COVID-19 Group Research Articles

Dysregulated nicotinamide adenine dinucleotide metabolome in patients hospitalized with COVID-19.

Nicotinamide adenine dinucleotide (NAD+) depletion has been postulated as a contributor to the severity of COVID-19; however, no study has prospectively characterized NAD+ and its metabolites in relation to disease severity in patients with COVID-19. We measured NAD+ and its metabolites in 56 hospitalized patients with COVID-19 and in two control groups without COVID-19: (1) 31 age- and sex-matched adults with comorbidities, and (2) 30 adults without comorbidities. Blood NAD+ concentrations in COVID-19 group were only slightly lower than in the control groups (p < 0.05); however, plasma 1-methylnicotinamide concentrations were significantly higher in patients with COVID-19 (439.7 ng/mL, 95% CI: 234.0, 645.4 ng/mL) than in age- and sex-matched controls (44.5 ng/mL, 95% CI: 15.6, 73.4) and in healthy controls (18.1 ng/mL, 95% CI 15.4, 20.8; p < 0.001 for each comparison). Plasma nicotinamide concentrations were also higher in COVID-19 group and in controls with comorbidities than in healthy control group. Plasma concentrations of 2-methyl-2-pyridone-5-carboxamide (2-PY), but not NAD+, were significantly associated with increased risk of death (HR = 3.65; 95% CI 1.09, 12.2; p = 0.036) and escalation in level of care (HR = 2.90, 95% CI 1.01, 8.38, p = 0.049). RNAseq and RTqPCR analyses of PBMC mRNA found upregulation of multiple genes involved in NAD+ synthesis as well as degradation, and dysregulation of NAD+-dependent processes including immune response, DNA repair, metabolism, apoptosis/autophagy, redox reactions, and mitochondrial function. Blood NAD+ concentrations are modestly reduced in COVID-19; however, NAD+ turnover is substantially increased with upregulation of genes involved in both NAD+ biosynthesis and degradation, supporting the rationale for NAD+ augmentation to attenuate disease severity.

Synergy Between NK Cells and Monocytes in Potentiating Cardiovascular Disease Risk in Severe COVID-19.

Evidence suggests that COVID-19 predisposes to cardiovascular diseases (CVDs). While monocytes/macrophages play a central role in the immunopathogenesis of atherosclerosis, less is known about their immunopathogenic mechanisms that lead to CVDs during COVID-19. Natural killer (NK) cells, which play an intermediary role during pathologies like atherosclerosis, are dysregulated during COVID-19. Here, we sought to investigate altered immune cells and their associations with CVD risk during severe COVID-19. We measured plasma biomarkers of CVDs and determined phenotypes of circulating immune subsets using spectral flow cytometry. We compared these between patients with severe COVID-19 (severe, n=31), those who recovered from severe COVID-19 (recovered, n=29), and SARS-CoV-2-uninfected controls (controls, n=17). In vivo observations were supported using in vitro assays to highlight possible mechanistic links between dysregulated immune subsets and biomarkers during and after COVID-19. We performed multidimensional analyses of published single-cell transcriptome data of monocytes and NK cells during severe COVID-19 to substantiate in vivo findings. During severe COVID-19, we observed alterations in cardiometabolic biomarkers including oxidized-low-density lipoprotein, which showed decreased levels in severe and recovered groups. Severe patients exhibited dysregulated monocyte subsets, including increased frequencies of proinflammatory intermediate monocytes (also observed in the recovered) and decreased nonclassical monocytes. All identified NK-cell subsets in the severe COVID-19 group displayed increased expression of activation and tissue-resident markers, such as CD69 (cluster of differentiation 69). We observed significant correlations between altered immune subsets and plasma oxidized-low-density lipoprotein levels. In vitro assays revealed increased uptake of oxidized-low-density lipoprotein into monocyte-derived macrophages in the presence of NK cells activated by plasma of patients with severe COVID-19. Transcriptome analyses confirmed enriched proinflammatory responses and lipid dysregulation associated with epigenetic modifications in monocytes and NK cells during severe COVID-19. Our study provides new insights into the involvement of monocytes and NK cells in the increased CVD risk observed during and after COVID-19.

Investigation of ADAMTS-13 levels in patients with COVID-19 infection

Introduction: Coronavirus disease 2019 (COVID-19) patients are predisposed to thrombotic events. COVID-19 coagulopathy can be associated with ADAMTS-13 (a disintegrin-like and metalloprotease with thrombospondin type I repeats 13) levels. ADAMTS-13, the cleaving protease of highly thrombogenic ultra-large von Willebrand Factor (vWF) multimers, was rarely investigated in COVID-19 patients and inconsistent results were obtained. We measured ADAMTS-13 levels of patients admitted to emergency department. Methodology: A prospective study was carried out with 180 individuals at the Emergency Department of Uşak Training and Research Hospital. The patients were divided into three groups: mild COVID-19 (group 2), severe COVID-19 with oxygen saturation below 94% (group 3), and control group (group 1). ADAMTS-13 levels were analyzed with an enzyme linked immunosorbent assay (ELISA) kit (SunRed, Shanghai, China). Demographic data, clinical findings, and routine laboratory test results (alanine aminotransferase (ALT), aspartate aminotransferase (AST), white blood cell, lymphocyte, platelet, C-reactive protein (CRP), lactate dehydrogenase (LDH), prothrombin time, international normalized ratio (INR), partial thromboplastin time, D-dimer, creatinine, urea) were evaluated. Results: ADAMTS-13 serum levels were slightly lower in groups 2 and 3 compared to the control group, with no significant difference between the ADAMTS-13 median values (p &gt; 0.05). Groups 1 and 2 exhibited comparable outcomes. Group 3 demonstrated notably elevated levels of CRP, LDH, D-dimer, AST, ALT, creatinine; and decreased platelet counts and INR levels (p &lt; 0.05). Conclusions: COVID-19-associated coagulopathy is still unclear. Based on our data, ADAMTS-13 levels cannot be used as a biomarker to help stratify patients’ risks at the time of admission.

Long COVID in children and adolescents: a historical cohort study with a population-based control group from Iran

BackgroundAfter recovering from the acute phase of COVID-19, some of the infected children manifest long COVID symptoms. The present study aims to identify long COVID symptoms in children and adolescents admitted to hospitals in Bushehr, Iran, during 2021 to 2023, and compare them with the non-affected group.MethodsThis historical cohort study with a population-based control group was conducted on 141 children and adolescents with COVID-19 hospitalized in Bushehr city hospitals and 141 non-affected peers. Out of 10 comprehensive health service centers in Bushehr city, 5 centers were selected by random sampling and the non-Covid-19 group was chosen from them (matched by gender and age with the affected group). The data were collected using the data recorded in the patients’ records, conducting telephone interviews and completing the prevalent long COVID symptom form. Data were analyzed using SPSS version 18. Descriptive statistics, Chi-square/Fisher’s exact tests, and stepwise logistic regression were used. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated, with p < 0.05 as the significance level.ResultsThe mean age of the hospitalized children with COVID-19 was 79 ± 5.24 months old, 57.4% of whom were boys. Also, 46 individuals of the COVID-19 group (32.6%) manifested long COVID symptoms. The most prevalent symptoms included fatigue (54.3%), impaired attention or concentration (41.3%) and depression or anxiety symptoms (34.7%). Among the hospitalized children experiencing long-term COVID symptoms, 65.2% exhibited moderate disease severity. A significant relationship was identified between disease severity and muscle and joint pain (P = 0.025), as well as between the length of hospital stay and cough (P = 0.022), weight loss (P = 0.047), and symptoms of depression or anxiety (P = 0.008). Older age [(6–11 y; OR = 3.18, CI = 1.03–9.88); (12 ≥ y; OR = 4.57, CI = 1.40-14.96)] and having history of smoking or being exposed to secondhand smoke (OR = 12.45, CI = 3.14–49.36) were considered as risk factors for long COVID.ConclusionsThe variables of age and history of exposure to tobacco smoke exhibited a significant independent relationship with the occurrence of long-term COVID symptoms in children hospitalized due to COVID-19. Specifically, as age increases and the history of tobacco smoke exposure rises, the likelihood of experiencing long-term COVID symptoms also increases.

Proteolytic imbalance in plasma of patients with multiple sclerosis following COVID-19

Background. The present research was conducted with the following objectives: 1) to determine the plasma levels of five matrix metalloproteinases (MMPs), namely MMP-1, -2, -3, -8, -10, and tissue inhibitor of metalloproteinase-1 (TIMP-1); 2) to analyze protease activity profiles in plasma using a zymographic method; and 3) to perform preliminary analysis on plasma peptide pool composition in patients with multiple sclerosis (MS) with and without COVID-19 history. Materials and methods. We examined 97 patients with MS: 41 had been diagnosed with COVID-19 in the past 4–6 months (MS + COVID group), and 56 did not suffer from SARS-CoV-2 infection previously (MS group). The plasma of healthy volunteers (n = 30) with no evidence of disease was used as control. The enzyme-linked immunosorbent assay was used to measure MMP and TIMP-1 concentrations. Plasma MMP activity was verified by gelatin-substrate zymography. Peptide pools were extracted from the plasma of MS patients and healthy subjects. Then size exclusion chromatography was used to identify separate fractions present in peptide pools. Results. We found that plasma concentration of MMP-2 was remarkably increased in the MS group compared with healthy controls, while in the MS + COVID patients, the levels of two other MMPs, MMP-1 and -10, were elevated. Zymography showed four dominant gelatinolytic bands of 92, 84, 72, and 62 kDa in MS plasma samples, whereas only traces of MMP were detected in healthy subjects. Most of MS plasma samples showed MMP-2 lytic activity, but only a few contained MMP-9. Finally, we determined the concentration of circulating peptides. The levels of plasma peptides were higher in patients from both the MS and MS + COVID group compared to control subjects. According to our results, the development of MS was accompanied by changes in both quantity and quality of peptide pool composition compared to healthy controls. Conclusions. Thus, an advanced understanding of the role of MMPs in MS pathogenesis following infection is important in developing optimized interventions to improve health and clinical outcomes during COVID-19.

Healthcare workers’ compliance with COVID-19 prevention and control measures at De Martino Hospital, Mogadishu, Somalia: a cross-sectional study

BackgroundHealthcare workers are a high-risk group for COVID-19 and protecting them is crucial for healthcare delivery. Limited studies have explored compliance with infection prevention and control (IPC) practices among Somali healthcare workers. This study aimed to determine compliance with IPC practices among healthcare workers in De Martino Public Hospital, Somalia.MethodsA cross-sectional study was conducted at the De Martino Public Hospital, Mogadishu, Somalia from August to October 2022, with the participation of 204 healthcare workers (response rate = 97%). Compliance was assessed using responses to 25 questions on a five-point Likert-type scale, and a median score of 20 was used to dichotomize compliance scores. A chi-square test and logistic regression analysis were performed to check the associations between healthcare workers’ socio-demographic information, IPC-related factors, work conditions and practices on COVID-19, and IPC compliance during healthcare interventions using SPSS 23 version.ResultsIn total, 58.3% of the participants had good compliance with IPC. There were significant associations between IPC compliance and the type of healthcare worker (doctors and doctor assistants: 72.3%, nurses and paramedical staff: 67.3%, non-clinical staff: 5.7%, p < 0.01). After adjusting for potential confounding factors, compared to non-clinical staff, doctors and doctor assistants (OR: 12.11, 95% CI: 2.23–65.84) and nurses and paramedical staff (OR: 21.38, 95% CI: 4.23–108.01) had higher compliance with IPC measures. There were no significant associations between compliance and sex, marital status, vaccination status, or smoking (p > 0.05 for all).ConclusionsLow levels of compliance with COVID-19 IPC measures were observed among hospital workers. Prioritizing awareness campaigns and behavior change interventions, especially among non-clinical staff, is crucial for effective COVID-19 infection prevention and control within hospitals.

Altered functional brain connectivity, efficiency, and information flow associated with brain fog after mild to moderate COVID-19 infection.

COVID-19 is associated with increased risk for cognitive decline but very little is known regarding the neural mechanisms of this risk. We enrolled 49 adults (55% female, mean age = 30.7 ± 8.7), 25 with and 24 without a history of COVID-19 infection. We administered standardized tests of cognitive function and acquired brain connectivity data using MRI. The COVID-19 group demonstrated significantly lower cognitive function (W = 475, p < 0.001, effect size r = 0.58) and lower functional connectivity in multiple brain regions (mean t = 3.47 ±0.36, p = 0.03, corrected, effect size d = 0.92 to 1.5). Hypo-connectivity of these regions was inversely correlated with subjective cognitive function and directly correlated with fatigue (p < 0.05, corrected). These regions demonstrated significantly reduced local efficiency (p < 0.026, corrected) and altered effective connectivity (p < 0.001, corrected). COVID-19 may have a widespread effect on the functional connectome characterized by lower functional connectivity and altered patterns of information processing efficiency and effective information flow. This may serve as an adaptation to the pathology of SARS-CoV-2 wherein the brain can continue functioning at near expected objective levels, but patients experience lowered efficiency as brain fog.

Comparison and Analysis of Clinical Characteristics of Common COVID-19 and NSIP Patients

Objective: To investigate the relationship between coronavirus disease 2019 (COVID-19) and non-specific interstitial pneumonia (NSIP), with a focus on the clinical features of COVID-19 and NSIP, and the key points of differential diagnosis. Methods: The clinical data of 20 patients with common-type COVID-19 and NSIP admitted to Linyi People’s Hospital from January 21, 2020, to June 21, 2022, were retrospectively analyzed. Gender, age, history of residence in Hubei province, underlying diseases, clinical manifestations, laboratory test results (including blood routine indexes, inflammatory markers, liver function indexes, and coagulation indexes), and computed tomography (CT) scan images were compared between the two groups. Results: COVID-19 patients were younger than NSIP patients (P &lt; 0.05). Nine COVID-19 patients had a travel history to Hubei province, while none of the NSIP patients did (P &lt; 0.05). Eight COVID-19 patients had underlying chronic conditions, fewer than the NSIP group (12 patients; P &lt; 0.05). Both groups experienced symptoms such as shortness of breath, expectoration, fatigue, and runny nose, but fever and cough were more severe and more frequent in the COVID-19 group. Compared to normal reference ranges, both groups exhibited normal white blood cell counts (WBC) and liver function indexes, but elevated lymphocyte counts (LYMP), inflammatory markers, and coagulation indexes, with reduced neutrophil counts (NE). WBC and LYMP were higher in the COVID-19 group compared to the NSIP group. Male patients in the COVID-19 group had higher erythrocyte sedimentation rates and C-reactive protein values than those in the NSIP group, while procalcitonin levels were lower in the COVID-19 group, although the differences were not statistically significant (all P &gt; 0.05). The NE count in the COVID-19 group was significantly lower than in the NSIP group (P &lt; 0.05). Alanine aminotransferase, total bilirubin, and indirect bilirubin were significantly higher in the COVID-19 group compared to the NSIP group (P &lt; 0.05). Chest CT scans of both groups showed bilateral patchy ground-glass opacities, but the lesions in COVID-19 patients were scattered. NSIP patients’ chest CTs showed diffuse lesions centered around the hilum or multiple lesions in both lungs, with pleural involvement being rare. Conclusion: While there are certain specific clinical, laboratory, and imaging findings in both COVID-19 and NSIP, the specificity of these features is not high. Differentiating the two requires careful consideration of epidemiological history, nucleic acid testing, and antigen-antibody levels.

ENaC gene variants and their involvement in Covid‑19 severity.

Epidemiological studies report the association of diverse cardiovascular conditions with coronavirus disease 2019 (COVID-19), but the causality has remained to be established. Specific genetic factors and the extent to which they can explain variation in susceptibility or severity are largely elusive. The present study aimed to evaluate the link between 32 cardio-metabolic traits and COVID-19. A total of 60 participants were enrolled, who were categorized into the following 4 groups: A control group with no COVID-19 or any other underlying pathologies, a group of patients with a certain form of dyslipidemia and predisposition to atherosclerotic disease, a COVID-19 group with mild or no symptoms and a COVID-19 group with severe symptomatology hospitalized at the Intensive Care Unit of Sotiria Hospital (Athens, Greece). Demographic, clinical and laboratory data were recorded and genetic material was isolated, followed by simultaneous analysis of the genes related to dyslipidemia using a custom-made next-generation sequencing panel. In the COVID-19 group with mild or absent symptoms, the variant c.112C>T:p.P38S was detected in the sodium channel epithelial 1 subunit α (SCNN1A) gene, with a major allele frequency (Maf) of <0.01. In the COVID-19 group with severe symptoms, the variant c.786G>A:p.T262T was detected in the SCNN1B gene, which encodes for the β-subunit of the epithelial sodium channel ENaC, with a Maf <0.01. None of the two rare variants were detected in the control or dyslipidemia groups. In conclusion, the current study suggests that ENaC variants are likely associated with genetic susceptibility to COVID-19, supporting the rationale for the risk and protective genetic factors for the morbidity and mortality of COVID-19.

Integrating transcriptomics, eQTL, and Mendelian randomization to dissect monocyte roles in severe COVID-19 and gout flare.

There are considerable similarities between the pathophysiology of gout flare and the dysregulated inflammatory response in severe COVID-19 infection. Monocytes are the key immune cells involved in the pathogenesis of both diseases. Therefore, it is critical to elucidate the molecular basis of the function of monocytes in gout and COVID-19 in order to develop more effective therapeutic approaches. The single-cell RNA sequencing (scRNA-seq), large-scale genome-wide association studies (GWAS), and expression quantitative trait loci (eQTL) data of gout and severe COVID-19 were comprehensively analyzed. Cellular heterogeneity and intercellular communication were identified using the scRNA-seq datasets, and the monocyte-specific differentially expressed genes (DEGs) between COVID-19, gout and normal subjects were screened. In addition, the correlation of the DEGs with severe COVID-19 and gout flare was analyzed through GWAS statistics and eQTL data. The scRNA-seq analysis exhibited that the proportion of classical monocytes was increased in both severe COVID-19 and gout patient groups compared to healthy controls. Differential expression analysis and MR analysis showed that NLRP3 was positively associated with the risk of severe COVID-19 and involved 11 SNPs, of which rs4925547 was not significantly co-localized. In contrast, IER3 was positively associated with the risk of gout and involved 9 SNPs, of which rs1264372 was significantly co-localized. Monocytes have a complex role in gout flare and severe COVID-19, which underscores the potential mechanisms and clinical significance of the interaction between the two diseases.

Retinal Microvasculature Changes Linked to Executive Function Impairment after COVID-19

Background/Objectives: Studies using optical coherence tomography angiography (OCTA) have revealed that individuals recovering from COVID-19 have a reduced retinal vascular density (VD) and larger foveal avascular zones (FAZs) than healthy individuals, with more severe cases showing greater reductions. We aimed to examine aspects of the retinal microvascularization in patients with post-COVID-19 condition (PCC) classified by COVID-19 severity and how these aspects relate to cognitive performance. Methods: This observational cross-sectional study included 104 PCC participants from the NAUTILUS Project, divided into severe (n = 59) and mild (n = 45) COVID-19 groups. Participants underwent cognitive assessments and OCTA to measure VD and perfusion density (PD) in the superficial capillary plexus (SVP) and FAZ. Analysis of covariance and partial Pearson and Spearman correlations were used to study intergroup differences and the relationships between cognitive and OCTA variables. Results: Severe PCC participants had significantly lower central (p = 0.03) and total (p = 0.03) VD, lower central (p = 0.02) PD measurements, and larger FAZ areas (p = 0.02) and perimeters (p = 0.02) than mild cases. Severe cases showed more cognitive impairment, particularly in speed processing (p = 0.003) and executive functions (p = 0.03). Lower central VD, lower central PD, and larger FAZ areas and perimeters were associated with worse executive function performance in the entire PCC sample and in the mild COVID-19 group. Conclusions: Retinal microvascular alterations, characterized by reduced VD and PD in the SVP and larger FAZ areas, were associated with cognitive impairments in PCC individuals. These findings suggest that severe COVID-19 leads to long-lasting microvascular damage, impacting retinal and cognitive health.

The Interaction of Complement and Intrinsic Coagulation System: A Comparative Study between COVID-19 and Bacterial Sepsis Patients.

Background/Objectives: Through the past several years, a constant interaction has been implicated between complement and coagulation cascades. SARS-CoV-2 infection and bacterial sepsis are potent activators of both cascades. This study aims to compare the extent of complement and intrinsic coagulation pathway activation (and the interplay between them) among patients with COVID-19 and bacterial sepsis. Methods: Serum and plasma samples were collected from 25 ICU patients (11 patients with COVID-19 and 14 patients with bacterial sepsis) at two time points (on admission and either on improvement or deterioration). The activities of coagulation factors XI and XII and complement factors C3a and C5a were measured at both time points. Results: The activities of factors XI and XII were increased in both groups of patients and at both time points. However, there were no statistically significant differences between SARS-CoV-2 and bacterial sepsis patients. On the other hand, both C3a and C5a were significantly higher in the COVID-19 group on admission. This correlation was preserved on reassessment. Conclusions: Complement activation seems to be more enhanced in COVID-19 than bacterial sepsis. However, the lack of statistical significance in factors XI and XII indicates t the presence of additional pathways for complement activation in SARS-CoV-2 infection.

Increased luminal area of large conducting airways in patients with COVID-19 and post-acute sequelae of COVID-19: a retrospective case-control study.

Coronavirus disease 2019 (COVID-19) is associated with enlarged luminal areas of large conducting airways. In 10-30% of patients with acute COVID-19 infection, symptoms persist for more than 4 wk (referred to as post-acute sequelae of COVID 19, or PASC), and it is unknown if airway changes are associated with this persistence. Thus, we aim to investigate whether luminal area of large conducting airways is different between patients with PASC and COVID-19 and healthy controls. In this retrospective case-control study, 75 patients with PASC (48 females) were age-, height-, and sex-matched to 75 patients with COVID-19 and 75 healthy controls. Using three-dimensional digital reconstruction from computed tomography imaging, we measured luminal areas of seven conducting airways, including trachea, right and left main bronchi, bronchus intermediate, right and left upper lobe, and left lower lobe bronchi. Kruskal-Wallis H test was used to compare measurements between the three groups, as appropriate. Airway luminal areas between COVID-19 and PASC groups were not different (all, P > 0.66). There were no group differences in airway luminal area (PASC vs. control) for trachea and right main bronchus. However, in the remaining five airways, airway luminal areas were 12-39% larger among patients with PASC than in controls (all, P < 0.05). Patients diagnosed with COVID-19 and PASC have greater airway luminal area in most large conducting airways compared with healthy controls. No differences in luminal area between patients with COVID-19 and PASC suggest persistence of changes or insufficient time for reversal of changes.NEW & NOTEWORTHY Three-dimensional reconstruction of airways has shown increased luminal area in patients with COVID-19 and post-acute sequelae of COVID-19 when compared with healthy controls. These findings suggest the role of large conducting airways in the pathogenesis of post-acute sequelae of COVID 19.

Epithelial Antimicrobial Peptide/Protein and Cytokine Expression Profiles Obtained from Nasopharyngeal Swabs of SARS-CoV-2-Infected and Non-Infected Subjects.

Immune responses of the epithelia of the upper respiratory tract are likely crucial in early inhibition of the viral replication and finally clearance of SARS-CoV-2. We aimed to compare the expression profiles of antimicrobial peptides/proteins (AMPs) and related cytokines observed in the nasopharynx of SARS-CoV-2-infected patients and non-infected controls and to assess the associations between these parameters and COVID-19 patients' outcomes. We included 45 subjects who had tested positive for SARS-CoV-2 and 22 control subjects who had tested negative for SARS-CoV-2. Biomaterial for SARS-CoV-2 detection, as well as gene and protein expression studies, was obtained from all subjects using nasopharyngeal swabs which were performed a maximum of 7 days before inclusion in the study. Univariable and multivariable statistics were performed. When compared to the controls, the mRNA expression levels of human β-defensin 1 (hBD-1), LL-37, and trappin-2 were significantly higher in specimens of nasopharyngeal swabs from COVID-19 patients. Protein expression of hBD-1 was also increased in the COVID-19 group. mRNA expression levels of interferon-ɣ (IFN-ɣ), tumor necrosis factor- ɑ (TNF-ɑ), and interleukin-6 (IL-6) measured in SARS-CoV-2-infected patients were significantly higher than those observed in the controls, which could also be confirmed in the protein levels of IFN-ɣ and IL-6. A significant correlation between mRNA and protein levels could be observed only for IL-6. Univariable analysis revealed that low IFN-ɣ mRNA levels were associated with severe/fatal outcomes. The occurrence of COVID-19 pneumonia was significantly associated with lower expression levels of IL-6 mRNA, IFN-ɣ mRNA, and TNF-ɑ mRNA. Concerning the severe/fatal outcomes, the multivariable logistic regression model revealed that none of the aforementioned parameters remained significant in the model. However, the logistic regression model revealed that higher TNF-ɑ mRNA expression was a significant independent predictor of absence of pneumonia [odds ratio: 0.35 (95% CI 0.14 to 0.88, p = 0.024)]. In conclusion, nasopharyngeal expression of AMPs (hBD-1, LL-37, and trappin-2) and cytokines (IL-6, IFN-ɣ, and TNF-ɑ) is upregulated in response to early SARS-CoV-2 infection, indicating that these AMPs and cytokines play a role in the local host defense against the virus. Upregulated nasopharyngeal TNF-ɑ mRNA expression during the early phase of SARS-CoV-2 infection was a significant independent predictor of the absence of COVID-19 pneumonia. Hence, high TNF-ɑ mRNA expression in the nasopharynx appears to be a protective factor for lung complications in COVID-19 patients.

Adequate serum 25-hydroxy-vitamin D levels are correlated with low anti-PF4 levels in mild COVID-19 Patients: An observational study.

The worldwide spread of coronavirus disease 2019 (COVID-19) has resulted in an unparalleled health emergency of global proportions. Around 31% of individuals with COVID-19 experience thrombosis associated with hypercoagulation. COVID-19 patients have shown an increase in platelet activation, but the mechanism has not been fully understood yet. One theory suggests that this could be related to the heparin-induced thrombocytopenia phenomenon, where platelet activation involves anti-PF4 antibodies that are associated with thrombosis. Vitamin D has been established to exert an influence on immunological responses and inflammation. The aim of this study is to analyze the correlation between serum 25-hydroxy-cholecalciferol [25(OH)D] levels and anti-PF4 antibodies among COVID-19 patients. A cross-sectional study was conducted among 160 COVID-19 patients at Cipto Mangunkusumo General Hospital and Wisma Atlit Hospital Jakarta from October 2021 to January 2022. The mean serum 25(OH)D level was 15.1 ng/mL. A significant negative correlation was found between serum 25(OH)D and anti-PF4 levels in mild COVID-19 patients (P = .035; R = -0.236). Remarkably, P-selectin levels were significantly higher in the moderate COVID-19 group compared to the severe group (P = .031). Serum 25(OH)D level had a significant negative correlation with anti-PF4 level in mild COVID-19 patients. Thus, it is highly recommended to ensure that serum 25(OH)D levels are maintained above 30 ng/mL. Remarkably, the P-selectin level was significantly higher in the moderate COVID-19 group compared to the severe group.

Oculomic stratification of COVID-19 patients' intensive therapy unit admission status and mortality by retinal morphological findings.

To investigate if retinal thickness has predictive utility in COVID-19 outcomes by evaluating the statistical association between retinal thickness using OCT and of COVID-19-related mortality. Secondary outcomes included associations between retinal thickness and length of stay (LoS) in hospital. In this retrospective cohort study, OCT scans from 230 COVID-19 patients admitted to the Intensive Care Unit (ITU) were compared with age and gender-matched patients with pneumonia from before March 2020. Total retinal, GCL + IPL, and RNFL thicknesses were recorded, and analysed with systemic measures collected at the time of admission and mortality outcomes, using linear regression models, Pearson's R correlation, and Principal Component Analysis. Retinal thickness was significantly associated with all-time mortality on follow up in the COVID-19 group (p = 0.015), but not 28-day mortality (p = 0.151). Retinal and GCL + IPL layer thicknesses were both significantly associated with LoS in hospital for COVID-19 patients (p = 0.006 for both), but not for patients with pneumonia (p = 0.706 and 0.989 respectively). RNFL thickness was not associated with LoS in either group (COVID-19 p = 0.097, pneumonia p = 0.692). Retinal thickness associated with LoS in hospital and long-term mortality in COVID-19 patients, suggesting that retinal structure could be a surrogate marker for frailty and predictor of disease severity in this group of patients, but not in patients with pneumonia from other causes.

A six-year study in a real-world population reveals an increased incidence of dyslipidemia during COVID-19.

Recent studies conducted in COVID-19 survivors suggest that SARS-CoV-2 infection is associated with an increased risk of dyslipidemia. However, it remains unclear whether this augmented risk is confirmed in the general population and how this phenomenon is impacting the overall burden of cardiometabolic diseases. To address these aspects, we conducted a 6-year longitudinal study to examine the broader effects of COVID-19 on dyslipidemia incidence within a real-world population (228,266 subjects) residing in Naples, Southern Italy. The pre-COVID-19 and the COVID-19 groups were balanced for demographic and clinical factors using propensity score matching. Our analysis spans over a period of three years during the pandemic (2020-2022), comparing dyslipidemia incidence with pre-pandemic data (2017-2019), with a follow-up time of at least 1,095 days corresponding to 21,349,215 person-years. During the COVID-19 period we detected an increased risk of developing any dyslipidemia when compared with the pre-COVID-19 triennium (OR = 1.29, 95% CI 1.19-1.39). Importantly, these estimates were adjusted for comorbidities by a multivariate analysis. Taken together, our data reveal a notable rise in dyslipidemia incidence amid the COVID-19 pandemic, suggesting to establish specialized clinical monitoring protocols for COVID-19 survivors to mitigate the risk of dyslipidemia development.

Assessing the impact of enhanced hygiene precautions during the COVID-19 pandemic on surgical site infection risk in abdominal surgeries

BackgroundA surgical site infection (SSI) is a postoperative infection that occurs at or near the surgical incision. SSIs significantly increase morbidity, mortality, length of hospital stay, and healthcare costs. The World Health Organization (WHO) has established hospital hygiene precaution guidelines for the prevention of SSIs, which were enhanced during the COVID-19 pandemic. The current study aims to explore the effect of the COVID-19 pandemic on SSI incidence among initially uninfected postoperative patients. We hypothesize that these enhanced precautions would reduce the incidence of SSIs.Materials and methodsA retrospective study comparing surgical outcomes before and during the pandemic. Patients who had abdominal surgery between June and December 2019 (Non-COVID-19) or between February and June 2020 (COVID-19) were included. The two groups were matched in a 1:1 ratio based on age, Sex, acuity (elective or emergent), surgical approach, and comorbidities. Electronic medical records were reviewed to identify SSIs and hospital readmissions within 30 days after surgery. Pearson's chi-square test and Fisher's exact test were used.ResultsData was collected and analyzed from 976 patients who had surgery before the COVID-19 pandemic (non-COVID group) and 377 patients who had surgery during the pandemic (COVID group). After matching, there were 377 patients in each group. In our study, we found 23 surgical site infections (SSIs) in both laparoscopic and open surgeries. The incidence of SSIs was significantly higher in the non-COVID period compared to the COVID period [17 cases (4.5%) vs. 6 cases (1.6%), respectively, p = 0.032], especially in non-COVID open surgeries. The incidence of SSIs in laparoscopic surgeries was also higher during the non-COVID period, but not statistically significant.ConclusionsEnhanced hygiene precautions during the COVID -19 pandemic may have reduced SSIs rates following abdominal surgery.

Decreased Protein C Pathway Activity in COVID-19 Compared to Non-COVID Sepsis: An Observational and Comparative Cohort Study.

Sepsis-associated coagulopathy increases risk of mortality. Impairment of the anticoagulant protein C (PC) pathway may contribute to the thrombotic phenotype in coronavirus disease 2019 (COVID-19) sepsis. This study assessed the functionality of this pathway in COVID-19 and non-COVID sepsis by measuring its key enzymes, thrombin and activated PC (APC). The study population included 30 patients with COVID-19, 47 patients with non-COVID sepsis, and 40 healthy controls. In healthy controls, coagulation activation and subsequent APC formation was induced by 15 µg/kg recombinant activated factor VII one hour before blood sampling. APC and thrombin in plasma were measured using oligonucleotide-based enzyme capture assays. The indirect thrombin markers prothrombin-fragment 1+2 (F1+2) and thrombin-antithrombin complex (TAT) were also measured. Compared with stimulated healthy controls, median thrombin, F1+2, and TAT levels were higher in patients with COVID-19 (up to 6-fold, p < 2 × 10-6) and non-COVID sepsis (up to 4.7-fold, p < 0.010). APC levels were 2.4-fold higher in patients with COVID-19 (7.44 pmol/L, p = 0.011) and 3.4-fold higher in non-COVID sepsis patients (10.45 pmol/L, p = 2 × 10-4) than in controls (3.08 pmol/L). Thrombin markers and APC showed correlation in both COVID-19 (r = 0.364-0.661) and non-COVID sepsis patients (r = 0.535-0.711). After adjustment for PC levels, median APC/thrombin, APC/F1+2, and APC/TAT ratios were 2-fold (p = 0.036), 6-fold (p = 3 × 10-7) and 3-fold (p = 8 × 10-4) lower in the COVID-19 group than in the non-COVID sepsis group, and the latter two were also lower in the COVID-19 group than in stimulated healthy controls. In conclusion, it was found that a comparatively lower anticoagulant APC response in COVID-19 patients as compared to non-COVID sepsis patients, potentially linked to endothelial dysfunction, contributes to the prothrombotic phenotype of COVID-19 sepsis.

Abstract P207: Regulation of Fetal-Placental ACE and ACE2 in COVID-19 Exposed Pregnancies Compared to Hypertensive and Healthy Pregnancies

Introduction: Higher risks of preterm birth and fetal growth restriction are observed in COVID-19 pregnancies. The infection mechanism, linked to a potential depletion of the cardioprotective protein ACE2, which serves as a receptor for SARS-CoV-2, could pose additional risks for mothers and fetuses. An ACE2/ACE imbalance, favoring ACE, has been seen in hypertensive (HT) pregnancies and is linked to poor outcomes, including pre-eclampsia. This study aims to assess whether similar changes in ACE and ACE2 regulation in placentas and umbilical cord blood occur in COVID-19 compared to HT and healthy (Ctrl) pregnancies, and whether this imbalance is associated with impaired vascular structure. Methods: A retrospective cohort study recruited 77 pregnancies (25 COVID-19, 16 HT, 36 Ctrl) at Montreal Hospital Sacré-Coeur. Placental infarction was assessed in histological sections, umbilical cord fibrosis by Masson's trichrome staining, and placental ACE2 content by immunohistochemistry. ACE and ACE2 activity were measured by fluorometric assay in umbilical cord plasma. Data are presented as mean 95% CI. Linear regression was used for correlations, Kruskal-Wallis and Mann-Whitney tests for group comparisons. Results: Maternal age, gestational age, and the proportion of male/female fetuses were similar between groups. Ctrl group had lower rates of C-section delivery, obesity, and gestational diabetes compared to COVID-19 and HT pregnancies. Although ACE2 content in placentas was reduced in HT pregnancies, the COVID-19 group had significantly higher content compared to HT and Ctrl pregnancies (23.4 CI=20.4-26.4 vs. 15.5 CI=9.7-21.3 and 17.6 CI=15.1-20.1, respectively, p&lt;0.01). The ACE2/ACE activity ratio in cord blood was significantly reduced in COVID-19 and HT groups compared to Ctrl (3.1 CI=2.4-3.6, 2.5 CI=1.7-3.1, and 4.1 CI=3.5-4.8, p&lt;0.01), indicating an imbalance favoring ACE activity in HT and COVID-19 groups. The ACE2/ACE ratio negatively correlated with umbilical cord fibrosis (slope=-3.1 CI= -6.1 to -0.1, p=0.04) and was significantly lower in placentas with tissue infarction (2.5 CI=1.2-3.8 vs. 4.6 CI=3.8-5.3, p&lt;0.01). Conclusion: HT pregnancies have reduced ACE2 content and an ACE2/ACE activity imbalance in cord blood. COVID-19 pregnancies show a similar imbalance in cord blood but significantly higher ACE2 content in the placenta. This imbalance is associated with structural changes in fetal-placental vessels, suggesting a link to poor pregnancy outcomes.