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Background To help inform COVID-19 vaccination recommendations, we evaluated the impact of age and dosing interval on clinical benefit of a third dose of mRNA-1273. Methods Approximately 17 000 participants from the phase 3 Coronavirus Efficacy trial who previously received 2 doses of 100 µg mRNA-1273 were evaluated for COVID-19 between September 2021 and April 2022 during uptake of a third booster dose of 50 µg of mRNA-1273. Cox models assessed booster relative efficacy of a third dose. Results Initial booster relative efficacy against Delta COVID-19 was 83% (95% confidence interval, 60–93) 14 days postdose and 83% (67–91) 60 days later. Initial booster efficacy against Omicron COVID-19 was 56% (44–65) at 14 days postdose and 4% (−27 to 28) 120 days later. For those aged ≥65 years, initial booster efficacy against Omicron COVID-19 was 86% (69–93) compared with 50% (36–61) for those <65 years. Placebo crossover to 2 doses of mRNA-1273 induced a median 5-month difference from the second to third dose between the original randomized arms. Postboost, the mRNA-1273 arm had a 24% (16%, 32%) lower risk of Omicron COVID-19 compared to the placebo-mRNA-1273 arm. Modeling predicted a 41% postboost reduction in Omicron COVID-19 for a 15- versus 7-month interval between the second and third doses. Conclusions Boosting reduced Delta COVID-19 risk by 83% through 2 months and reduced Omicron COVID-19 risk by 56% but declined by 4 months. A 15- versus 7-month dosing interval predicted a 41% postboost reduction in Omicron COVID-19 but increased preboost risk. Primary Funding Source The National Institutes of Health/National Institute of Allergy and Infectious Diseases. Registration for the COVE Trial.  ClinicalTrials.gov ID# NCT04470427 [ABSTRACT FROM AUTHOR]

Objective: In the past 5 years, a large number of serological assays for large‐scale detection of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) antigen emerged. Serological assays for SARS‐CoV‐2 were needed to support clinical diagnosis and epidemiological investigations. However, there were limited data on the diagnostic accuracy of these serological assays. We aimed to compare the diagnostic accuracy of 11 commercial serological assays for coronavirus disease‐2019 (COVID‐19) by taking the reverse transcriptase polymerase chain reaction (RT‐PCR) assays as the reference standard, which served as the control arm to conduct an indirect comparison of diagnostic accuracy for 11 different SARS‐CoV‐2 serological assays. Methods: This meta‐analysis was conducted following the PRISMA 2020 reporting guideline. Electronic searches were performed using the Cochrane Library, PubMed, Embase, Web of Science, Chinese Biological Medicine Database (CBM), China National Knowledge Infrastructure (CNKI), WANFANG, and Chinese Weipu (VIP) databases. Fifty‐seven articles, including 11 serologic‐based IgG, IgM, and total antibodies assays for SARS‐CoV‐2, published before June 2024, were included in this meta‐analysis. The main outcome of this meta‐analysis used to evaluate the performance of 11 assays included pooled diagnostic odds ratio (DOR), area under the summary receiver operating characteristic (AUC), and summary receiver operating characteristic curve (SROC). The R software was used for adjusted indirect comparison to calculate the relative diagnostic odds ratio (RDOR) with corresponding 95% confidence intervals (CIs), and indirect comparison forest plots showed the results. Results: A total of 57 articles met the eligibility criteria for inclusion in our meta‐analysis. The pooled DOR and the AUC for access SARS‐CoV‐2 IgG were 564.28 (95% CI 229.58−1386.91) and 1.00, and as for EDI novel coronavirus COVID‐19 IgG those were 85.27 (95% CI 53.99−134.68) and 0.95, for EDI novel coronavirus COVID‐19 IgM were 49.42 (95% CI 16.47−148.30) and 0.86, for iFlash‐SARS‐CoV‐2 IgG were 652.31 (95% CI 362.32−1174.41) and 0.97, for iFlash‐SARS‐CoV‐2 IgM were 36.72 (95% CI 12.42−108.54) and 0.76, for MAGLUMI 2019‐nCoV IgG were 145.44 (95% CI 59.37−356.30) and 0.90, for MAGLUMI 2019‐nCoV IgM were 21.59 (95% CI 14.27−32.67) and 0.59, for ortho‐clinical anti‐SARS‐CoV‐2 IgG were 719.46 (95% CI 262.34−1973.13) and 1.00, for ortho‐clinical anti‐SARS‐CoV‐2 total were 1104.60 (95% CI 395.64−3083.99) and 1.00, for Siemens SARS‐CoV‐2 total (COV2T) were 1143.37 (95% CI 316.49−4130.62) and 0.99, for Wantai SARS‐CoV‐2 total Ab were 1014.98 (95% CI 618.48−1665.66) and 1.00. The pooled DOR for assays‐based IgG (n = 43), assays‐based total antibody (n = 35), and assays‐based IgM (n = 20) was 242.88 (95% CI 157.66−374.16), 1215.90 (95% CI 547.14−2702.07), and 40.99 (95% CI 22.63−74.25). The diagnostic accuracy of assays‐based total antibody performed better than those of assays‐based IgG and assays‐based IgM; assays‐based IgG performed better than assays‐based IgM. Conclusion: This study suggested that the Siemens SARS‐CoV‐2 total (COV2T), ortho‐clinical anti‐SARS‐CoV‐2 total, and Wantai SARS‐CoV‐2 total had the best overall diagnostic accuracy. The diagnostic efficacy of the assays‐based total antibody had statistically significantly higher accuracy than those of assays‐based IgG and assays‐based IgM for COVID‐19. [ABSTRACT FROM AUTHOR]

Research into innovative non-pharmacological therapeutic routes via the utilization of natural elements like zinc (Zn) has been motivated by the discovery of new severe acute respiratory syndrome-related coronavirus 2 (SARS-COV2) variants and the ineffectiveness of certain vaccination treatments during COVID-19 pandemic. In addition, research on SARS-COV-2's viral cellular entry and infection mechanism has shown that it may seriously harm reproductive system cells and impair testicular function in young men and adolescents, which may lead to male infertility over time. In this context, we conducted a narrative review to give an overview of the data pertaining to Zn's critical role in testicular tissue, the therapeutic use of such micronutrients to enhance male fertility, as well as in the potential mitigation of COVID-19, with the ultimate goal of elucidating the hypothesis of the potential use of Zn supplements to prevent the possible harmful effects of SARS-COV2 infection on testis physiological function, and subsequently, on male fertility. [ABSTRACT FROM AUTHOR]

A significant proportion of patients after SARS-CoV-2 infection suffer from long-lasting symptoms. Although many different symptoms are described, the majority of patients complains about neuropsychological symptoms. Additionally, a subgroup of patients fulfills diagnostic criteria for ME/CFS. We analyzed a registry of all patients presenting in the out-patients clinic at a German university center. For patients with more than one visit, changes in reported symptoms from first to second visit were analyzed. A total of 1022 patients were included in the study, 411 of them had more than one visit. 95.5% of the patients reported a polysymptomatic disease. At the first visit 31.3% of the patients fulfilled ME/CFS criteria after a median time of 255 days post infection and and at the second visit after a median of 402 days, 19.4% still suffered from ME/CFS. Self-reported fatigue (83.7–72.7%) and concentration impairment (66.2–57.9%) decreased from first to second visit contrasting non-significant changes in the structured screening. A significant proportion of SARS-CoV-2 survivors presenting with ongoing symptoms present with ME/CFS. Although the proportion of subjective reported symptoms and their severity reduce over time, a significant proportion of patients suffer from long-lasting symptoms necessitating new therapeutic concepts. [ABSTRACT FROM AUTHOR]

The lungs are exposed to a hostile environment from both sites: the airways and the vasculature. However, an efficient gas exchange of oxygen (O2) and CO2 is only possible through a very thin alveolo‐capillary membrane. Therefore, maintaining cell barrier integrity is essential for respiratory health and function. On the vascular site, endothelial cells form a natural barrier, while in the airways epithelial cells are most important for protection of the lung tissues. Moreover, fibroblasts, by transforming to myofibroblasts, are essential for wound closure after mechanical and chemical microinjuries in the respiratory tract. Along this line, loss of cell resistance in vascular endothelial and lung epithelial cells enhances invasion of pathogens (e.g., SARS‐CoV‐2) and results in pulmonary edema formation, while increasing barrier function of pulmonary (myo)fibroblasts blocks gas exchange in patients with pulmonary fibrosis. Therefore, electrical cell‐substrate impedance sensing‐based quantification of changes in cell barrier function in lung endothelial and epithelial cells as well as fibroblasts after application of harmful triggers (e.g., hypoxia, receptor agonists, and toxicants) is a convenient and state‐of‐the‐art technique. After isolation of primary cells from mouse models and human tissues, changes in cell resistance can be detected in real time. By using lung cells from gene‐deficient mouse models, microRNAs or the small‐interfering RNA technology essential proteins for cell adhesion, for example, ion channels of the transient receptor potential family are identified in comparison to wild‐type control cells. In the future, these proteins may be useful as drug targets for novel therapeutic options in patients with lung edema or pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

Purpose: Secondary opportunistic coinfections are a significant contributor to morbidity and mortality in intensive care unit (ICU) patients, but can be difficult to identify. Presently, new blood RNA biomarkers were tested in ICU patients to diagnose viral, bacterial, and biofilm coinfections. Methods: COVID-19 ICU patients had whole blood drawn in RNA preservative and stored at −80°C. Controls and subclinical infections were also studied. Droplet digital polymerase chain reaction (ddPCR) quantified 6 RNA biomarkers of host neutrophil activation to bacterial (DEFA1), biofilm (alkaline phosphatase [ALPL], IL8RB/CXCR2), and viral infections (IFI27, RSAD2). Viral titer in blood was measured by ddPCR for SARS-CoV2 (SCV2). Results: RNA biomarkers were elevated in ICU patients relative to controls. DEFA1 and ALPL RNA were significantly higher in severe versus incidental/moderate cases. SOFA score was correlated with white blood cell count (0.42), platelet count (−0.41), creatinine (0.38), and lactate dehydrogenase (0.31). ALPL RNA (0.59) showed the best correlation with SOFA score. IFI27 (0.52) and RSAD2 (0.38) were positively correlated with SCV2 viral titer. Overall, 57.8% of COVID-19 patients had a positive RNA biomarker for bacterial or biofilm infection. Conclusions: RNA biomarkers of host neutrophil activation indicate the presence of bacterial and biofilm coinfections in most COVID-19 patients. Recognizing coinfections may help to guide the treatment of ICU patients. [ABSTRACT FROM AUTHOR]

Purpose: Outbreak of SARS-CoV2 and the COVID-19 pandemic had posed a threat to the healthcare system. The world had witnessed the failure of the healthcare system in the diagnosis, surveillance, and development of therapeutics effective against COVID-19. Hence, research emphasis has been given to technological inventions in developing robust and effective tools to fight against respiratory viral outbreaks, including SARS-CoV2. Methods: The scientific literature was searched and retrieved from PubMed, PubMed Central, the Cochrane Central Register of Controlled Trials (CENTRAL), and Scielo databases. The scientific literature was screened and selected based on recent studies in the area of nanotechnology based inventions and applications in developing diagnostics, surveillance tools, PPE kits, therapeutics, and vaccines. Results: Based on the scientific literature, there are enormous developments in designing robust diagnostics, surveillance tools, therapeutics, and vaccines. These findings show an increasing demand for nanotechnology-based inventions to tackle zoonotic spillover. Nanotechnology remains a growing area as interdisciplinary science and technology- enable a variety of inventions used in the COVID-19 pandemic. PPE design is a classic example where nanotechnology-driven materials are extensively used. Masks and other fabrics were also developed using nanotechnology-based materials. Conclusion: The study provides insights into nanotechnology based inventions in the fight against respiratory viral pathogens, including SARS-CoV2, and associated diseases. The study showed the application of nanotechnology in the development of diagnostics, surveillance tools, therapeutics, and vaccines. [ABSTRACT FROM AUTHOR]

Background & Aims: COVID-19 is one of the most significant diseases of recent years, spreading globally through human-to-human transmission. The purpose of this study is to investigate the seroepidemiological titers of SARS-CoV-2 antibodies in the urban population of Urmia city based on samples from individuals who referred to local laboratories. This study aims to provide new insights into the epidemiologic behavior of COVID-19 in society. Materials & Methods: Approximately 4,000 people who referred to the laboratories of Urmia participated in this study. Plasma levels of IgM and IgG antibodies were measured, and the frequency of positive antibody titers in the entire population was calculated based on demographic characteristics such as age and gender. IgM and IgG levels were compared between the two genders. Additionally, IgM and IgG levels were compared across age groups: children and adolescents under 20 years old; young adults (20–40 years old); middle-aged individuals (40-60 years old); and the elderly (60 years and older). Results: In this study, the frequencies of IgM+ and IgG+ were determined as well as the frequency of (IgM/IgG+) among the participants. Plasma levels of IgG were not different between women and men, whereas IgM levels were higher in women than in men. The plasma levels of antibodies in the age groups of children and young people were lower than in the middle-aged and elderly age groups. Conclusion: The findings of this study highlight that older adults and individuals with confirmed infections mounted a stronger antibody response. Additionally, the differences in IgM levels between genders warrant further research to explore their potential clinical significance.

Abstract The first outbreaks of coronavirus CoV, SARS-CoV and MERS-CoV have occurred in China and Saudi Arabia over the past decade, respectively. From the end of 2019, a great battle began by the world scientific community against SARS-CoV-2, the virus that caused COVID-19, a pathology that generated devastating consequences on all existing continents. Several mutations have already been detected in the structure of the virus, which have been responsible for the generation of many types of variants since the detection of the first COVID-19 virus identified in China. The worrisome mutations arising from the first genome of SARS-CoV-2 have been intensively studied. Some mutations increase the transmissibility of the disease through Spike, the protein responsible for binding the virus in the human cell. Among the numerous strains, the most discussed are called by the WHO as “variants of concern”. This study aims to review if COVID-19 severity may be variant dependent. Our study found tree publications that associate severity of COVI-19 symptoms to different SARS-CoV-2 variants. The most part of publications do not establish which variant is being expressed during studies. More studies with this focus are needed for a better understanding of the disease and respective variants.

Louis Chhor,1,2 Stefan Saggese,2 Garun S Hamilton,1,3 Martin Ian MacDonald1 1Monash Lung, Sleep, Allergy & Immunology, Monash Health, Melbourne, Victoria, Australia; 2Department of General Medicine, Monash Health, Melbourne, Victoria, Australia; 3School of Clinical Sciences, Monash University, Melbourne, Victoria, AustraliaCorrespondence: Louis Chhor, Department of General Medicine, Dandenong Hospital, 135 David St, Dandenong, VIC, 3175, Australia, Tel +61 3 9544 1000, Email louis.chhor2@easternhealth.org.auObjective: To compare clinical characteristics and outcomes of hospitalized acute exacerbations of COPD (AECOPD)s secondary to SARS-CoV-2 versus other respiratory viruses amongst a highly vaccinated population in the Omicron era.Design: Retrospective cohort study; analysis of hospital medical records and linked pathology and radiology reports.Setting: Tertiary health network in Victoria, Australia; January 2022–August 2022.Main Outcome Measures: Key clinical information including comorbidities, vaccination status, treatments administered and outcomes such as hospital length of stay, ICU admission, non-invasive ventilation usage and inpatient mortality.Results: One hundred ninety-nine viral AECOPDs - 125 SARS-CoV-2 and 74 other viruses were identified. Of the SARS-CoV-2 group. 13.6% were unvaccinated, 17.6% partially and 68.0% fully vaccinated. The SARS-CoV-2 group were older (77.2 vs 68.9, p < 0.00001) with more comorbidities (1[1– 2] vs 1[0– 2], p = 0.008) and lower candidacy for full resuscitation (25.6% vs 56.8%, p < 0.0001). Mortality tended to be higher among SARS-CoV2 admission (9.6% v 2.7%, p = 0.066) but rates of ICU admission (10.4% v 13.5%, p = 0.507), length of hospitalisation (5[3– 8] vs 5[3– 9], p = 0.9) and readmission within 30 days (25% vs 33.3%, p = 0.184) were similar.Conclusion: In a highly vaccinated population in the Omicron era, COPD patients requiring hospitalisation with SARS-CoV-2 are older with more comorbidities than those admitted with other respiratory viruses. Length of hospitalisation and ICU utilisation was similar. Inpatient mortality may be higher.Keywords: SARS-CoV2, coronavirus, COPD, viral exacerbations

Abstract Background Over the past decade, numerous studies on potential factors contributing to ventilation-induced lung injury have been carried out. Mechanical power has been pointed out as the parameter that encloses all ventilation-induced lung injury-contributing factors. However, studies conducted to date provide data regarding mechanical power during the early hours of mechanical ventilation that may not accurately reflect the impact of power throughout the period of mechanical ventilatory support on intensive care unit mortality. Methods Retrospective observational study conducted at a single center in Spain. Patients admitted to the intensive care unit, > o = 18 years of age, and ventilated for over 24 h were included. We extracted the mechanical power values throughout the entire mechanical ventilation in controlled modes period from the clinical information system every 2 min. First, we calculate the cutoff-point for mechanical power beyond which there was a greater change in the probability of death. After, the sum of time values above the safe cut-off point was calculated to obtain the value in hours. We analyzed if the number of hours the patient was under ventilation with a mechanical power above the safe threshold was associated with intensive care unit mortality, invasive mechanical ventilation days, and intensive care unit length of stay. We repeated the analysis in different subgroups based on the degree of hypoxemia and in patients with SARS CoV-2 pneumonia. Results The cut-off point of mechanical power at with there is a higher increase in intensive care unit mortality was 18 J/min. The greater the number of hours patients were under mechanical power > 18 J/min the higher the intensive care unit mortality in all the study population, in patients with SARS CoV-2 pneumonia and in mild to moderate hypoxemic respiratory failure. The risk of death in the intensive care unit increases 0.1% for each hour with mechanical power exceeding 18 J/min. The number of hours with mechanical power > 18 J/min also affected the days of invasive mechanical ventilation and intensive care unit length of stay. Conclusions The number of hours with mechanical power > 18 J/min is associated with mortality in the intensive care unit in critically ill patients. Continuous monitoring of mechanical power in controlled modes using an automated clinical information system could alert the clinician to this risk.

Abstract Background The architecture and dynamics of T cell populations are critical in orchestrating the immune response to SARS-CoV-2. In our study, we used T Cell Receptor sequencing (TCRseq) to investigate TCR repertoires in 173 post-infection COVID-19 patients. Methods The cohort included 98 mild and 75 severe cases with a median age of 53. We amplified and sequenced the TCR β chain Complementary Determining Region 3 (CDR3b) and performed bioinformatic analyses to assess repertoire diversity, clonality, and V/J allelic usage between age, sex and severity groups. CDR3b amino acid sequence inference was performed by clustering structural motifs and filtering validated reactive CDR3b to COVID-19. Results Our results revealed a pronounced decrease in diversity and an increase in clonal expansion in the TCR repertoires of severe COVID-19 patients younger than 55 years old. These results reflect the observed trends in patients older than 55 years old (both mild and severe). In addition, we identified a significant reduction in the usage of key V alleles (TRBV14, TRBV19, TRBV15 and TRBV6-4) associated with disease severity. Notably, severe patients under 55 years old had allelic patterns that resemble those over 55 years old, accompanied by a skewed frequency of COVID-19-related motifs. Conclusions Present results suggest that severe patients younger than 55 may have a compromised TCR repertoire contributing to a worse disease outcome. Graphical Abstract

Abstract Background Few data are available on the long-term mortality and functional status of geriatric patients surviving after hospitalization for COVID-19. We compared the mortality and functional status 18 months after hospitalization for geriatric patients who were hospitalized for COVID-19 or another diagnosis. Methods This was a multicentric cohort study in Paris from January to June 2021. We included patients aged 75 years and over who were hospitalized with COVID-19 or not during this period and compared their vital and functional status 18 months after hospitalization. Results We included 254 patients (63 hospitalized for COVID-19). As compared with patients hospitalized for other reasons, those hospitalized for COVID-19 were younger (mean [SD] age 86 [6.47] vs. 88 [6.41] years, p = 0.03), less frail (median Clinical Frailty Scale score 5 [4–6] vs. 6 [4–6], p 0.007) and more independent at baseline (median activities of daily living score 5.5 [4–6] vs. 5 [3.5–6], p 0.03; instrumental activities of daily living score 3 [1–4] vs. 2 [0–3], p 0.04). At 18 months, 50.8% (n = 32/63) of COVID-19 patients had died versus 66% (n = 126/191) of non-COVID-19 patients (p 0.03). On multivariate analysis, COVID-19 positivity was not significantly associated with 18-month mortality (adjusted hazard ratio 0.67, 95% confidence interval 0.40 to 1.13). At 18 months, the two groups did not differ in activities of daily living or frailty scores. Conclusions In this multicenter study of long-term mortality in geriatric patients discharged alive after hospitalization, positive COVID-19 status was not associated with excess mortality.

Despite the progress in medical data collection the actual burden of SARS‐CoV‐2 remains unknown due to under‐ascertainment of cases. This was apparent in the acute phase of the pandemic and the use of reported deaths has been pointed out as a more reliable source of information, likely less prone to under‐reporting. Since daily deaths occur from past infections weighted by their probability of death, one may infer the total number of infections accounting for their age distribution, using the data on reported deaths. We adopt this framework and assume that the dynamics generating the total number of infections can be described by a continuous time transmission model expressed through a system of nonlinear ordinary differential equations where the transmission rate is modeled as a diffusion process allowing to reveal both the effect of control strategies and the changes in individuals behavior. We develop this flexible Bayesian tool in Stan and study 3 pairs of European countries, estimating the time‐varying reproduction number (Rt$$ {R}_t $$) as well as the true cumulative number of infected individuals. As we estimate the true number of infections we offer a more accurate estimate of Rt$$ {R}_t $$. We also provide an estimate of the daily reporting ratio and discuss the effects of changes in mobility and testing on the inferred quantities. [ABSTRACT FROM AUTHOR]

Background: Over the past decade, numerous studies on potential factors contributing to ventilation-induced lung injury have been carried out. Mechanical power has been pointed out as the parameter that encloses all ventilation-induced lung injury-contributing factors. However, studies conducted to date provide data regarding mechanical power during the early hours of mechanical ventilation that may not accurately reflect the impact of power throughout the period of mechanical ventilatory support on intensive care unit mortality. Methods: Retrospective observational study conducted at a single center in Spain. Patients admitted to the intensive care unit, > o = 18 years of age, and ventilated for over 24 h were included. We extracted the mechanical power values throughout the entire mechanical ventilation in controlled modes period from the clinical information system every 2 min. First, we calculate the cutoff-point for mechanical power beyond which there was a greater change in the probability of death. After, the sum of time values above the safe cut-off point was calculated to obtain the value in hours. We analyzed if the number of hours the patient was under ventilation with a mechanical power above the safe threshold was associated with intensive care unit mortality, invasive mechanical ventilation days, and intensive care unit length of stay. We repeated the analysis in different subgroups based on the degree of hypoxemia and in patients with SARS CoV-2 pneumonia. Results: The cut-off point of mechanical power at with there is a higher increase in intensive care unit mortality was 18 J/min. The greater the number of hours patients were under mechanical power > 18 J/min the higher the intensive care unit mortality in all the study population, in patients with SARS CoV-2 pneumonia and in mild to moderate hypoxemic respiratory failure. The risk of death in the intensive care unit increases 0.1% for each hour with mechanical power exceeding 18 J/min. The number of hours with mechanical power > 18 J/min also affected the days of invasive mechanical ventilation and intensive care unit length of stay. Conclusions: The number of hours with mechanical power > 18 J/min is associated with mortality in the intensive care unit in critically ill patients. Continuous monitoring of mechanical power in controlled modes using an automated clinical information system could alert the clinician to this risk. [ABSTRACT FROM AUTHOR]

COVID-19 vaccine evaluations are mainly focused on antibody analyses, but there is growing interest in measuring the cellular immune responses from the researchers evaluating these vaccines. The cellular responses to several COVID-19 vaccines have been studied using the enzyme-linked immunospot (ELISPOT) assay for IFN-γ. However, the ELISPOT assay is no longer used only for research purpose and so the performance of this assay must be validated. Since the bioanalytical validation of ELISPOT-IFN-γ is essential for evaluating the method's effectiveness and establishing confidence in a vaccine's immunogenicity, the present work validates the ELISPOT-IFN-γ assay's performance in determining the frequency of IFN-γ-producing cells after stimulation with the SARS-CoV-2 spike protein. The validation was performed in peripheral blood mononuclear cells from volunteers immunized with anti-COVID-19 vaccines. According to the findings, the LOD was 17 SFU and the LLOQ was 22 SFU, which makes the method highly sensitive and suitable for evaluating low levels of cellular responses. The procedure's accuracy is confirmed by the correlation coefficients for the spike protein and anti-CD3+, being 0.98 and 0.95, respectively. The repeatability and intermediate precision tests were confirmed to be reliable by obtaining a coefficient of variation of ≤25%. The results obtained in this validation enable the assay to be employed for studying antigen-specific cells and evaluating cellular responses to vaccines. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to see if the CHA2DS2-VASc score (Cardiac failure or dysfunction, Hypertension, Age ≥ 75 [Doubled], Diabetes, Stroke [Doubled]—Vascular disease, Age 65–74 and Sex category [Female] score) could have potential clinical relevance in predicting the outcome of hospitalization time, need for ICU hospitalization, survival time, in-hospital mortality, and mortality at 3 and 6 months after discharge home. Materials: A retrospective analysis of 2183 patients with COVID-19 hospitalized at the COVID-19 Centre of the University Hospital in Wrocław, Poland, between February 2020 and June 2021, was performed. All medical records were collected as part of the COronavirus in LOwer Silesia—the COLOS registry project. The CHA2DS2-VASc score was applied for all subjects, and the patients were observed from admission to hospital until the day of discharge or death. Further information on patient deaths was prospectively collected following the 90 and 180 days after admission. The new risk stratification derived from differences in survival curves and long-term follow-up of our patients was obtained. Primary outcomes measured included in-hospital mortality and 3-month and 6-month all-cause mortality, whereas secondary outcomes included termination of hospitalization from causes other than death (home discharges/transfer to another facility or deterioration/referral to rehabilitation) and non-fatal adverse events during hospitalization. Results: It was shown that gender had no effect on mortality. Significantly shorter hospitalization time was observed in the group of patients with low CHA2DS2-VASc scores. Among secondary outcomes, CHA2DS2-VASc score revealed predictive value in both genders for cardiogenic (5.79% vs. 0.69%; p < 0.0001), stroke/TIA (0.48% vs. 9.92%; p < 0.0001), acute heart failure (0.97% vs. 18.18%; p < 0.0001), pneumonia (43% vs. 63.64%; p < 0.0001), and acute renal failure (7.04% vs. 23.97%; p < 0.0001). This study points at the usefulness of the CHA2DS2-VASc score in predicting the severity of the course of COVID-19. Conclusions: Routine use of this scale in clinical practice may suggest the legitimacy of extending its application to the assessment of not only the risk of thromboembolic events in the COVID-19 cohort. [ABSTRACT FROM AUTHOR]

Introduction: The high prevalence of deep vein thrombosis (DVT) in patients admitted to intensive care unit (ICU) for COVID-19-related acute respiratory distress syndrome (ARDS) would justify systematic screening of these patients or higher therapeutic dose of heparin for thromboprophylaxis. Material and method: We performed a systematic echo-Doppler of the lower limb proximal veins during the first 48 h (visit 1) and from 7 to 9 days after visit 1 (visit 2) in consecutive patients admitted to the ICU of a university-affiliated tertiary hospital for severe proven COVID-19 during the second wave. All patients received intermediate-dose heparin (IDH). The primary objective was to determine DVT incidence on venous Doppler ultrasound. Secondary objectives were to determine whether the presence of DVT modifies the anticoagulation regimen, the incidence of major bleeding according to International Society on Thrombosis and Haemostasis (ISTH) criteria, and the mortality rate of patients with and without DVT. Results: We included 48 patients (30 [62.5%] men) with a median age of 63 years [IQR, 54–70]. The prevalence of proximal deep vein thrombosis was 4.2% (2/48). In these two patients, after DVT diagnosis, anticoagulation was changed from intermediate to curative dose. Two patients (4.2%) had a major bleeding complication according to ISTH criteria. Among the 48 patients, 9 (18.8%) died before hospital discharge. No DVT or pulmonary embolism was diagnosed in these deceased patients during their hospital stay. Conclusion: In critically ill patients with COVID-19, management with IDH results in a low incidence of DVT. Although our study is not designed to demonstrate any difference in outcome, our results do not suggest any signal of harm when using intermediate-dose heparin (IDH) COVID-19 with a frequency of major bleeding complications less than 5%. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic underscores the critical need to integrate immunomics within the One Health framework to effectively address zoonotic diseases across humans, animals, and environments. Employing advanced high-throughput technologies, this interdisciplinary approach reveals the complex immunological interactions among these systems, enhancing our understanding of immune responses and yielding vital insights into the mechanisms that influence viral spread and host susceptibility. Significant advancements in immunomics have accelerated vaccine development, improved viral mutation tracking, and broadened our comprehension of immune pathways in zoonotic transmissions. This review highlights the role of animals, not merely as carriers or reservoirs, but as essential elements of ecological networks that profoundly influence viral epidemiology. Furthermore, we explore how environmental factors shape immune response patterns across species, influencing viral persistence and spillover risks. Moreover, case studies demonstrating the integration of immunogenomic data within the One Health framework for COVID-19 are discussed, outlining its implications for future research. However, linking humans, animals, and the environment through immunogenomics remains challenging, including the complex management of vast amounts of data and issues of scalability. Despite challenges, integrating immunomics data within the One Health framework significantly enhances our strategies and responses to zoonotic diseases and pandemic threats, marking a crucial direction for future public health breakthroughs. [ABSTRACT FROM AUTHOR]

Background: Few data are available on the long-term mortality and functional status of geriatric patients surviving after hospitalization for COVID-19. We compared the mortality and functional status 18 months after hospitalization for geriatric patients who were hospitalized for COVID-19 or another diagnosis. Methods: This was a multicentric cohort study in Paris from January to June 2021. We included patients aged 75 years and over who were hospitalized with COVID-19 or not during this period and compared their vital and functional status 18 months after hospitalization. Results: We included 254 patients (63 hospitalized for COVID-19). As compared with patients hospitalized for other reasons, those hospitalized for COVID-19 were younger (mean [SD] age 86 [6.47] vs. 88 [6.41] years, p = 0.03), less frail (median Clinical Frailty Scale score 5 [4–6] vs. 6 [4–6], p 0.007) and more independent at baseline (median activities of daily living score 5.5 [4–6] vs. 5 [3.5–6], p 0.03; instrumental activities of daily living score 3 [1–4] vs. 2 [0–3], p 0.04). At 18 months, 50.8% (n = 32/63) of COVID-19 patients had died versus 66% (n = 126/191) of non-COVID-19 patients (p 0.03). On multivariate analysis, COVID-19 positivity was not significantly associated with 18-month mortality (adjusted hazard ratio 0.67, 95% confidence interval 0.40 to 1.13). At 18 months, the two groups did not differ in activities of daily living or frailty scores. Conclusions: In this multicenter study of long-term mortality in geriatric patients discharged alive after hospitalization, positive COVID-19 status was not associated with excess mortality. [ABSTRACT FROM AUTHOR]

AbstractThe ongoing global pandemic caused by viral pathogens like SARS-CoV-2 (COVID-19) underscores that viral transmission is not confined by geographical boundaries. Thus, the development of novel antiviral therapies is critical to mitigate this crisis. Pyranopyrazoles have gained significant attention in medicinal chemistry due to their bioactive properties. In this study, we present a new series of pyranopyrazoles and their annulated derivatives, which were assessed for antiviral activity using a validated QSAR model and tested for their inhibitory effects against the viral 3CLpro enzyme. The findings were corroborated by various in silico techniques, including molecular docking, molecular dynamics simulations, and DFT calculations. Additionally, ADME studies were conducted to evaluate the pharmacokinetics and pharmacodynamics of the novel lead compound 2. These investigations identified a series of metabolically stable pyranopyrazoles and their annulated derivatives as effective inhibitors of the SARS-CoV-2 3CLpro enzyme, offering a promising therapeutic option for COVID-19. We believe that pyranopyrazoles warrant further evaluation and chemical optimization for potential use in COVID-19 treatment. [ABSTRACT FROM AUTHOR]

Introduction: Since COVID-19 first surfaced in 2019, it has seriously threatened public health. The most prevalent symptoms are respiratory ones. This study aimed to present the correlation between the severity of the clinical presentation of the disease and the results of respiratory function tests conducted within 6 months after hospital discharge. Methodology: This retrospective study included 99 patients with confirmed SARS-CoV-2 virus infection. Of all patients 24.2% had accentuated bronchovascular pattern, 9.1% had unilateral, and 29.3% had bilateral pneumonia. In comparison, 35.4% patients had diffuse changes, which were described as acute respiratory distress syndrome (ARDS) on computed tomography (CT). Results: Patients with unilateral, bilateral pneumonia or diffuse lung damage had significantly lower forced vital capacity (FVC) values. They were treated with non-invasive mechanical ventilation (NIV) or invasive mechanical ventilation (MV) and had lower FVC values (0.039). A negative, weak correlation existed between CT findings during the infection and Diffusing capacity for carbon monoxide (DLCO) measured after the infection (0.003). A negative, weak correlation was found between oxygen therapy, the use of NIV, and MV findings during the infection with DLCO. A negative correlation was noted between leukocyte values during the infection and forced expiratory volume in the first second (FEV1) and FVC after the infection. Conclusions: Patients with COVID-19 infection who need oxygen support and MV continue to suffer from loss of respiratory function after the resolution of COVID-19 infection. These findings highlight the negative predictive value of pulmonary tests in the long-term follow-up for the development of PC-ILD as well as decreased pulmonary capacity. [ABSTRACT FROM AUTHOR]

Purpose: Although some immune protection from close contact with individuals who have coronavirus disease 2019 (COVID-19) has been documented, there is limited data on the seroprevalence of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals who were in lockdown with confirmed COVID-19 cases. This study investigated immunogenicity against SARS-CoV-2 in household members and people who lived near home-quarantined patients with COVID-19. Materials and Methods: This cross-sectional study was conducted during the community-based care that took place during lockdowns in District 10, Ho Chi Minh City, Vietnam from July to September 2021. SARS-CoV-2 antibody levels were determined in index cases of COVID-19, household contacts, and a no-contact group from the same area. Results: A total of 770 participants were included (355 index cases, 103 household contacts, and 312 no contacts). All index cases were unvaccinated, but >90% of individuals in the household and no-contact groups had received ≥1 vaccine dose. SARS-CoV-2 neutralizing antibodies (Nabs) were present in >77% of unvaccinated index cases versus 64%/65.4% in the household/no-contact groups (p=0.001). Antibody concentrations in unvaccinated index cases were significantly higher than those in household contacts and no contacts, with no difference between the latter groups. In all cases, antibody levels declined markedly ≥6 weeks after infection, and failed to persist beyond this time in the household and no-contact groups. Conclusion: Community-based care may have helped to create community immunogenicity, but Nabs did not persist, highlighting a need for vaccination for all individuals before, or from 6 weeks after, infection with SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Background: The architecture and dynamics of T cell populations are critical in orchestrating the immune response to SARS-CoV-2. In our study, we used T Cell Receptor sequencing (TCRseq) to investigate TCR repertoires in 173 post-infection COVID-19 patients. Methods: The cohort included 98 mild and 75 severe cases with a median age of 53. We amplified and sequenced the TCR β chain Complementary Determining Region 3 (CDR3b) and performed bioinformatic analyses to assess repertoire diversity, clonality, and V/J allelic usage between age, sex and severity groups. CDR3b amino acid sequence inference was performed by clustering structural motifs and filtering validated reactive CDR3b to COVID-19. Results: Our results revealed a pronounced decrease in diversity and an increase in clonal expansion in the TCR repertoires of severe COVID-19 patients younger than 55 years old. These results reflect the observed trends in patients older than 55 years old (both mild and severe). In addition, we identified a significant reduction in the usage of key V alleles (TRBV14, TRBV19, TRBV15 and TRBV6-4) associated with disease severity. Notably, severe patients under 55 years old had allelic patterns that resemble those over 55 years old, accompanied by a skewed frequency of COVID-19-related motifs. Conclusions: Present results suggest that severe patients younger than 55 may have a compromised TCR repertoire contributing to a worse disease outcome. [ABSTRACT FROM AUTHOR]

During the COVID-19 pandemic, pancreatic surgery for pancreatic neuroendocrine tumors (PNETs) with surgical indications was postponed or canceled. Patients with PNET patients who underwent pancreatic surgery during the COVID-19 restriction period (3 years) were compared with a similar cohort of patients who underwent surgery in the previous 3 years. Data on patients' characteristics, waiting time, and surgical and pathology outcomes were evaluated. During the study period, 370 patients received surgery for PNETs, 205 (55%) during the first period, and 165 (45%) during the pandemic. A lengthening of the waiting list (182 [IQR 100–357] vs. 60 [40–88] days, p < 0.001) and increased use of anti-tumor medical treatments (any therapy, peptide receptor radionuclide therapy, and somatostatin analogs; all p < 0.001) was found. During the pandemic, surgery occurred after a median of 381 days [IQR 200–610] from diagnosis (vs. 103 [IQR 52–192] of the pre-COVID-19 period, p < 0.001). No statistically significant differences in tumor size and grading distribution were found between the two periods (both p > 0.05), yet only a modest increase of the median Ki67 values in cases operated during the pandemic (4% vs. 3%, p = 0.03). Lastly, these latter patients experienced less major postoperative complications (13% vs. 24%, p = 0.007). During COVID-19, the surgical waiting list of PNET patients was drastically extended, and bridge therapies were preferred. This did not result in more advanced cases at final pathology. PRRT and SSA are valid alternative therapies for PNETs when surgery is not feasible. [ABSTRACT FROM AUTHOR]

During and subsequent to a natural disaster, there is an expectation that certain elements of society will continue to operate with a degree of normalcy. For example, it is expected that emergency medical services will continue to function and remain reliable for the community served. Expectations such as these are based on the presumed reliability of government and the assumption that those responsible for the relevant infrastructure will have made plans to ensure it remains functional and taken steps to mitigate known weaknesses. The COVID-19 pandemic provides a case in point. Specifically, data captured during the pandemic are now the subject of ongoing review and analysis, and the findings from such studies are being used to inform planning and preparedness for the next public health disaster. This particular study was conducted in response to circumstantial evidence indicating that frontline workers in the healthcare profession may share some of the same ambivalence towards transmission mitigation as seen in the general population when confronted with new and emerging communicable diseases. This is a concern, as when medical personnel are either unable or unwilling to take reasonable steps to protect themselves and their patients, it undermines the readiness of the essential service. To explore this situation in greater depth, the study examines the real-time responses from a sample of frontline personnel interviewed during the pandemic. The results indicate that there are a number of opportunities to improve workforce readiness to assure reliable continuity during the next outbreak, epidemic or pandemic. [ABSTRACT FROM AUTHOR]

Early in the SARS-CoV2 pandemic, in this journal, Hou et al. (BMC Med 18:216, 2020) interpreted public genotype data, run through functional prediction tools, as suggesting that members of particular human populations carry potentially COVID-risk-increasing variants in genes ACE2 and TMPRSS2 far more often than do members of other populations. Beyond resting on predictions rather than clinical outcomes, and focusing on variants too rare to typify population members even jointly, their claim mistook a well known artifact (that large samples reveal more of a population's variants than do small samples) as if showing real and congruent population differences for the two genes, rather than lopsided population sampling in their shared source data. We explain that artifact, and contrast it with empirical findings, now ample, that other loci shape personal COVID risks far more significantly than do ACE2 and TMPRSS2—and that variation in ACE2 and TMPRSS2 per se unlikely exacerbates any net population disparity in the effects of such more risk-informative loci. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes virus-induced-senescence. There is an association between shorter telomere length (TL) in coronavirus disease 2019 (COVID-19) patients and hospitalization, severity, or even death. However, it remains unknown whether virus-induced-senescence is reversible. We aim to evaluate the dynamics of TL in COVID-19 patients 1 year after recovery from intensive care units (ICU). Longitudinal study enrolling 49 patients admitted to ICU due to COVID-19 (August 2020 to April 2021). Relative telomere length (RTL) quantification was carried out in whole blood by monochromatic multiplex real-time quantitative PCR (MMqPCR) assay at hospitalization (baseline) and 1 year after discharge (1-year visit). The association between RTL and ICU length of stay (LOS), invasive mechanical ventilation (IMV), prone position, and pulmonary fibrosis development at 1-year visit was evaluated. The median age was 60 years, 71.4% were males, median ICU-LOS was 12 days, 73.5% required IMV, and 38.8% required a prone position. Patients with longer ICU-LOS or who required IMV showed greater RTL shortening during follow-up. Patients who required pronation had a greater RTL shortening during follow-up. IMV patients who developed pulmonary fibrosis showed greater RTL reduction and shorter RTL at the 1-year visit. Patients with longer ICU-LOS and those who required IMV had a shorter RTL in peripheral blood, as observed 1 year after hospital discharge. Additionally, patients who required IMV and developed pulmonary fibrosis had greater telomere shortening, showing shorter telomeres at the 1-year visit. These patients may be more prone to develop cellular senescence and lung-related complications; therefore, closer monitoring may be needed. [ABSTRACT FROM AUTHOR]

Background: Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 varies widely in its presentation and severity, with low mortality in high-income countries. In this study in 16 Latin American countries, we sought to characterize patients with MIS-C in the pediatric intensive care unit (PICU) compared with those hospitalized on the general wards and analyze the factors associated with severity, outcomes, and treatment received. Study Design: An observational ambispective cohort study was conducted including children 1 month to 18 years old in 84 hospitals from the REKAMLATINA network from January 2020 to June 2022. Results: A total of 1239 children with MIS-C were included. The median age was 6.5 years (IQR 2.5-10.1). Eighty-four percent (1043/1239) were previously healthy. Forty-eight percent (590/1239) were admitted to the PICU. These patients had more myocardial dysfunction (20% vs 4%; P < 0.01) with no difference in the frequency of coronary abnormalities (P = 0.77) when compared to general ward subjects. Of the children in the PICU, 83.4% (494/589) required vasoactive drugs, and 43.4% (256/589) invasive mechanical ventilation, due to respiratory failure and pneumonia (57% vs 32%; P = 0.01). On multivariate analysis, the factors associated with the need for PICU transfer were age over 6 years (aOR 1.76 95% CI 1.25-2.49), shock (aOR 7.06 95% CI 5.14-9.80), seizures (aOR 2.44 95% CI 1.14-5.36), thrombocytopenia (aOR 2.43 95% CI 1.77-3.34), elevated C-reactive protein (aOR 1.89 95% CI 1.29-2.79), and chest x-ray abnormalities (aOR 2.29 95% CI 1.67-3.13). The overall mortality was 4.8%. Conclusions: Children with MIS-C who have the highest risk of being admitted to a PICU in Latin American countries are those over age six, with shock, seizures, a more robust inflammatory response, and chest x-ray abnormalities. The mortality rate is five times greater when compared with high-income countries, despite a high proportion of patients receiving adequate treatment. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 causes COVID-19, a global health crisis with diverse symptoms, posing diagnostic challenges. The scarcity of testing equipment leads to long wait times for COVID-19 tests. To address this challenge, we propose a surface plasmon resonance biosensor configured as: Prism (BK7)/Copper (Cu)/Nickle (Ni)/graphene. This configuration proves advantageous for the detection of the SARS-CoV-2 virus. Addition of graphene as a 2D material enhances the sensitivity for detecting biomolecules. Graphene serves as a bio recognizing material, facilitating the binding of ample biomolecules on the sensing surface. Through optimization, we achieve a maximum sensitivity of 399.80°/RIU, coupled with remarkable detection accuracy and figure of merit. Hence, the proposed biosensor holds promise for biosensing applications, offering higher sensitivity and utilizing advanced fabrication techniques. [ABSTRACT FROM AUTHOR]

In this work, we use a network representation of the globular crystalline structure of a given protein as a graph structure with N nodes and E edges in order to analyze quantitatively the flow information and to identify key sites within the globular structure. Each node nj represents a |$ C_{\alpha}^{i}$| carbon of the main backbone whereas the node's degree ki is a measure of its physical interactions. In order to identify biologically relevant and active nodes, we compute local per residue closeness |$ C_{c}(i)$|⁠ , betweenness |$ C_{b}(i)$| and eigenvector centralities |$ C_{e}(i)$|⁠. Further analysis is done by embedding a stochastic dynamic discrete Markov chain in order to evaluate the dynamics of a set of normal random walkers (NRW's) within the network. From this, we compute the mean first passage time matrix M and the stationary occupation probability vector ψi for each node. These two measures provide very useful information on the dynamical process embed within the |$ C_{\alpha}$| network. We apply this to SARS-CoV2 Mpro main protease which is a key enzyme in the virus replication cycle. In particular, we focus our attention to the properties of the catalytic dyad integrated by His41-Cys145 in Mpro main protease since this active site has been under intense scrutiny as a pharmaceutical target. In addition, our results show the existence of additional relevant aminoacids that might play a fundamental role on signal propagation and allosteric pathways in SARS-CoV main proteases. [ABSTRACT FROM AUTHOR]

ObjectivesThis study aimed to investigate the association of baseline coagulation proteins with hospitalization variables in COVID-19 patients admitted to ICU, as well as coagulation system changes after one-year post-discharge, taking into account gender-specific bias in the coagulation profile.MethodsWe conducted a prospective longitudinal study on 49 ICU-admitted COVID-19 patients. Proteins were measured using a Luminex 200™. The association between coagulation protein levels and hospitalization variables was carried out by generalized linear models adjusted by the most relevant covariates.ResultsAt ICU admission, lower factor XII, antithrombin, and protein C levels were linked to the need for invasive mechanical ventilation (IMV) or its duration (p=0.028; p=0.047 and p=0.015, respectively). Likewise, lower factor XII, antithrombin, and prothrombin levels were associated with longer ICU length of stay (ICU LOS) (p=0.045; p=0.022; p=0.036, respectively). From baseline to the end of the follow-up, factor XII, antithrombin, prothrombin, and protein C levels notably increased in patients with longer ICU LOS. One-year post-discharge, differences were found for factor IX, aPTT, and INR. Gender-stratified analysis showed sustained alterations in males.ConclusionsDepleted specific coagulation factors on ICU admission are associated with increased severity in critically ill COVID-19 patients. Most coagulation alterations recover one-year post-discharge, except for factor IX, aPTT and INR, which remain reduced.

ABSTRACT Objective In the past 5 years, a large number of serological assays for large‐scale detection of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) antigen emerged. Serological assays for SARS‐CoV‐2 were needed to support clinical diagnosis and epidemiological investigations. However, there were limited data on the diagnostic accuracy of these serological assays. We aimed to compare the diagnostic accuracy of 11 commercial serological assays for coronavirus disease‐2019 (COVID‐19) by taking the reverse transcriptase polymerase chain reaction (RT‐PCR) assays as the reference standard, which served as the control arm to conduct an indirect comparison of diagnostic accuracy for 11 different SARS‐CoV‐2 serological assays. Methods This meta‐analysis was conducted following the PRISMA 2020 reporting guideline. Electronic searches were performed using the Cochrane Library, PubMed, Embase, Web of Science, Chinese Biological Medicine Database (CBM), China National Knowledge Infrastructure (CNKI), WANFANG, and Chinese Weipu (VIP) databases. Fifty‐seven articles, including 11 serologic‐based IgG, IgM, and total antibodies assays for SARS‐CoV‐2, published before June 2024, were included in this meta‐analysis. The main outcome of this meta‐analysis used to evaluate the performance of 11 assays included pooled diagnostic odds ratio (DOR), area under the summary receiver operating characteristic (AUC), and summary receiver operating characteristic curve (SROC). The R software was used for adjusted indirect comparison to calculate the relative diagnostic odds ratio (RDOR) with corresponding 95% confidence intervals (CIs), and indirect comparison forest plots showed the results. Results A total of 57 articles met the eligibility criteria for inclusion in our meta‐analysis. The pooled DOR and the AUC for access SARS‐CoV‐2 IgG were 564.28 (95% CI 229.58−1386.91) and 1.00, and as for EDI novel coronavirus COVID‐19 IgG those were 85.27 (95% CI 53.99−134.68) and 0.95, for EDI novel coronavirus COVID‐19 IgM were 49.42 (95% CI 16.47−148.30) and 0.86, for iFlash‐SARS‐CoV‐2 IgG were 652.31 (95% CI 362.32−1174.41) and 0.97, for iFlash‐SARS‐CoV‐2 IgM were 36.72 (95% CI 12.42−108.54) and 0.76, for MAGLUMI 2019‐nCoV IgG were 145.44 (95% CI 59.37−356.30) and 0.90, for MAGLUMI 2019‐nCoV IgM were 21.59 (95% CI 14.27−32.67) and 0.59, for ortho‐clinical anti‐SARS‐CoV‐2 IgG were 719.46 (95% CI 262.34−1973.13) and 1.00, for ortho‐clinical anti‐SARS‐CoV‐2 total were 1104.60 (95% CI 395.64−3083.99) and 1.00, for Siemens SARS‐CoV‐2 total (COV2T) were 1143.37 (95% CI 316.49−4130.62) and 0.99, for Wantai SARS‐CoV‐2 total Ab were 1014.98 (95% CI 618.48−1665.66) and 1.00. The pooled DOR for assays‐based IgG (n = 43), assays‐based total antibody (n = 35), and assays‐based IgM (n = 20) was 242.88 (95% CI 157.66−374.16), 1215.90 (95% CI 547.14−2702.07), and 40.99 (95% CI 22.63−74.25). The diagnostic accuracy of assays‐based total antibody performed better than those of assays‐based IgG and assays‐based IgM; assays‐based IgG performed better than assays‐based IgM. Conclusion This study suggested that the Siemens SARS‐CoV‐2 total (COV2T), ortho‐clinical anti‐SARS‐CoV‐2 total, and Wantai SARS‐CoV‐2 total had the best overall diagnostic accuracy. The diagnostic efficacy of the assays‐based total antibody had statistically significantly higher accuracy than those of assays‐based IgG and assays‐based IgM for COVID‐19.

Background: COVID-19 (Coronavirus Disease-19) is a respiratory infection caused by the SARS-CoV-2 virus. In 2020, the World Health Organization (WHO) declared COVID-19 a global pandemic due to the rapid rise in cases and mortality rates worldwide. The pandemic has impacted millions of people and continues to pose a significant global public health threat. Accurate diagnosis of the disease depends on laboratory testing, with RT-PCR widely recognized as the gold standard for confirming COVID-19. Aims: To describe an overview of COVID-19 test results at Laboratory Faculty of Medicine, Universitas Swadaya Gunung Jati, Cirebon, Indonesia, from 2021-2022. Methods: This study used a descriptive observational method. The sample was collected in July 2024 using a total sampling technique. The sample includes all 135,713 patients who had COVID-19 tests at Laboratory Faculty of Medicine Swadaya Gunung Jati Univesity between 2021 and 2022. Data were collected from medical records of COVID-19 test. The variables of this study include gender, age, and COVID-19 test results. A statistical analysis was used to determine frequency distribution. Results: The results of the study showed that among the sample who tested for COVID-19, the majority are male (50.9%) and early adolescent age group (23.9%). RT-PCR test findings were positive in 16.3% of patients and negative in 83.7% of patients. Among PCR positive cases, the majority are female (17.4%), with seniors age groups >65 years accounting for 39.0%. Conclusion: Most of the tested samples are males and early adolescent age groups, with more negative PCR results than positive ones. Among positive cases, the highest number was found in females and seniors age group. It is recommended that females and seniors age groups keep protected during COVID-19 outbreaks. Received: 25 September 2024 | Reviewed: 22 October 2024 | Revised: 30 November 2024 | Accepted: 11 December 2024.

Aim: To correlate hematological, inflammatory indicators and serological responses among COVID-19 patients to point out the significant biomarkers for disease management and prognosis.Materials & methods: Standard analytical and molecular methods were used to assess various inflammatory and serological Responses among COVID-19 patients (ICU- (n = 99) and non-ICU patients (n = 64) as compared with health control (n = 40).Results: Significant differences in the Hb, WBC, Lymphocyte count, CRP and serum ferritin (p

Background: The AYUSH 64 formulation helps to treat mild to moderate cases of COVID-19. Although several drugs have been proposed to combat COVID-19, no medication is available for SARS-CoV-2 infection. The RNA-dependent RNA polymerase (RdRp) is the pivotal enzyme of SARS-CoV-2 replication, so it could be considered a better drug target for experimental studies. Objective: The AYUSH-64 formulation plants exhibited multiple therapeutic properties; thus, the present study aims to screen the phytocompounds of these plants against SARS CoV2 RdRp to identify specific compounds that could potentially affect COVID-19 infection. Materials and methods: PatchDock and AutoDock tools were used for docking experiments. MD simulations and Density Functional Theory (DFT) calculations of protein-ligand Picroside-I and Remdesivir complexes were carried out in GROMACS v2019.4 and Gaussian 09 software, respectively. Results: Among the tested, five phytocompounds (Picroside I, Oleanolic acid, Arvenin I, II, and III) from AYUSH-64 medicinal plants showed possible binding with RdRp catalytic residues (Ser759, Asp760, and Asp761). Of these, Picroside I exhibited hydrogen bond interactions with NTP entry channel residues (Arg553 and Arg555). The MM-PBSA free energy, RMSD, Rg, PCA, and RMSF analysis suggested that the Picroside I complex showed stable binding interactions with RdRp in the 50 ns simulation. In addition to this, Picroside I revealed its robust and attractive nature toward the target protein, as confirmed by DFT. Conclusion: The results of this study have proposed that Picroside I from AYUSH 64 medicinal plant compounds was the selective binder of catalytic and NTP entry channel residues of SARS-CoV2 RdRp thereby; it may considered as a potential inhibitor of SARS-CoV2 RdRp.

Abstract The COVID-19 pandemic has posed a major challenge to healthcare systems globally. Millions of people have been infected, and millions of deaths have been reported worldwide. Glucocorticoids have attracted worldwide attention for their potential efficacy in the treatment of COVID-19. Various glucocorticoids with different dosages and treatment durations have been studied in patients with different severities, with a suitable dosage and treatment duration not yet defined. This study aimed to investigate whether in-hospital survival differs between critically ill patients treated with low-dose glucocorticoids, high-dose glucocorticoids or no glucocorticoids. All critically ill patients admitted to the intensive care unit of the Charité Hospital—Universitätsmedizin Berlin between February 2020 and December 2021 with COVID-19 pneumonia receiving supplemental oxygen were eligible to participate in this multicenter real-world data study. Patients were retrospectively assigned to one of three groups: the high corticosteroid dose (HighC) group (receiving 6 mg parenteral dexamethasone or an equivalent corticosteroid dosage for ten days), the low corticosteroid dose (LowC) group (receiving less than 6 mg parenteral dexamethasone or an equivalent corticosteroid dosage for ten days), or the no corticosteroid (NoC) group. Overall survival and risk effects were compared among groups within the total observation period, as well as at 35 days after the onset of COVID-19 symptoms. Adjusted multivariable Cox proportional hazard regression analysis was performed to compare the risk of death between the treatment groups. Out of 1561 critically ill COVID-19 patients, 1014 were included in the baseline analysis. In the survival study, 1009 patients were assigned to the NoC (n = 346), HighC (n = 552), or LowC group (n = 111). The baseline characteristics were balanced between groups, except for age, BMI, APACHE II score, SOFA and SAPS II. While the 35-day survival did not show any differences, a landmark analysis of the patients surviving beyond 35 days revealed differences between groups. The restricted mean survival time was 112 days in the LowC group [95% CI: 97 – 128], 133 days in the HighC group [95% CI: 124 – 141] and 144 days in the NoC group [95% CI: 121 – 167]. The multivariable-adjusted Cox proportional hazard analysis indicated that, regardless of age, sex, health status or invasive oxygenation, a low-dose treatment increased the hazard of death of critically ill COVID-19 patients by a factor of 2.09 ([95% CI: 0.99, 4.4], p = 0.05) and a high-dose corticosteroid treatment increased the risk by a factor of 1.07 ([95% CI: 0.53, 2.15], p = 0.85) compared to no treatment with glucocorticoids. The analysis reveals that corticosteroid treatment does not influence the survival of critically ill COVID-19 patients in the intensive care unit within 35 days. Our evaluations further suggest that regardless of ventilation status, the decision-making process for administering corticosteroid therapy should account for the individual severity of the illness.

Introduction: Although Coronavirus disease 2019 (COVID-19) vaccination is critical to control its spread, vaccine hesitancy varies significantly among the United States population; moreover, some vaccine recipients experienced various adverse effects. We aim to assess the impact of COVID-19 vaccine hesitancy in a university-affiliated community, the factors affecting participants' decisions, and their adverse effects. Methods: A pre-vaccination online Institutional Review Board IRB-approved survey was emailed in Nov/Dec 2020, 2 months before the implementation of state-policy protocols for COVID-19 vaccination. A post-vaccination survey was emailed in May/June 2021, two months after protocol execution. A third follow-up survey was sent in Nov/Dec 2021, and a fourth was sent in June/July 2022. The study population included three groups of adult participants: university students, faculty, and staff-(MS), university health system patients- (MP), and Cancer Center patients-(MCP). The study was designed as a longitudinal cohort study. Statistical analyses were performed using SPSS. Results: With a combined response rate of 26% (40,578/157,292) among the four surveys, 15,361 participants completed the first survey (MS = 4,983, MP = 9,551, and MCP = 827). 2/3 of participants (63.5%) were willing to get vaccinated, with a significant difference in acceptance among groups, MS:56.6%, MP:66.2%, and MCP:71.6% (p < 0.05). Vaccine acceptance rates reached 89% in the second survey after the vaccine's approval, with a lower acceptance rate of MS:84.6% than with MP:90.74% and MCP:92.47% participants (p<0.05). Safety and effectiveness concerns were the main factors affecting participants' decisions in all the first three surveys; however, participants reported these concerns decreased between pre-vaccination, post-vaccination, and follow-up surveys with 87%, 56%, and 46%, respectively(p < 0.05). More than two-thirds of the participants (70%) reported having either minor/moderate symptoms (61.6%) or major symptoms (8.6%) after getting some of the vaccine doses (p<0.05). Conclusion: The hesitance of COVID-19 vaccination was associated with concerns regarding its safety and efficacy. Vaccine acceptance rose higher than expected after protocol execution, likely due to continuous education, whereas safety and efficacy remain factors hindering vaccine acceptance. Continuous education focusing on safety and efficacy of the vaccine can reduce vaccine hesitancy and raise the rates of vaccination. [ABSTRACT FROM AUTHOR]

PARP-catalysed ADP-ribosylation (ADPr) is important in regulating various cellular pathways. Until recently, PARP-dependent mono-ADP-ribosylation has been poorly understood due to the lack of sensitive detection methods. Here, we utilised an improved antibody to detect mono-ADP-ribosylation. We visualised endogenous interferon (IFN)-induced ADP-ribosylation and show that PARP14 is a major enzyme responsible for this modification. Fittingly, this signalling is reversed by the macrodomain from SARS-CoV-2 (Mac1), providing a possible mechanism by which Mac1 counteracts the activity of antiviral PARPs. Our data also elucidate a major role of PARP9 and its binding partner, the E3 ubiquitin ligase DTX3L, in regulating PARP14 activity through protein-protein interactions and by the hydrolytic activity of PARP9 macrodomain 1. Finally, we also present the first visualisation of ADPr-dependent ubiquitylation in the IFN response. These approaches should further advance our understanding of IFN-induced ADPr and ubiquitin signalling processes and could shed light on how different pathogens avoid such defence pathways. Synopsis: Mono-ADP-ribosylation has emerged as a crucial factor in innate immune responses, but is understudied due to the lack of sensitive detection methods. This study visualizes endogenous interferon-induced ADP-ribosylation and shows that PARP14 is a major enzyme responsible for this signalling event. Immunity responses induce PARP14-dependent ADP-ribosylation. SARS2-CoV2 Mac1 can remove PARP14-dependent ADP-ribosylation. PARP14, PARP9 and DTX3L regulate the formation of ubiquitin and ADPr foci in the cytoplasm. PARP14 activity is regulated by PARP9/DTX3L, through (1) the hydrolytic activity of PARP9 and (2) PARP14 interaction with DTX3L. Innate immune responses induce PARP14-dependent ADP-ribosylation that is tightly regulated by PARP9 and DTX3L. [ABSTRACT FROM AUTHOR]

• Determining the risk for intensive care in COVID-19 patients is essential. • Artificial neural networks may provide reliable predictions. • We used a data ensemble refinement greedy algorithm (DERGA) on data from 1596 patients. • The optimal prediction model was based on only four hematological parameters. • The best prediction corresponded to a particularly high accuracy of 97.12 %. It is important to determine the risk for admission to the intensive care unit (ICU) in patients with COVID-19 presenting at the emergency department. Using artificial neural networks, we propose a new Data Ensemble Refinement Greedy Algorithm (DERGA) based on 15 easily accessible hematological indices. A database of 1596 patients with COVID-19 was used; it was divided into 1257 training datasets (80 % of the database) for training the algorithms and 339 testing datasets (20 % of the database) to check the reliability of the algorithms. The optimal combination of hematological indicators that gives the best prediction consists of only four hematological indicators as follows: neutrophil-to-lymphocyte ratio (NLR), lactate dehydrogenase, ferritin, and albumin. The best prediction corresponds to a particularly high accuracy of 97.12 %. In conclusion, our novel approach provides a robust model based only on basic hematological parameters for predicting the risk for ICU admission and optimize COVID-19 patient management in the clinical practice. [ABSTRACT FROM AUTHOR]

The impact of COVID‐19 on paracoccidioidomycosis (PCM) in Argentina and the consequences generated by the pandemic are discussed. From 2018 to 3 years after the pandemic declaration, 285 proven PCM patients were registered. No association between both diseases was documented. PCM frequency decreased to extremely low levels in 2020. Mandatory social isolation and the emotional and psychological effects generated under pandemic circumstances led to delays in diagnosis, severe disseminated cases, and other challenges for diagnosis in subsequent years. Probable underdiagnosis should be considered due to the overlap of clinical manifestations, the low index of suspicion and the lack of sensitive diagnostic tools. [ABSTRACT FROM AUTHOR]

Introduction: Studies investigating the effects of SARS-CoV-2 on male reproductive function are few and heterogeneous, and results are often conflicting. This systematic review and meta-analysis was carried out on studies conducted in men with active or anamnestic SARS-CoV-2 infection to evaluate its consequences on the male sex hormone profile and semen parameters. Materials and method: This meta-analysis follows the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) protocols. PubMed, Scopus, Cochrane, and Embase databases were searched to identify relevant studies. We originally selected 3553 articles. After the eligibility phase, 16 articles met our inclusion criteria encompassing 11 case-control studies and 5 cohort studies (2 prospective and 3 retrospective studies). We performed the quantitative analysis with Comprehensive Meta-Analysis Software. Cochran-Q and heterogeneity (I2) indexes were used to assess statistical heterogeneity. Sensitivity analysis and publication bias tests were also performed. Results: Overall, 1250 patients with active or recent (up to 80 days before) COVID-19 infection and 1232 matched healthy controls were included. Sperm concentration, total sperm count, and total motility were significantly lower in patients compared with controls. Patients also showed lower levels of total testosterone and follicle-stimulating hormone, and higher levels of luteinizing hormone, 17β-estradiol, and prolactin compared with healthy controls. None of the included studies found the presence of SARS-CoV-2 mRNA in the semen of infected patients. Conclusion: The present systematic review and meta-analysis suggests the presence of an association between SARS-CoV-2 infection and primary testicular damage manifested with a picture of altered steroidogenesis and worsening spermatogenesis. The absence of the virus in the seminal fluid indicates a low possibility of sexual transmission of the infection to partners and offspring. However, our findings mostly show short-term follow-up, while few studies have considered the long-term consequences of the viral infection, thus further studies are needed to evaluate the long-term consequences on male reproductive health. [ABSTRACT FROM AUTHOR]

Background: In early infected or severe coronavirus disease 2019 (COVID-19) patients, circulating NK cells are consistently reduced, despite being highly activated or exhausted. The aim of this paper was to establish whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (SP) may directly trigger NK cells and through which receptor(s). Methods: SP-stimulated human NK cells have been evaluated for the expression of activation markers, cytokine release, and cytotoxic activity, as well as for gene expression profiles and NF-κB phosphorylation, and they have been silenced with specific small interfering RNAs. Results: SPs from the Wuhan strain and other variants of concern (VOCs) directly bind and stimulate purified NK cells by increasing activation marker expression, cytokine release, and cytolytic activity, prevalently in the CD56brightNK cell subset. VOC-SPs differ in their ability to activate NK cells, G614, and Delta-Plus strains providing the strongest activity in the majority of donors. While VOC-SPs do not trigger ACE2, which is not expressed on NK cells, or other activating receptors, they directly and variably bind to both Toll-like receptor 2 (TLR2) and TLR4. Moreover, SP-driven NK cell functions are inhibited upon masking such receptors or silencing the relative genes. Lastly, VOC-SPs upregulate CD56dimNK cell functions in COVID-19 recovered, but not in non-infected, individuals. Conclusions: TLR2 and TLR4 are novel activating receptors for SP in NK cells, suggesting a new role of these cells in orchestrating the pathophysiology of SARS-CoV-2 infection. The pathogenic relevance of this finding is highlighted by the fact that free SP providing NK cell activation is frequently detected in a SARS-CoV-2 inflamed environment and in plasma of infected and long-COVID-19 subjects. [ABSTRACT FROM AUTHOR]

Background: Literature reporting the onset of Creutzfeldt-Jakob disease (CJD) immediately after COVID-19 infection has strengthened a possible causal link between infection and neurodegeneration. Here, we report a novel case undergoing detailed neuropathological assessment. Case report: Two months after he had contracted SARS-CoV-2 infection, a 54-year-old man manifested a subacute onset of ataxia, headache, anosmia, and hallucinations, followed by rapidly progressive cognitive decline. Electroencephalography documented unspecific slowing with periodic polyphasic delta waves. Brain MRI showed hyperintensities of basal ganglia and thalami on DWI/FLAIR. CSF tested positive for the 14-3-3 protein, and prion seeding activity was demonstrated by the real-time quaking-induced conversion assay. The patient died 2 months after the neurologic onset. The neuropathological examination confirmed the diagnosis of CJD and ruled out COVID-19-related encephalitis. Discussion: To disentangle the link between COVID-19 infection and CJD, neuropathology is essential determining the extent of changes related to both conditions. In our patient, we did not find any specific abnormality related to COVID-19. Our conclusion is in line with the current worldwide epidemiological data that do not show an increase in CJD cases since the beginning of the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]