Risk Of Severe Coronavirus Disease 2019 Research Articles

Implementation of AZD7442 (Tixagevimab/Cilgavimab) COVID-19 Pre-exposure Prophylaxis (PrEP) in the Largest Health Maintenance Organization in Israel: Real-world Uptake and Sociodemographic and Clinical Characteristics Across Immunocompromised Patient Groups.

AZD7442 is a combination of two neutralizing antibodies (tixagevimab/cilgavimab) with demonstrated efficacy in reducing the risk of symptomatic coronavirus disease 2019 (COVID-19) among individuals at high risk of severe COVID-19 ≤ 6months after administration. On February 15, 2022, the Israeli Ministry of Health (IMoH) authorized the administration of 300mg AZD7442 as pre-exposure prophylaxis (PrEP) against severe acute respiratory syndrome coronavirus 2infection among immunocompromised individuals aged ≥ 12years. This study describes the real-world uptake of AZD7442 in Israel. This descriptive, observational study analyzed data from Israel's largest health maintenance organization, Clalit Health Services (CHS). Individuals were assessed for AZD7442 eligibility between February 13 and December 11, 2022, and were included if they were aged ≥ 12years, had ≥ 1year of continuous CHS membership, had≥ 1 moderate or severe immunocompromising condition, and were eligible for AZD7442 per IMoH recommendations during this time frame. Overall, 19,161 AZD7442-eligible individuals with immunocompromising conditions were identified during the study period; 2829 (14.8%) received AZD7442. A higher proportion of individuals receiving AZD7442 were older (aged ≥ 65years), male, not current smokers and residents in large cities; required more physician visits (> 50 visits); and had ≥ 1 COVID-19 hospitalization over 12months, while uptake was lowest among ultra-orthodox Jewish individuals. AZD7442 uptake was also higher among individuals with multiple comorbidities (Charlson Comorbidity Index ≥ 5), including hypertension, diabetes and chronic kidney disease. In specific immunocompromised types, AZD7442 uptake was highest among individuals with lung transplantation (41%), primary immunodeficiency (32%), bone marrow transplantation (29%) and multiple myeloma (25%) or those receiving anti-CD20 therapy (26%) and was lowest in individuals with lymphoma (8%). These results show AZD7442 uptake among the eligible population of Israel in 2022 was relatively low, at 14.8%. Uptake was generally higher among immunocompromised individuals who may be perceived to be frail or at highest risk of COVID-19 infection and complications, although at 25-41%, further improvements in uptake would be more impactful. These results also indicate there is opportunity to expand AZD7442 uptake across immunocompromised groups and ensure more equitable uptake among some other sociodemographic groups. Overall, this study will help inform and reassess future implementation strategies for vulnerable populations.

Use of Sotrovimab in Pregnancy: Experiences from the COVID-19 International Drug Pregnancy Registry.

Available data regarding the safety and efficacy of sotrovimab in pregnant patients remain limited due to their exclusion from clinical trials. The COVID-19 International Drug Pregnancy Registry (COVID-PR) was established to gather comprehensive safety data from pregnant women who have received monoclonal antibody (mAb) or antiviral treatments for mild, moderate, or severe coronavirus disease 2019 (COVID-19) during pregnancy. Participants actively contributed self-reported data concerning their COVID-19 symptoms, in addition to sociodemographic and health-related characteristics. Obstetric, neonatal, and infant outcomes were also documented, with follow-up extending up to 12 months after childbirth. As of 30 November 2023, sotrovimab was administered to 39 participants enrolled in the COVID-PR. At the time of this report, 26 participants had given birth, with nine deliveries performed via cesarean section. The infants' birthweight ranged from 2381g to 4762g, with a mean of 3439.91g. Twenty-five infants were born at ≥37weeks. A total of 31 adverse events (AEs) were reported by 12 participants. The most frequently reported AE was gestational hypertension, observed in three participants. COVID-19 re-infection, fatigue, gestational diabetes, headache, and morning sickness were each reported by two participants. Of the reported AEs, eight (in five participants) were classified as serious, including four AEs (prolonged labor, pre-eclampsia, polyhydramnios, premature labor) that affected pregnancy. Seven of these eight serious AEs (SAEs) were found to be unrelated to sotrovimab, with one event (urinary retention) not assessable. A total of 44 AEs were reported in 19 delivered infants or in utero fetuses. The most common were COVID-19 (n=6 events), ear infection (n=5 events), neonatal dyspnea (n=3 events), and respiratory syncytial virus infection (n=3 events). Sixteen AEs (in 11 infants/fetuses) were classified as serious, including one report each of fetal cardiac disorder, congenital ankyloglossia, persistent right umbilical vein, and congenital hydronephrosis; the latter was considered a major congenital malformation. For all assessable SAEs, causality of sotrovimab treatment was ruled out based on lack of a temporal relationship alone or in combination with absence of a plausible mechanism. A sizable proportion of sotrovimab-treated participants in the COVID-PR had underlying medical conditions associated with an increased risk of severe COVID-19. None of the assessable SAEs were considered to be related to sotrovimab treatment.

Immunophenotype of lymphocytes and real-world outcome of COVID-19 infection in children with hematology and oncology

BackgroundPatients with immunocompromise were suspected to encounter a high risk for severe coronavirus disease 2019 (COVID-19) infection on early period; however, data is lacking nowadays and immune response remain unclear.MethodsIn this retrospective study, internet questionnaire survey and medical records were acquired in pediatric hematology oncology patients. Clinical severity, immunological characteristics, and outcomes were analyzed from December 1, 2022 to January 31, 2023 at the 3rd year of pandemic in China.ResultsA total of 306 patients were included, with 21 patients (6.9%) asymptomatic, 262 (85.6%) mild severity, 17 (5.6%) moderate severity, 5 (1.6%) severe severity, and 1 (0.3%) critical severity. Seventy-eight (25.5%) patients were on intensive chemotherapy, and 32.0% children were on maintenance chemotherapy. Delays in cancer therapy occurred in 86.7% patients. Univariable analysis revealed active chemotherapy (P < 0.0001), long duration of symptom (P < 0.0001), low lymphocytes count (P = 0.095), low CD3 + and CD8 + T cell count (P = 0.013, P = 0.022), high percentage of CD4 + TCM (P = 0.016), and low percentage of transitional B cells (P = 0.045) were high risk factors for severe COVID-19 infection. Cox regression model showed that the absolute lymphocytes count (P = 0.027) and long duration of symptom (P = 0.002) were the independent factors for severity. Patients with CD8 + dominant and B cell depletion subtype wasn’t related with severity, but had higher percentage of CD8 + effector memory T cells (TEM) and terminally differentiated effector memory T cells (TEMRA) (P < 0.001, P < 0.001), and a longer COVID-19 duration (P = 0.045).ConclusionThe severity was relatively mild in children with immunodeficiencies in the third year of COVID-19 pandemic. Low lymphocyte count and long duration of symptom were the independent risk factors with COVID-19 severity. Delays in cancer care remain a major concern and the long outcome is pending.

Comprehensive analysis of immunogenic cell death-related gene and construction of prediction model based on WGCNA and multiple machine learning in severe COVID-19

The death of coronavirus disease 2019 (COVID-19) is primarily due to from critically ill patients, especially from ARDS complications caused by SARS-CoV-2. Therefore, it is essential to contribute an in-depth understanding of the pathogenesis of the disease and to identify biomarkers for predicting critically ill patients at the molecular level. Immunogenic cell death (ICD), as a specific variant of regulatory cell death driven by stress, can induce adaptive immune responses against cell death antigens in the host. Studies have confirmed that both innate and adaptive immune pathways are involved in the pathogenesis of SARS-CoV-2 infection. However, the role of ICD in the pathogenesis of severe COVID-19 has rarely been explored. In this study, we systematically evaluated the role of ICD-related genes in COVID-19. We conducted consensus clustering, immune infiltration analysis, and functional enrichment analysis based on ICD differentially expressed genes. The results showed that immune infiltration characteristics were altered in severe and non-severe COVID-19. In addition, we used multiple machine learning methods to screen for five risk genes (KLF5, NSUN7, APH1B, GRB10 and CD4), which are used to predict COVID-19 severity. Finally, we constructed a nomogram to predict the risk of severe COVID-19 based on the classification and recognition model, and validated the model with external data sets. This study provides a valuable direction for the exploration of the pathogenesis and progress of COVID-19, and helps in the early identification of severe cases of COVID-19 to reduce mortality.

Severe acute respiratory syndrome coronavirus 2 infection in patients with hematological malignancies in the Omicron era: Respiratory failure, need for mechanical ventilation and mortality in seronegative and seropositive patients

AbstractBackground: Patients with hematological malignancies (HM) have a high risk of severe coronavirus disease 2019 (COVID‐19), also in the Omicron period.Material and methods: Retrospective single‐center study including HM patients with severe acute respiratory syndrome Coronavirus 2 (SARS‐CoV2) infection from January 2022 to March 2023. Study outcomes were respiratory failure (RF), mechanical ventilation (MV), and COVID‐related mortality, comparing patients according to SARS‐CoV2 serology.Results: Note that, 112 patients were included: 39% had negative SARS‐CoV2 serology. Seronegative were older (71.5 vs. 65.0 years, p = 0.04), had more often a lymphoid neoplasm (88.6% vs. 69.1%, p = 0.02), underwent anti‐CD20 therapy (50.0% vs. 30.9% p = 0.04) and had more frequently a severe disease (23.0% vs. 3.0%, p = 0.02) than seropositive.Kaplan‐Meier showed a higher risk for seronegative patients for RF (p = 0.014), MV (p = 0.044), and COVID‐related mortality (p = 0.021). Negative SARS‐CoV2 serostatus resulted in a risk factor for RF (hazards ratio [HR] 2.19, 95% confidence interval [CI] 1.03–4.67, p = 0.04), MV (HR 3.37, 95% CI 1.06–10.68, p = 0.04), and COVID‐related mortality (HR 4.26, 95% CI 1.09–16.71, p = 0.04).Conclusions: HM patients with negative SARS‐CoV2 serology, despite vaccinations and previous infections, have worse clinical outcomes compared to seropositive patients in the Omicron era. The use of serology for SARS‐CoV2 diagnosis could be an easy tool to identify patients prone to developing complications.

Assessing antiviral treatment efficacy and risk factors for severe COVID-19 in kidney transplant recipients during the Omicron subvariant-dominant period: a retrospective study

BackgroundKidney transplant recipients (KTRs) are at risk of severe coronavirus disease 2019 (COVID-19), and even now that Omicron subvariants have become dominant, cases of severe disease are certain to occur. The aims of this retrospective study were to evaluate the efficacy of antiviral treatment for COVID-19 and to identify risk factors for severe disease in KTRs during Omicron subvariant-dominant periods.MethodsA total of 65 KTRs diagnosed with COVID-19 who received antiviral treatment between July 2022 and September 2023 were analyzed. Mild cases received oral molnupiravir (MP) as outpatient therapy, while moderate or worse cases received intravenous remdesivir (RDV) as inpatient therapy. In principle, mycophenolate mofetil was withdrawn and switched to everolimus. We investigated the efficacy of antiviral treatment and compared the clinical parameters of mild/moderate and severe/critical cases to identify risk factors for severe COVID-19.ResultsAmong 65 cases, 49 were mild, 6 were moderate, 9 were severe, and 1 was of critical severity. MP was administered to 57 cases; 49 (86%) improved and 8 (14%) progressed. RDV was administered to 16 cases; 14 (87%) improved and 2 (13%) progressed. Seventeen (26%) cases required hospitalization, and none died. Comparisons of the severe/critical group (n = 10) with the mild/moderate group (n = 55) demonstrated that the severe/critical group had a significantly higher median age (64 vs. 53 years, respectively; p = 0.0252), prevalence of diabetes (70% vs. 22%, respectively; p = 0.0047) and overweight/obesity (40% vs. 11%, respectively; p = 0.0393), as well as a significantly longer median time from symptom onset to initial antiviral therapy (3 days vs. 1 day, respectively; p = 0.0026). Multivariate analysis showed that a longer time from symptom onset to initial antiviral treatment was an independent risk factor for severe COVID-19 (p = 0.0196, odds ratio 1.625, 95% confidence interval 1.081–2.441).ConclusionThese findings suggest that a longer time from symptom onset to initial antiviral treatment is associated with a higher risk of severe COVID-19 in KTRs. Initiating antiviral treatment as early as possible is crucial for preventing severe outcomes; this represents a valuable insight into COVID-19 management in KTRs.

COVID-19 mortality in 1984 Bhopal gas tragedy survivors: implications for chemically exposed populations.

Leakage of methyl isocyanate from the Union Carbide plant in Bhopal, India, killed thousands and left deleterious trans-generational effects. Gas-exposed populations experience higher rates of lung and metabolic diseases, and immune dysregulation, all associated with adverse outcomes in coronavirus disease 2019 (COVID-19). We used publicly available, official data from government sources to estimate COVID-19-associated crude mortality in populations with and without a history of gas exposure. Overall, there were 1240 deaths among patients hospitalized with known COVID-19 in Bhopal, of which 453 (36.53%) were in gas-exposed individuals, 726 (58.55%) were in gas-unexposed individuals and the exposure status of 61 (4.92%) individuals could not be determined. There were 351 and 375 deaths in gas-unexposed people in the first (April 2020-February 2021) and second (March 2021-July 2021) waves, respectively; in the gas-exposed population, there were 300 and 153 deaths in the two respective waves. The overall annualized crude mortality of COVID-19 was 3.84 (95% CI 3.41 to 4.33) times higher in the gas-exposed population at 83.6 (95% CI 76.1 to 91.7) per 100 000 compared with the gas-unexposed population, at 21.8 (95% CI 20.2 to 23.4) per 100,000. When stratified by age, compared with unexposed people, the gas-exposed individuals experienced 1.88 (95% CI 1.61 to 2.21) and 1.24 (95% CI 1.02 to 1.50) times the mortality rates in the age groups of 35-65 and >65 y, respectively. These findings indicate that gas-exposed individuals are likely to have a higher risk of severe COVID-19 and death and need to be specifically targeted and recognized for preventive and promotive efforts.

Pre-Exposure Prophylaxis and Treatment with Tixagevimab/Cilgavimab for COVID-19 among Immunocompromised Pediatric Patients.

Background: Patients treated with hemato-oncological malignancies (HO) or undergoing cellular therapies such as hematopoietic stem cell transplantation (HSCT) or chimeric antigen receptor T cells (CAR-T) were significantly affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite the success of SARS-CoV-2 vaccination, immunocompromised patients remain at increased risk for severe coronavirus disease (COVID-19), rendering this group of population a high priority for additional prevention and treatment options. Tixagevimab and Cilgavimab (TIXA/CILGA, AZD7442, Evusheld®) is a combination of two fully human, long-acting monoclonal antibodies. TIXA/CILGA have been approved as pre-exposure prophylaxis and treatment in patients at risk of severe disease with impaired vaccine response. Our objective was to describe the efficacy and safety among immunocompromised pediatric patients. Methods: This was an observational multicenter cohort study of immunocompromised pediatric patients receiving TIXA/CILGA conducted at nine Polish centers of Pediatric Oncology, Hematology and Bone Marrow Transplantation. We analyzed patients in two groups; those treated with HO and those undergoing cellular therapies: HSCT or CAR-T cells. In addition, two other cohorts were identified: patients given TIXA/CILGA as pre-exposure prophylactic and therapeutic intervention. Results: A total of 78 patients were evaluated during the study period: 69 (88.5%) received TIXA/CILGA as pre-exposure prophylaxis and 9 (11.5%) as a treatment strategy. A total of 52 (66.6%) patients were treated with standard chemotherapy at HO departments; 21 (27%) underwent HSCT, and 5 (6.4%) received CAR-T cell therapy. All children with COVID-19 receiving TIXA/CILGA presented a mild degree of severity. The most common clinical manifestations were fever, cough and coryza. At least one adverse event (AE) was reported in two (3.8%) patients excluding standard injection site reactions. Reported AEs were mild or moderate in intensity. One child reported mild myalgia and one reported moderate bone pain and weakness. Conclusions: In our observational multicenter cohort study, we explored the use of TIXA/CILGA as pre-exposure prophylaxis and treatment for COVID-19 among immunocompromised pediatric patients. While our findings suggest a potential benefit in preventing and managing COVID-19 in this vulnerable population, it is important to note the study's non-comparative design. Our results highlight the need for well-designed clinical trials to confirm these observations and further assess the efficacy and safety of TIXA/CILGA in immunocompromised children.

Urinary cadmium concentration is associated with the severity and clinical outcomes of COVID-19: a bicenter observational cohort study

BackgroundCadmium and nickel exposure can cause oxidative stress, induce inflammation, inhibit immune function, and therefore has significant impacts on the pathogenesis and severity of many diseases. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can also provoke oxidative stress and the dysregulation of inflammatory and immune responses. This study aimed to assess the potential associations of cadmium and nickel exposure with the severity and clinical outcomes of patients with coronavirus disease 2019 (COVID-19).MethodsWe performed a retrospective, observational, bicenter cohort analysis of patients with SARS-CoV-2 infection in Taiwan between June 2022 and July 2023. Cadmium and nickel concentrations in blood and urine were measured within 3 days of the diagnosis of acute SARS-CoV-2 infection, and the severity and clinical outcomes of patients with COVID-19 were analyzed.ResultsA total of 574 patients were analyzed and divided into a severe COVID-19 group (hospitalized patients) (n = 252; 43.9%), and non-severe COVID-19 group (n = 322; 56.1%). The overall in-hospital mortality rate was 11.8% (n = 68). The severe COVID-19 patients were older, had significantly more comorbidities, and significantly higher neutrophil/lymphocyte ratio, C-reactive protein, and interleukin-6 than the non-severe COVID-19 patients (all p < 0.05). Blood and urine cadmium and urine nickel concentrations were significantly higher in the severe COVID-19 patients than in the non-severe COVID-19 patients. Among the severe COVID-19 patients, those in higher urine cadmium/creatinine quartiles had a significantly higher risk of organ failure (i.e., higher APACHE II and SOFA scores), higher neutrophil/lymphocyte ratio, lower PaO2/FiO2 requiring higher invasive mechanical ventilation support, higher risk of acute respiratory distress syndrome, and higher 60-, 90-day, and all-cause hospital mortality (all p < 0.05). Multivariable logistic regression models revealed that urine cadmium/creatinine was independently associated with severe COVID-19 (adjusted OR 1.643 [95% CI 1.060–2.547], p = 0.026), and that a urine cadmium/creatinine value > 2.05 μg/g had the highest predictive value (adjusted OR 5.349, [95% CI 1.118–25.580], p = 0.036).ConclusionsUrine cadmium concentration in the early course of COVID-19 could predict the severity and clinical outcomes of patients and was independently associated with the risk of severe COVID-19.

Clinical characteristics and prognosis of SARS-CoV-2 infection in children with hematological malignancies: A multicenter, retrospective study in China

BackgroundData on SARSCoV-2 infection in children with hematological malignancies (HM) are limited. Here, we describe the clinical features of children with HM after SARS-CoV-2 infection and investigate the potential risk factors for disease severity. MethodsChildren with HM and SARS-CoV-2 infection from five hospitals in five cities in Henan, China from October 2022 to January 2023 were retrospectively included. Clinical information and Coronavirus disease 2019 (COVID-19) vaccination status were collected for further analyses. ResultsA total of 285 children with HM and SARS-CoV-2 infections were included. COVID-19 was asymptomatic in 3.2% of the patients (n = 9), mild in 89.1% (n = 254), moderate in 5.3% (n = 15), severe in 1.8% (n = 5), and critical in 0.7% (n = 2). Fever (92.4%) and cough (56.9%) were the most common symptoms. Most (249, 88.3%) children were managed at home during their COVID-19 illness. Of the 36 children admitted to the hospital, two required intensive care unit care, 11 required supplementary oxygen, and two non-invasive ventilation. A total of 283 (99.3%) children fully recovered and two (0.7%) died due to COVID-19. Significant risk factors for increased severity of infection in multivariable analyses were the presence of comorbidity (OR, 10.4; 95%CI, 2.8–38.7; p < 0.0001), neutropenia (OR, 10.4; 95%CI, 2.6–41.8; p = 0.001), and lymphopenia (OR, 4.2; 95%CI, 1.2–15.4; p = 0.029). A total of 30.9% (88/285) of the children received at least one dose of the inactivated COVID-19 vaccine at COVID-19 diagnosis. Compared with children who received at least one dose of the COVID-19 vaccine, fever was significantly more common in unvaccinated children (79.3% vs. 93.8%, p < 0.001). ConclusionsChildren with HM are not at an increased risk of severe COVID-19 compared to the general pediatric population. However, comorbidities such as lymphopenia and neutropenia may increase the risk of developing moderate or severe/critical disease. Our data may help in management decisions for this vulnerable population.

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.