), interleukin-6 (IL-6), neutrophil-to-lymphocyte ratio (NLR), ferritin, platelet count, absolute neutrophil count (ANC), absolute lymphocyte count (ALC), and serum albumin were collected. Multiple inflammatory scores were calculated, including inflammation scores (IS1–IS4), the systemic inflammatory index (SII), the C-reactive protein-to-albumin ratio (CAR), the lymphocyte-to-C-reactive protein ratio (LCR), and the prognostic nutritional index (PNI). Statistical analyses were performed to compare inflammatory scores among groups and assess correlations with clinical outcomes. Results: The CrCl < 30 group exhibited significantly higher levels of inflammatory markers and inflammatory scores compared with the other groups (p < 0.001). Among the additional scores, CAR and SII were significantly elevated in patients with lower CrCl levels, while LCR and PNI were decreased. CAR showed a strong positive correlation with COVID-19 severity (r = 0.65, p < 0.001), and PNI was inversely correlated with mortality (r = −0.58, p < 0.001). Multivariate regression analysis indicated that lower CrCl levels, higher IS3 and CAR, and lower PNI were independent predictors of severe COVID-19 outcomes. Conclusions: CKD patients with lower CrCl levels have an amplified inflammatory response during COVID-19 infection, as evidenced by elevated inflammatory scores. The additional inflammatory scores, particularly CAR and PNI, may serve as valuable tools for risk stratification and management of COVID-19 in CKD patients. Early identification of patients with high CAR and low PNI could improve clinical outcomes through timely therapeutic interventions.

Environment, climate, socio-economics & restrictions impact on COVID-19 in Northen Italy

Abstract Up to now, studies on environmental, climatic, socio-economic factors, and non-pharmacological interventions (NPI) show diverse associations, often contrasting, with COVID-19 spread or severity. Most studies used large-scale, aggregated data, with limited adjustment for individual factors, and most of them focused on viral spread rather than severe outcomes. Moreover, evidence simultaneously evaluating variables belonging to different exposure domains is scarce, and none analysing their collective impact on an individual level. Our population-based retrospective cohort study aimed to assess the comprehensive role played by exposure variables belonging to four different domains, environmental, climatic, socio-economic, and non-pharmacological interventions (NPI), on individual COVID-19-related risk of hospitalization and death, analysing data from all patients (n.68472) tested positive to a SARS-CoV-2 swab in Modena Province (Northern Italy) between February 2020 and August 2021. Using adjusted Cox proportional hazard models, we estimated the risk of severe COVID-19 outcomes, investigating dose-response relationships through restricted cubic spline modelling for hazard ratios. Several significant associations emerged: long-term exposure to air pollutants (NO2, PM10, PM2.5) was linked to hospitalization risk in a complex way and showed an increased risk for death; while humidity was inversely associated; temperature showed a U-shaped risk; wind speed showed a linear association with both outcomes. Precipitation increased hospitalization risk but decreased mortality. Socio-economic and NPI indices showed clear linear associations, respectively negative and positive, with both outcomes. Our findings offer insights for evidence-based policy decisions, improving precision healthcare practices, and safeguarding public health in future pandemics. Refinement of pandemic response plans by healthcare authorities could benefit significantly. Key messages • Evaluating simultaneously four exposure domains on COVID-19 outcomes informs public health policy for future pandemic management. • The comprehension of risk factors associated with severe outcomes, such as hospitalization and mortality, is pivotal for planning responses to similar health emergencies in the future.

Environmental, climatic, socio-economic factors and non-pharmacological interventions: A comprehensive four-domain risk assessment of COVID-19 hospitalization and death in Northern Italy

IntroductionUp to now, studies on environmental, climatic, socio-economic factors, and non-pharmacological interventions (NPI) show diverse associations, often contrasting, with COVID-19 spread or severity. Most studies used large-scale, aggregated data, with limited adjustment for individual factors, most of them focused on viral spread than severe outcomes. Moreover, evidence simultaneously evaluating variables belonging to different exposure domains is scarce, and none analysing their collective impact on an individual level. MethodsOur population-based retrospective cohort study aimed to assess the comprehensive role played by exposure variables belonging to four different domains, environmental, climatic, socio-economic, and non-pharmacological interventions (NPI), on individual COVID-19-related risk of hospitalization and death, analysing data from all patients (no. 68472) tested positive to a SARS-CoV-2 swab in Modena Province (Northern Italy) between February 2020 and August 2021.Using adjusted Cox proportional hazard models, we estimated the risk of severe COVID-19 outcomes, investigating dose-response relationships through restricted cubic spline modelling for hazard ratios. ResultsSeveral significant associations emerged: long-term exposure to air pollutants (NO2, PM10, PM2.5) was linked to hospitalization risk in a complex way and showed an increased risk for death; while humidity was inversely associated; temperature showed a U-shaped risk; wind speed showed a linear association with both outcomes. Precipitation increased hospitalization risk but decreased mortality. Socio-economic and NPI indices showed clear linear associations, respectively negative and positive, with both outcomes. ConclusionsOur findings offer insights for evidence-based policy decisions, improving precision healthcare practices, and safeguarding public health in future pandemics. Refinement of pandemic response plans by healthcare authorities could benefit significantly.

Mental illness and COVID-19 vaccination: a multinational investigation of observational & register-based data

Individuals with mental illness are at higher risk of severe COVID-19 outcomes. However, previous studies on the uptake of COVID-19 vaccination in this population have reported conflicting results. Using data from seven cohort studies (N = 325,298) included in the multinational COVIDMENT consortium, and the Swedish registers (N = 8,080,234), this study investigates the association between mental illness (defined using self-report measures, clinical diagnosis and prescription data) and COVID-19 vaccination uptake. Results from the COVIDMENT cohort studies were pooled using meta-analyses, the majority of which showed no significant association between mental illness and vaccination uptake. In the Swedish register study population, we observed a very small reduction in the uptake of both the first and second dose of a COVID-19 vaccine among individuals with vs. without mental illness; the reduction was however greater among those not using psychiatric medication. Here we show that uptake of the COVID-19 vaccine is generally high among individuals both with and without mental illness, however the lower levels of vaccination uptake observed among subgroups of individuals with unmedicated mental illness warrants further attention.

Navigating the Evolving Landscape of COVID-19: Strategies to Increase Vaccine Confidence and Improve Vaccination Rates in the United States.

The COVID-19 pandemic has had a significant impact on every individual in the United States. The launch of the COVID-19 vaccines is estimated to have averted millions of deaths and reduced over 18 million COVID-19-related hospitalizations. In September 2023, the updated 2023-2024 COVID-19 vaccine, which includes a monovalent component that corresponds to the omicron variant XBB.1.5, reflecting the predominant circulating variant at the time of strain selection, was approved and was recommended for use in all people ≥ 6 months of age. Despite this recommendation, the US uptake of the updated COVID-19 vaccines over the 2023-2024 season has been far from optimal, placing many people at unnecessary risk of severe COVID-19 outcomes. This paper provides an overview of the current state of COVID-19 in 2023-2024 and barriers to vaccine uptake. With the continued evolution of the virus, the potential for more virulent variants, reduced public acceptance of vaccination, and the potential barriers that contributed to low vaccine uptake are explored to provide solutions for improving COVID-19 protection for future seasons.

COVID-19 Vaccination Recommendations: Challenges and Strategies for High-Risk Populations

<p>COVID-19（新冠併發重症）大流行對全球，尤其是有潛在醫療狀況的易感染之高風險族群，造成深遠的影響。為因應全球不斷演變的疫情趨勢以及台灣持續增加病例的疫苗防治需求，台灣家庭醫學醫學會建立了針對易感染之高風險族群的COVID-19疫苗接種建議。本研究進行全面性的文獻回顧並經由專家小組討論後，擬定具證據力的建議以作為防疫策略參考。總計提出25項建議，說明糖尿病、肥胖症、慢性腎臟疾病、心血管疾病和呼吸系統疾病病友感染COVID-19後的重症風險為高，因此強調COVID-19 mRNA（訊息核糖核酸）疫苗在這些易感染之高風險族群中的安全性和有效性以及家庭醫師在COVID-19疫情的關鍵作用，包括常規篩檢、衛教、疫苗接種服務的提供和持續的研究。此建議為醫界與政府相關單位在為易感染高風險族群制定疫苗接種計畫時，提供了兼具客觀實證依據與符合臨床實務需求的具體指引，同時強化家庭醫師在防疫工作中的核心角色，透過持續的監測與積極推動疫苗施打，在不斷變化的COVID-19疫情趨勢中發揮重要作用。</p> <p> </p><p>The COVID-19 pandemic has had a profound global impact, particularly on high-risk populations, such as those with underlying medical conditions. In response to the evolving pandemic landscape and the constant surge in the need to vaccinate among vulnerable cases in Taiwan, the Taiwan Association of Family Medicine (TAFM) has developed recommendations on COVID-19 vaccination for high-risk groups. Based on a comprehensive literature review and expert panel discussions, a total of 25 evidence-based recommendations have been developed to serve as a reference for vaccination strategies, highlighting the increased risk of severe COVID-19 outcomes among individuals with complications such as diabetes, obesity, chronic kidney disease, cardiovascular disease, and respiratory illnesses. The recommendations emphasize the safety and effectiveness of COVID-19 vaccines, particularly mRNA vaccines, for the aforementioned high-risk populations and underscore the critical roles of family physicians in response to severe COVID-19 outcomes, including routine screening, health education, vaccine administration, and continuous research to optimize strategies. The TAFM recommendations provide a robust, evidence-based framework that meets clinical practice requirements and provides effective guidelines for physicians, healthcare institutions, and governments in tailoring vaccination efforts to address the unique needs of high-risk groups in Taiwan. Ongoing monitoring and proactive vaccination drives are essential for ensuring the effectiveness of these recommendations in the evolving COVID-19 landscape, while also accentuating the continuous efforts of family physicians in preventing endemic diseases.</p> <p> </p>

SARS-CoV-2-Specific T Lymphocytes Analysis in mRNA-Vaccinated Patients with B-Cell Lymphoid Malignancies on Active Treatment.

Patients with B-lymphocyte malignancies (BCMs) receiving B-lymphocyte-targeted therapies have increased risk of severe COVID-19 outcomes and impaired antibody response to SARS-CoV-2 mRNA vaccination in comparison to non-hematologic oncologic patients or general population. Consequently, it is vital to explore vaccine-induced T-lymphocyte responses in patients referred for the understanding of immune protection against SARS-CoV2 infections. The objective of the present study was to analyze the recall immune responses carried out by T lymphocytes after two COVID-19 mRNA vaccine doses. We enrolled 40 patients with BCMs and 10 healthy controls (HCs) after 4 weeks from the second mRNA vaccine dose. Spike (S)-specific T-lymphocyte responses were assessed in peripheral blood mononuclear lymphocytes (PBMCs) by intracellular IFN-γ staining combined with flow cytometry. Furthermore, the humoral response was assessed with the measurement of anti-spike antibodies. From March to July 2021, 40 patients (median age 68) received mRNA vaccines. The overall antibody response for BCMs was 52.5% versus 100% for the healthy controls (p = 0.008). The antibody response was different across BCMs: 18.75% for non-Hodgkin lymphoma, 54.5% for chronic lymphocytic leukemia, and 92.3% for multiple myeloma. Responses varied by malignancy type and treatment, with anti-CD20 therapies showing the lowest response (6.7%). T-lymphocyte analysis revealed reduced numbers and altered differentiation stages in patients compared to the controls. However, the vaccine-induced T response was generally robust, with variations in specific T subpopulations. mRNA vaccines induced significant humoral and cellular immune responses in B-cell lymphoid malignancy patients, although responses varied by treatment type and malignancy. Further research is needed to optimize vaccination strategies in this population.

Evaluating the Utility of Clinical Scores APACHE, CURB, SOFA, and NEWS2 at Admission and 5-Days after Symptom Onset in Predicting Severe COVID-19 in Patients with Diabetes.

The elevated risk of severe COVID-19 outcomes in patients with diabetes underscores the need for effective predictive tools. This study aimed to assess the predictive accuracy of APACHE II, CURB-65, SOFA, and NEWS2 scores at critical time points in diabetic patients diagnosed with COVID-19, aiming to guide early and potentially life-saving interventions. In a prospective cohort study conducted from January 2021 to December 2023, adult patients with type 1 or type 2 diabetes and confirmed SARS-CoV-2 infection were evaluated. Clinical scores were calculated at admission and five days post-symptom onset, with data analyzed using receiver operating characteristic (ROC) curves and logistic regression to determine areas under the curve (AUC) and hazard ratios (HR) for severe outcomes. Among the 141 diabetic patients studied, ROC analysis revealed high AUC values for SOFA (0.771 at admission, 0.873 at day five) and NEWS2 (0.892 at admission, 0.729 at day five), indicating strong predictive accuracy for these scores. The APACHE II score's AUC improved from 0.698 at admission to 0.806 on day five, reflecting worsening patient conditions. Regression analysis showed significant HRs associated with exceeding threshold scores: The SOFA score HR at day five was 3.07 (95% CI: 2.29-4.12, p < 0.001), indicating a threefold risk of severe outcomes. Similarly, the APACHE II score showed an HR of 2.96 (95% CI: 2.21-3.96, p < 0.001) at day five, highlighting its utility in predicting severe disease progression. The SOFA and NEWS2 scores demonstrated excellent early predictive accuracy for severe COVID-19 outcomes in diabetic patients, with significant AUC and HR findings. Continuous score monitoring, especially of APACHE II and SOFA, is crucial for managing and potentially mitigating severe complications in this vulnerable population. These tools can effectively assist in the timely escalation of care, thus potentially reducing morbidity and mortality among diabetic patients during the COVID-19 pandemic.

Safety of CoronaVac and ChAdOx1 vaccines against SARS-CoV-2 in patients with rheumatoid arthritis: data from the Brazilian multicentric study safer

BackgroundPatients with immune-mediated rheumatic diseases (IMRDs) have been prioritized for COVID-19 vaccination to mitigate the infection severity risks. Patients with rheumatoid arthritis (RA) are at a high risk of severe COVID-19 outcomes, especially those under immunosuppression or with associated comorbidities. However, few studies have assessed the safety of the COVID-19 vaccine in patients with RA.ObjectiveTo evaluate the safety of vaccines against SARS-CoV-2 in patients with RA.MethodsThis data are from the study “Safety and Efficacy on COVID-19 Vaccine in Rheumatic Diseases,” a Brazilian multicentric prospective phase IV study to evaluate COVID-19 vaccine in IMRDs in Brazil. Adverse events (AEs) in patients with RA of all centers were assessed after two doses of ChAdOx1 (Oxford/AstraZeneca) or CoronaVac (Sinovac/Butantan). Stratification of postvaccination AEs was performed using a diary, filled out daily and returned at the end of 28 days for each dose.ResultsA total of 188 patients with RA were include, 90% female. CoronaVac was used in 109 patients and ChAdOx1 in 79. Only mild AEs were observed, mainly after the first dose. The most common AEs after the first dose were pain at the injection (46,7%), headache (39,4%), arthralgia (39,4%), myalgia (30,5%) and fatigue (26,6%), and ChAdOx1 had a higher frequency of pain at the injection (66% vs 32 %, p < 0.001) arthralgia (62% vs 22%, p < 0.001) and myalgia (45% vs 20%, p < 0.001) compared to CoronaVac. The more common AEs after the second dose were pain at the injection (37%), arthralgia (31%), myalgia (23%), headache (21%) and fatigue (18%). Arthralgia (41,4% vs 25%, p = 0.02) and pain at injection (51,4% vs 27%, p = 0.001) were more common with ChAdOx1. No serious AEs were related. With Regard to RA activity level, no significant difference was observed between the three time periods for both COVID-19 vaccines.ConclusionIn the comparison between the two immunizers in patients with RA, local reactions and musculoskeletal symptoms were more frequent with ChAdOx1 than with CoronaVac, especially after the first dose. In summary, the AE occurred mainly after the first dose, and were mild, like previous data from others immunizing agents in patients with rheumatoid arthritis. Vaccination did not worsen the degree of disease activity.

History of childhood maltreatment associated with hospitalization or death due to COVID-19: a cohort study

BackgroundChildhood maltreatment (CM) has been indicated in adverse health outcomes across the lifespan, including severe infection-related outcomes. Yet, data are scarce on the potential role of CM in severe COVID-19-related outcomes as well as on mechanisms underlying this association.MethodsWe included 151,427 individuals in the UK Biobank who responded to questions on the history of CM in 2016 and 2017 and were alive on January 31, 2020. Binomial logistic regression models were performed to estimate the association between a history of CM and severe COVID-19 outcomes (i.e. hospitalization or death due to COVID-19), as well as COVID-19 diagnosis and vaccination as secondary outcomes. We then explored the potential mediating roles of socio-economic status, lifestyle and pre-pandemic comorbidities, and the effect modification by polygenic risk score for severe COVID-19 outcomes.ResultsThe mean age of the study population at the start of the pandemic was 67.7 (SD = 7.72) years, and 56.5% were female. We found the number of CM types was associated with the risk of severe COVID-19 outcomes in a graded manner (pfor trend < 0.01). Compared to individuals with no history of CM, individuals exposed to any CM were more likely to be hospitalized or die due to COVID-19 (odds ratio [OR] = 1.54 [95%CI 1.31–1.81]), particularly after physical neglect (2.04 [1.57–2.62]). Largely comparable risk patterns were observed across groups of high vs. low genetic risks for severe COVID-19 outcomes (pfor difference > 0.05). Mediation analysis revealed that 50.9% of the association between CM and severe COVID-19 outcomes was explained by suboptimal socio-economic status, lifestyle, and pre-pandemic diagnosis of psychiatric disorders or other chronic medical conditions. In contrast, any CM exposure was only weakly associated with COVID-19 diagnosis (1.06 [1.01–1.12]) while significantly associated with not being vaccinated for COVID-19 (1.21 [1.13–1.29]).ConclusionsOur results add to the growing knowledge base indicating the role of childhood maltreatment in negative health outcomes across the lifespan, including severe COVID-19-related outcomes. The identified factors underlying this association represent potential intervention targets for mitigating the harmful effects of childhood maltreatment in COVID-19 and similar future pandemics.

Navigating uncharted waters: assessing the impact of the COVID-19 pandemic on hematopoietic stem cell transplantation: challenges and innovations.

The COVID-19 pandemic has significantly impacted hematopoietic stem cell transplantation (HSCT), necessitating adaptations across pre-transplant, transplantation, and post-transplant phases. HSCT recipients with compromised immune systems face heightened risks of severe COVID-19 outcomes, including increased mortality. The pandemic prompted significant changes in treatment strategies, with many patients experiencing delays or deferrals in autologous stem cell transplantation (ASCT), alongside adjustments to chemotherapy regimens to prevent disease recurrence. Clinical practices have evolved to address pandemic-related challenges, including a decrease in allo-HSCT procedures, a shift towards using domestic donors and peripheral blood stem cells over bone marrow grafts, and integration of telemedicine to reduce patient burden. These adaptations aim to balance COVID-19 exposure risks with the need for lifesaving HSCT. Innovations in response to the pandemic include stringent infection control measures, modified conditioning regimens, and revised post-transplant care protocols to mitigate infection risks. The importance of optimizing antiviral treatments, exploring new immunomodulatory interventions, and researching broadly neutralizing antibodies for HSCT recipients has been underscored. Despite the difficulties, the pandemic has catalyzed significant learning and innovation in HSCT practices, emphasizing the need for ongoing adaptation and research to protect this vulnerable patient population.

Real-world severe COVID-19 outcomes associated with use of antivirals and neutralising monoclonal antibodies in Scotland

We sought to investigate the incidence of severe COVID-19 outcomes after treatment with antivirals and neutralising monoclonal antibodies, and estimate the comparative effectiveness of treatments in community-based individuals. We conducted a retrospective cohort study investigating clinical outcomes of hospitalisation, intensive care unit admission and death, in those treated with antivirals and monoclonal antibodies for COVID-19 in Scotland between December 2021 and September 2022. We compared the effect of various treatments on the risk of severe COVID-19 outcomes, stratified by most prevalent sub-lineage at that time, and controlling for comorbidities and other patient characteristics. We identified 14,365 individuals treated for COVID-19 during our study period, some of whom were treated for multiple infections. The incidence of severe COVID-19 outcomes (inpatient admission or death) in community-treated patients (81% of all treatment episodes) was 1.2% (n = 137/11894, 95% CI 1.0-1.4), compared to 32.8% in those treated in hospital for acute COVID-19 (re-admissions or death; n = 40/122, 95% CI 25.1-41.5). For community-treated patients, there was a lower risk of severe outcomes (inpatient admission or death) in younger patients, and in those who had received three or more COVID-19 vaccinations. During the period in which BA.2 was the most prevalent sub-lineage in the UK, sotrovimab was associated with a reduced treatment effect compared to nirmaltrelvir + ritonavir. However, since BA.5 has been the most prevalent sub-lineage in the UK, both sotrovimab and nirmaltrelvir + ritonavir were associated with similarly lower incidence of severe outcomes than molnupiravir. Around 1% of those treated for COVID-19 with antivirals or neutralising monoclonal antibodies required hospital admission. During the period in which BA.5 was the prevalent sub-lineages in the UK, molnupiravir was associated with the highest incidence of severe outcomes in community-treated patients.

Exploring Prior Antibiotic Exposure Characteristics for COVID-19 Hospital Admission Patients: OpenSAFELY.

Previous studies have demonstrated the association between antibiotic use and severe COVID-19 outcomes. This study aimed to explore detailed antibiotic exposure characteristics among COVID-19 patients. Using the OpenSAFELY platform, which integrates extensive health data and covers 40% of the population in England, the study analysed 3.16 million COVID-19 patients with at least two prior antibiotic prescriptions. These patients were compared to up to six matched controls without hospitalisation records. A machine learning model categorised patients into ten groups based on their antibiotic exposure history over the three years before their COVID-19 diagnosis. The study found that for COVID-19 patients, the total number of prior antibiotic prescriptions, diversity of antibiotic types, broad-spectrum antibiotic prescriptions, time between first and last antibiotics, and recent antibiotic use were associated with an increased risk of severe COVID-19 outcomes. Patients in the highest decile of antibiotic exposure had an adjusted odds ratio of 4.8 for severe outcomes compared to those in the lowest decile. These findings suggest a potential link between extensive antibiotic use and the risk of severe COVID-19. This highlights the need for more judicious antibiotic prescribing in primary care, primarily for patients with higher risks of infection-related complications, which may better offset the potential adverse effects of repeated antibiotic use.

Uptake, effectiveness and safety of COVID-19 vaccines in individuals at clinical risk due to immunosuppressive drug therapy or transplantation procedures: a population-based cohort study in England

BackgroundImmunocompromised individuals are at increased risk of severe COVID-19 outcomes, underscoring the importance of COVID-19 vaccination in this population. The lack of comprehensive real-world data on vaccine uptake, effectiveness and safety in these individuals presents a critical knowledge gap, highlighting the urgency to better understand and address the unique challenges faced by immunocompromised individuals in the context of COVID-19 vaccination.MethodsWe analysed data from 12,274,946 people in the UK aged > 12 years from 01/12/2020 to 11/04/2022. Of these, 583,541 (4.8%) were immunocompromised due to immunosuppressive drugs, organ transplants, dialysis or chemotherapy. We undertook a cohort analysis to determine COVID-19 vaccine uptake, nested case–control analyses adjusted for comorbidities and sociodemographic characteristics to determine effectiveness of vaccination against COVID-19 hospitalisation, ICU admission and death, and a self-controlled case series assessing vaccine safety for pre-specified adverse events of interest.ResultsOverall, 93.7% of immunocompromised individuals received at least one COVID-19 vaccine dose, with 80.4% having received three or more doses. Uptake reduced with increasing deprivation (hazard ratio [HR] 0.78 [95%CI 0.77–0.79] in the most deprived quintile compared to the least deprived quintile for the first dose). Estimated vaccine effectiveness against COVID-19 hospitalisation 2–6 weeks after the second and third doses compared to unvaccinated was 78% (95%CI 72–83) and 91% (95%CI 88–93) in the immunocompromised population, versus 85% (95%CI 83–86) and 86% (95%CI 85–89), respectively, for the general population. Results showed COVID-19 vaccines were protective against intensive care unit (ICU) admission and death in both populations, with effectiveness of over 92% against COVID-19-related death and up to 95% in reducing ICU admissions for both populations following the third dose. COVID-19 vaccines were generally safe for immunocompromised individuals, though specific doses of ChAdOx1, mRNA-1273 and BNT162b2 raised risks of specific cardiovascular/neurological conditions.ConclusionsCOVID-19 vaccine uptake is high in immunocompromised individuals on immunosuppressive drug therapy or who have undergone transplantation procedures, with documented disparities by deprivation. Findings suggest that COVID-19 vaccines are protective against severe COVID-19 outcomes in this vulnerable population, and show a similar safety profile in immunocompromised individuals and the general population, despite some increased risk of adverse events. These results underscore the importance of ongoing vaccination prioritisation for this clinically at-risk population to maximise protection against severe COVID-19 outcomes.

Molnupiravir Use Among Patients with COVID-19 in Real-World Settings: A Systematic Literature Review.

Molnupiravir (MOV) is an oral antiviral for the treatment of individuals with mild-to-moderate COVID-19 and at high risk of progression to severe disease. Our objective was to conduct a systematic literature review (SLR) of evidence on the effectiveness of MOV in reducing the risk of severe COVID-19 outcomes in real-world outpatient settings. The SLR was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines and using pre-determined population, intervention, comparison, outcome, time, and study design inclusion criteria. Eligible studies were published between January 1, 2021, and March 10, 2023, and evaluated the real-world effectiveness of MOV compared to no treatment in reducing the risk of severe COVID-19 outcomes among outpatients ≥ 18years of age with a laboratory-confirmed diagnosis of SARS-CoV-2 infection. Nine studies from five countries were included in the review. The size of the MOV-treated group ranged from 359 to 7818 individuals. Omicron variants of SARS-CoV-2 were dominant in all study periods. Most studies noted differences in the baseline characteristics of the MOV-treated and untreated control groups, with the treated groups generally being older and with more comorbidities. Eight studies reported that treatment with MOV was associated with a significantly reduced risk of at least one severe COVID-19 outcome in at least one age group, with greater benefits consistently observed among older age groups. In this SLR study, treatment with MOV was effective in reducing the risk of severe outcomes from COVID-19 caused by Omicron variants, especially for older individuals. Differences in the ages and baseline comorbidities of the MOV-treated and control groups may have led to underestimation of the effectiveness of MOV in many observational studies. Real-world studies published to date thus provide additional evidence supporting the continued benefits of MOV in non-hospitalized adults with COVID-19.

Immune Response after Anti-SARS-CoV-2 mRNA Vaccination in Relation to Cellular Immunity, Vitamin D and Comorbidities in Hemodialysis Patients.

In the global threat of SARS-CoV-2, individuals undergoing maintenance dialysis represent a vulnerable population with an increased risk of severe COVID-19 outcomes. Therefore, immunization against SARS-CoV-2 is an essential component of healthcare strategy for these patients. Existing data indicate that they tend to exhibit a reduced immune response to vaccines compared to the general population. Our study aimed to assess both humoral and cellular immune responses following two doses of an anti-SARS-CoV-2 mRNA vaccine, an ability to maintain adequate antibody titers over time, and potential relations with vitamin D, comorbidities and other factors in hemodialysis patients based on a single center experience. A total of 41/45 patients (91.1%) responded to the second dose of the anti-SARS-CoV-2 mRNA vaccine. The titer of anti-SARS-CoV-2 IgG class antibodies and levels of T cells three to four weeks after vaccination were lower in dialysis patients than in healthy controls. Antibodies titer in dialysis patients had a positive correlation with B lymphocytes and was related to cardiovascular diseases. The level of CD4+ cells had a negative correlation with hemodialysis vintage, as did the vitamin D level with post-vaccination seroconversion and decline in anti-SARS-CoV-2 antibodies titer during six months after vaccination. Hemodialysis patients had decreased amounts of CD4+ and CD8+ cells and lower levels of anti-SARS-CoV-2 antibodies than healthy controls. Therefore, chronic hemodialysis could lead to diminished cellular immunity and humoral immune response to the anti-SARS-CoV-2 mRNA vaccination and reduced protection from COVID-19. Comorbidity in cardiovascular diseases was associated with a lower level of specific anti-SARS-CoV-2 antibody titer. Vitamin D may be important in maintaining stable levels of anti-SARS-CoV-2 antibodies, while the duration of dialysis treatment could be one of the factors decreasing anti-SARS-CoV-2 antibody titer and determining lower CD4+ cell counts.

Impact of prior antihypertensive treatment on COVID-19 outcomes, by active ingredient

ObjectivesTo assess the impact of prior chronic treatment with angiotensin-converting enzyme inhibitors (ACEIs)/ angiotensin-receptor blockers (ARBs), both as a group and by active ingredient, on severity (risk of hospitalization and mortality), progression of and susceptibility to COVID-19.MethodsWe conducted a multiple population-based case–control study in Galicia (north-west Spain). The study data were sourced from medical, administrative and clinical databases. We assessed: (1) risk of hospitalization, by selecting all patients hospitalized due to COVID-19 with PCR + as cases, and a random sample of subjects without a PCR + as controls; (2) COVID-19 mortality risk; (3) risk of disease progression; and (4) susceptibility to SARS-CoV-2, considering all patients with PCR + as cases, and the same subjects used in the previous model as controls. Adjusted odds ratios (aORs) were calculated.ResultsACEIs and ARBs were shown to decrease the risk of hospitalization (aOR = 0.78 [95%CI 0.69–0.89] and aOR = 0.80 [95%CI 0.72–0.90] respectively), risk of mortality (aOR = 0.71 [95%CI 0.52–0.98] and aOR = 0.69 [95%CI 0.52–0.91] respectively), and susceptibility to the virus (aOR = 0.88 [95%CI 0.82–0.94] and aOR = 0.92 [95%CI 0.86–0.97] respectively). By active ingredient: use of enalapril was associated with a significantly lower risk of hospitalization (aOR = 0.72 [95%CI 0.61–0.85]), mortality (aOR = 0.59 [95%CI 0.38–0.92]) and susceptibility to COVID-19 (aOR = 0.86 [95%CI 0.79–0.94]); and use of candesartan was associated with a decreased risk of hospitalization (aOR = 0.76 [95%CI 0.60–0.95]), mortality (aOR = 0.36 [95%CI 0.17–0.75]) and disease progression (aOR = 0.73 [95%CI 0.56–0.95]).ConclusionThis large-scale real-world data study suggest that enalapril and candesartan are associated with a considerable reduction in risk of severe COVID19 outcomes.

Attitudes Toward COVID-19 Vaccines Among Pregnant and Recently Pregnant Individuals

Pregnant people and infants are at high risk of severe COVID-19 outcomes. Understanding changes in attitudes toward COVID-19 vaccines among pregnant and recently pregnant people is important for public health messaging. To assess attitudinal trends regarding COVID-19 vaccines by (1) vaccination status and (2) race, ethnicity, and language among samples of pregnant and recently pregnant Vaccine Safety Datalink (VSD) members from 2021 to 2023. This cross-sectional surveye study included pregnant or recently pregnant members of the VSD, a collaboration of 13 health care systems and the US Centers for Disease Control and Prevention. Unvaccinated, non-Hispanic Black, and Spanish-speaking members were oversampled. Wave 1 took place from October 2021 to February 2022, and wave 2 took place from November 2022 to February 2023. Data were analyzed from May 2022 to September 2023. Self-reported or electronic health record (EHR)-derived race, ethnicity, and preferred language. Self-reported vaccination status and attitudes toward monovalent (wave 1) or bivalent Omicron booster (wave 2) COVID-19 vaccines. Sample- and response-weighted analyses assessed attitudes by vaccination status and 3 race, ethnicity, and language groupings of interest. There were 1227 respondents; all identified as female, the mean (SD) age was 31.7 (5.6) years, 356 (29.0%) identified as Black race, 555 (45.2%) identified as Hispanic ethnicity, and 445 (36.3%) preferred the Spanish language. Response rates were 43.5% for wave 1 (652 of 1500 individuals sampled) and 39.5% for wave 2 (575 of 1456 individuals sampled). Respondents were more likely than nonrespondents to be White, non-Hispanic, and vaccinated per EHR. Overall, 76.8% (95% CI, 71.5%-82.2%) reported 1 or more COVID-19 vaccinations; Spanish-speaking Hispanic respondents had the highest weighted proportion of respondents with 1 or more vaccination. Weighted estimates of somewhat or strongly agreeing that COVID-19 vaccines are safe decreased from wave 1 to 2 for respondents who reported 1 or more vaccinations (76% vs 50%; χ21 = 7.8; P < .001), non-Hispanic White respondents (72% vs 43%; χ21 = 5.4; P = .02), and Spanish-speaking Hispanic respondents (76% vs 53%; χ21 = 22.8; P = .002). Decreasing confidence in COVID-19 vaccine safety in a large, diverse pregnant and recently pregnant insured population is a public health concern.

Effectiveness of COVID-19 vaccines against severe outcomes in cancer patients: Real-world evidence from self-controlled risk interval and retrospective cohort studies

BackgroundThe effectiveness of COVID-19 vaccines is generally reduced in cancer patients compared to the general population. However, there are only a few studies that compare the relative risk of breakthrough infections and severe COVID-19 outcomes in fully vaccinated cancer patients versus their unvaccinated counterparts. MethodsTo assess the effectiveness of COVID-19 vaccines in cancer patients, we employed (1) a self-controlled risk interval (SCRI) design, and (2) a retrospective matched cohort design. A SCRI design was used to compare the risk of breakthrough infection in vaccinated cancer patients during the period immediately following vaccination (“control window”) and the period in which immunity is achieved (“exposure windows”). The retrospective matched cohort design was used to compare the risk of severe COVID-19 outcomes between vaccinated and unvaccinated cancer patients. For both studies, data were extracted from the Korea Disease Control and Prevention Agency-COVID-19-National Health Insurance Service cohort, including demographics, medical history, and vaccination records of all individuals confirmed with COVID-19. We used conditional Poisson regression to calculate the incidence rate ratio (IRR) for breakthrough infection and Cox regression to estimate the hazard ratio (HR) for severe outcomes. ResultsOf 14,448 cancer patients diagnosed with COVID-19 between October 2020 and December 2021, a total of 217 and 3996 cancer patients were included in the SCRI and cohort study respectively. While the risk of breakthrough infections, measured by the incidence rate in the control and exposure windows, did not show statistically significant difference in vaccinated cancer patients (IRR=0.88, 95% CI: 0.64–1.22), the risk of severe COVID-19 outcomes was significantly lower in vaccinated cancer patients compared to those unvaccinated (HR=0.27, 95% CI: 0.22–0.34). ConclusionCOVID-19 vaccines significantly reduce the risk of severe outcomes in cancer patients, though their efficacy against breakthrough infections is less evident.