COVID-19 Outcomes Research Articles

The Impact of Pentraxin 3 Serum Levels and Angiotensin-Converting Enzyme Polymorphism on Pulmonary Infiltrates and Mortality in COVID-19 Patients.

The aim of this study was to examine the impact of the pentraxin 3 (PTX3) serum level and angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism on the severity of radiographic pulmonary infiltrates and the clinical outcomes of COVID-19. The severity of COVID-19 pulmonary infiltrates was evaluated within a week of admission by analyzing chest X-rays (CXR) using the modified Brixia (MBrixa) scoring system. The insertion (I)/deletion (D) polymorphism of the ACE gene and the serum levels of PTX3 were determined for all patients included in the study. This study included 80 patients. Using a cut-off serum level of PTX3 ≥ 2.765 ng/mL, the ROC analysis (AUC 0.871, 95% CI 0.787-0.954, p < 0.001) showed a sensitivity of 85.7% and specificity of 78.8% in predicting severe MBrixa scores. Compared to ACE I/I polymorphism, D/D polymorphism significantly increased the risk of severe CXR infiltrates, OR 7.7 (95% CI: 1.9-30.1), and p = 0.002. Significant independent predictors of severe CXR infiltrates include hypertension (OR 7.71), PTX3 (OR 1.20), and ACE D/D polymorphism (OR 18.72). Hypertension (OR 6.91), PTX3 (OR 1.47), and ACE I/I polymorphism (OR 0.09) are significant predictors of poor outcomes. PTX3 and ACE D/D polymorphism are significant predictors of the severity of COVID-19 pneumonia. PTX3 is a significant predictor of death.

A Multimorbidity Analysis of Hospitalized Patients With COVID-19 in Northwest Italy: Longitudinal Study Using Evolutionary Machine Learning and Health Administrative Data.

Multimorbidity is a significant public health concern, characterized by the coexistence and interaction of multiple preexisting medical conditions. This complex condition has been associated with an increased risk of COVID-19. Individuals with multimorbidity who contract COVID-19 often face a significant reduction in life expectancy. The postpandemic period has also highlighted an increase in frailty, emphasizing the importance of integrating existing multimorbidity details into epidemiological risk assessments. Managing clinical data that include medical histories presents significant challenges, particularly due to the sparsity of data arising from the rarity of multimorbidity conditions. Also, the complex enumeration of combinatorial multimorbidity features introduces challenges associated with combinatorial explosions. This study aims to assess the severity of COVID-19 in individuals with multiple medical conditions, considering their demographic characteristics such as age and sex. We propose an evolutionary machine learning model designed to handle sparsity, analyzing preexisting multimorbidity profiles of patients hospitalized with COVID-19 based on their medical history. Our objective is to identify the optimal set of multimorbidity feature combinations strongly associated with COVID-19 severity. We also apply the Apriori algorithm to these evolutionarily derived predictive feature combinations to identify those with high support. We used data from 3 administrative sources in Piedmont, Italy, involving 12,793 individuals aged 45-74 years who tested positive for COVID-19 between February and May 2020. From their 5-year pre-COVID-19 medical histories, we extracted multimorbidity features, including drug prescriptions, disease diagnoses, sex, and age. Focusing on COVID-19 hospitalization, we segmented the data into 4 cohorts based on age and sex. Addressing data imbalance through random resampling, we compared various machine learning algorithms to identify the optimal classification model for our evolutionary approach. Using 5-fold cross-validation, we evaluated each model's performance. Our evolutionary algorithm, utilizing a deep learning classifier, generated prediction-based fitness scores to pinpoint multimorbidity combinations associated with COVID-19 hospitalization risk. Eventually, the Apriori algorithm was applied to identify frequent combinations with high support. We identified multimorbidity predictors associated with COVID-19 hospitalization, indicating more severe COVID-19 outcomes. Frequently occurring morbidity features in the final evolved combinations were age>53, R03BA (glucocorticoid inhalants), and N03AX (other antiepileptics) in cohort 1; A10BA (biguanide or metformin) and N02BE (anilides) in cohort 2; N02AX (other opioids) and M04AA (preparations inhibiting uric acid production) in cohort 3; and G04CA (Alpha-adrenoreceptor antagonists) in cohort 4. When combined with other multimorbidity features, even less prevalent medical conditions show associations with the outcome. This study provides insights beyond COVID-19, demonstrating how repurposed administrative data can be adapted and contribute to enhanced risk assessment for vulnerable populations.

Inpatient mortality and outcomes of COVID-19 among patients with non-ischemic cardiomyopathy: A propensity matched analysis

BackgroundPatients with chronic medical conditions, particularly cardiovascular diseases, are at a greater risk of adverse outcomes due to COVID-19. The effect of COVID-19 on patients with non-ischemic cardiomyopathy (NICM) is not known well. ObjectivesTo study the impact of COVID-19 infection on NICM hospital mortality and other outcomes. MethodsThis study included a cohort of patients from the 2020 and 2021 National Inpatient Sample databases. Patients hospitalized for COVID-19 with and without NICM were matched using a 1:1 propensity score-matching ratio. Outcomes analyzed were in-hospital mortality, rates of acute kidney injury (AKI), acute myocardial infarction (AMI), cardiogenic shock, cardiac arrest, mechanical ventilation, tracheal intubation, pulmonary embolism (PE), ventricular tachycardia (VT), ventricular fibrillation (VF), length of stay (LOS), and total hospitalization charges. ResultsA total of 2,532,652 patients met the inclusion criteria (1,199,008 females [47.3 %], predominantly white 1,456,203 (57.5 %); mean [SD] age 63 [5.4] years), including 64,155 (2.5 %) patients with a history of NICM. Following propensity matching, 10,258 COVID-19 patients with and without NICM were matched. Patients with NICM had higher rates of AMI (11.1 vs. 7.1 %, p < 0.001), cardiogenic shock (2 vs. 0.6 %, p < 0.001), cardiac arrest (4.4 vs. 3.2 %, p < 0.01), mechanical ventilation (13.7 vs 12 %, p < 0.01), VT (8.5 vs. 2.2 %, p < 0.001), and VF (1.0 vs 0.25 %, p < 0.001). The odds ratios for in-hospital mortality, AKI, and PE did not differ significantly. ConclusionA History of NICM does not affect COVID-19 mortality but increases the risk of cardiovascular complications.

One-year outcomes in COVID-19 and non-COVID-19 intensive care unit survivors

PurposeTo determine differences in one-year multi-domain health outcomes in COVID-19 and non-COVID-19 intensive care unit (ICU) survivors. Materials and methodsAdult ICU survivors treated for COVID-19 were compared to a control group consisting of survivors admitted for respiratory distress due to other causes, i.e. non-COVID-19 ARDS or pneumonia. Occurrence of physical (frailty, fatigue, physical symptoms), mental (anxiety, depression, post-traumatic stress) and cognitive symptoms, and quality of life (QoL) scores were measured, using validated questionnaires, before and one year after ICU treatment. ResultsIn total, 506 COVID-19 survivors could be compared to 228 non-COVID-19 survivors. At one-year follow-up, COVID-19 ICU survivors had less physical (76.2% vs. 86.9%, p = 0.001) and mental symptoms (32.0% vs. 47.1%, p < 0.001) than the control group. Cognitive symptoms were comparable (22.5% vs. 17.2%, p = 0.12). However, compared to pre-ICU health symptoms and scores, COVID-19 survivors experienced an increase in symptom occurrence rates in all domains and a decrease in QoL, whereas the control group only experienced an increase in mental and cognitive symptoms, with a similar QoL at one-year follow-up. ConclusionsCOVID-19 ICU survivors experience equal or less health problems but a greater decline in QoL one year after ICU admission compared to non-COVID-19 ARDS or pneumonia survivors.

Effects of Recent Prior Dengue Infection on Risk and Severity of Subsequent SARS-CoV-2 Infection: A Retrospective Cohort Study.

Elucidating whether prior dengue potentially confers cross-protection against COVID-19 is of public health importance in tropical countries at risk of overlapping dengue and COVID-19 epidemics. However, studies to date have yielded conflicting results. We aimed to assess effects of recent prior dengue infection on risk and severity of subsequent SARS-CoV-2 infection among adult Singaporeans. A retrospective cohort study including all adult Singaporeans aged ≥18 years was conducted from 1 July 2021 through 31 October 2022, when a dengue outbreak driven by the DENV3 serotype preceded subsequent waves of SARS-CoV-2 Delta/Omicron transmission in Singapore. SARS-CoV-2 and dengue infection status were classified using national registries. Cox regression models adjusted for demographics, COVID-19 vaccination status, comorbidity, and socioeconomic-status were used to assess risks and severity (hospitalization, severe illness) of SARS-CoV-2 infection occurring after previous recorded dengue infection. A total of 3 366 399 individuals were included, contributing 1 399 696 530 person-days of observation. A total of 13 434 dengue infections and 1 253 520 subsequent SARS-CoV-2 infections were recorded; with an average of 94.7 days (standard deviation = 83.8) between dengue infection and SARS-CoV-2 infection. Preceding dengue infection was associated with a modest increase in risk of subsequent SARS-CoV-2 infection (adjusted hazards ratio [aHR] = 1.13; 95% confidence interval [CI], 1.08-1.17), and significantly elevated risk of subsequent COVID-19 hospitalization (aHR = 3.25; 95% CI, 2.78-3.82) and severe COVID-19 (aHR = 3.39; 95% CI, 2.29-5.03). Increased risk of SARS-CoV-2 infection and adverse COVID-19 outcomes were observed following preceding dengue infection in a national population-based cohort of adult Singaporeans. This observation is of significance in tropical countries with overlapping dengue and COVID-19 outbreaks.

Exploring SARS-CoV-2 infection and vaccine-induced immunity in chronic myeloid leukemia patients: insights from real-world data in Brazil and the United States

This study investigates COVID-19 outcomes and immune response in chronic myeloid leukemia (CML) patients post-SARS-CoV-2 vaccination, comparing effectiveness of various vaccine options. Data from 118 CML patients (85 in Brazil, 33 in the US) showed similar infection rates prior (14% Brazil, 9.1% US) and post-vaccination (24.7% vs. 27.3%, respectively). In Brazil, AstraZeneca and CoronaVac were the most commonly used vaccine brands, while in the US, Moderna and Pfizer-BioNTech vaccines dominated. Despite lower seroconversion in the Brazilian cohort, all five vaccine brands analyzed prevented severe COVID-19. Patients who received mRNA and recombinant viral vector vaccines (HR: 2.20; 95%CI 1.07–4.51; p < .031) and those that had achieved at least major molecular response (HR: 1.51; 95% CI 1.01–3.31; p < .0001) showed higher seroconversion rates. Our findings suggest that CML patients can generate antibody responses regardless of the vaccine brand, thereby mitigating severe COVID-19. This effect is more pronounced in patients with well-controlled disease.

Genomic Landscape of Susceptibility to Severe COVID-19 in the Slovenian Population.

Determining the genetic contribution of susceptibility to severe SARS-CoV-2 infection outcomes is important for public health measures and individualized treatment. Through intense research on this topic, several hundred genes have been implicated as possibly contributing to the severe infection phenotype(s); however, the findings are complex and appear to be population-dependent. We aimed to determine the contribution of human rare genetic variants associated with a severe outcome of SARS-CoV-2 infections and their burden in the Slovenian population. A panel of 517 genes associated with severe SARS-CoV-2 infection were obtained by combining an extensive review of the literature, target genes identified by the COVID-19 Host Genetic Initiative, and the curated Research COVID-19 associated genes from PanelApp, England Genomics. Whole genome sequencing was performed using PCR-free WGS on DNA from 60 patients hospitalized due to severe COVID-19 disease, and the identified rare genomic variants were analyzed and classified according to the ACMG criteria. Background prevalence in the general Slovenian population was determined by comparison with sequencing data from 8025 individuals included in the Slovenian genomic database (SGDB). Results show that several rare pathogenic/likely pathogenic genomic variants in genes CFTR, MASP2, MEFV, TNFRSF13B, and RNASEL likely contribute to the severe infection outcomes in our patient cohort. These results represent an insight into the Slovenian genomic diversity associated with a severe COVID-19 outcome.

Preferential and sustained platelet activation in COVID-19 survivors with mental disorders

Pre-existing mental disorders are considered a risk factor for severe COVID-19 outcomes, possibly because of higher vascular burden. Moreover, an unconventional platelet activation characterizes COVID-19 and contributes to inflammatory and thrombotic manifestations. In the light of the inflammation theory of mental disorders, we hypothesized that patients with mental disorders could be sensitive to the SARS-CoV-2 elicited platelet activation. We investigated platelet activation in 141 COVID-19 survivors at one month after clearance of the virus, comparing subjects with or without an established pre-existing diagnosis of mental disorder according to the DSM-5. We found that platelets from patients with a positive history of psychiatric disorder underwent unconventional activation more frequently than conventional activation or no activation at all. Such preferential activation was not detected when platelets from patients without a previous psychiatric diagnosis were studied. When testing the effects of age, sex, and psychiatric history on the platelet activation, GLZM multivariate analysis confirmed the significant effect of diagnosis only. These findings suggest a preferential platelet activation during acute COVID-19 in patients with a pre-existing psychiatric disorder, mediated by mechanisms associated with thromboinflammation. This event could have contributed to the higher risk of severe outcome in the psychiatric population.

Liver and Inflammatory Biomarkers Are Related to High Mortality in Hospitalized Patients with COVID-19 in Brazilian Amazon Region.

COVID-19 is a multisystem disease with many clinical manifestations, including liver damage and inflammation. The objective of this study is to analyze inflammation biomarkers in relation to the clinical outcome and respiratory symptoms of COVID-19. This is a retrospective cohort of patients with COVID-19 admitted to the Hospital Regional do Baixo Amazonas from 2020 to 2022. Data were collected from electronic medical records from admission to the 30th day of hospitalization and soon after hospital discharge. A total of 397 patients were included in the study. In the longitudinal follow-up of liver markers, a significant difference was found for AST on day 14, with a higher median in the death group. Among the hematological markers, lymphopenia was observed throughout the follow-up, with the death group having the most altered values. When comparing the evolution of biomarkers in the Non-Invasive Ventilation (NIV) and Invasive Mechanical Ventilation (IMV) groups, AST showed a significant difference only on day 14 and GGT on day 1, being greater in the IMV group, and indirect bilirubin on day 7 being more altered in the NIV group. In conclusion, death during hospitalization or a more severe form of COVID-19 was related to significant changes in liver and inflammatory biomarkers.

Ursodeoxycholic acid and COVID-19 outcomes: a cohort study and data synthesis of state-of-art evidence

ABSTRACT Background The potential of ursodeoxycholic acid (UDCA) in inhibiting angiotensin-converting enzyme 2 was demonstrated. However, conflicting evidence emerged regarding the association between UDCA and COVID-19 outcomes, prompting the need for a comprehensive investigation. Research design and methods Patients diagnosed with COVID-19 infection were retrospectively analyzed and divided into two groups: the UDCA-treated group and the control group. Kaplan–Meier recovery analysis and Cox proportional hazards models were used to evaluate the recovery time and hazard ratios. Additionally, study-level pooled analyses for multiple clinical outcomes were performed. Results In the 115-patient cohort, UDCA treatment was significantly associated with a reduced recovery time. The subgroup analysis suggests that the 300 mg subgroup had a significant (adjusted hazard ratio: 1.63 [95% CI, 1.01 to 2.60]) benefit with a shorter duration of fever. The results of pooled analyses also show that UDCA treatment can significantly reduce the incidence of severe/critical diseases in COVID-19 (adjusted odds ratio: 0.68 [95% CI, 0.50 to 0.94]). Conclusions UDCA treatment notably improves the recovery time following an Omicron strain infection without observed safety concerns. These promising results advocate for UDCA as a viable treatment for COVID-19, paving the way for further large-scale and prospective research to explore the full potential of UDCA.

One-year post-acute COVID-19 syndrome and mortality in South Korea: a nationwide matched cohort study using claims data.

Current understanding of post-COVID-19 syndrome in South Korea is primarily based on survey studies or research targeting specific patient groups, such as those hospitalized. Moreover, the majority of relevant studies have been conducted in European and North American populations, which may limit their applicability to the South Korean context. To address this gap, our study explores the one-year outcomes of COVID-19, focusing on the potential post-acute syndrome and all-cause mortality in South Korea. This retrospective cohort study used nationwide claims data in South Korea, including adults aged >18 with records between January 20, 2020, and February 25, 2021. Patients were classified into COVID-19 and non-COVID-19 groups and matched 1:1 based on propensity scores. Primary outcomes were 12-month post-acute COVID-19 syndrome and all-cause mortality. The study involved 34,802 matched patients. The COVID-19 group had significantly elevated risks of coagulopathies (OR = 2.70 [2.24, 3.28]; p < 0.001), chronic lower respiratory diseases (OR = 1.96 [1.80, 2.14]; p < 0.001), symptoms of the circulatory and respiratory systems (OR = 1.91 [1.80, 2.04]; p < 0.001), mood disorders (OR = 1.67 [1.51, 1.86]; p < 0.001), cardiac diseases (OR = 1.39 [1.21, 1.59]; p < 0.001), and symptoms of cognition, perception, emotional state, and behavior (OR = 1.15 [1.04, 1.27]; p = 0.005). All-cause mortality was higher in the COVID-19 group during the 6 months (OR = 1.34 [1.06, 1.69]; p = 0.015), but gradually decreased, reaching an OR of 0.996 ([0.83, 1.19]; p = 0.964) at 1 year. In South Korea, the 12-month post-acute COVID-19 syndrome includes coagulopathies, respiratory issues, mood disorders, and cardiac diseases. The risk of all-cause mortality post-COVID-19 is heightened for up to 6 months, then significantly decreases and resolves within a year.

Gaps in Long COVID treatments research: A scoping review

Background Long COVID affects 6 to 10% of people following SARS-CoV-2 infection. It has been documented worldwide, with over 200 symptoms reported. This scoping review assesses the evidence on Long COVID treatments to identify gaps in the evidence-base to inform research prioritisation. Methods We searched four databases (MEDLINE, Embase, Cochrane’s Trial register, Epistemonikos) supplemented by a grey literature search up to April 2023. Two reviewers screened articles and extracted data. Data were analysed using a thematic approach. Results Of 3675 records identified, 26 studies were included. Most were in high-income countries (92%), with two in upper-middle-income countries (8%). None reported inclusion of children, nor pregnant women and only 37.5% included adults over 64 years. Five (20.8%) presented ethnicity data, of these 92.9% of participants were of white ethnicity. Treatments included nutritional supplements (46%), conventional medicines (38%), hyperbaric medicine (8%), COVID-19 vaccination (4%) and complementary, alternative medicine (4%). Conclusion This scoping review highlights that more than four years after the start of the pandemic, research gaps remain for Long COVID treatments. There is a lack of research in low-income countries, despite trials being best placed locally to reflect different population demographics. There is a lack of inclusion of population sub-groups, particularly children, pregnant women and ethnic minority groups. Inclusion of these groups in future research is important given they may be at a higher risk of adverse outcomes of COVID-19, and a lack of appropriate treatments for Long COVID may contribute to the widening of health inequalities.

Navigating vaccination choices: The intersecting dynamics of institutional trust, belonging and message perception among Congolese migrants in London, UK (a reflexive thematic analysis).

The COVID-19 pandemic disproportionately impacted intersectionally marginalised migrants, revealing systemic disparities in health outcomes and vaccine uptake. Understanding the underlying social and structural factors influencing health behaviours is necessary to develop tailored interventions for migrants, but these factors have been seldom explored. This qualitative study aimed to explore contextual factors shaping COVID-19 vaccination decision-making among Congolese migrants in the UK.A community-based participatory research study was designed and led by a community-academic partnership in London, UK (2021-2022). Peer-led, semi-structured interviews were conducted in Lingala with 32 adult Congolese migrants and explored beliefs, perceptions and lived experiences of migration, healthcare, vaccination and the COVID-19 pandemic. Reflexive thematic analysis generated two themes and a model conceptualising the vaccination decision-making process. Participants and community partners were financially compensated; ethics was granted by the University of London ethics committee (REC: 2021.0128).Participants highlighted the incompatibility of lockdown restrictions with their communal culture, which intensified feelings of exclusion and alienation. Concerns about COVID-19 vaccination were attributed to safety and effectiveness, partly informed by experiences and legacies of racial discrimination and exploitation. Inequality in the pandemic response and COVID-19 outcomes heightened participants' sense that their views and needs were being overlooked, and government sources and information were perceived as coercive. Our model depicts the interplay between institutional trust, belonging, and message perception, which shaped participants' vaccination decisions and led to (non-)engagement with COVID-19 vaccination. This research enhances understanding of how social and contextual factors may influence migrants' engagement with health interventions. It underscores the importance of partnering with migrant communities to understand their needs in context and co-design tailored interventions and inclusive messaging strategies that promote trust and belonging. Implementing systemic changes to address structural inequalities will be crucial to create an environment that supports engagement with health-protective behaviours and enhances health outcomes among migrant communities.

Unveiling the detrimental vicious cycle linking skeletal muscle and COVID-19: A systematic review and meta-analysis.

Skeletal muscle catabolism supports multiple organs and systems during severe trauma and infection, but its role in COVID-19 remains unclear. This study investigates the interactions between skeletal muscle and COVID-19. The PubMed, EMbase, and The Cochrane Library databases were systematically searched from January 2020 to August 2023 for cohort studies focusing on the impact of skeletal muscle on COVID-19 prevalence and outcomes, and longitudinal studies examining skeletal muscle changes caused by COVID-19. Skeletal muscle quantity (SMQN) and quality (SMQL) were assessed separately. The random-effect model was predominantly utilized for statistical analysis. Seventy studies with moderate to high quality were included. Low SMQN/SMQL was associated with an increased risk of COVID-19 infection (OR=1.62, p<0.001). Both the low SMQN and SMQL predicted COVID-19-related mortality (OR=1.53, p=0.016; OR=2.18, p=0.001, respectively). Mortality risk decreased with increasing SMQN (OR=0.979, p=0.009) and SMQL (OR=0.972, p=0.034). Low SMQN and SMQL were also linked to the need for intensive care unit/mechanical ventilation, increased COVID-19 severity, and longer hospital stays. Significant skeletal muscle wasting, characterized by reduced volume and strength, was observed during COVID-19 infection and the pandemic. This study reveals a detrimental vicious circle between skeletal muscle and COVID-19. Effective management of skeletal muscle could be beneficial for treating COVID-19 infections and addressing the broader pandemic. These findings have important implications for the management of future virus pandemics. PROSPERO CRD42023395476.

Diabetes mellitus in sub-saharan Africa during the COVID-19 pandemic: A scoping review.

The COVID-19 pandemic impacted the healthcare and outcomes of individuals with various chronic diseases. However, there is a paucity of data on the impact of the COVID-19 pandemic on diabetes mellitus (DM) in low-resource settings. To address this, we conducted a scoping review to explore the literature published on diabetes-related COVID-19 outcomes and care during the COVID-19 pandemic in countries of sub-Saharan Africa. We applied our search strategy to PubMed, Web of Science, CINAHL, African Index Medicus, Google Scholar, Cochrane Library, Scopus, Science Direct, ERIC and Embase to obtain relevant articles published from January 2020 to March 2023. Two independent reviewers were involved in screening the retrieved articles. Data from eligible articles were extracted from quantitative, qualitative and mixed-methods studies. Quantitative evidence was summarised using descriptive statistics, while a thematic framework was used to identify and categorise themes from qualitative evidence. We found 42 of the retrieved 360 articles eligible, mainly from South Africa, Ethiopia and Ghana (73.4%). The incidence of DM among COVID-19 cases was 13.7/1,000 person-days observation. COVID-19 was associated with increased odds of death (OR 1.30-9.0, 95% CI), hospitalisation (OR 3.30-3.73: 95% CI), and severity (OR: 1.30-4.05, 95% CI) in persons with DM. Challenges in caring for DM during the pandemic were inadequate patient self-management, difficulties in healthcare access, and inadequate healthcare resources. The COVID-19 pandemic was characterised by a high incidence of DM in persons infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and high COVID-19-associated mortality, severity, and hospitalisation among people persons with DM. The pandemic also created difficulties in DM self-management and worsened the quality of DM care services. Policymakers should devise preventive and management strategies for DM during emerging and re-emerging infectious disease epidemics and outbreaks, given that such occurrences are increasingly frequent in the region.

Pathway-Based Mendelian Randomization for Pre-Infection IL-6 Levels Highlights Its Role in Coronavirus Disease.

Interleukin 6 (IL-6) levels at hospital admission have been suggested for disease prognosis, and IL-6 antagonists have been suggested for the treatment of patients with severe COVID-19. However, less is known about the relationship between pre-COVID-19 IL-6 levels and the risk of severe COVID-19. To fill in this gap, here we extensively investigated the association of genetically instrumented IL-6 pathway components with the risk of severe COVID-19. We used a two-sample Mendelian randomization study design and retrieved genetic instruments for blood biomarkers of IL-6 activation, including IL-6, soluble IL-6 receptor, IL-6 signal transducer, and CRP, from respective large available GWASs. To establish associations of these instruments with COVID-19 outcomes, we used data from the Host Genetics Initiative and GenOMICC studies. Our analyses revealed inverse associations of genetically instrumented levels of IL-6 and its soluble receptor with the risk of developing severe disease (OR = 0.60 and 0.94, respectively). They also demonstrated a positive association of severe disease with the soluble signal transducer level (OR = 1.13). Only IL-6 associations with severe COVID-19 outcomes reached the significance threshold corrected for multiple testing (p < 0.003; with COVID-19 hospitalization and critical illness). These potential causal relationships for pre-COVID-19 IL-6 levels with the risk of developing severe symptoms provide opportunities for further evaluation of these factors as prognostic/preventive markers of severe COVID-19. Further studies will need to clarify whether the higher risk for a severe disease course with lower baseline IL-6 levels may also extend to other infectious diseases.

Mental health symptom associations with COVID-19 testing and vaccination among urban American Indian and Alaska Native people

BackgroundThe COVID-19 pandemic has substantially impacted American Indian and Alaska Native (AI/AN) communities. Rates of infection, hospitalization, and mortality have been severe relative to non-Hispanic whites. While AI/AN communities have had some of the highest levels of COVID-19 vaccination, utilization rates remain suboptimal and there is a need to identify facilitators and barriers to testing and vaccination. MethodsWe examined cross-sectional survey data from January to May 2021, among 619 AI/AN patients from five tribal health organizations (AK, CO, KS, NM, WA). Exposures include perceived stress, Kessler distress, PTSD screening, and AUDIT-C alcohol misuse screen. Poisson regression was used to estimate associations with prevalence of COVID-19 testing and vaccination. ResultsOver three-quarters of participants were tested for COVID-19 and nearly half were vaccinated. Perceived stress and positive PTSD screening were associated with reduced vaccination prevalence, Prevalence Ratio (PR) 0.83 (0.73, 0.93) and PR 0.80 (0.66, 0.98), respectively. There was reduced prevalence of COVID-19 testing in subgroups with lower reported psychological resilience and PTSD, PR 0.78 (0.64, 0.95). ConclusionsPast-month perceived stress and positive PTSD screening are associated with reduced prevalence of COVID-19 vaccination in urban AI/AN people. Subgroups reporting limited resilience and PTSD symptoms had lower prevalence of COVID-19 testing. The complex relationship between mental health and COVID-19 testing and vaccination warrants further exploration to identify interventions to improve health among urban AI/AN people, a population with known disparities in both mental health and COVID-19 outcomes.

Pre-Existing Atrial Fibrillation in Hospitalized Patients with COVID-19: Insights from the CARDIO COVID 19-20 Registry.

Pre-existing (chronic) atrial fibrillation (AF) has been identified as a risk factor for cardiovascular complications and mortality in patients with COVID-19; however, evidence in Latin America (LATAM) is scarce. This prospective and multicenter study from the CARDIO COVID 19-20 database includes hospitalized adults with COVID-19 from 14 countries in LATAM. A parsimonious logistic regression model was used to identify the main factors associated with mortality in a simulated case-control setting comparing patients with a history of AF to those without. In total, 3260 patients were included, of which 115 had AF. The AF group was older, had a higher prevalence of comorbidities, and had greater use of cardiovascular medications. In the model, AF, chronic kidney disease, and a respiratory rate > 25 at admission were associated with higher in-hospital mortality. The use of corticosteroids did not reach statistical significance; however, an effect was seen through the confidence interval. Thus, pre-existing AF increases mortality risk irrespective of other concomitant factors. Chronic kidney disease and a high respiratory rate at admission are also key factors for in-hospital mortality. These findings highlight the importance of comorbidities and regional characteristics in COVID-19 outcomes, in this instance, enhancing the evidence for patients from LATAM.

Patient self-inflicted lung injury associated pneumothorax/pneumomediastinum is a risk factor for worse outcomes of severe COVID-19: a case-control study

We aimed to determine the clinical characteristics of patient self-inflicted lung injury (P-SILI)-associated pneumothorax/pneumomediastinum, to reveal its risk factors, and to assess its impact on severe COVID-19 cases. In total, 229 patients were included in this case-control study. They were randomly divided into either the case group or the control group as per the inclusion and exclusion criteria. The two groups were further analyzed to reveal the risk factors of spontaneous pneumothorax/pneumomediastinum (SP/P). Finally, risk factors for death were analyzed in the case group and the relationship between death and SP/P was also analyzed among all patients. The mean age of patients was 59.69 ± 17.01 years, most of them were male (74.2%), and 62.0% of them had comorbidities upon admission. A respiratory rate higher than 30 BPM was a risk factor for SP/P (OR 7.186, 95% CI 2.414–21.391, P < 0.001). Patients with delayed intubation due to early application of HFNC or NIV had a higher mortality rate when they developed SP/P (P < 0.05). Additionally, advanced age increased the risk of death (P < 0.05). Finally, SP/P may be a risk factor for death among patients with severe COVID-19 (OR 2.047). P-SILI occurs in severe COVID-19 with acute respiratory failure. It is necessary to identify the risk factors of P-SILI, the indicators of severe P-SILI, and the preventive measures.

IL-13 decreases susceptibility to airway epithelial SARS-CoV-2 infection but increases disease severity in vivo.

Treatments available to prevent progression of virus-induced lung diseases, including coronavirus disease 2019 (COVID-19) are of limited benefit once respiratory failure occurs. The efficacy of approved and emerging cytokine signaling-modulating antibodies is variable and is affected by disease course and patient-specific inflammation patterns. Therefore, understanding the role of inflammation on the viral infectious cycle is critical for effective use of cytokine-modulating agents. We investigated the role of the type 2 cytokine IL-13 on SARS-CoV-2 binding/entry, replication, and host response in primary HAE cells in vitro and in a model of mouse-adapted SARS-CoV-2 infection in vivo. IL-13 protected airway epithelial cells from SARS-CoV-2 infection in vitro by decreasing the abundance of ACE2-expressing ciliated cells rather than by neutralization in the airway surface liquid or by interferon-mediated antiviral effects. In contrast, IL-13 worsened disease severity in mice; the effects were mediated by eicosanoid signaling and were abolished in mice deficient in the phospholipase A2 enzyme PLA2G2D. We conclude that IL-13-induced inflammation differentially affects multiple steps of COVID-19 pathogenesis. IL-13-induced inflammation may be protective against initial SARS-CoV-2 airway epithelial infection; however, it enhances disease progression in vivo. Blockade of IL-13 and/or eicosanoid signaling may be protective against progression to severe respiratory virus-induced lung disease.