Search

The global spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) since 2019 has led to a continuous evolution of viral variants, with the latest concern being the Omicron (B.1.1.529) variant. In this study, classical molecular dynamics simulations were conducted to elucidate the biophysical aspects of the Omicron spike protein's receptor-binding domain (RBD) in its interaction with human angiotensin-converting enzyme 2 (hACE2) and a neutralizing antibody, comparing it to the wildtype (WT). To model the Omicron variant, 15 in silico mutations were introduced in the RBD region of WT (retrieved from PDB). The simulations of WT spike-hACE2 and Omicron spike-hACE2 complexes revealed comparable binding stability and dynamics. Notably, the Q493R mutation in the Omicron spike increased interactions with hACE2, particularly with ASP38 and ASP355. Additionally, mutations such as N417K, T478K, and Y505H contributed to enhanced structural stability in the Omicron variant. Conversely, when comparing WT with Omicron in complex with a neutralizing antibody, simulation results demonstrated poorer binding dynamics and stability for the Omicron variant. The E484K mutation significantly decreased binding interactions, resulting in an overall decrease in binding energy (∼-57 kcal/mol) compared to WT (∼-84 kcal/mol). This study provides valuable molecular insights into the heightened infectivity of the Omicron variant, shedding light on the specific mutations influencing its interactions with hACE2 and neutralizing antibodies.

Vaccinating patients receiving dialysis may prevent morbidity and mortality in this vulnerable population. The National Forum of End-Stage Renal Disease Networks (the Forum) published a revised vaccination toolkit in 2021 to update evidence and recommendations on vaccination for patients receiving dialysis. Significant changes in the last 10 years include more data supporting the use of a high-dose influenza vaccine, the introduction of the Heplisav-B vaccine for hepatitis B, and changes in pneumococcal vaccines, including the approval of the PCV15 and PCV20 to replace the PCV13 and PPSV23 vaccines. Additional key items include the introduction of vaccines against severe acute respiratory syndrome coronavirus 2, the virus that causes coronavirus disease 2019 (COVID-19), and a new vaccine to prevent respiratory syncytial virus disease. Historically, influenza and pneumococcal vaccinations were routinely administered by dialysis facilities, and because of possible risks of hematogenous spread of hepatitis B, dialysis providers often have detailed hepatitis B vaccine protocols. In March 2021, COVID-19 vaccines were made available for dialysis facilities to administer, although with the end of the public health emergency, vaccine policies by dialysis facilities against COVID-19 remains uncertain. The respiratory syncytial virus vaccine was authorized in 2023, and how dialysis facilities will approach this vaccine also remains uncertain. This review summarizes the Forums vaccination toolkit and discusses the role of the dialysis facility in vaccinating patients to reduce the risk of severe infections.

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]

Copyright of Revista Latinoamericana de Hipertension is the property of Revista Latinoamericana de Hipertension and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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]

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]

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]

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]

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]

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]

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]

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]

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]

BACKGROUND CONTEXT: COVID-19 has been shown to adversely affect multiple organ systems, yet little is known about its effect on perioperative complications after spine surgery or the optimal timing of surgery after an infection. We used the NIH National COVID Cohort Collaborative (N3C) database to characterize the risk profile in patients undergoing spine surgery during multiple time windows following COVID-19 infection. METHODS: We queried the National COVID Cohort Collaborative, a database of 17.4 million persons with 6.9 million COVID-19 cases, for patients undergoing lumbar spinal fusion surgery. Patients were stratified into those with an initial documented COVID-19 infection within 3 time periods: 0 to 2 weeks, 2 to 6 weeks, or 6 to 12 weeks before surgery. RESULTS: A total of 60,541 patients who underwent lumbar spinal fusion procedures were included. Patients who underwent surgery within 2 weeks of their COVID-19 diagnosis had a significantly increased risk for venous thromboembolic events (OR 2.29, 95% CI 1.58-3.32), sepsis (OR 1.56, 95% CI 1.03-2.36), 30-day mortality (OR 5.55, 95% CI 3.53-8.71), and 1-year mortality (OR 2.70, 95% CI 1.91-3.82) compared with patients who were COVID negative during the same period. There was no significant difference in the rates of acute kidney injury or surgical site infection. Patients undergoing surgery between 2 and 6 weeks or between 6 and 12 weeks from the date of COVID-19 infection did not show significantly elevated rates of any complication analyzed. CONCLUSIONS: Patients undergoing lumbar spinal fusion within 2 weeks from initial COVID-19 diagnosis are at increased risk for perioperative venous thromboembolic events and sepsis. This effect does not persist beyond 2 weeks, however, so it may be warranted to postpone non-urgent spine surgeries for at least 2 weeks following a COVID-19 infection or to consider a more aggressive VTE chemoprophylaxis regimen for urgent surgery in COVID-19 patients.

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 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 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

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]

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]

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]

Context: Patients with inflammatory bowel disease (IBD) were found to have the higher intestinal expression of Angiotensin-Converting Enzyme2 (ACE2) that could consequently increase susceptibility to COVID-19 infection. Objective: This study reports the outcomes of COVID-19 infection in a large cohort of IBD patients. We compare levels of serum ACE and IFN-α between COVID19 patients with and without IBD. We performed a cross-sectional retrospective multicenter study. Methods: We enrolled patients with IBD screened for SARS-COV-2 in six medical centres in Iran from June to November 2020. The blood samples were drawn to measure COVID-19 IgM and IgG, and serum levels of sACE2, sACE1, and interferon-α, regardless of suspicious symptoms have done the molecular test. Results: A total of 534 IBD patients were included in the study. Of these, 109 (20.0%) cases had detectable IgG and IgM against SARS-CoV-2. sACE2 levels were higher in IBD patients than controls, whereas ACE1and IFN-α levels were similar among groups. [ABSTRACT FROM AUTHOR]

Background: Severe cases of COVID‐19 often lead to the development of acute respiratory syndrome, a critical condition believed to be caused by the harmful effects of SARS‐CoV‐2 on type II alveolar cells. These cells play a crucial role in producing pulmonary surfactants, which are essential for proper lung function. Specifically focusing on surfactant proteins, including Surfactant protein A (SP‐A), Surfactant protein B, Surfactant protein C, and Surfactant protein D (SP‐D), changes in the levels of pulmonary surfactants may be a significant factor in the pathological changes seen in COVID‐19 infection. Objective: This study aims to gain insights into surfactants, particularly their impacts and changes during COVID‐19 infection, through a comprehensive review of current literature. The study focuses on the function of surfactants as prognostic markers, diagnostic factors, and essential components in the management and treatment of COVID‐19. Finding: In general, pulmonary surfactants serve to reduce the surface tension at the gas–liquid interface, thereby significantly contributing to the regulation of respiratory mechanics. Additionally, these surfactants play a crucial role in the innate immune system within the pulmonary microenvironment. Within the spectrum of COVID‐19 infections, a compelling association is observed, characterized by elevated levels of SP‐D and SP‐A across a range of manifestations from mild to severe pneumonia. The sudden decline in respiratory function observed in COVID‐19 patients may be attributed to the decreased synthesis of surfactants by type II alveolar cells. Conclusion: Collectin proteins such as SP‐A and SP‐D show promise as biomarkers, offering potential avenues for predicting and monitoring pulmonary alveolar injury in the context of COVID‐19. This clarification enhances our understanding of the molecular complexities contributing to respiratory complications in severe COVID‐19 cases, providing a foundation for targeted therapeutic approaches using surfactants and refined clinical management strategies. Highlights: SARS‐CoV‐2 affects alveolar type II cells, which limits the synthesis and secretion of pulmonary surfactant into the alveolar space, ultimately leading to lung failure.Surfactant proteins A and D, as members of the lectin‐C family, play a prominent role in COVID‐19 infection. SP‐D exhibits a higher affinity for binding the spike protein of SARS‐CoV‐2 compared to SP‐A.In COVID‐19 infection, the levels of SP‐D and SP‐A were significantly higher in cases of mild to moderate pneumonia than in severe or critical cases. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization has officially acknowledged the emergence of Coronavirus Disease 2019 (COVID-19), attributed to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, as a rapidly escalating global public health issue and declared it a pandemic. SARS-CoV-2 infection can lead to varied and multiorgan pathologies, with the most notable impacts occurring in the lungs (characterized by phases of diffuse alveolar damage, microthrombi, and bronchopneumonia), heart (involving lymphocytic myocarditis), kidney (resulting in acute tubular injury), and vasculature (involving microthrombi and deep vein thrombi). Objectives: To summarize, resolve contradiction and provide solid evidence on multiorgan histopathological changes caused by SARS-CoV2 infection. Material and method: Histological data obtained from autopsy and biopsy studies were gathered following the guidelines of the Preferred Reporting Items for Systematic Review (PRISMA). An extensive electronic search was conducted on databases such as PubMed, Science Direct, Scopus, and Google Scholar, covering the period from database inception to March 2022. The collected studies underwent a systematic literature search, and a thorough critical review was performed. Result: After excluding studies that did not meet the eligibility criteria, a total of 58 articles were included in the review. We estimate the histopathological findings of 13 organ. For the pool proportion of exudative, proliferative and fibrotic phase of diffuse alveolar damage of lung is (70.666%, 56.126% and 33.031%) respectively. For liver steotosis is 35.808%. For acute tubular injury of kidney is 74.872%. For adrenal cortical necrosis is 13.113%. For brain gliosis is 13.865%. For heart necrosis is 5.477%. For gastrointestinal tract the pool proportion of inflammatory cells infiltration is 6.171%. For placental infarction is 25.684%. For orchitis is 29.019%. For perivascular inflammation of skin is 35.176%. For lymphocytic depletion of white pulp of spleen is 69.204%. For hemophagiocytosis of lymph node is 7.022%. For bone marrow fibrosis is 8.473%. Conclusion: COVID-19 is characterized as a multiorgan infection closely associated with a hyperinflammatory state, believed to initiate with diffuse alveolar damage and immuno-thrombotic microangiopathy. The extensive activation of the immune system and microvascular damage may contribute to indirect harm to other organs, although the direct impact of the virus on these tissues cannot be ruled out. [ABSTRACT FROM AUTHOR]

Viral infections are some of the most common sources of respiratory illness in pediatric and adult populations worldwide. Influenza and coronaviruses are viral pathogens that could lead to severe respiratory illness and death. More recently, respiratory illness from coronaviruses, accounts for more than 1 million deaths in the United States alone. This article will explore the epidemiology, pathogenesis, diagnosis, treatment, and prevention of severe acute respiratory syndrome caused by coronavirus-2, and Middle Eastern respiratory syndrome.

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.

Legislation provides a framework for effective and coordinated disaster preparedness and response. This article evaluates the strengths and shortcomings of South Africa’s disaster risk management (DRM) legislation in guiding the response to the COVID-19 pandemic. Since its promulgation in 2002, South Africa’s DRM legislation has been hailed as one of the most progressive legislations globally. However, the severe respiratory syndrome coronavirus 2, commonly known as the COVID-19 pandemic, exposed inadequacies in most existing DRM legislation worldwide, including in South Africa. This led to an inadequate response to the pandemic. A content-based literature review was conducted. Forty-nine peer-reviewed articles, reports, op-eds and newspaper articles were included in the review. The review highlighted significant inadequacies of South African DRM legislation, including the placement of the National Disaster Management Centre and the establishment of new structures for COVID-19 response. Based on the findings of this study, disaster managers, as the primary implementers of the disaster management legislation, must motivate the constant review of the disaster management legislation as a way of mitigating social, economic, political and environmental impacts of disasters, which emanate from the inadequacies existing in the disaster legislation. Contribution: The study’s findings contribute to the effective management of the disaster management fraternity by suggesting amendment of the legislation based on the experience during the pandemic. The recommendations made to disaster managers will assist with responding appropriately to future pandemics and other disasters.

The present study aimed to evaluate the effectiveness of two doses of CoronaVac in preventing SARS-CoV-2 symptomatic disease with virological confirmation, as well as in the prevention of COVID-19 moderate and severe cases. A test-negative unmatched case-control design was used, in which cases were patients with suspected COVID-19 (presenting at least two of the following symptoms: fever, chills, sore throat, headache, cough, runny nose, olfactory or taste disorders) with virological confirmation, and controls were those whose SARS-CoV-2 test was negative. As for exposure, participants were classified as unvaccinated, or vaccinated with a complete schedule. Suspected COVID-19 cases were identified from March to November 2021, in two cities located in the State of São Paulo, Brazil. All participants signed the Informed Consent Form before enrollment. RT-PCR results and vaccination data were obtained from the local surveillance systems. Up to two phone calls were made to obtain information on the outcome of the cases. A total of 2981 potential participants were screened for eligibility, of which 2163 were included, being 493 cases and 1670 controls. Vaccination, age, the reported contact with a COVID-19 suspected or confirmed case in the 14 days before symptoms onset, and the educational level were the variables independently associated with the outcome. The adjusted vaccine effectiveness for symptomatic COVID-19 (AVE) was 39.0 % (95 % CI 6.0–60.0 %). The AVE in the prevention of moderate and severe disease was 91.0 % (95 % CI 76.0–97.0 %). Our results were influenced by the waning of the Gamma variant, in the second trimester of 2021, followed by the increase in vaccination coverage, and a drop in the number of cases in the second half of the year. The study demonstrated the high effectiveness of CoronaVac in preventing moderate/severe COVID-19 cases.