Risk Of Severe Coronavirus Disease 2019 Research Articles

Combined Protection of Vaccination and Nirmatrelvir-Ritonavir Against Hospitalization in Adults With COVID-19.

Among adults at risk for severe coronavirus disease 2019 (COVID-19), the lowest hospitalization rate was among those who received nirmatrelvir-ritonavir after 3 or more messenger RNA vaccine doses (adjusted hazard ratio, 0.22; 95% confidence interval, .19-.24). Eligible adults, including those previously vaccinated, should be considered for COVID-19 antiviral treatment.

Humoral and cellular immune responses against SARS-CoV-2 post-vaccination in immunocompetent and immunocompromised cancer populations.

The study was prompted by a desire to better assess the immune status of patients among our cancer host cohort, one of the largest in the New York metropolitan region. Hackensack Meridian Health is the largest healthcare system in New Jersey and cared for more than 75,000 coronavirus disease 2019 patients in its hospitals. The John Theurer Cancer Center sees more than 35,000 new cancer patients a year and performs more than 500 hematopoietic stem cell transplants. As a result, the work was undertaken to assess the effectiveness of vaccination in inducing humoral and cellular responses within this demographic.

Allograft function predicts mortality in kidney transplant recipients with severe COVID-19: a paradoxical risk factor.

Kidney transplant recipients (KTRs) are at a higher risk of severe coronavirus disease (COVID-19) because of their immunocompromised status. However, the effect of allograft function on the prognosis of severe COVID-19 in KTRs is unclear. In this study, we aimed to analyze the correlation between pre-infection allograft function and the prognosis of severe COVID-19 in KTRs. This retrospective cohort study included 82 patients who underwent kidney transplantation at the Sichuan Provincial Peoples Hospital between October 1, 2014 and December 1, 2022 and were diagnosed with severe COVID-19. The patients were divided into decreased eGFR and normal eGFR groups based on the allograft function before COVID-19 diagnosis (n=32 [decreased eGFR group], mean age: 43.00 years; n=50 [normal eGFR group, mean age: 41.88 years). We performed logistic regression analysis to identify risk factors for death in patients with severe COVID-19. The nomogram was used to visualize the logistic regression model results. The mortality rate of KTRs with pre-infection allograft function insufficiency in the decreased eGFR group was significantly higher than that of KTRs in the normal eGFR group (31.25% [10/32] vs. 8.00% [4/50], P=0.006). Pre-infection allograft function insufficiency (OR=6.96, 95% CI: 1.4633.18, P=0.015) and maintenance of a mycophenolic acid dose >1500 mg/day before infection (OR=7.59, 95% CI: 1.0853.20, P=0.041) were independent risk factors, and the use of nirmatrelvir/ritonavir before severe COVID-19 (OR=0.15, 95% CI: 0.030.72, P=0.018) was a protective factor against death in severe COVID-19. Pre-infection allograft function is a good predictor of death in patients with severe COVID-19. Allograft function was improved after treatment for severe COVID-19, which was not observed in patients with non-severe COVID-19.

The causal relationship between gut microbiota and COVID-19: A two-sample Mendelian randomization analysis.

Recent studies have shown that gut microbiota is associated with coronavirus disease 2019 (COVID-19). However, the causal impact of the gut microbiota on COVID-19 remains unclear. We performed a bidirectional Mendelian randomization. The summary statistics on the gut microbiota from the MiBioGen consortium. Summary statistics for COVID-19 were obtained from the 6th round of the COVID-19 Host Genetics Initiative genome-wide association study meta-analysis. Inverse variance weighting was used as the main method to test the causal relationship between gut microbiota and COVID-19. Reverse Mendelian randomization analysis was performed. Mendelian randomization analysis showed that Intestinimas.id.2062 was associated with an increased risk of severe COVID-19. Bifidobacterium.id.436, LachnospiraceaeUCG010.id.11330, RikenellaceaeRC9gutgroup.id.11191 increase the risk of hospitalized COVID-19. RuminococcaceaeUCG014.id.11371 shows the positive protection on hospitalized COVID-19. There is no causal relationship between gut microbiota and infection with COVID-19. According to the results of reverse Mendelian randomization analysis, no significant causal effect of COVID-19 on gut microbiota was found. The study found that gut microbiota with COVID-19 has a causal relationship. This study provides a basis for the theory of the gut-lung axis. Further randomized controlled trials are needed to clarify the protective effect of probiotics against COVID-19 and the specific protective mechanisms. This study has important implications for gut microbiota as a nondrug intervention for COVID-19.

COVID-19 Reinfection Has Better Outcomes Than the First Infection in Solid Organ Transplant Recipients.

Solid organ transplant recipients face an increased risk of severe coronavirus disease 2019 (COVID-19) and are vulnerable to repeat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. In nonimmunocompromised individuals, SARS-CoV-2 reinfections are milder likely because of cross-protective immunity. We sought to determine whether SARS-CoV-2 reinfection exhibits milder manifestations than primary infection in transplant recipients. Using a large, prospective cohort of adult transplant patients with COVID-19, we identified patients with SARS-CoV-2 reinfections. We performed a 1:1 nearest neighbor propensity score matching to control potential confounders, including the COVID-19 variant. We compared outcomes including oxygen requirement, hospitalization, and intensive care unit admission within 30 d after diagnosis between patients with reinfection and those with the first episode of COVID-19. Between 2020 and 2023, 103 reinfections were identified in a cohort of 1869 transplant recipients infected with SARS-CoV-2 (incidence of 2.7% per year). These included 50 kidney (48.5%), 27 lung (26.2%), 7 heart (6.8%), 6 liver (5.8%), and 13 multiorgan (12.6%) transplants. The median age was 54.5 y (interquartile range [IQR], 40.5-65.5) and the median time from transplant to first infection was 6.6 y (IQR, 2.8-11.2). The time between the primary COVID-19 and reinfection was 326 d (IQR, 226-434). Three doses or more of SARS-CoV-2 vaccine are received by 87.4% of patients. After propensity score matching, reinfections were associated with significantly lower hospitalization (5.8% versus 19.4%; risk ratio, 0.3; 95% CI, 0.12-0.71) and oxygen requirement (3.9% versus 13.6%; risk ratio, 0.29; 95% CI, 0.10-0.84). In a within-patient analysis only in the reinfection group, the second infection was milder than the first (3.9% required oxygen versus 19.4%, P < 0.0001), and severe first COVID-19 was the only predictor of severe reinfection. Transplant recipients with COVID-19 reinfection present better outcomes than those with the first infection, providing clinical evidence for the development of cross-protective immunity.

Risk Factors for Severe and Critical Coronavirus Disease 2019 in Children.

Coronavirus disease 2019 (COVID-19) is generally mild in children; however, severe or critical cases may occur. In this nationwide study, we analyzed clinical manifestations in children diagnosed with severe acute respiratory syndrome coronavirus 2 to identify high-risk groups for severe or critical disease and compared the clinical features between the Delta- and Omicron-dominant periods. Data were retrieved from the National Health Insurance Service (NHIS) database and merged with the Korea Disease Control and Prevention Agency-COVID-19-NHIS cohort, which includes information on COVID-19 cases and vaccination records. We included individuals <20 years old diagnosed with COVID-19 during both periods (Delta: July 25, 2021-January 15, 2022; Omicron: January 16, 2022-March 31, 2022). Proportion of severe or critical cases was higher during the Delta period than during the Omicron period. The Omicron period saw increased hospitalization for pneumonia and croup and increased likelihood of hospitalization for neurological manifestations. The risk of severe COVID-19 depended on age group (Delta: highest for 12-19 years; Omicron: 0-4 years). This risk was high in children with multiple complex chronic conditions during both periods and with obesity or asthma during the Delta but not during the Omicron period. Two-dose COVID-19 vaccination provided strong protection against severe disease in the Delta period (adjusted odds ratio: 0.20), with reduced effectiveness in the Omicron period (adjusted odds ratio: 0.91). However, it significantly reduced the risk of critical illness (adjusted odds ratio: 0.14). These findings can facilitate identification of children at high risk of severe or critical COVID-19, who may require intensive medical support, and development of vaccination policies.

The causal relationship between COVID-19 and estimated glomerular filtration rate: a bidirectional Mendelian randomization study

BackgroundPrevious Mendelian studies identified a causal relationship between renal function, as assessed by estimated glomerular filtration rate (eGFR), and severe infection with coronavirus disease 2019 (COVID-19). However, much is still unknown because of the limited number of associated single nucleotide polymorphisms (SNPs) of COVID-19 and the lack of cystatin C testing. Therefore, in the present study, we aimed to determine the genetic mechanisms responsible for the association between eGFR and COVID-19 in a European population.MethodsWe performed bidirectional Mendelian randomization (MR) analysis on large-scale genome-wide association study (GWAS) data; log-eGFR was calculated from the serum levels of creatinine or cystatin C by applying the Chronic Kidney Disease Genetics (CKDGen) Meta-analysis Dataset combined with the UK Biobank (N = 1,004,040) and on COVID-19 phenotypes (122,616 COVID-19 cases and 2,475,240 controls) from COVID19-hg GWAS meta-analyses round 7. The inverse-variance weighted method was used as the main method for estimation.ResultsAnalyses showed that the genetically instrumented reduced log-eGFR, as calculated from the serum levels of creatinine, was associated with a significantly higher risk of severe COVID-19 (odds ratio [OR]: 2.73, 95% confidence interval [CI]: 1.38–5.41, P < 0.05) and significantly related to COVID-19 hospitalization (OR: 2.36, 95% CI: 1.39–4.00, P < 0.05) or infection (OR: 1.24, 95% CI: 1.01–1.53, P < 0.05). The significance of these associations remained when using log-eGFR based on the serum levels of cystatin C as genetically instrumented. However, genetically instrumented COVID-19, regardless of phenotype, was not related to log-eGFR, as calculated by either the serum levels of creatinine or cystatin C.ConclusionsOur findings suggest that genetical predisposition to reduced kidney function may represent a risk factor for COVID-19. However, a consistent and significant effect of COVID-19 on kidney function was not identified in this study.

Sex hormones and the total testosterone:estradiol ratio as predictors of severe acute respiratory syndrome coronavirus 2 infection in hospitalized men.

The predictive ability of the early determination of sex steroids and the total testosterone:estradiol ratio for the risk of severe coronavirus disease 2019 or the potential existence of a biological gradient in this relationship has not been evaluated. To assess the relationship of sex steroid levels and the total testosterone:estradiol ratio with the risk of severe acute respiratory syndrome coronavirus 2 infection in men, defined as the need for intensive care unit admission or death, and the predictive ability of each biomarker. This was a prospective observational study. We included all consecutive adult men with severe acute respiratory syndrome coronavirus 2 infections in a single center admitted to a general hospital ward or to the intensive care unit. Sex steroids were evaluated at the centralized laboratory of our hospital. We recruited 98 patients, 54 (55.1%) of whom developed severe coronavirus disease in 2019. Compared to patients with nonsevere coronavirus disease 2019, patients with severe coronavirus disease 2019 had significantly lower serum levels of total testosterone (111±89vs. 191±143ng/dL; p<0.001), dehydroepiandrosterone (1.69±1.26vs. 2.96±2.64ng/mL; p<0.001), and dehydroepiandrosterone sulfate (91.72±76.20vs. 134.28±98.261μg/dL; p=0.009), significantly higher levels of estradiol (64.61±59.35vs. 33.78±13.78 pg/mL; p=0.001), and significantly lower total testosterone:estradiol ratio (0.28±0.31vs. 0.70±0.75; p<0.001). The lower the serum level of androgen and the lower the total testosterone:estradiol ratio values, the higher the likelihood of developing severe coronavirus disease 2019, with the linear trend in the adjusted analyses being statistically significant for all parameters except for androstenedione (p=0.064). In the receiver operating characteristic analysis, better predictive performance was shown by the total testosterone:estradiol ratio, with an area under the curve of 0.77 (95% confidence interval 0.68-0.87; p<0.001). Our results suggest that men with severe acute respiratory syndrome coronavirus 2 infection, decreased androgen levels and increased estradiol levels have a higher likelihood of developing an unfavorable outcome. The total testosterone:estradiol ratio showed the best predictive ability.

Disparities in Coronavirus Disease 2019 Clinical Outcomes and Vaccination Coverage Among Migrants With Human Immunodeficiency Virus in the PISCIS Cohort: A Population-Based Propensity Score-Matched Analysis.

Coronavirus disease 2019 (COVID-19) disproportionately affects migrants and ethnic minorities, including those with human immunodeficiency virus (HIV). Comprehensive studies are needed to understand the impact and risk factors. Using data from the PISCIS cohort of people with HIV (PWH) in Catalonia, Spain, we investigated COVID-19 outcomes and vaccination coverage. Among 10 640 PWH we compared migrants and non-migrants assessing rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing, diagnosis, and associated clinical outcomes through propensity score matching and multivariable Cox regression. The cohort (mean age, 43 years; 83.5% male) included 57.4% (3053) Latin American migrants. Migrants with HIV (MWH) had fewer SARS-CoV-2 tests (67.8% vs 72.1%, P < .0001) but similar COVID-19 diagnoses (29.2% vs 29.4%, P = .847) compared to Spanish natives. Migrants had lower complete vaccination (78.9% vs 85.1%, P < .0001) and booster doses (63.0% vs 65.5%, P = .027). COVID-19 hospitalizations (8.1% vs 5.1%, P < .0001) and intensive care unit (ICU) admissions (2.9% vs 1.2%, P < .0001) were higher among migrants, with similar hospitalization duration (5.5 vs 4.0 days, P = .098) and mortality (3 [0.2%] vs 6 [0.4%], P = .510). Age ≥40 years, CD4 counts <200 cells/μL, ≥2 comorbidities, and incomplete/nonreception of the SARS-CoV-2 vaccine increased the risk of severe COVID-19 among migrants. MWH had lower rates of SARS-CoV-2 testing and vaccination coverage, although the rates of COVID-19 diagnosis were similar between migrants and non-migrants. Rates of COVID-19-associated hospitalizations and ICU admissions were higher among migrants in comparison with non-migrants, with similar hospitalization duration and mortality. These findings can inform policies to address disparities in future pandemic responses for MWH.

Increased Estimated GFR Is Negatively Associated With the Risk of SARS-CoV-2 Infection and Severe COVID-19 Within Normal to Mildly Decreased Levels: Nested Case-Control Study.

While accumulating evidence indicates chronic kidney disease as a risk factor for coronavirus disease 2019 (COVID-19), the association between normal or mildly decreased kidney function and COVID-19 is unaddressed. Here, we have examined the association of an increase in estimated glomerular filtration rate (eGFR) with the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe COVID-19 outcomes among patients within normal to mildly decreased kidney function. The patients who participated in both health screenings from period I (2017-2018) to II (2019-2020) were enrolled to our study. All participants were categorized into four groups according to the changes in eGFR stage from period I to II: 1) persistently stage G1, 2) from stage G2 to G1, 3) from stage G1 to G2, 4) persistently stage G2. In addition, the changes in eGFR value were defined by subtracting its value of period I from II. Patients were followed up for SARS-CoV-2 infection from January 1, 2021 to any diagnosis of COVID-19 or December 31, 2021, whichever happened first. In addition, those with SARS-CoV-2 infection were followed-up for one month after diagnosis to analyze severe COVID-19. Adjusted odds ratio (aOR) was calculated using multivariable-adjusted logistic regression. We identified 159,427 patients with and 1,804,798 patients without SARS-CoV-2 infection. The risk of SARS-CoV-2 infection decreased when eGFR stage changed from G2 to G1 (aOR, 0.957; 95% confidence interval [CI], 0.938-0.977) and persistently maintained at G1 (aOR, 0.966; 95% CI, 0.943-0.990), compared with the persistently stage G2 group. In addition, the risk showed an inverse relationship with changes in eGFR value, which was depicted by restricted cubic spline curves. For the overall risk of severe COVID-19, the persistently stage G1 showed the lowest risk (aOR, 0.897; 95% CI, 0.827-0.972), followed by those from stage G1 to G2 (aOR, 0.900; 95% CI, 0.828-0.978) and those from stage G2 to G1 (aOR, 0.931; 95% CI, 0.871-0.995), compared with the persistently stage G2 group. An increase in eGFR was negatively associated with the risk of SARS-CoV-2 infection and severe COVID-19 among normal or mildly decreased kidney function. For severe COVID-19, maintaining higher baseline eGFR may act as a protective factor against its risk.

Effect of SARS-CoV-2 Breakthrough Infection on HIV Reservoirs and T-Cell Immune Recovery in 3-Dose Vaccinated People Living with HIV.

People living with human immunodeficiency virus (PLWH) are a vulnerable population with a higher risk of severe coronavirus disease 2019 (COVID-19); therefore, vaccination is recommended as a priority. Data on viral reservoirs and immunologic outcomes for PLWH breakthrough infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are currently limited. In this study, we investigated the effects of SARS-CoV-2 breakthrough infection on hematological parameters, human immunodeficiency virus (HIV) reservoir size, and T-cell recovery in PLWH receiving antiretroviral therapy (ART) after SARS-CoV-2 booster vaccination. The results indicated that during breakthrough infection, booster vaccination with homologous and heterologous vaccines was safe in PLWH after receiving two doses of inactivated vaccination. The absolute CD4 counts decreased in the heterologous group, whereas the CD8 counts decreased in the homologous booster group after breakthrough infection in PLWH. Breakthrough infection increased HIV reservoirs and was associated with increased T-cell activation in PLWH who received virally suppressed ART and a 3-dose vaccination. According to our data, the breakthrough infection of SARS-CoV-2 may put PLWH at a greater risk for increased HIV reservoirs, even if these individuals were virally suppressed with ART after 3-dose SARS-CoV-2 vaccination.

Clinical characteristics and outcomes of COVID-19 infection in Chinese patients with hematologic malignancies in the Omicron era

ABSTRACT Patients with hematologic malignancies are often immunodeficient and therefore have a higher risk of severe symptoms from coronavirus disease 2019 (COVID-19). We retrospectively examined a cohort of 289 patients from 16 hospitals in Zhejiang Province who had hematologic malignancies and COVID-19 during a period when the Omicron variant was predominant. Univariate analysis showed that some clinical characteristics, including elder age (P = 0.014), multiple comorbid conditions (P = 0.011), and receipt of active antineoplastic therapy (P = 0.018) were associated with an increased risk of severe COVID-19. Patients with severe/critical COVID-19 had significantly lower levels of lymphocytes and serum albumin, and significantly higher levels of D-dimer, lactate dehydrogenase, C-reactive protein, and interleukin-6 (all P < 0.05). Fifty-four patients (18.7%) had symptoms lasting ≥3 weeks, suggesting that persistent long-term COVID-19 infection is likely present in a significant proportion of patients. Receipt of the inactivated vaccine was unrelated to disease severity (P = 0.143), which indicated that many patients with hematologic malignancies may not have effective humoral immunity to inactivated vaccines.

T cell responses to SARS-CoV-2 infection and vaccination are elevated in B cell deficiency and reduce risk of severe COVID-19.

Individuals with primary and pharmacologic B cell deficiencies have high rates of severe disease and mortality from coronavirus disease 2019 (COVID-19), but the immune responses and clinical outcomes after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination have yet to be fully defined. Here, we evaluate the cellular immune responses after both SARS-CoV-2 infection and vaccination in patients receiving the anti-CD20 therapy rituximab (RTX) and those with low B cell counts due to common variable immune deficiency (CVID) disease. Assessment of effector and memory CD4+ and CD8+ T cell responses to SARS-CoV-2 revealed elevated reactivity and proliferative capacity after both infection and vaccination in B cell-deficient individuals, particularly within the CD8+ T cell compartment, in comparison with healthy controls. Evaluation of clinical outcomes demonstrates that vaccination of RTX-treated individuals was associated with about 4.8-fold reduced odds of moderate or severe COVID-19 in the absence of vaccine-induced antibodies. Analysis of T cell differentiation demonstrates that RTX administration increases the relative frequency of naïve CD8+ T cells, potentially by depletion of CD8+CD20dim T cells, which are primarily of an effector memory or terminal effector memory (TEMRA) phenotype. However, this also leads to a reduction in preexisting antiviral T cell immunity. Collectively, these data indicate that individuals with B cell deficiencies have enhanced T cell immunity after both SARS-CoV-2 infection and vaccination that potentially accounts for reduced hospitalization and severe disease from subsequent SARS-CoV-2 infection.

Risk factors for COVID-19 hospitalization and mortality in patients with chronic kidney disease: a nationwide cohort study.

Several studies have demonstrated an increased risk of severe coronavirus disease 2019 (COVID-19) in chronic kidney disease (CKD) patients. However, few have investigated the impact of CKD stage and dialysis modality. The primary aim of this study was to investigate the association between CKD stage, dialysis modality and risk of severe COVID-19. Secondly, we aimed to study the impact of comorbidities and drugs on the risk of severe COVID-19 in the CKD population. This nationwide observational study was based on data from the Swedish Renal Registry and three other national registries. Patients with non-dialysis CKD stage 3b-5 or dialysis on 1 January 2020 were included and followed until 31 December 2021. The primary outcome was COVID-19 hospitalization; the secondary outcome was COVID-19 mortality. Associations were investigated using logistic regression models, adjusting for confounders. The study population comprised 7856 non-dialysis CKD patients and 4018 dialysis patients. The adjusted odds ratios (aOR) for COVID-19 hospitalization and mortality were highest in the dialysis group [aOR 2.24, 95% confidence interval (CI) 1.79-2.81; aOR 3.10, Cl 95% 2.03-4.74], followed by CKD 4 (aOR 1.33, 95% CI 1.05-1.68; aOR 1.66, Cl 95% 1.07-2.57), as compared with CKD 3b. No difference in COVID-19 outcomes was observed between patients on hemodialysis and peritoneal dialysis. Overall comorbidity burden was one of the strongest risk factors for severe COVID-19 and the risk was also increased in patients prescribed insulin, proton pump inhibitors, diuretics, antiplatelets or immunosuppressants. Worsening CKD stage and comorbidity are independent risk factors for severe COVID-19 in the Swedish CKD population.

Spike Protein Genetic Evolution in Patients at High Risk of Severe Coronavirus Disease 2019 Treated by Monoclonal Antibodies.

High-risk patients, often immunocompromised and not responding to vaccine, continue to experience severe coronavirus disease 2019 (COVID-19) and death. Monoclonal antibodies (mAbs) were shown to be effective to prevent severe COVID-19 for these patients. Nevertheless, concerns about the emergence of resistance mutations were raised. We conducted a multicentric prospective cohort study, including 264 patients with mild to moderate COVID-19 at high risk for progression to severe COVID-19 and treated early with casirivimab/imdevimab, sotrovimab, or tixagevimab/cilgavimab. We sequenced the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome during follow-up and searched for emerging spike mutations. Immunocompromised patients have a 6-fold increased risk of developing mutations, which are associated with a prolonged duration of viral clearance but no clinical worsening. Emerging P337S/R/L/H, E340D/K/A/Q/V/G, and K356T/R substitutions in patients treated with sotrovimab are associated with higher viral RNA loads for up to 14 days post-treatment initiation. Tixagevimab/cilgavimab is associated with a 5-fold increased risk of developing mutations. R346K/I/T/S and K444R/N/M substitutions associated with tixagevimab/cilgavimab have been identified in multiple SARS-CoV-2 lineages, including BQ.1 and XBB. The probability of emerging mutations arising in response to mAbs is significant, emphasizing the crucial need to investigate these mutations thoroughly and assess their impact on patients and the evolutionary trajectory of SARS-CoV-2.

Risk of severe coronavirus disease 2019 despite vaccination in patients requiring treatment with immune-suppressive drugs: A nationwide cohort study of US Veterans.

Patients taking immune-suppressive drugs are at increased risk of severe coronavirus disease 2019 (COVID-19), not fully ameliorated by vaccination. We assessed the contributions of clinical and demographic factors to the risk of severe disease despite vaccination in patients taking immune-suppressive medications for solid organ transplantation (SOT), rheumatoid arthritis (RA), inflammatory bowel disease (IBD), or psoriasis. Veterans Health Administration electronic health records were used to identify patients diagnosed with RA, IBD, psoriasis, or SOT who had been vaccinated against severe acute respiratory syndrome coronavirus 2, were subsequently infected, and had received immune-suppressive drugs within 3 months before infection. The association of severe (defined as hypoxemia, mechanical ventilation, dexamethasone use, or death) versus non-severe COVID-19 with the use of immune-suppressive and antiviral drugs and clinical covariates was assessed by multivariable logistic regression. Severe COVID-19 was more common in patients with SOT (230/1011, 22.7%) than RA (173/1355, 12.8%), IBD (51/742, 6.9%), or psoriasis (82/1125, 7.3%). Age was strongly associated with severe COVID-19, adjusted odds ratio (aOR) of 1.04 (CI 1.03-1.05) per year. Comorbidities indicating chronic brain, heart, lung, or kidney damage were also associated with severity, aOR 1.35-2.38. The use of glucocorticoids was associated with increased risk (aOR 1.66, CI 1.39-2.18). Treatment with antivirals was associated with reduced severity, for example, aOR 0.28 (CI 0.13-0.62) for nirmatrelvir/ritonavir. The risk of severe COVID-19 despite vaccination is substantial in patients taking immune-suppressive drugs, more so in patients with SOT than in patients with inflammatory diseases. Age and severe comorbidities contribute to risk, as in the general population. Oral antivirals were very beneficial but not widely used.

Interleukin-6 and the determinants of severe COVID-19: A retrospective cohort study.

Cytokines, notably interleukin-6 (IL-6), increase considerably in patients with severe corona virus disease 2019 (COVID-19). This vigorous immune response may cause end-organ failure or death; hence, measuring IL-6 in the context of patient characteristics may help predict outcomes and encourage early comprehensive therapy. This study investigated the association between serum IL-6 levels, COVID-19 severity, and demographic, clinical, and biochemical characteristics. COVID-19 inpatients in NMC hospitals were investigated between November 2020 and November 2021. Several patient variables related to serum IL-6 and COVID-19 severity have been examined. The study included 374 COVID-19 inpatients, 235 of whom had severe disease with a median age of 51. The elderly had an increased risk of severe COVID-19 (73.8%) compared with young adults (71%), with higher white blood cells, D-dimer, Lactate dehydrogenase, creatinine, ferritin, prothrombin time, Procalcitonin, and fibrinogen levels (P < .001). C-reactive protein, troponin, intensive care unit admission, disease severity score, and mortality were significantly associated with higher serum IL-6 levels (P = .05) in the univariate analysis, but this significance disappeared in the multivariate analysis. IL-6, along with other demographic and clinical variables affected COVID-19 severity. These characteristics may predict patients at risk of severe disease and assist in establishing early comprehensive disease outcome strategies. Large-scale clinical research is needed to emphasize IL-6 and COVID-19.

ABX464 (obefazimod) for patients with COVID-19 at risk for severe disease: miR-AGE, a randomized, double-blind placebo-controlled trial.

ABX464 (obefazimod) is a small molecule that upregulates a single microRNA (miR-124) in immune cells and reduces the production of various inflammatory cytokines and chemokines. We assessed the efficacy and safety of the standard of care (SoC) plus oral obefazimod (SoC plus ABX464), 50 mg once daily, versus the SoC plus placebo for prevention of severe acute respiratory syndrome in patients with coronavirus disease 2019 (COVID-19) who are at risk for severe disease. Eligible patients for this phase 2/3 double-blind, placebo-controlled miR-AGE study were randomized (2:1) into 2 groups: SoC-ABX464 (n= 339) and SoC-placebo (n= 170). The primary end point was the percentage of patients who did not require use of high-flow oxygen or invasive or noninvasive mechanical ventilation within 28 days. The safety analyses included patients who had been randomly assigned and had received at least 1 dose of the study treatment. At the time of the interim analysis, obefazimod showed no benefit over placebo when added to the SoC; the study enrollment was stopped for futility. The evaluation of the safety of obefazimod in 505 patients showed significantly more treatment-emergent adverse events in the SoC-ABX464 group than in the SoC-placebo group (P= .007). Frequently reported AEs in the SoC-ABX464 group included headache (14.6%), abdominal pain (9.6%), diarrhea (9.0%), back pain (6.9%), and nausea (6.0%). No treatment-related changes in laboratory parameters were reported. For patients who have severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and are at risk for severe COVID-19, obefazimod, 50 mg, provided no benefit over placebo when added to the SoC, although it did have a good safety profile (comparable to that reported in many therapeutic areas).

Outbreaks of COVID-19 in a tuberculosis treatment sanatorium on the Thailand-Myanmar border: a retrospective cohort analysis

Background Tuberculosis (TB) is a chronic condition, with overlapping symptoms to those of coronavirus disease 2019 (COVID-19). There has been inconsistent evidence on whether TB is a predisposing factor for developing severe COVID-19. The aim of this report is to explore whether TB influences the severity of COVID-19. Methods COVID-19 cases at two TB sanatoria on the Thailand-Myanmar border were reviewed. Demographic, clinical and laboratory data including TB treatment and co-morbidities, were analyzed. Characteristics and COVID-19 clinical outcomes were compared between two groups of patients: TB and those without TB (the caretakers and the medical personnel). Multivariable ordered logistic regression was conducted to compare the risk of severe COVID-19 between the two groups. Results Between September 2021 and March 2022, 161 COVID-19 cases were diagnosed. Over half of the COVID-19 patients were infected with TB (n= 104, 64.6%), and the rest were not (n=57, 35.4%). The median (interquartile range) age was 48 (33.5-57.0) and 27 (23-33) years in the TB and in the non-TB COVID-19 patients, respectively. Before COVID-19 infection, 67.1% (106/158) of patients had received at least one dose of COVID-19 vaccine. The median cycle threshold value at diagnosis was not different between TB (18.5, IQR 16.1-32.3) and non-TB patients (18.8, 15.1-30.0). Fever, gastrointestinal symptoms and ageusia were more common in non-TB patients. Six patients (3.8%, 6/156) all from the TB group became severe of which five (3.2%, 5/156) required oxygen therapy. One TB patient died (1/104, 0.96%) of lung cancer. After adjustment for potential confounders, the final clinical severity was not different between the two groups (adjusted odds ratio 1.40, 95% confidence interval 0.16–12.39). Conclusions TB was not associated with severe outcomes in the two TB sanatoria. The high uptake of COVID-19 vaccination and active screening could have impacted on disease progression and prevented unfavorable outcomes.

Clinical Practice Patterns, Health Resource Use and Risk Factors for Severe Conditions Among Children Hospitalized With COVID-19 in Japan.

The trends in clinical practice patterns and health resource use, as well as risk factors for severe conditions among children hospitalized with coronavirus disease-2019 (COVID-19), remain unclear. We conducted a retrospective observational study consisting of 9876 children hospitalized with COVID-19 during 2020-2022 using the Medical Data Vision database in Japan. We investigated trends in patient characteristics, health resource use, treatment patterns and laboratory data. Additionally, log-binomial regression models were used to investigate the risk factors associated with severe COVID-19 among pediatric inpatients with COVID-19. We observed decreasing trends in the lengths of hospital stays, healthcare costs, computed tomography use, and antibiotic use, and increasing trends in treatment with intravenous hydration and use of antipyretics, antiepileptics, antiemetics and antivirals from the first wave to the seventh wave of COVID-19 pandemic. During the 3-year period, the risk of severe COVID-19 was almost stable at 3%. Risk factors associated with severe COVID-19 were children aged 0 years [risk ratio (RR): 1.69; 95% confidence interval (CI): 1.02-2.78], the number of complex chronic diseases (RR for 1 disease: 4.49; 95% CI: 2.76-7.32; RR for 2 or more diseases: 10.2; 95% CI: 5.19-20.3) and asthma (RR: 1.84; 95% CI: 1.06-3.20). Our study observed the changes in practice patterns and health resource use for children hospitalized with COVID-19 and identified risk factors associated with severe COVID-19. These findings indicate the importance of vigilant monitoring and tailored treatment strategies in children with these risk factors.