Clinical Severity Of COVID-19 Research Articles

Lithium in the time of COVID: forever vigilant

BackgroundThere have been case reports of renal dysfunction with lithium toxicity among severely ill COVID-19 patients. Lithium levels may be affected by comorbid conditions and the presence of infective disease states like the SARS-CoV-2 which clearly adds systemic health burden. This study aimed to review the effect SARS-CoV-2 has on serum Li levels and the possible mechanism underlying it.MethodsRetrospective data from all clinical service encounters within the University of Michigan health system between September 2019 and September 2023 were reviewed. The study cohort included 98 patients with an average age of 45 years (62% female) who were diagnosed with any subtype of bipolar disorder, actively taking Li, and infected with SARS-CoV-2 during the study timeframe.ResultsThere was no overarching effect of a SARS-CoV-2 infection on Li chemistry in the overall sample. Higher serum Li levels were not significantly associated with SARS-CoV-2 infection nor total comorbidity index. However, higher Li levels were observed in males while infected with SARS-CoV-2 when compared with no infection. eGFR remained unassociated with serum Li level. Receiving COVID vaccination was associated with lower serum Li levels (Coeff. = − 0.88, p = 0.048).ConclusionsPatients with a diagnosis of BD, treated with Li, and infected with SARS-CoV-2 were not likely to present with elevated Li levels unless they are male or unvaccinated. Elevated serum Li level was not associated with significant renal dysfunction in this cohort. The case reports of severe renal complications and Li toxicity may be among cases of greater overall clinical severity of COVID-19. These findings are reassuring that Li may be used in the context of a COVID-19 illness but emphasize the ongoing need for clinical vigilance.

Association between HTLV-1/2 infection and COVID-19 severity in a migrant Shipibo-Konibo population in Lima, Peru.

The migrant community of the Shipibo-Konibo indigenous people in Lima, Peru were extremely vulnerable during the COVID-19 pandemic. Additionally, infection with human T-cell lymphotropic virus type 1 and 2 (HTLV-1/2) is endemic in this population causing immunosuppression. The aim of the study was to describe the association between HTLV-1/2 infection and the clinical severity of COVID-19. This was a cross-sectional descriptive study involving a survey of adult Shipibo-Konibo indigenous migrants residing in Cantagallo-Rímac who were identified as suspected or confirmed cases of COVID-19. Blood samples were collected for SARS-CoV-2 antibody and HTLV-1/2 ELISA testing. A confirmatory Western Blot test was performed for those with a positive ELISA test. A total of 182 individuals were surveyed and sampled. No significant association was found between HTLV-1/2 infection and the clinical severity of COVID-19. The prevalence of HTLV-1/2 was 8.8% (95%CI: 5.0-14.1) with Western Blot. Age was the only statistically significant risk factor for developing a more severe form of COVID-19 (OR: 1.03; 95%CI: 1.00-1.06; p = 0.032). There was no association found between HTLV-1/2 infection and the clinical severity of COVID-19. The prevalence of HTLV-1/2 infection in the Shipibo-Konibo population is high and warrants continuous monitoring in the advent of other infectious disease outbreaks and the development of HTLV-associated comorbidities.

Autoimmune Manifestations in a Cohort of Egyptian COVID-19 Patients

Abstract Introduction COVID-19 infection can result in a range of symptoms, from asymptomatic to severe, requiring intensive care and ventilatory support. Research has explored the association between COVID-19 and autoimmune conditions, including the detection of autoantibodies in COVID-19 patients. However, results are not conclusive, prompting us to conduct a cross-sectional study to evaluate the prevalence of autoimmune rheumatic manifestations in a cohort of Egyptian individuals diagnosed with COVID-19. Methods Ninety individuals with COVID-19 were included in the study. Patients were classified based on WHO criteria and laboratory data was collected. Autoimmune markers (ANA, RF, ACL IgM, ACL IgG) were measured and patients were grouped based on positive and negative results. Correlational analysis was conducted to assess the association between each marker and clinical severity of COVID-19 and autoimmune rheumatological manifestations. Results Of the studied patients, 13.3% had a positive ANA, 15.6% had a positive RF, 8.9% had a positive ACL IgM, and 5.6% had a positive ACL IgG. However, there was no statistically significant difference between severity groups regarding the results of ANA, RF, ACL IgM, and IgG. All patients with a positive ANA were present among severe and critical COVID-19 cases, and all patients with positive RF, ACL IgM, or ACL IgG were among moderate, severe, and critical cases. Conclusion Our study provides insight into the prevalence of autoimmune rheumatic manifestations in COVID-19 patients. While our results were inconclusive regarding the association between autoimmune markers and severity of disease, we found a statistically significant higher prevalence of several symptoms in critical COVID-19 patients. Our study highlights the importance of further investigation into the relationship between COVID-19 and autoimmune conditions.

Correlation of NLR and D-dimer Levels with Clinical Severity of COVID-19 and Determination of Cut-off Values at a Hospital in Cirebon

Correlation of NLR and D-dimer Levels with Clinical Severity of COVID-19 and Determination of Cut-off Values at a Hospital in Cirebon

Impact of vaccination on COVID-19 severity during the second wave in Brunei Darussalam, 2021.

Coronavirus disease (COVID-19) vaccinations have been shown to prevent infection with efficacies ranging from 50% to 95%. This study assesses the impact of vaccination on the clinical severity of COVID-19 during the second wave in Brunei Darussalam in 2021, which was due to the Delta variant. Patients included in this study were randomly selected from those who were admitted with COVID-19 to the National Isolation Centre between 7 August and 6 October 2021. Cases were categorized as asymptomatic, mild (symptomatic without pneumonia), moderate (pneumonia), severe (needing supplemental oxygen therapy) or critical (needing mechanical ventilation) but for statistical analysis purposes were dichotomized into asymptomatic/mild or moderate/severe/critical cases. Univariate and multivariable analyses were conducted to identify risk factors associated with moderate/severe/critical disease. Propensity score-matched analysis was also performed to evaluate the impact of vaccination on disease severity. The study cohort of 788 cases (mean age: 42.1±14.6years; 400 males) comprised 471 (59.8%) asymptomatic/mild and 317 (40.2%) moderate/severe/critical cases. Multivariable logistic regression analysis showed older age group (≥45 years), diabetes mellitus, overweight/obesity and vaccination status to be associated with increased severity of disease. In propensity score-matched analysis, the relative risk of developing moderate/severe/critical COVID-19 for fully vaccinated (two doses) and partially vaccinated (one dose) cases was 0.33 (95% confidence interval [CI]: 0.16-0.69) and 0.62 (95% CI: 0.46-0.82), respectively, compared with a control group of non-vaccinated cases. The corresponding relative risk reduction (RRR) values were 66.5% and 38.4%, respectively. Vaccination was also protective against moderate/severe/critical disease in a subgroup of overweight/obese patients (RRR: 37.2%, P=0.007). Among those who contracted COVID-19, older age, having diabetes, being overweight/obese and being unvaccinated were significant risk factors for moderate/severe/critical disease. Vaccination, even partial, was protective against moderate/severe/critical disease.

Prostaglandin E2/Leukotriene B4 balance and viral load in distinct clinical stages of COVID-19: A cross-sectional study

BackgroundProstaglandin E2 (PGE2) and leukotriene B4 (LTB4) are eicosanoids involved in modulation of the antiviral immune response. Recent studies have identified increased levels of several eicosanoids in the plasma and bronchoalveolar lavage of patients with coronavirus disease (COVID-19). This study investigated correlations between plasma levels of PGE2 and LTB4 and clinical severity of COVID-19. MethodsThis cross-sectional study involved non-infected (n = 10) individuals and COVID-19 patients classified as cured (n = 13), oligosymptomatic (n = 29), severe (n = 15) or deceased (n = 11). Levels of D-dimer a, known COVID-19 severity marker, PGE2 and LTB4 were measured by ELISAs and data were analysed with respect to viral load. ResultsPGE2 plasma levels were decreased in COVID-19 patients compared to the non-infected group. Changes in PGE2 and LTB4 levels did not correlate with any particular clinical presentations of COVID-19. However, LTB4 was related to decreased SARS-CoV-2 burden in patients, suggesting that only LTB4 is associated with control of viral load. ConclusionsOur data indicate that PGE2/LTB4 plasma levels are not associated with COVID-19 clinical severity. Hospitalized patients with COVID-19 are treated with corticosteroids, which may influence the observed eicosanoid imbalance. Additional analyses are required to fully understand the participation of PGE2 receptors in the pathophysiology of COVID-19.

Covid-19: Course and prognosis in patients with severe clinical form

Our aim is to identify factors of unfavorable prognostic significance in hospitalized patients with severe COVID-19, an analysis of clinical and demographic characteristics and routine laboratory tests was performed. For the following period: March - July 2023, 25 patients with severe COVID-19 needing intensive care and treatment were hospitalized in Military Medical Academy Sofia (Bulgaria). The diagnosis has been confirmed by RT-PCR analysis for SARS-CoV-2 detection. According to the prognosis, the target group of patients were divided into two groups - discharger and deceased. The average age of the analyzed cohort was 77.6 years. The most commonly reported clinical symptoms include fever, cough, shortness of breath, and neurological symptoms. We found that all patients with severe COVID-19 were comorbid and elderly. The average hospital stay in intensive care is 11.9 days. Nearly half of the cases had fatal outcome (12/25). Among the factors associated with the clinical severity of COVID-19 and mortality are advanced age, presence of chronic concomitant diseases, development of pneumonia and/or neurological complications, as well as deviations in some laboratory parameters.

Increased Levels of Galectin-3 in Critical COVID-19.

Severe COVID-19 is related to hyperinflammation and multiple organ injury, including respiratory failure, thus requiring intensive care unit (ICU) admission. Galectin-3, a carbohydrate-binding protein exhibiting pleiotropic effects, has been previously recognized to participate in inflammation, the immune response to infections and fibrosis. The aim of this study was to evaluate the relationship between galectin-3 and the clinical severity of COVID-19, as well as assess the prognostic accuracy of galectin-3 for the probability of ICU mortality. The study included 235 COVID-19 patients with active disease, treated in two different Greek hospitals in total. Our results showed that median galectin-3 serum levels on admission were significantly increased in critical COVID-19 patients (7.2 ng/mL), as compared to the median levels of patients with less severe disease (2.9 ng/mL, p = 0.003). Galectin-3 levels of the non-survivors hospitalized in the ICU were significantly higher than those of the survivors (median 9.1 ng/mL versus 5.8 ng/mL, p = 0.001). The prognostic accuracy of galectin-3 for the probability of ICU mortality was studied with a receiver operating characteristic (ROC) curve and a multivariate analysis further demonstrated that galectin-3 concentration at hospital admission could be assumed as an independent risk factor associated with ICU mortality. Our results were validated with galectin-3 measurements in a second patient cohort from a different Greek university hospital. Our results, apart from strongly confirming and advancing previous knowledge with two patient cohorts, explore the possibility of predicting ICU mortality, which could provide useful information to clinicians. Therefore, galectin-3 seems to establish its involvement in the prognosis of hospitalized COVID-19 patients, suggesting that it could serve as a promising biomarker in critical COVID-19.

The effect of the visceral adiposity index on the severity of COVID-19 disease: results of a cross-sectional study.

Obesity has been identified as a contributing factor that exacerbates the severity of COVID-19 and is associated with an increased risk of mortality among hospitalized patients. Assessing visceral adipose tissue cannot be solely determined by obesity and body mass index (BMI) alone. In our study, we investigated the relationship between the visceral adiposity index (VAI) and the clinical severity of COVID-19. A total of 315 adult patients hospitalized with COVID-19 were included in the study. The cohort consisted of 146 male patients, and the median age was 60 (48-74) years. Comparative analyses were conducted to evaluate gender-based differences in VAI levels and the impact of VAI on the extent of radiological lung involvement. The median VAI level was significantly higher in women compared to men (6.1 vs. 4.0, p<0.001). Furthermore, patients with radiologically severe lung involvement demonstrated a higher median VAI level compared to those with mild involvement (5.7 vs. 4.2, p=0.003). This difference was particularly notable among male patients, where the median VAI level was significantly higher. Logistic regression analysis revealed that each integer increase in the median VAI value was associated with a 1.1-fold (1.01-1.14) increase in the severity of radiological lung involvement (p=0.011). Our study highlights a significant correlation between VAI and the clinical severity of COVID-19, particularly among male patients. The findings suggest that VAI, as an indicator of visceral adiposity, holds potential as a valuable tool for assessing COVID-19 severity and identifying high-risk individuals, particularly males.

Hospitalizations and Clinical Severity of COVID-19 Among Infants Under 1-Year-old.

This study evaluated COVID-19 hospitalizations and clinical severity in infants (<1-year-old, n = 2,667), March 2020-March 2021. Hospitalizations were associated with younger age [OR (95%CI): <1 month, 26.3 (16.1-43.1), 1-2 months, 4.7 (3.1-7.34), 3-11 months, 1.0 (referece, 1.0-1.0)] and symptomatic disease, mainly with fever. Moderate-severe COVID-19 disease was associated with infants age above 3 months [OR (95% CI): 4.0 (1.4-11.1)], ethnicity and underlying conditions.

Clinical Utility of SARS-CoV-2 Antibody Titer Multiplied by Binding Avidity of Receptor-Binding Domain (RBD) in Monitoring Protective Immunity and Clinical Severity.

Conventional serum antibody titer, which expresses antibody level, does not provide antigen binding avidity of the variable region of the antibody, which is essential for the defense response to infection. Here, we quantified anti-SARS-CoV-2 antibody binding avidity to the receptor-binding domain (RBD) by competitive binding-inhibition activity (IC50) between SARS-CoV-2 S1 antigen immobilized on the DCP microarray and various RBD doses added to serum and expressed as 1/IC50 nM. The binding avidity analyzed under equilibrium conditions of antigen-antibody binding reaction is different from the avidity index measured with the chaotropic agent, such as urea, under nonequilibrium and short-time conditions. Quantitative determination of the infection-protection potential of antibodies was assessed by ABAT (antigen binding avidity antibody titer), which was calculated by the quantity (level) × quality (binding avidity) of antibodies. The binding avidity correlated strongly (r = 0.811) with cell-based virus-neutralizing activity. Maturation of the protective antibody induced by repeated vaccinations or SARS-CoV-2 infection was classified into three categories of ABAT, such as an initial, low, and high ABAT. Antibody maturity correlated with the clinical severity of COVID-19. Once a mature high binding avidity was achieved, it was maintained for at least 6-8 months regardless of the subsequent change in the antibody levels.

Plasma Sphingomyelin Disturbances: Unveiling Its Dual Role as a Crucial Immunopathological Factor and a Severity Prognostic Biomarker in COVID-19.

SARS-CoV-2 infection triggers distinct patterns of disease development characterized by significant alterations in host regulatory responses. Severe cases exhibit profound lung inflammation and systemic repercussions. Remarkably, critically ill patients display a "lipid storm", influencing the inflammatory process and tissue damage. Sphingolipids (SLs) play pivotal roles in various cellular and tissue processes, including inflammation, metabolic disorders, and cancer. In this study, we employed high-resolution mass spectrometry to investigate SL metabolism in plasma samples obtained from control subjects (n = 55), COVID-19 patients (n = 204), and convalescent individuals (n = 77). These data were correlated with inflammatory parameters associated with the clinical severity of COVID-19. Additionally, we utilized RNAseq analysis to examine the gene expression of enzymes involved in the SL pathway. Our analysis revealed the presence of thirty-eight SL species from seven families in the plasma of study participants. The most profound alterations in the SL species profile were observed in patients with severe disease. Notably, a predominant sphingomyelin (SM d18:1) species emerged as a potential biomarker for COVID-19 severity, showing decreased levels in the plasma of convalescent individuals. Elevated SM levels were positively correlated with age, hospitalization duration, clinical score, and neutrophil count, as well as the production of IL-6 and IL-8. Intriguingly, we identified a putative protective effect against disease severity mediated by SM (d18:1/24:0), while ceramide (Cer) species (d18:1/24:1) and (d18:1/24:0)were associated with increased risk. Moreover, we observed the enhanced expression of key enzymes involved in the SL pathway in blood cells from severe COVID-19 patients, suggesting a primary flow towards Cer generation in tandem with SM synthesis. These findings underscore the potential of SM as a prognostic biomarker for COVID-19 and highlight promising pharmacological targets. By targeting sphingolipid pathways, novel therapeutic strategies may emerge to mitigate the severity of COVID-19 and improve patient outcomes.

Post-acute COVID-19 in three doses vaccinated autoimmune rheumatic diseases patients: frequency and pattern of this condition

BackgroundData on post-acute COVID-19 in autoimmune rheumatic diseases (ARD) are scarce, focusing on a single disease, with variable definitions of this condition and time of vaccination. The aim of this study was to evaluate the frequency and pattern of post-acute COVID-19 in vaccinated patients with ARD using established diagnosis criteria.MethodsRetrospective evaluation of a prospective cohort of 108 ARD patients and 32 non-ARD controls, diagnosed with SARS-CoV-2 infection (RT-PCR/antigen test) after the third dose of the CoronaVac vaccine. Post-acute COVID-19 (≥ 4 weeks and > 12 weeks of SARS-CoV-2 symptoms) were registered according to the established international criteria.ResultsARD patients and non-ARD controls, balanced for age and sex, had high and comparable frequencies of ≥ 4 weeks post-acute COVID-19 (58.3% vs. 53.1%, p = 0.6854) and > 12 weeks post-acute COVID-19 (39.8% vs. 46.9%, p = 0.5419). Regarding ≥ 4 weeks post-acute COVID-19, frequencies of ≥ 3 symptoms were similar in ARD and non-ARD controls (54% vs. 41.2%, p = 0.7886), and this was also similar in > 12 weeks post-acute COVID-19 (68.3% vs. 88.2%, p = 0.1322). Further analysis of the risk factors for ≥ 4 weeks post-acute COVID-19 in ARD patients revealed that age, sex, clinical severity of COVID-19, reinfection, and autoimmune diseases were not associated with this condition (p > 0.05). The clinical manifestations of post-acute COVID-19 were similar in both groups (p > 0.05), with fatigue and memory loss being the most frequent manifestations.ConclusionWe provide novel data demonstrating that immune/inflammatory ARD disturbances after third dose vaccination do not seem to be a major determinant of post-acute COVID-19 since its pattern is very similar to that of the general population. Clinical Trials platform (NCT04754698).

Association between mannose binding lectin gene polymorphisms and clinical severity of COVID-19 in children.

Mannose-binding lectin (MBL) is a member of innate immunity and acts with MASP (MBL-associated serine protease) to activate the lectin pathway of the complement system. MBL gene polymorphisms are associated with susceptibility to infectious diseases. This study investigated whether MBL2 genotype, serum MBL levels, and serum MASP-2 levels affect the course of SARS-CoV-2 infection. Pediatric patients diagnosed with COVID-19 by positive real-time polymerase chain reaction (PCR) were included in the study. Single nucleotide polymorphisms in the promoter and exon 1 in the MBL2 gene (rs11003125, rs7096206, rs1800450, rs1800451, rs5030737) were identified by a PCR and restriction fragment length polymorphisms analysis. Serum MBL and MASP-2 levels were measured by ELISA. COVID-19 patients were divided into asymptomatic and symptomatic. Variables were compared between these two groups. A total of 100 children were included in the study. The mean age of the patients was 130 ± 67.2 months. Of the patients, 68 (68%) were symptomatic, and 32 (32%) were asymptomatic. The polymorphisms in the - 221nt and - 550nt promoter regions did not differ between groups (p > 0.05). All codon 52 and codon 57 genotypes were determined as wild-type AA. AB genotypes were found 45.6% in symptomatic patients while 23.5% in asymptomatics. Moreover, BB genotype was detected 9.4% in symptomatic and 6.3% in asymptomatic patients (p < 0.001). B allele was more frequent in symptomatic patients (46.3%) compared to asymptomatic patients (10.9%). (p < 0.001). Serum MBL and MASP-2 levels did not differ statistically between the groups (p = 0.295, p = 0.073). These findings suggest that codon 54 polymorphism in the MBL2 gene exon-1 region can be associated with the symptomatic course of COVID-19.

Comparison of Neutralizing Sars Cov-2 Igg Antibody Levels in Hospitalized Patients at Dr. Mohammad Hoesin Palembang Hospital

ABSTRACT COVID-19 is an acute respiratory disease that spreads rapidly throughout the world caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Published research on levels of SARS-CoV-2 antibodies in hospitalized COVID-19 patients is still limited. Research on sero-epidemiology and its correlation with the clinical severity of COVID-19 is needed as a database for pandemic governance, especially research on neutralizing antibodies. This study was designed to compare the levels of IgG SARS CoV-2 on the tenth day in hospitalized patients with various clinical severity at RSUP Dr. Mohammad Hoesin Palembang. This research is an observational-analytic study with a cross-sectional design. The study was conducted in the COVID-19 isolation ward of RSMH Palembang from December 2021 to March 2022. IgG SARS CoV-2 level was measured in patients with confirmed COVID-19. Differences in IgG values of SARS CoV-2 were tested with the Mann Whitney test. The effect of various confounding variables in this study was tested using bivariate and multivariate tests in the form of a chi-square test and multiple linear regression on the scale of the dependent variable. The study included 50 patients, consisting of 22 patients with mild-moderate severity and 28 patients with severely-critically ill. Bivariate analysis showed there was no significant difference of IgG SARS-CoV-2 between two groups. From the data analysis using the ROC curve, the cut-off point for SARS-CoV-2 IgG levels in predicting the severity of COVID-19 disease was 500 AU/mL. IgG SARS-CoV-2 level of more than 500 AU/mL causes an increased risk of 3.69 (95% CI 1.13-11.98) times to suffer from severe-critical COVID-19. Serum IgG SARS-CoV-2 levels were found to be significantly higher in patients with severe-critical symptoms than patients with mild-moderate symptoms in COVID-19 hospitalized patients at Dr. Mohammad Hoesin Palembang hospital. Keywords: COVID-19, severity of COVID-19, IgG SARS-CoV-2

The 3′UTR region of the DNA repair gene PARP-1 May increase the severity of COVID-19 by altering the binding of antiviral miRNAs

COVID-19 may cause the release of systemic inflammatory cytokines resulting in severe inflammation. PARP-1 has been identified as a nuclear enzyme that is activated by DNA strand breaks. It has been suggested that PARP-1 has a role in the cytokine storm shown as a cause of mortality in COVID-19, and its inhibition may adversely affect the replication of SARS -CoV-2. We aimed to investigate the relationship between PARP-1 gene polymorphisms and the clinical severity of COVID-19. rs8679 TT genotype was found to increase with the COVID-19 disease severity. The 3′UTR polymorphism rs8679 may cause PARP-1 activity as a result of viral replication increase by changing the binding site of antiviral or anti-inflammatory miRNAs. PARP-1 may affect the severity of COVID-19 by cytokine release and maybe a possible treatment target.

Role of Vitamin D, ACE2 and the Proteases as TMPRSS2 and Furin on SARS-CoV-2 Pathogenesis and COVID-19 Severity

COVID-19, the 21st century pandemic disease caused by SARS-CoV-2, has shown a wide clinical spectrum ranging from asymptomatic to deadly serious pneumonia. In our study, the relationship between the pathogenesis and clinical severity of COVID-19 and vitamin D, ACE2, Furin and TMPRSS2 was investigated. Serum 25(OH)D, 1,25(OH)2D and ACE2 protein were measured in 85 COVID-19 cases, divided into 5 groups, according to disease severity, from asymptomatic to severe and including a healthy control group. Expression levels of ACE2, VDR, TMPRSS2 and Furin mRNAs in PBMC were also measured. The relationship of the parameters within each group, the severity of the disease and the effect on the patients' fate were investigated. Statistically significant differences were found between the severity of COVID-19 and all study parameters, except for serum 25(OH)D. A strong negative correlation was found between serum ACE2 protein, 1,25(OH)2D, and ACE2 mRNA, and disease severity, length of hospital stay and death/survival rate. Vitamin D deficiency increased the death risk by 5.6-fold (95% CI 0.75-41.47), and the levels of 1,25(OH)2D lower than 1 ng/mL increased the risk of death by 3.8-fold (95% CI 1.07-13.30). This study suggests that vitamin D supplementation could be beneficial in the treatment and/or prevention of COVID-19.

The role of the HLA allelic repertoire on the clinical severity of COVID-19 in Canadians, living in the Saskatchewan province

AimsThe HLA system has been implicated as an underlying determinant for modulating the immune response to SARS-CoV-2. In this study, we aimed to determine the association of patients’ HLA genetic profiles with the disease severity of COVID-19 infection. MethodsProspective study was conducted on COVID-19 patients (n = 40) admitted to hospitals in Saskatoon, Canada, between March and December 2020. Next-generation sequencing was performed on the patient samples to obtain high-resolution HLA typing profiles. The statistical association between HLA allelic frequency and disease severity was examined. The disease severity was categorized based on the length of hospital stay and intensive care needs or demise during the hospital stay. ResultsHLA allelic frequencies of the high and low-severity cohorts were normalized against corresponding background allelic frequencies. In the high-severity cohort, A*02:06 (11.8-fold), B*51:01 (2.4-fold), B*15:01(3.1-fold), C*01:02 (3.3-fold), DRB1*08:02 (31.2-fold), DQ*06:09 (11-fold), and DPB1*04:02(4-fold) were significantly overrepresented (p < 0.05) making these deleterious alleles. In the low-severity cohort, A*24:02 (2.8-fold), B*35:01 (2.8-fold), DRB1*04:07 (5.3-fold), and DRB1*08:11 (22-fold) were found to be significantly overrepresented (p < 0.05) making these protective alleles. These above alleles interact with NK cell antiviral activity via the killer immunoglobulin-like receptors (KIR). The high-severity cohort had a higher predilection for HLA alleles associated with KIR subgroups; Bw4-80I (1.1-fold), and C1 (1.6-fold) which promotes NK cell inhibition, while the low-severity cohort had a higher predilection for Bw4-80T (1.6-fold), and C2 (1.6-fold) which promote NK cell activation. ConclusionIn this study, the HLA allelic repository with the distribution of deleterious and protective alleles was found to correlate with the severity of the clinical course in COVID-19. Moreover, the interaction of specific HLA alleles with the KIR-associated subfamily modulates the NK cell-mediated surveillance of SARS-CoV-2. Both deleterious HLA alleles and inhibitory KIR appear prominently in the severe COVID-19 group focusing on the importance of NK cells in the convalescence of COVID-19.

Evaluation of ischemia-modified albumin in the diagnosis and the clinical severity of COVID-19 in children

Background. There is no specific biomarker used in the diagnosis of COVID-19 and predicting its clinical severity. This study aimed to investigate the utility of ischemia-modified albumin (IMA) in diagnosing and predicting clinical severity in children with COVID-19. Methods. Between October 2020 and March 2021, 41 cases constituted the COVID-19 group and 41 cases constituted the healthy control group. IMA levels were measured at admission (IMA-1) and 48-72 hours (IMA- 2) in the COVID-19 group. In the control group, it was measured at admission. COVID-19 clinical severity was classified as asymptomatic infection, mild, moderate, severe, or critical disease. Patients were divided into two groups (asymptomatic/mild and moderate/severe) to evaluate IMA levels in terms of clinical severity. Results. In the COVID-19 group, the mean IMA-1 level was 0.901&amp;#xb1;0.099, and the mean IMA-2 level was 0.866&amp;#xb1;0.090. The mean level of IMA-1 in the control group was 0.787&amp;#xb1;0.051. When IMA-1 levels of COVID-19 and control cases were compared, the difference was statistically significant (p &amp;lt; 0.001). When clinical severity and laboratory data are compared, C-reactive protein, ferritin and ischemia-modified albumin ratio (IMAR) were statistically significantly higher in moderate-severe clinical cases (p=0.034, p=0.034, p=0.037 respectively). However, IMA-1 and IMA-2 levels were similar between the groups (p=0.134, p=0.922, respectively). Conclusions. To date, no study has been conducted on IMA levels in children with COVID-19. The IMA level may be a new marker for the diagnosis of COVID-19 in children. Studies with a larger number of cases are needed to predict clinical severity.

Estimation of disease burden and clinical severity of COVID-19 caused by Omicron BA.2 in Shanghai, February-June 2022

ABSTRACT An outbreak of COVID-19 caused by the SARS-CoV-2 Omicron BA.2 sublineage occurred in Shanghai, China from February 26 to June 30, 2022. We use official reported data retrieved from Shanghai municipal Health Commissions to estimate the incidence of infections, severe/critical infections, and deaths to assess the disease burden. By adjusting for right censoring and RT-PCR sensitivity, we provide estimates of clinical severity, including the infection fatality ratio, symptomatic case fatality ratio, and risk of developing severe/critical disease upon infection. The overall infection rate, severe/critical infection rate, and mortality rate were 2.74 (95% CI: 2.73-2.74) per 100 individuals, 6.34 (95% CI: 6.02-6.66) per 100,000 individuals and 2.42 (95% CI: 2.23-2.62) per 100,000 individuals, respectively. The severe/critical infection rate and mortality rate increased with age, noted in individuals aged 80 years or older. The overall fatality ratio and risk of developing severe/critical disease upon infection were 0.09% (95% CI: 0.09-0.10%) and 0.27% (95% CI: 0.24-0.29%), respectively. Having received at least one vaccine dose led to a 10-fold reduction in the risk of death for infected individuals aged 80 years or older. Under the repeated population-based screenings and strict intervention policies implemented in Shanghai, our results found a lower disease burden and mortality of the outbreak compared to other settings and countries, showing the impact of the successful outbreak containment in Shanghai. The estimated low clinical severity of this Omicron BA.2 epidemic in Shanghai highlight the key contribution of vaccination and availability of hospital beds to reduce the risk of death.