Coronavirus Disease 2019 Outcomes Research Articles

Management of immunosuppression in lung transplant recipients and COVID-19 outcomes: an observational retrospective cohort-study

BackgroundThe aim of this study was to assess the impact of immunosuppression management on coronavirus disease 2019 (COVID-19) outcomes.MethodsWe performed a single-center retrospective study in a cohort of 358 lung transplant recipients (LTx) over the period from March 2020 to April 2022. All included symptomatic patients had at least one positive SARS-CoV-2 rt-PCR. We used a composite primary outcome for COVID-19 including increased need for oxygen since the hospital admission, ICU transfer, and in-hospital mortality. We assessed by univariate and multivariate analyses the risk factors for poor outcomes.ResultsOverall, we included 91 LTx who contracted COVID-19. The COVID-19 in-hospital mortality rate reached 4.4%. By hierarchical clustering, we found a strong and independent association between the composite poor outcome and the discontinuation of at least one immunosuppressive molecule among tacrolimus, cyclosporine, mycophenolate mofetil, and everolimus. Obesity (OR = 16, 95%CI (1.96; 167), p = 0.01) and chronic renal failure (OR = 4.6, 95%CI (1.4; 18), p = 0.01) were also independently associated with the composite poor outcome. Conversely, full vaccination was protective (OR = 0.23, 95%CI (0.046; 0.89), p = 0.047).ConclusionThe administration of immunosuppressive drugs such as tacrolimus, cyclocporine or everolimus can have a protective effect in LTx with COVID-19, probably related to their intrinsic antiviral capacity.

Profile and Outcomes of COVID-19 Infection in Pediatric Patients with and without Cancer: A Case–Control Study

Abstract Objectives Pediatric patients with cancer are considered a vulnerable population to the ill effects of coronavirus disease 2019 (COVID-19). We hereby studied the difference between clinical characteristics, lab parameters, and outcomes of COVID-19 among children suffering from cancer and those without cancer. We also analyzed risk factors for the occurrence of moderate-to-severe COVID-19 disease in pediatric cancer patients. Materials and Methods This retrospective case–control study was carried out using the medical record review method over 6 months in a tertiary-care center in India. All patients below 18 years of age, with reverse-transcriptase polymerase chain reaction (RTPCR) confirmed COVID-19, were screened for enrolment. Patients were split into two groups: Group A comprised of patients with cancer, while group B consisted of patients without any underlying comorbidity. Patients with other comorbidity except cancer and inadequately recorded case sheets were excluded. Details regarding demography, clinical features, investigations, treatment, and outcomes were recorded. Statistical Analysis Microsoft Excel and Statistical Package for the Social Sciences (SPSS) software, version 25 was used for data analysis. A p-value less than 0.05 was considered significant. Results Two-hundred-five pediatric inpatients with RTPCR-established COVID-19 infection were screened and final analyses were performed on 97 patients, of which 31 children were classified into group A and 66 into group B. Median age of enrolled children was 5 years with 58.8% males. The prevalence of cancer as a comorbidity in pediatric inpatients with COVID-19 was 15%. Fifty-five percent of cancer patients had hematological malignancies, while 45% had solid tumors. Fever (p = 0.001) and gastrointestinal manifestations (p = 0.0001) were significantly less common among pediatric cancer patients. Children with cancer had significantly more leukopenia (p = 0.003), neutropenia (p = 0.003), and lymphopenia (p = 0.005). The case fatality rate was higher in children with cancer (3.2%) as compared to noncancer patients (1.5%, p = 1.0). Few risk factors for moderate-to-severe COVID-19 among children with cancer included age less than 2 years (p = 0.06), undernutrition (p = 0.33), advanced stage of cancer (p = 0.49), and presence of coinfection (p = 0.35) Conclusion Cancer is a significant comorbidity among pediatric COVID-19 patients. While children with cancer have less severe COVID-19, their case fatality rate is higher than those without cancer. Younger age, undernutrition, advanced stage of cancer, and presence of coinfections may predispose to the development of moderate-to-severe COVID-19 among pediatric cancer patients.

Malnutrition elevates delirium and ICU stay among critically ill older adult COVID-19 patients.

Malnutrition among intensive care unit (ICU) patients is associated with a higher risk of mortality and prolonged hospitalization. However, the influence of malnutrition on severe outcomes of ICU patients with coronavirus disease 2019 (COVID-19) is unclear. By evaluating the effect of malnutrition on the outcomes of COVID-19 in the ICU in older adult patients, this study will contribute to new knowledge of assessing the nutritional status and recovery of these patients. In the current single center prospective study, 310 critically ill COVID-19 patients with an age range of ≥65 years were recruited. Data on demographic characteristics, laboratory parameters, comorbidities, medications, and types of mechanical ventilation were collected in the first 24 h of ICU admission. Malnutrition was defined based on the two-step approach of the Global Leadership Initiative on Malnutrition (GLIM) scale at baseline. During the 45 days after the baseline, we collected data on delirium incidence, mortality, invasive mechanical ventilation (IMV) requirement, length of ICU and hospital admission, and re-hospitalization. In this study, the prevalence of malnutrition was 63.4% among critically ill COVID-19 patients. During the 45-day follow-up, 190 (61.3%) COVID-19 deaths were recorded among the baseline 310 patients. After controlling for potential confounders, malnutrition was associated with an increased risk of delirium so malnourished COVID-19 patients had a significantly 35% higher risk of delirium than those without malnutrition (HR: 1.35, 95% CI: 1.01-1.83). Such a significant association was not for COVID-19 mortality and IMV requirement. In addition, malnutrition was associated with a significantly 84% greater odds of prolonged ICU admission (OR: 1.84, 95% CI: 1.09-3.10). No significant association was seen between malnutrition and re-hospitalization and also prolonged hospital admission. Malnutrition was associated with an increased risk of delirium and prolonged ICU admission among critically ill older adult COVID-19 patients. Prevention, diagnosis, and treatment of malnutrition could be a key component in improving outcomes in these patients.

The Effect of Implementation of the National Early Warning Scoring System 2 on the Outcomes of COVID-19 Hospitalized Patients

Abstract Introduction It is crucial to have tools to predict the clinical deterioration of coronavirus disease 2019 (COVID-19) patients. We aimed to study the efficacy of the National Early Warning Scoring System (NEWS2) application in predicting the risk of clinical relapse and outcomes in hospitalized COVID-19 patients at Palestinian specialized centers for COVID-19. Patients and Methods A quasi-experimental design was applied. A sample of 384 adult patients was divided into two groups. For the pre-NEWS phase (control group) and the post-NEWS phase (study group), all study participants were observed until death or hospital discharge. Results Comparing the pre-NEWS phase with the post-NEWS phase, a significant decrease was found in the mean length of hospital stay from 8.1 ± 5.5 to 6.4 ± 5.3 days (p = 0.002) and a reduction in the mortality rate from 19.8% during the pre-NEWS phase to 12.5% during the post-NEWS phase (p = 0.071). The predictive value of NEWS was an excellent predictor of admission to the intensive care unit (ICU), as indicated by an area under the receiver operating characteristic curve of 0.91 (95% confidence interval: 0.87–0.96, p < 0.001). Also, a significant difference in the frequency of monitoring patients' vital signs was observed between the control group (pre-NEWS phase) and the study group (post-NEWS phase) following clinical deterioration (10.1 ± 7.8 [pre-NEWS phase] vs. 23.4 ± 0.7 [post-NEWS phase], p < 0.001). Conclusion Implementation of NEWS2 showed a significant improvement in hospitalized COVID-19 patient outcomes (length of stay, predicted ICU admissions, mortality rate, and frequency of vital signs measurements), which indirectly raised the follow-up of those patients by the medical team and attributed to a significant prediction of their deterioration.

COVID-19 in pregnancy: A cross-sectional study on clinical features, disease severity, and health outcome.

Assessing the impact of coronavirus disease 2019 (COVID-19) reveals unique challenges for pregnant women, who experience distinct clinical manifestations and health outcomes compared to their non-pregnant counterparts. We aimed to evaluate the clinical features, disease severity, and health outcomes of COVID-19 in pregnant women and compare them to those of non pregnant women. In this population-based study, we included all women diagnosed with COVID-19 across the province of Tehran during the first two years of the epidemic. Descriptive statistics, the chi-squared test, and the logistic regression model were applied. Overall, 79,338 non-pregnant women and 3249 pregnant women diagnosed with COVID-19 were included. Pregnant women were most commonly in the age group of 25 - 34 years (54%, n = 1758), while the age group of 34-44 had the highest representation among non-pregnant women (56%, n = 44,492). After accounting for age and comorbidities, pregnancy was associated with an increased risk of requiring intensive care (odds ratio [OR] 1.38, confidence interval [CI] 1.223 - 1.564). However, the probability of dying due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was lower in pregnant women compared to non-pregnant women (OR 0.55, CI 0.394-0.793). Cough (41%) and fever (30%) were the most frequent clinical presentations in pregnant women, whereas cough (57%) and muscle ache (38%) were the most common symptoms in non-pregnant women. Furthermore, diarrhea (P < 0.001) and skin lesions (P < 0.001) were reported more frequently by pregnant patients than non-pregnant patients. A significant prevalence of diabetes (P < 0.001), hypertension (P < 0.001), cancers (P < 0.001), and chronic hematological diseases (P < 0.001) was observed in pregnant patients. In conclusion, COVID-19-infected pregnant women exhibit different clinical manifestations and a more severe clinical course but have better health outcomes compared to their non-pregnant counterparts.

The Effect of Antihyperglycemic Medications on COVID-19: A Meta-analysis and Systematic Review from Observational Studies.

Diabetes, a chronic disease worldwide, may be associated with a poorer prognosis in patients with coronavirus disease 2019 (COVID-19). While some antihyperglycemic medications may be beneficial, others may increase the risk of adverse clinical outcomes of COVID-19. We aimed to analyze the effect of antihyperglycemic medications on COVID-19. We searched the Web of Science, Cochrane Library, EMBASE, PubMed, and Scopus databases from December 2019 to June 2022 to identify literature related to patients with COVID-19 and type 2 diabetes mellitus (T2DM) treated with antihyperglycemic medications. 56 studies were included in the analysis. Metformin (OR 0.66; 95% CI 0.58-0.74; p < 0.05), Glucagon-like peptide-1 receptor agonist (GLP-1ra) (OR 0.73; 95% CI 0.59-0.91; p < 0.05), and sodium-dependent glucose transporters 2 inhibitor (SGLT 2i) (OR 0.77; 95% CI 0.69-0.87; p < 0.05) were associated with lower mortality risk, while insulin was associated with increased mortality risk (OR 1.40; 95% CI 1.26-1.55; p < 0.05). Meanwhile, metformin (OR 0.65; 95% CI 0.50-0.85; p < 0.05) and GLP-1ra (OR 0.84; 95% CI 0.76-0.94; p < 0.05) were significantly associated with decreased severe manifestation risk. What's more, metformin (OR 0.77; 95% CI 0.62-0.96; p < 0.05), GLP-1ra (OR 0.86; 95% CI 0.81-0.92; p < 0.05), and SGLT 2i (OR 0.87; 95% CI 0.79-0.97; p < 0.05) were also associated with a decreased risk of hospitalization, but insulin were associated with an increased risk of hospitalization (OR 1.31; 95% CI 1.12-1.52; p < 0.05). Nevertheless, the results of the subgroup analyses showed that the effects of different glucose-lowering agents on COVID-19 may be related to in-hospital use or out-hospital use, elderly or non-elderly patients use, and different geography. Metformin, GLP-1ra, and SGLT 2i have shown a positive effect on clinical outcomes in COVID-19, particularly in non-elderly individuals. However, insulin use may pose a higher risk, especially in elderly patients, so need with caution. Meanwhile, DPP-4i, TZD, α-GLUi, and sulfonylureas appeared to have a neutral effect. These results need to be validated in future clinical studies.

Clinical effectiveness of coronavirus disease 2019 vaccination in patients with multiple sclerosis stratified by disease-modifying treatment.

Coronavirus disease 2019 (COVID-19) vaccination has been associated with a dampened humoral and/or cellular immune response in patients with multiple sclerosis (MS) who were concurrently on disease-modifying treatment (DMT) with B-cell depleting agents or sphingosine-1-phosphate receptor modulators (S1PRMs). Our main goal was to investigate the impact of these DMT classes on the clinical effectiveness of COVID-19 vaccination. Since March 2020, demographics and clinical data of patients with MS who developed COVID-19 have been collected at the Belgian National MS Centre in Melsbroek. Patients were considered to be 'protected by vaccination' if they were (i) fully vaccinated and (ii) tested positive for COVID-19 in the period ranging from 14 days to 6 months after the last administered vaccine. On 19 December 2022, 418 COVID-19 cases were retrospectively identified in 389 individual patients. Hospitalization and mortality rates resulting from the infection were 10.8% and 2.4%, respectively. Being 'unprotected by vaccination' was significantly associated with a worse COVID-19 outcome (i.e., hospitalization and/or death) in the total cohort (N = 418, odds ratio [OR] 3.96), in patients on ongoing DMT other than anti-CD20 agents or S1PRMs (N = 123, OR 31.75) and in patients without DMT (N = 182, OR 5.60), but not in those receiving anti-CD20 agents (N = 91, OR 0.39); the S1PRMs subgroup was considered too small (22 infections) for any meaningful analysis. Coronavirus disease 2019 vaccination protects against severe infection in patients with MS but it was not possible to confirm this effect in those on DMT with B-cell depleting agents.

Obesity, Inflammation, and Clinical Outcomes in COVID-19: A Multicenter Prospective Cohort Study.

Obesity is a risk factor for coronavirus disease 2019 (COVID-19)-related outcomes; however, the mechanism remains unclear. The objective of this analysis was to determine whether inflammation mediates the association between obesity and COVID-19 outcomes. The International Study of Inflammation in Covid-19 (ISIC): A Prospective Multi-Center Observational Study Examining the Role of Biomarkers of Inflammation in Predicting Covid-19 Related Outcomes in Hospitalized Patients. Ten hospitals in the United States and Europe. Adults hospitalized specifically for COVID-19 between February 1, 2020, through October 19, 2022. Inflammatory biomarkers, including soluble urokinase plasminogen activator receptor (suPAR), were measured at admission. Associations were examined between body-mass index (BMI, kg/m2) and a composite of death, need for mechanical ventilation, and renal replacement therapy, stratified by pre- and post-Omicron variants. The contribution of inflammation to the relationship between obesity and outcomes was assessed. Among 4644 participants (mean age 59.3, 45.6% male, 21.8% BMI≥35), those with BMI>40 (n=485) had 55% higher odds of the composite outcome (95% CI[1.21 to 1.98]) compared to non-obese individuals (BMI<30, n=2358) in multivariable analysis. In multiple mediation analysis, only suPAR remained a significant mediator between BMI and composite outcome. Associations were amplified for participants younger than 65 years and with pre-Omicron variants. Obesity is associated with worse outcomes in COVID-19, notably in younger participants and in the pre-Omicron era. Inflammation, as measured by suPAR, is a significant mediator of the association between obesity and COVID-19 outcomes.

Evaluating the potential mediating role of ADAMTS13 activity in the relationship between obesity and the severity of COVID-19: A retrospective cohort study.

Obesity and low enzyme A disintegrin and metalloproteinase with thrombospondin type-1 motif-13 (ADAMTS13) activity have been linked to poor coronavirus disease 2019 (COVID-19). Given that obesity may influence ADAMTS13 activity, it is feasible; however, it remains unclear whether ADAMTS13 activity acts as a mediator between obesity and COVID-19 outcomes. We investigated the link between body mass index (BMI) and COVID-19 outcomes, using ADAMTS13 activity as a mediator. ADAMTS13 activity was measured in 86 hospitalized COVID-19 patients. BMI, ADAMTS13 activity, and COVID-19 outcomes were assessed. Obese patients had a high odds ratio for low ADAMTS13 levels. When different levels of ADAMTS13 activity were considered, the severity of COVID-19 in obese patients was 4.5 times that in the normal BMI group. Furthermore, increased coagulopathy indicators correlated with low ADAMTS13 activity. Patients with elevated ALT and AST levels showed a 3 to 4-fold increase in the chances of low ADAMTS13 activity (OR:3.19, 95% CI:1.22-8.90, P = .021; OR:2.17, 95% CI:0.91-5.27, P = .082, respectively). When ADAMTS13 activity was considered, obese patients had greater COVID-19 severity and slower viral clearance than those with normal BMI. Low ADAMTS13 activity and impaired liver function are associated with poor COVID-19 outcomes. These findings encourage researchers to use molecular component identification to study the effects of obesity on the von Willebrand factor (VWF)/ADAMTS13 axis, COVID-19 pathogenesis, and outcomes.

Organ-Dysfunction Markers in Mild-to-Moderate COVID-19 Convalescents.

Background: A coronavirus disease 2019 (COVID-19) outbreak led to a worldwide pandemic. COVID-19 not only caused acute symptoms during the severe phase of the disease, but also induced long-term side effects on the functioning of many organs and systems. Symptoms that were associated with the disease and present at least 3 months after recovery were named long COVID. The aim of this study was to assess if mild-to-moderate COVID-19 may lead to the dysfunction of respiratory, cardiovascular, neural, and renal systems in healthy blood donors who recovered from the disease at least 6 months earlier. Methods: Here, we examined 294 adults among volunteer blood donors divided into convalescents (n = 215) and healthy controls (n = 79). Concentrations of soluble CD163, TGF beta, Lp-PLA2, NCAM-1, S100, NGAL, and creatinine were measured either by ELISA or automated methods. The probability value p < 0.05 was considered as statistically significant. Results: We found significant differences in Lp-PLA2, S100, and NCAM-1 between convalescents and never-infected subjects. Lp-PLA2 and NCAM-1 were lower, and S100 higher, in convalescents than in the control group. Conclusion: Mild-to-moderate COVID-19 convalescents are at a low risk of developing lung fibrosis or chronic kidney disease. However, they should regularly carry out their prophylaxis examinations for early detection of possible negative outcomes of COVID-19.

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.

Outcome of COVID-19 in patients with a history of acute leukemia; A Narrative Review

The chemotherapy and immunosuppressive medication may be associated with the suppressed immune system of a cancer patient making them susceptible to Coronavirus disease 2019 (COVID-19) with unclear mechanisms. We reviewed current studies on the clinical courses of leukemia patients with a risk of SARS-CoV-2 infection through searches in Pubmed databases and Google search engines. The criterion used for review includes their relevance to the defined review question, which is the outcome of COVID‐19 among leukemic patients and the relevant therapeutic interventions therewith. Patients with acute leukemia are among the most vulnerable groups of patients at risk of severe COVID-19 outcomes with several protocol management modifications proposed. The development of COVID-19 vaccines was an important milestone in reducing the risk of contracting and developing severe COVID-19 symptoms in leukemic patients after remission status. The European Society for Blood and Marrow Transplantation (EBMT), a collaborative network of centers and individuals working in the field of BMT and cellular therapy, has been updating its recommendations since the start of the COVID-19 pandemic.

Prevalence of Diabetes, Ketosis, and Ketoacidosis and Their Correlation With Mortality in Critical COVID-19 Patients: A Single-Center Retrospective Study.

Aim We aimed to find out the prevalence of diabetes, ketosis, and ketoacidosis in coronavirus disease 2019 (COVID-19) critically ill patients and to explore the clinical impact of the development of ketosis and ketoacidosis on the outcome of COVID-19 critically ill patients and identify them as potential risk factors for these patients. Methods We collected data on COVID-19 patients admitted to the intensive care unit (ICU) retrospectively. The study population will be classified into two groups based on the presence of diabetes or ketosis. Results The study comprises data on 253 ICU patients admitted with COVID-19 pneumonia. Two hundred patients (79.05%) had diabetes or prediabetes on admission. Seventy-six patients (30%) presented with ketosis. Nine patients had progressed to diabetic ketoacidosis during their ICU stay. Concerning the outcome, among 150 patients who died (59.3%), there was significantly higher mortality among the ketotic patients (69.7%) compared to nonketotic patients (54.8%) with a P-value < 0.027. We noted that the peak blood glucose level during ICU stay was statistically significantly higher in nonsurvivors (mean 345 mg/dl) compared to survivors (mean 298 mg/dl) with a P-value of 0.006. Our data showed that peak serum levels of lactate, procalcitonin (PCT), C-reactive protein, white blood cells (WBC), D dimer, and lactate dehydrogenase strongly positively correlated to the length of ICU stay. We used the ROC curve (receiver operating characteristic curve) to assess the relation between many laboratories and mortality. We noted that uncontrolled hyperglycemia and other laboratory variables are significant predictors of mortality of COVID-19 patients (e.g., peak blood glucose (P = 0.004), PCT (P = 0.047), and P < 0.001 of other laboratories (e.g. lactate, PH, WBC, D dimer, ferritin). Conclusion We reported a high prevalence of diabetes and ketosis among COVID-19 patients admitted to the ICU. Ketosis is associated with an increased mortality risk. Uncontrolled hyperglycemia is a significant predictor of mortality in critically ill COVID-19 patients.

The correlation between neutrophil lymphocyte ratio in pregnant women with COVID-19 and neonatal outcome

Background and objectives. Coronavirus Disease 2019 (COVID-19) in pregnancy periods can adversely affect the neonatal outcomes. Neutrophil Lymphocyte Ratio (NLR) were reported as sensitive markers and good predictor of COVID-19 progression in symptomatic pregnant women. The aim of this study to find correlation on NLR value of the pregnant women with COVID-19 to the neonatal outcome. Materials and methods. We retrospectively included neonates who was delivered from pregnant women with COVID-19 at Dr. Soetomo Hospital from June 2021 to July 2022. NLR value of the pregnant women were calculated. Demographic data and clinical characteristic were taken from medical records. The diagnosis of COVID-19 in pregnant women is confirmed by PCR nasopharyngeal swab, as well as in the neonates who undergo nasopharyngeal swab a maximum of 24 hours after birth. Results. Total of 1058 births delivered between June 2021- July 2022, 224 neonates (21.17%) met inclusion criteria. We analyzed the severity of maternal factors described by NLR and correlated with neonate outcomes, such as mortality, Apgar Score (AS), birth weight, gestational age, type of delivery and Polymerase Chain Reaction (PCR) swab of the neonates. the results of our analysis, the maternal NLR was correlated with the birth weight (p=0.005). However, NLR of the pregnant women are not correlated with mortality of the neonates (p=0.681), type of delivery (p= 1), AS at 1 minute (p= 0.158), AS at 5 minutes (p= 0.158), gestational age (p= 0.110) length of stay (LOS) (p=0,258) and PCR swab of the neonates (p= 1). Conclusions. NLR value in the majority of pregnant women with COVID-19 was found to be increasing, but these results are not related for the neonatal outcome except the birth weight.

High frequencies of alpha common cold coronavirus/SARS-CoV-2 cross-reactive functional CD4+ and CD8+ memory T cells are associated with protection from symptomatic and fatal SARS-CoV-2 infections in unvaccinated COVID-19 patients.

Cross-reactive SARS-CoV-2-specific memory CD4+ and CD8+ T cells are present in up to 50% of unexposed, pre-pandemic, healthy individuals (UPPHIs). However, the characteristics of cross-reactive memory CD4+ and CD8+ T cells associated with subsequent protection of asymptomatic coronavirus disease 2019 (COVID-19) patients (i.e., unvaccinated individuals who never develop any COVID-19 symptoms despite being infected with SARS-CoV-2) remains to be fully elucidated. This study compares the antigen specificity, frequency, phenotype, and function of cross-reactive memory CD4+ and CD8+ T cells between common cold coronaviruses (CCCs) and SARS-CoV-2. T-cell responses against genome-wide conserved epitopes were studied early in the disease course in a cohort of 147 unvaccinated COVID-19 patients who were divided into six groups based on the severity of their symptoms. Compared to severely ill COVID-19 patients and patients with fatal COVID-19 outcomes, the asymptomatic COVID-19 patients displayed significantly: (i) higher rates of co-infection with the 229E alpha species of CCCs (α-CCC-229E); (ii) higher frequencies of cross-reactive functional CD134+CD137+CD4+ and CD134+CD137+CD8+ T cells that cross-recognized conserved epitopes from α-CCCs and SARS-CoV-2 structural, non-structural, and accessory proteins; and (iii) lower frequencies of CCCs/SARS-CoV-2 cross-reactive exhausted PD-1+TIM3+TIGIT+CTLA4+CD4+ and PD-1+TIM3+TIGIT+CTLA4+CD8+ T cells, detected both ex vivo and in vitro. These findings (i) support a crucial role of functional, poly-antigenic α-CCCs/SARS-CoV-2 cross-reactive memory CD4+ and CD8+ T cells, induced following previous CCCs seasonal exposures, in protection against subsequent severe COVID-19 disease and (ii) provide critical insights into developing broadly protective, multi-antigen, CD4+, and CD8+ T-cell-based, universal pan-Coronavirus vaccines capable of conferring cross-species protection.

An Adaptive Combined Learning of Grading System for Early Stage Emerging Diseases

Currently, individual artificial intelligence (AI) algorithms face significant challenges in effectively diagnosing and predicting early stage emerging serious diseases. Our investigation indicates that these challenges primarily arise from insufficient clinical treatment data, leading to inadequate model training and substantial disparities among algorithm outcomes. Therefore, this study introduces an adaptive framework aimed at increasing prediction accuracy and mitigating instability by integrating various AI algorithms. In analyzing two cohorts of early cases of the coronavirus disease 2019 (COVID-19) in Wuhan, China, we demonstrate the reliability and precision of the adaptive combined learning algorithm. Employing an adaptive combination with three feature importance methods (Random Forest (RF), Scalable end-to-end Tree Boosting System (XGBoost), and Sparsity Oriented Importance Learning (SOIL)) for two cohorts, we identified 23 clinical features with significant impacts on COVID-19 outcomes. Subsequently, the adaptive combined prediction leveraged and enhanced the advantages of individual methods based on three forecasting algorithms (RF, XGBoost, and Logistic regression). The average accuracy for both cohorts exceeded 0.95, with the area under the receiver operating characteristics curve (AUC) values of 0.983 and 0.988, respectively. We established a severity grading system for COVID-19 based on the combined probability of death. Compared to the original classification, there was a significant decrease in the number of patients in the severe and critical levels, while the levels of mild and moderate showed a substantial increase. This severity grading system provides a more rational grading in clinical treatment. Clinicians can utilize this system for effective and reliable preliminary assessments and examinations of patients with emerging diseases, enabling timely and targeted treatment.

Analysis of neuropsychological and laboratory parameters in patients with cerebrovascular disease and SARS-CoV-2 compared to those without SARS-CoV-2

Background. Severe acute respiratory syndrome сoronavіrus 2 (SARS-CoV-2, formerly known as 2019-nCoV) is the cause of coronavirus disease 2019 (COVID-19), and was first reported in Wuhan, China. However, it is also contagious to humans and spreads rapidly around the world through close contact between infected people or through a relatively simple transmission mechanism (airborne transmission). COVID-19 is known to affect almost all systems of the human body. Initial reports suggest that hypertension may be a risk factor for susceptibility to SARS-CoV-2 infection, a more severe course of COVID-19, and increased mortality associated with COVID-19. It is estimated that 1–3 % of COVID-19 patients experience transient ischemic attacks with a frequency similar to other coronavirus infections (SARS-CoV-1 and MERS-CoV). The cause of ischemic stroke associated with COVID-19 is unknown, but previous studies have suggested that an inflammatory cytokine storm may cause hypercoagulation and endothelial damage. We see that COVID-19 is closely related to neurological complications because there are potential factors that can cause them. Materials and methods. Cerebrovascular diseases were analyzed in 111 patients infected with SARS-CoV-2 (n = 71) and those without a history of SARS-CoV-2 (n = 40). The subject of the study was neuropsychological and laboratory indicators. The following methods were used: psychometric — Beck Anxiety Inventory, Hamilton Depression Rating Scale, Fatigue Assessment Scale; neuropsychological — Mini-Mental State Examination, Montreal Cognitive Assessment, Frontal Assessment Battery; clinical — neurological status; polymerase chain reaction to detect COVID-19 RNA; statistical methods. Results. In patients who suffered transient ischemic attack and ischemic stroke with a minimal neurological deficit and COVID-19, there were elevations in the erythrocyte sedimentation rate, leukocytes, segmented neutrophils, while an increase in C-reactive protein was noted in all participants with cerebrovascular disease and COVID-19, with more significant levels among those with ischemic stroke. All subgroups with COVID-19 showed an increase in D-dimer and fibrinogen with higher content in patients after ischemic stroke. Also in this subgroup, the procalcitonin index exceeded the norm, which indicates the severity of the course of COVID-19 with the addition of co-infection. Data of neuropsychological tests in patients with ischemic stroke with a minimal neurological deficit with SARS-CoV-2 revealed a decrease in the Montreal Cognitive Assessment score, indicating mild cognitive changes in these patients. The level of anxiety in patients with hypertension with frequent crises and ischemic stroke with a minimal neurological deficit was above the reference values, with a slight predominance in patients who did not have COVID-19. It follows that both laboratory and neuropsychological parameters differed in three subgroups depending on cerebrovascular disease, as well as the presence and absence of SARS-CoV-2, which makes it possible to develop more appropriate diagnostic methods in order to predict the course and outcome of COVID-19.

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.

Comparative Effectiveness of mRNA-1273 and BNT162b2 COVID-19 Vaccines Among Older Adults: Systematic Literature Review and Meta-Analysis Using the GRADE Framework.

The mRNA vaccines mRNA-1273 and BNT162b2 demonstrated high efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in phase 3 clinical trials, including among older adults. To inform coronavirus disease 2019 (COVID-19) vaccine selection, this systematic literature review (SLR) and meta-analysis assessed the comparative effectiveness of mRNA-1273 versus BNT162b2 in older adults. We systematically searched for relevant studies reporting COVID-19 outcomes with mRNA vaccines in older adults aged ≥ 50years by first cross-checking relevant published SLRs. Based on the cutoff date from a previous similar SLR, we then searched the WHO COVID-19 Research Database for relevant articles published between April 9, 2022, and June 2, 2023. Outcomes of interest were SARS-CoV-2 infection, symptomatic SARS-CoV-2 infection, severe SARS-CoV-2 infection, COVID-19-related hospitalization, and COVID-19-related death following ≥ 2 vaccine doses. Random effects meta-analysis models were used to pool risk ratios (RRs) across studies. Heterogeneity was evaluated using chi-square testing. Evidence certainty was assessed per GRADE framework. Twenty-four non-randomized real-world studies reporting clinical outcomes with mRNA vaccines in individuals aged ≥ 50years were included in the meta-analysis. Vaccination with mRNA-1273 was associated with significantly lower risk of SARS-CoV-2 infection (RR 0.72 [95% confidence interval (CI) 0.64‒0.80]), symptomatic SARS-CoV-2 infection (RR 0.72 [95% CI 0.62‒0.83]), severe SARS-CoV-2 infection (RR 0.67 [95% CI 0.57‒0.78]), and COVID-19-related hospitalization (RR 0.65 [95% CI 0.53‒0.79]) but not COVID-19-related death (RR 0.80 [95% CI 0.64‒1.00]) compared with BNT162b2. There was considerable heterogeneity between studies for all outcomes (I2 > 75%) except death (I2 = 0%). Multiple subgroup and sensitivity analyses excluding specific studies generally demonstrated consistent results. Certainty of evidence across outcomes was rated as low (type 3) or very low (type 4), reflecting the lack of randomized controlled trial data. Meta-analysis of 24 observational studies demonstrated significantly lower risk of asymptomatic, symptomatic, and severe infections and hospitalizations with the mRNA-1273 versus BNT162b2 vaccine in older adults aged ≥ 50years.

Evaluating the impact of childhood BMI on the risk of coronavirus disease 2019: A Mendelian randomization study.

Although the correlation between childhood obesity and coronavirus disease 2019 (COVID-19) has been explored, the causality of these remains uncertain. Thus, we conducted a two-sample Mendelian randomization (MR) analysis to identify the causal association. Instrumental variables of childhood obesity were selected from genome-wide association study involving 61,111 Europeans. Besides, we collected summary statistics of different COVID-19 outcomes (susceptibility, hospitalization, and severity) from genome-wide association study including more than 2 million Europeans. The inverse-variance weighted was applied to assess the causality of childhood obesity with COVID-19. Furthermore, we replicated the above association based on another study. Inverse-variance weighted results suggested that childhood obesity promoted the COVID-19 susceptibility but has not been validated in other approaches. For hospitalization and severity of COVID-19, we found that childhood obesity, respectively, increased 30 and 38% risk (P < 0.001), which were consistent in other MR approaches. Our study provides evidence for a causal relationship between childhood BMI and COVID-19 which is consistent with previous studies. Though these explanations are biologically plausible, further studies are warranted to elucidate the role of these. Our study suggests the potential causal associations of childhood obesity with COVID-19, especially hospitalization and severity of COVID-19.