"Ultrastructural changes of platelets in COVID-19 and chronic viral hepatitis patients ".

Platelet-viral interactions are evolving as a new concern. Coagulation disorder is a major consequence of the COVID-19 infection. In chronic hepatitis virus infections, defect in coagulation factors, thrombocytopenia and platelet function abnormalities are common. A SARS-CoV-2 infection on top of chronic viral hepatitis infection can be common in areas where viral hepatitis is endemic. Here, we investigate the platelet ultrastructural changes and estimate the serum platelet factor-4 (PF-4), ferritin, CRP, and D-dimer in COVID-19 patients (n = 60), COVID-19 patients with associated chronic viral hepatitis (n = 20), and healthy subjects (n = 20). Ultrastructural changes were demonstrated in all test groups, denoting platelet activation. In chronic viral hepatitis patients, Platelet ultrastrustural apoptotic changes were also seen. Significantly high levels of PF-4 were confirmed in moderate and severe COVID-19 patients (P.value <0.001), with a cut off value of 17 ng/ml for predicting disease severity. A positive correlation of PF-4 with the level of serum ferritin, CRP, and D-dimer (p value < 0.001) was noted, while negatively correlated with platelet count and platelet granule count (p value < 0.001). In our study, chronic viral hepatitis patients presented mild COVID-19 signs, and their PF-4 level was comparable with the subgroup of mild COVID-19 infection. The platelet's critical role in COVID-19 coagulopathy and chronic viral hepatitis is evidenced by the ultrastructural changes and the high levels of PF4. Moreover, a dual viral infection poses a substantial burden on the platelets, necessitating close monitoring of the patient's coagulation profile.

Impact of shift work and other work-related factors on anti-SARS-CoV-2 spike-protein serum concentrations in healthcare workers after primary mRNA vaccination - a retrospective cohort study.

BACKGROUND: Knowing whether shift work negatively affects the immune system's response to COVID-19 vaccinations could be valuable for planning future vaccination campaigns for healthcare workers. We aimed to determine the impact of working late or night shifts on serum anti-SARS-CoV-2 spike protein immunoglobulin G (anti-S) antibody levels after primary SARS-CoV-2-mRNA vaccination. METHODS: To obtain detailed information on shift work, we sent a separate online questionnaire to 1475 eligible healthcare workers who participated in a prospective longitudinal study conducted in 15 healthcare institutions in Switzerland. We asked all vaccinated healthcare workers with available anti-S antibody levels after vaccination to complete a brief online survey on their working schedules within one week before and after primary mRNA vaccination. We used multivariate regression to evaluate the association between work shifts around primary vaccination and anti-S antibody levels. We adjusted for confounders already known to influence vaccine efficacy (e.g. age, sex, immunosuppression, and obesity) and for variables significant at the 0.05 alpha level in the univariate analyses. RESULTS: The survey response rate was 43% (n = 638). Ninety-eight responders were excluded due to unknown vaccination dates, different vaccines, or administration of the second dose shortly (within 14 days) after or before serologic follow-up. Of the 540 healthcare workers included in our analysis, 175 (32.4%) had worked at least one late or night shift within seven days before and/or after primary vaccination. In the univariate analyses, working late or night shifts was associated with a nonsignificant -15.1% decrease in serum anti-S antibody levels (p = 0.090). In the multivariate analysis, prior infection (197.2% increase; p <0.001) and immunisation with the mRNA-1273 vaccine (63.7% increase compared to the BNT162b2 vaccine; p <0.001) were the strongest independent factors associated with increased anti-S antibody levels. However, the impact of shift work remained statistically nonsignificant (-13.5%, p = 0.108). CONCLUSION: Working late or night shifts shortly before or after mRNA vaccination against COVID-19 does not appear to significantly impact serum anti-S antibody levels. This result merits consideration since it supports flexible vaccination appointments for healthcare workers, including those working late or night shifts.

Cytokine profiles of mild-to-moderate SARS-CoV-2 infected and recovered pre-vaccinated individuals residing in Indonesia.

Background: Accumulating evidence suggests the involvement of cytokine-mediated inflammation, in clinical severity and death related to SARS-CoV-2 infection, especially among pre-vaccinated individuals. An increased risk of death was also described among SARS-CoV-2 recovered individuals, which might be correlated with prolonged inflammatory responses. Despite being among the countries with the highest cumulative deaths due to COVID-19, evidence regarding cytokine profiles among SARS-CoV-2 infected and recovered pre-vaccinated individuals in Indonesia is scarce. Thus, this study aimed to describe the cytokines profiles of pre-vaccinated individuals residing in Indonesia, with mild-to-moderate SARS-CoV-2 infection and those who recovered. Methods: Sixty-one sera from 24 hospitalized patients with mild-to-moderate SARS-CoV-2 infection, 24 individuals recovered from asymptomatic-to-moderate SARS-CoV-2 infection, and 13 healthy controls unexposed to SARS-CoV-2 were used in this study. Quantification of serum cytokine levels, including IL-6, IL-8, IP-10, TNF-α, CCL-2, CCL-3, CCL-4, and CXCL-13, was performed using a Luminex multi-analyte-profiling (xMAP)-based assay. Results: The levels of IL-8 along with CCL-2 and CCL-4, were significantly higher (p ≤ 0.01) in hospitalized patients with mild-to-moderate SARS-CoV-2 infection and recovered individuals compared to healthy controls. However, no significant difference was observed in these cytokine levels between infected and recovered individuals. On the other hand, there were no significant differences in several other cytokine levels, including IL-6, IL-10, TNF-α, CCL-3, and CXCL-13, among all groups. Conclusion: IL-8, CCL-2, and CCL-4 were significantly elevated in pre-vaccinated Indonesian individuals with mild-to-moderate SARS-CoV-2 infection and those who recovered. The cytokine profiles described in this study might indicate inflammatory responses not only among SARS-CoV-2 infected, but also recovered individuals.

COVID-19 increases extracorporeal coagulation during hemodialysis associated with upregulation of vWF/FBLN5 signaling in patients with severe/critical symptoms.

BACKGROUND: COVID-19 has been shown to increase the risk of extracorporeal coagulation during hemodialysis in patients, but the underlying mechanism remains unclear. This study aimed to investigate the effect and mechanism of COVID-19 on the risk of extracorporeal coagulation in patients with chronic kidney disease undergoing hemodialysis. METHODS: A retrospective analysis of the extracorporeal coagulation status of 339 hemodialysis patients at our center before and after COVID-19 infection was performed, including subgroup analyses. Post-infection blood composition was analyzed by protein spectrometry and ELISA. RESULTS: Compared to the pre-COVID-19 infection period, COVID-19-induced extracorporeal coagulation predominantly occurred in patients with severe/critical symptoms. Further proteomic analysis demonstrated that in patients with severe/critical symptoms, the coagulation cascade reaction, platelet activation, inflammation, and oxidative stress-related pathways were significantly amplified compared to those in patients with no/mild symptoms. Notably, the vWF/FBLN5 pathway, which is associated with inflammation, vascular injury, and coagulation, was significantly upregulated. CONCLUSIONS: Patients with severe/critical COVID-19 symptoms are at a higher risk of extracorporeal coagulation during hemodialysis, which is associated with the upregulation of the vWF/FBLN5 signaling pathway. These findings highlight the importance of early anticoagulant therapy initiation in COVID-19 patients with severe/critical symptoms, particularly those undergoing hemodialysis. Additionally, vWF/FBLN5 upregulation may be a novel mechanism for virus-associated thrombosis/coagulation.

Risk stratification and prognosis prediction using cardiac biomarkers in COVID-19: a single-centre retrospective cohort study.

OBJECTIVE: There is a need for a robust tool to stratify the patient's risk with COVID-19. We assessed the prognostic values of cardiac biomarkers for COVID-19 patients. METHODS: This is a single-centre retrospective cohort study. Consecutive laboratory-confirmed COVID-19 patients admitted to the Kobe City Medical Center General Hospital from July 2020 to September 2021 were included. We obtained cardiac biomarker values from electronic health records and institutional blood banks. We stratified patients with cardiac biomarkers as high-sensitive troponin I (hsTnI), N-terminal pro-B-type natriuretic peptide (NT-proBNP), creatine kinase (CK) and CK myocardial band (CK-MB), using the clinically relevant thresholds. Prespecified primary outcome measure was all-cause death. RESULTS: A total of 917 patients were included. hsTnI, NT-proBNP, CK and CK-MB were associated with the significantly higher cumulative 30-day incidence of all-cause death (hsTnI: <5.0 ng/L group; 4.3%, 5.0 ng/L-99%ile upper reference limit (URL) group; 8.8% and ≥99% ile URL group; 25.2%, p<0.001. NT-proBNP: <125 pg/mL group; 5.3%, 125-900 pg/mL group; 10.5% and ≥900 pg/mL group; 31.9%, p<0.001. CK:

Case study observational research: inflammatory cytokines in the bronchial epithelial lining fluid of COVID-19 patients with acute hypoxemic respiratory failure.

BACKGROUND: In this study, the concentrations of inflammatory cytokines were measured in the bronchial epithelial lining fluid (ELF) and plasma in patients with acute hypoxemic respiratory failure (AHRF) secondary to severe coronavirus disease 2019 (COVID-19). METHODS: We comprehensively analyzed the concentrations of 25 cytokines in the ELF and plasma of 27 COVID-19 AHRF patients. ELF was collected using the bronchial microsampling method through an endotracheal tube just after patients were intubated for mechanical ventilation. RESULTS: Compared with those in healthy volunteers, the concentrations of interleukin (IL)-6 (median 27.6 pmol/L), IL-8 (1045.1 pmol/L), IL-17A (0.8 pmol/L), IL-25 (1.5 pmol/L), and IL-31 (42.3 pmol/L) were significantly greater in the ELF of COVID-19 patients than in that of volunteers. The concentrations of MCP-1 and MIP-1ß were significantly greater in the plasma of COVID-19 patients than in that of volunteers. The ELF/plasma ratio of IL-8 was the highest among the 25 cytokines, with a median of 737, and the ELF/plasma ratio of IL-6 (median: 218), IL-1ß (202), IL-31 (169), MCP-1 (81), MIP-1ß (55), and TNF-α (47) were lower. CONCLUSIONS: The ELF concentrations of IL-6, IL-8, IL-17A, IL-25, and IL-31 were significantly increased in COVID-19 patients. Although high levels of MIP-1 and MIP-1ß were also detected in the blood samples collected simultaneously with the ELF samples, the results indicated that lung inflammation was highly compartmentalized. Our study demonstrated that a comprehensive analysis of cytokines in the ELF is a feasible approach for understanding lung inflammation and systemic interactions in patients with severe pneumonia.

A randomized clinical trial investigating the impact of magnesium supplementation on clinical and biochemical measures in COVID-19 patients.

BACKGROUND: This study sought to examine the impact of magnesium supplementation on clinical outcomes and biochemical factors among hospitalized patients with COVID-19. METHODS: This double-blind, randomized clinical trial was conducted at Razi Hospital, Ahvaz, Iran, between September 2021 and March 2022. Participants aged 18-70 years with moderate disease severity were enrolled. Magnesium supplementation (300 mg daily) was administered to the intervention group, while the control group received a placebo. Clinical outcomes, including the need for oxygen therapy, oxygen saturation, respiratory rate, fever, hs-CRP and TNF-α levels, as well as quality of life and mental health, were assessed. Blood samples were collected to measure biochemical variables. RESULTS: The main result was the count of individuals requiring oxygen therapy. Additional outcomes comprised of oxygen saturation, respiratory rate, fever, hs-CRP and TNF-α levels, as well as quality of life and mental health. Out of 64 participants, 60 completed the study. The results showed that magnesium supplementation significantly reduced the number of patients requiring oxygen therapy (9 vs. 14; P < 0.001). Moreover, the magnesium group demonstrated improved oxygen saturation compared to the control group (4.55 ± 2.35 vs. 1.8 ± 1.67; P < 0.001). Furthermore, we observed a noteworthy enhancement in the quality of life and depression score in the magnesium group. No significant differences were observed in respiratory rate, fever, hs-CRP, and TNF-α levels (P > 0.05). CONCLUSION: The findings suggest that magnesium supplementation may have beneficial effects on clinical outcomes and arterial oxygen saturation in COVID-19 patients. More investigation is necessary to delve into its potential mechanisms and long-term effects on patient outcomes. TRIAL REGISTRATION: This study is registered on Iranian Registry of Clinical Trials (IRCT) under identifier IRCT20210413050957N1. (The registration date: May 1, 2021).

Severity of COVID-19 infection in patients with COVID-19 combined with diabetes.

PURPOSE: This study aimed to analyse the correlation between blood glucose control and the severity of COVID-19 infection in patients with diabetes. METHODS: Clinical and imaging data of a total of 146 patients with diabetes combined with COVID-19 who visited our hospital between December 2022 and January 2023 were retrospectively collected. The patients were divided into the 'good blood glucose control' group and the 'poor blood glucose control' group based on an assessment of their blood glucose control. The clinical data, computed tomography (CT) appearance and score and the severity of COVID-19 infection of the two groups were compared, with the severity of COVID-19 infection being the dependent variable to analyse other influencing factors. RESULTS: The group with poor blood glucose control showed a higher lobar involvement degree and total CT severity score (CTSS) than the group with good blood glucose control (13.30 ± 5.25 vs. 10.38 ± 4.84, p < 0.05). The two groups exhibited no statistically significant differences in blood lymphocyte, leukocyte, C-reaction protein, pleural effusion, consolidation, ground glass opacity or crazy-paving signs. Logistic regression analysis showed that the total CTSS significantly influences the clinical severity of patients (odds ratio 1.585, p < 0.05), whereas fasting plasma glucose and blood glucose control are not independent factors influencing clinical severity (both p > 0.05). The area under the curve (AUC) of CTSS prediction of critical COVID-19 was 0.895 with sensitivity of 79.3% and specificity of 88.1% when the threshold value is 12. CONCLUSION: Blood glucose control is significantly correlated with the CTSS; the higher the blood glucose is, the more severe the lung manifestation. The CTSS can also be used to evaluate and predict the clinical severity of COVID-19.

Can inflammatory plasma proteins predict Long COVID or Fatigue severity after SARS-CoV-2 infection?

OBJECTIVE: To investigate whether specific immune response plasma proteins can predict an elevated risk of developing Long COVID symptoms or fatigue severity after SARS-CoV-2 infection. METHODS: This study was based on 257 outpatients with test-confirmed SARS-CoV-2 infection between February 2020 and January 2021. At least 12 weeks after the acute infection, 92 plasma proteins were measured using the Olink Target 96 immune response panel (median time between acute infection and venous blood sampling was 38.8 [IQR: 24.0-48.0] weeks). The presence of Long COVID symptoms and fatigue severity was assessed 115.8 [92.5-118.6] weeks after the acute infection by a follow-up postal survey. Long COVID (yes/no) was defined as having one or more of the following symptoms: fatigue, shortness of breath, concentration or memory problems. The severity of fatigue was assessed using the Fatigue Assessment Scale (FAS). In multivariable-adjusted logistic and linear regression models the associations between each plasma protein (exposure) and Long COVID (yes/no) or severity of fatigue were investigated. RESULTS: Nine plasma proteins were significantly associated with Long COVID before, but not after adjusting for multiple testing (FDR-adjustment): DFFA, TRIM5, TRIM21, HEXIM1, SRPK2, PRDX5, PIK3AP1, IFNLR1 and HCLS1. Moreover, a total of 10 proteins were significantly associated with severity of fatigue before FDR-adjustment: SRPK2, ITGA6, CLEC4G, HEXIM1, PPP1R9B, PLXNA4, PRDX5, DAPP1, STC1 and HCLS1. Only SRPK2 and ITGA6 remained significantly associated after FDR-adjustment. CONCLUSIONS: This study demonstrates that certain immune response plasma proteins might play an important role in the pathophysiology of Long COVID and severity of fatigue after SARS-CoV-2 infection.

Monocyte-Mediated Thrombosis Linked to Circulating Tissue Factor and Immune Paralysis in COVID-19.

BACKGROUND: SARS-CoV-2 infections cause COVID-19 and are associated with inflammation, coagulopathy, and high incidence of thrombosis. Myeloid cells help coordinate the initial immune response in COVID-19. Although we appreciate that myeloid cells lie at the nexus of inflammation and thrombosis, the mechanisms that unite the two in COVID-19 remain largely unknown. METHODS: In this study, we used systems biology approaches including proteomics, transcriptomics, and mass cytometry to define the circulating proteome and circulating immune cell phenotypes in subjects with COVID-19. RESULTS: In a cohort of subjects with COVID-19 (n=35), circulating markers of inflammation (CCL23 [C-C motif chemokine ligand 23] and IL [interleukin]-6) and vascular dysfunction (ACE2 [angiotensin-converting enzyme 2] and TF [tissue factor]) were elevated in subjects with severe compared with mild COVID-19. Additionally, although the total white blood cell counts were similar between COVID-19 groups, CD14+ (cluster of differentiation) monocytes from subjects with severe COVID-19 expressed more TF. At baseline, transcriptomics demonstrated increased IL-6, CCL3, ACOD1 (aconitate decarboxylase 1), C5AR1 (complement component 5a receptor), C5AR2, and TF in subjects with severe COVID-19 compared with controls. Using stress transcriptomics, we found that circulating immune cells from subjects with severe COVID-19 had evidence of profound immune paralysis with greatly reduced transcriptional activation and release of inflammatory markers in response to TLR (Toll-like receptor) activation. Finally, sera from subjects with severe (but not mild) COVID-19 activated human monocytes and induced TF expression. CONCLUSIONS: Taken together, these observations further elucidate the pathological mechanisms that underlie immune dysfunction and coagulation abnormalities in COVID-19, contributing to our growing understanding of SARS-CoV-2 infections that could also be leveraged to develop novel diagnostic and therapeutic strategies.

TLRs1-10 Protein Expression in Circulating Human White Blood Cells during Bacterial and COVID-19 Infections.

INTRODUCTION: Toll-like receptors play crucial roles in the sepsis-induced systemic inflammatory response. Septic shock mortality correlates with overexpression of neutrophilic TLR2 and TLR9, while the role of TLR4 overexpression remains a debate. In addition, TLRs are involved in the pathogenesis of viral infections such as COVID-19, where the single-stranded RNA of SARS-CoV-2 is recognized by TLR7 and TLR8, and the spike protein activates TLR4. METHODS: In this study, we conducted a comprehensive analysis of TLRs 1-10 expressions in white blood cells from 71 patients with bacterial and viral infections. Patients were divided into 4 groups based on disease type and severity (sepsis, septic shock, moderate, and severe COVID-19) and compared to 7 healthy volunteers. RESULTS: We observed a significant reduction in the expression of TLR4 and its co-receptor CD14 in septic shock neutrophils compared to the control group (p < 0.001). Severe COVID-19 patients exhibited a significant increase in TLR3 and TLR7 levels in neutrophils compared to controls (p < 0.05). Septic shock patients also showed a similar increase in TLR7 in neutrophils along with elevated intermediate monocytes (CD14+CD16+) compared to the control group (p < 0.005 and p < 0.001, respectively). However, TLR expression remained unchanged in lymphocytes. CONCLUSION: This study provides further insights into the mechanisms of TLR activation in various infectious conditions. Additional analysis is needed to assess their correlation with patient outcome and to evaluate the impact of TLR-pathway modulation during septic shock and severe COVID-19.

Meta-analysis of the serum/plasma proteome identifies significant associations between COVID-19 with Alzheimer's/Parkinson's diseases.

In recent years, we have seen the widespread devastations and serious health complications manifested by COVID-19 globally. Although we have effectively controlled the pandemic, uncertainties persist regarding its potential long-term effects, including prolonged neurological issues. To gain comprehensive insights, we conducted a meta-analysis of mass spectrometry-based proteomics data retrieved from different studies with a total of 538 COVID-19 patients and 523 healthy controls. The meta-analysis revealed that top-enriched pathways were associated with neurological disorders, including Alzheimer's (AD) and Parkinson's disease (PD). Further analysis confirmed a direct correlation in the expression patterns of 24 proteins involved in Alzheimer's and 23 proteins in Parkinson's disease with COVID-19. Protein-protein interaction network and cluster analysis identified SNCA as a hub protein, a known biomarker for Parkinson's disease, in both AD and PD. To the best of our knowledge, this is the first meta-analysis study providing proteomic profiling evidence linking COVID-19 to neurological complications.

SARS-CoV-2 infection is not associated with the emergence of monoclonal gammopathies.

BACKGROUND: Upon infection activated plasma cells produce large quantities of antibodies which can lead to the emergence of a monoclonal component (MC), detectable by serum protein electrophoresis (SPEP). This study aims to investigate any correlation between SARS-CoV-2 infection and MC development and, if identified, whether it persists during follow-up. METHODS: SPEPs of 786 patients admitted to hospitals between March 01 2020 and March 31 2022 were evaluated. Positive (SARS-CoV-2+) and negative (SARS-CoV-2-) patients to nasopharyngeal swab for SARS-CoV-2 by RT-PCR were included. The persistence/new occurrence of MC was investigated for all patients during follow-up. Patient groups were compared by chi-square analysis. RESULTS: MC was identified in 12% of all patients admitted to hospital, of which 28.7% were SARS-CoV-2+. The most common immunoglobulin isotype in both groups was IgG-k. There was no correlation between MC development and SARS-CoV-2 infection (p = 0.173). Furthermore, the risk of MC persistence in SARS-CoV-2-negative patients was revealed to be higher than in the SARS-CoV-2+ at follow-up (HR = 0.591, p = 0.05). CONCLUSIONS: Our study suggests that the detection of MC during SARS-CoV-2 infection is most likely due to the hyperstimulation of the humoral immune system, as also occurs in other viral infections.

Characteristics of hematological parameters on admission in COVID-19 Omicron variant infected in Chinese population: a large-scale retrospective study.

BACKGROUND: The Omicron variant of SARS-CoV-2, currently the most prevalent strain, has rapidly spread in Jingzhou, China, due to changes in the country's epidemic prevention policy, resulting in an unprecedented increase in cases. Previous studies reported hematological parameters' predictive value in COVID-19 severity and prognosis, but their relevance for early diagnosis in patients infected by the Omicron variant, particularly in high-risk pneumonia cases, remains unclear. Our study aimed to evaluate these parameters as early warning indicators for Omicron-infected patients in fever clinics and those with pulmonary infections (PI). METHODS: A total of 2,021 COVID-19 patients admitted to the fever clinic and infectious disease department of Jingzhou Hospital Affiliated to Yangtze University from November 1, 2022, to December 31, 2022, were retrospectively recruited. Demographic and hematological parameters were obtained from the electronic medical records of eligible patients. These hematological parameters were analyzed by receiver operating characteristic (ROC) curves to determine whether they can be used for early diagnosis of COVID-19 patients in fever clinics and the presence of PI in COVID-19 patients. RESULTS: Statistical differences in hematological parameters were observed between COVID-19 patients with fever and PI and control groups (P < 0.01). The ROC curve further demonstrated that lymphocyte (LYM) counts, neutrophil (NEU) counts, monocyte-to-lymphocyte ratios (MLR), platelet-to-lymphocyte ratios (PLR), white blood cell counts (WBC), and mean corpuscular hemoglobin concentration (MCHC) were the top 6 indicators in diagnosing Omicron infection with fever, with area under the curve (AUC) values of 0.738, 0.718, 0.713, 0.702, 0.700, and 0.687, respectively (P < 0.01). Furthermore, the mean platelet volume (MPV) with an AUC of 0.764, red blood cell count (RBC) with 0.753, hematocrit (HCT) with 0.698, MLR with 0.694, mean corpuscular hemoglobin (MCH) with 0.676, and systemic inflammation response indexes (SIRI) with 0.673 were the top 6 indicators for the diagnosis of COVID-19 patients with PI (P < 0.01). CONCLUSIONS: LYM, NEU, MLR, PLR, WBC, and MCHC can serve as potential prescreening indicators for Omicron infection in fever clinics. Additionally, MPV, RBC, HCT, MLR, MCH, and SIRI can predict the presence of PI in COVID-19 patients infected by the Omicron variant.

Risk factors and titers of COVID-19 infection in a longitudinal statewide seroepidemiology cohort.

BACKGROUND: Virginia is a large state in the USA, yet it remains unclear what percentage of the population has had natural COVID-19 infection and whether risk factors for infection have changed over time. METHODS: Using a longitudinal cohort, from December 2021-July 2022 we performed follow up serology and a questionnaire on 784 individuals from across Virginia who had previously participated in a statewide COVID-19 seroepidemiology study in 2020. Children were also invited to participate and an additional 62 children also completed the study. Serology was performed using Roche nucleocapsid and spike serological assays. RESULTS: The majority of participants were white (78.6%), over 50 years old (60.9%), and reported having received COVID-19 vaccine (93.4%). 28.6% had evidence of prior COVID-19 infection (nucleocapsid positive). Reweighted by region, age, and sex to match the Virginia census data, the seroprevalence of nucleocapsid antibodies was estimated to be 30.6% (95% CI: 24.7, 36.6). We estimated that 25-53% of COVID-19 infections were asymptomatic. Infection rates were lower in individuals > 60 years old and were higher in Blacks and Hispanics. Infection rates were also higher in those without health insurance, in those with greater numbers of household children, and in those that reported a close contact or having undergone quarantine for COVID-19. Participants from Southwest Virginia had lower seropositivity (16.2%, 95% CI 6.5, 26.0) than other geographic regions. Boosted vaccinees had lower infection rates than non-boosted vaccinees. Frequenting indoor bars was a risk factor for infection, while frequently wearing an N95 mask was protective, though the estimates of association were imprecise. Infection rates were higher in children than adults (56.5% vs. 28.6%). Infection in the parent was a risk factor for child infection. Spike antibody levels declined with time since last vaccination, particularly in those that were vaccinated but not previously infected. Neutralizing antibody positivity was high (97-99%) for wild type, alpha, beta, gamma, delta, and omicron variants. Neutralizing antibody levels were higher in the follow-up survey compared to the first survey in 2020 and among individuals with evidence of natural infection compared to those without. CONCLUSIONS: In this longitudinal statewide cohort we observed a lower-than-expected COVID-19 infection rate as of August 2022. Boosted vaccinees had lower infection rates. Children had higher infection rates and infections tracked within households. Previously identified demographic risk factors for infection tended to persist. Even after the omicron peak, a large number of Virginians remain uninfected with COVID-19, underscoring the need for ongoing vaccination strategies.

The effect of 1-hydroxy-vitamin D treatment in hospitalized patients with COVID-19: A retrospective study.

BACKGROUND & AIMS: The efficacy of vitamin D supplementation in coronavirus disease 2019 (COVID-19) remains unclear. This study aimed to evaluate the effect of 1-hydroxy-vitamin D on the prevention of severe disease and mortality in patients hospitalized for COVID-19. METHODS: This retrospective study included 312 patients with COVID-19 who were admitted to our hospital between April 2021 and October 2021 (primarily the Delta variant) and between July 2022 and September 2022 (primarily Omicron variant). Serum 25-hydroxyvitamin D (25(OH)D) levels were measured at the time of admission and 1-hydroxy-vitamin D was prescribed by the treating physicians. The patients were divided into two groups: those administered 1-hydroxy-vitamin D (Vit D group) and those who were not (control group). The composite primary endpoint was the need for additional respiratory support, including high-flow oxygen therapy or invasive mechanical ventilation, and in-hospital mortality rate. RESULTS: Of 312 patients, 122 (39%) received 1-hydroxy-vitamin D treatment. Although the median age was not significantly higher in the Vit D group than in the control group (66 vs. 58 years old, P = 0.06) and there was no significant difference in the proportion of vitamin D deficiency (defined as serum 25(OH)D level less than 20 ng/mL, 77% vs. 65%, P = 0.07), patients in the control group had a more severe baseline profile compared to the Vit D group according to the Japanese disease severity definition for COVID-19 (P = 0.01). The proportion of those requiring more respiratory support and in-hospital mortality was significantly lower in the Vit D group than in the control group (6% vs. 14%, P = 0.01 log-rank test). After propensity score matching, a statistically significant difference in the primary endpoint was observed (P = 0.03 log-rank test). CONCLUSIONS: 1-hydroxy-vitamin treatment may improve outcomes in hospitalized patients with COVID-19, reducing composite outcomes including the need for additional respiratory support and in-hospital mortality.

An evaluation of matrix metalloproteinase-9 (Mmp-9) and tissue inhibitor metalloproteinase-1 (Timp-1) Serum levels and the Mmp-9/Timp-1 Ratio in Covid-19 patients.

Background: The progression of COVID-19 has different clinical presentations, which raises a number of immunological questions. Objectives: This study aimed to investigate MMP-9 and TIMP-1 levels in patients diagnosed with COVID-19 and whether the MMP-9/TIMP-1 ratio is associated with lung involvement in COVID-19. Methods: This study was conducted with 192 patients and 45 healthy controls. ELISA was used to measure the MMP-9 and TIMP-1. Results: The MMP-9 and TIMP-1 levels of the patients were found to be higher than those of the controls. MMP-9 and TIMP-1 were detected more in patients with lung involvement on chest CT scans than in those with no lung involvement on chest CT scans. A comparison of lung involvement levels revealed no difference was found between the groups. The MMP-9/TIMP-1 ratio was 5.8 in the group with lung involvement on chest CT scans and 6.1 in the group without lung involvement on chest CT scans. No difference was found between the two groups. A comparison with respect to lung involvement levels showed that the MMP-9/TIMP-1 ratio difference was found between the groups. Conclusion: Diagnostic and treatment methods targeting MMP-9 activity or neutrophil activation may be important in predicting lung involvement in COVID-19 and directing clinical outcomes.

A study of fibrinolytic system components in donor groups depending on various titers of circulating anti-SARS-CoV-2 IgG in the bloodstream.

The fibrinolytic system plays an important role in controlling blood coagulation at each stage, from thrombin generation to fibrin clot cleavage. Currently, long-term multiorgan dysfunction post-coronavirus disease 2019 (COVID-19) may include coagulation disorders. Little information is available about the potential causes of post-COVID-19 coagulopathy, but one of them may be subpopulation IgG produced by the immune system against SARS-CoV-2. This article describes the changes in the main parameters of the fibrinolytic system in donors with various titers of anti-SARS-CoV-2 IgG, which is part of a complex study of the hemostasis system in these donor groups. We determined the most significant parameters of the fibrinolytic system, such as potential activity and amount of plasminogen and tissue plasminogen activator (tPA), amount of plasminogen activator inhibitor-1 (PAI-1), inhibitory potentials of α-2-antiplasmin, α-1-antitrypsin, α-2-macroglobulin in the blood plasma of donor groups. The obtained results represent the maximum and minimum values of measurement parameters among donor groups with titers of anti-SARS-CoV-2 IgG at least 10 ±â€Š3 Index (S/C), and their statistical differences from the reference point [donor group with titer of anti-SARS-CoV-2 IgG 0 Index (S/C)]. We established the changes in fibrinolytic parameters depending on the titers of anti-SARS-CoV-2 IgG. One conclusion can be drawn from this: anti-SARS-CoV-2 IgG population may influence coagulation in the post-COVID-19 period. Further research in-vitro and in-vivo experimental models using selected and purified IgG may confirm our previous findings.