SARS-CoV-2 Research Articles

A SYSTEMATIC REVIEW AND META-ANALYSIS: RISK FACTORS OF MORTALITY COVID-19

Background: COVID-19 is still a threat throughout the world because of its high morbidity and mortality. Comorbid diseases like hypertension, diabetes mellitus, and heart disease are some of the factors in the high severity and mortality of COVID-19 patients. Purpose: The study aims to analyze the effect of risk factors on COVID-19 mortality using a systematic review and meta-analysis. Methods: Articles were taken from online journal portals Pubmed, Garuda, and Google Cendekia, and all were published from October 2019 to December 2021 in full text and with an observational study design. The keywords used in searching the articles were "COVID-19", "sars cov 2", "2019-nCoV", "2019 novel coronavirus", "COVID-19 deaths", and "COVID-19 mortality". The articles were collected using a PRISMA diagram; then, data extraction was carried out in a systematic review. The data was synthesized by using a meta-analysis technique using the RevMan application. Results: This study analyzed 59 articles and found that age, hypertension OR=3.09 (2.69-3.56), sex OR= 1.29 (1.08-1.53), and diabetes mellitus OR=3.03 (2.66-3.44) are the risk factors for COVID-19 death. Conclusion: The death in COVID-19 patients is influenced by elderly age, gender, and comorbid disease (diabetes and hypertension). These COVID-19-death-related factors can help health workers recognize and prevent a more severe stage of the disease through more appropriate handling and treatment.

Specification of a governance model for Covid-19

In the emergence of the SARS CoV-2 coronavirus and Covid-19, this work set out to investigate university governance as an effect of the pandemic and as a scientific response through the formation of a panel of experts or advice on risk management, communication and management. A documentary, systematic and retrospective study was carried out with a selection of sources indexed to international repositories, considering the period from 2019 to 2021. Three categories of discussion were found that were qualified by expert judges, establishing patrimonialism as the guiding axis of doe extracts of findings selected for meta-analysis. It is suggested to orient the research towards the incidence of the panel of experts in the decisions of governments as health policies in the face of the health and economic crisis.

Role of prior immunity in binding to spike of “future” Omicron subvariants

BackgroundThroughout the COVID-19 pandemic, virus evolution and large-scale vaccination programs have caused multiple exposures to SARS CoV-2 spike protein, resulting in complex antibody profiles. The binding of these to spike protein of “future” variants in the context of such heterogeneous exposure has not been studied. MethodsWe tested archival sera (Delta and Omicron period) stratified by anti-spike antibody (including IgG) levels for reactivity to Omicron-subvariants(BA.1, BA.2,BA.2.12.1, BA.2.75, BA.4/5 and BF.7) spike protein. Assessed antigenic distance between groups using Antigenic Cartography and performed hierarchical clustering of antibody data in a Euclidean distance framework. ResultsAntibody (including IgG) antibody reactivity to Wild-type (CLIA) and subvariants (ELISA) spike protein were similar between periods (p > 0.05). Both 'High S′ and ‘Low S’ of Delta and Omicron periods were closely related to “future” subvariants by Antigenic Cartography. Sera from different S groups clustered together with ‘Low S’ interspersed between ‘High S’ on hierarchical clustering, suggesting common binding sites. Further, anti-spike antibodies (including IgG) to Wild-type (S1/S2 and Trimeric S) clustered with Omicron-subvariant binding antibodies. ConclusionsHybrid immunity caused by cumulative virus exposure in Delta or Omicron periods resulted in equivalent binding to “future” variants, which might be due to binding to conserved regions of spike protein of future variants. A prominent finding is that the ‘Low S’ antibody demonstrates similar binding.

Effect of disease activity on the clinical outcome of SARS CoV-2 in patients with underlying rheumatic diseases; data from global rheumatology alliance

Objectives: To determine the effect of disease activity on clinical outcomes of coronavirus disease-2019 in patients with rheumatic diseases. Method: The prospective, cohort study was conducted from January 1st to June 30th, 2021, at Rheumatology department, Fauji Foundation Hospital, Rawalpindi. It comprised patients of rheumatic disorders who were affected by coronavirus disease-2019. The patients were categorised according to rheumatic disease activity into remission group I, low disease activity group II, moderate group III and high–activity group IV. Coronavirus disease-2019 outcomes compared included recovered vs death, hospitalisation yes vs no, mechanical ventilation yes vs no. The association of disease activity status with coronavirus disease-2019 outcomes was explored. Data was analysed using SPSS 23. Results: Of the 100 patients, 78(78%) were females and 22(22%) were males. The overall mean age was 45.60±13.7 years. There were 23(23%) patients in group I, 42(42%) patients in group II, 21(21%) patients in group III and 14(14%) patients in group IV. Overall,17(17%) patients died and 83(83%) patients survived. In group III, 7(33.3%) patients died, followed by 6(42.9%) in group IV (p<0.05). In total, 7(7%) patients needed mechanical ventilation, with 3(21.4%) being in group IV (p<0.05). Hospitalisation was needed in 33(33%) cases, and intergroup comparison was non-significant (p>0.05). Conclusion: Patients with severe rheumatic autoimmune disease affected by coronavirus disease-2019were more likely to die and require invasive ventilation. Key Words: Arthritis, Connective tissue diseases, Rheumatoid arthritis, Ankylosing spondylitis, Scleroderma, Vasculitis.

Neurodevelopmental delay in children exposed to maternal SARS-CoV-2 in-utero

It is unclear if SARS CoV-2 infection during pregnancy is associated with adverse neurodevelopmental repercussions to infants. We assessed pediatric neurodevelopmental outcomes in children born to mothers with laboratory-confirmed SARS CoV-2 infection during pregnancy. Neurodevelopmental outcomes of in-utero exposed children were compared to that of pre-pandemic control children in Los Angeles (LA), CA, USA and Rio de Janeiro, Brazil. Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III), the gold standard tool for evaluating neurodevelopment until 36 months of age and Ages and Stages Questionnaires (ASQ-3), a frequently used screening instrument for evaluating neurodevelopment in this same age group were the assessment tools used. Developmental delay (DD) was defined as having a score < − 2 SD below the norm (< 70) in at least one of three Bayley-III domains, (cognitive, motor or language) or a score below the cut-off (dark zone) in at least one of five ASQ-3 domains (communication, gross motor, fine motor, problem solving, personal-social). Exposed children were born between April 2020 and December 2022 while control children were born between January 2016 to December 2019. Neurodevelopmental testing was performed in 300 children total: 172 COVID-19 exposed children between 5–30 months of age and 128 control children between 6–38 months of age. Bayley-III results demonstrated that 12 of 128 exposed children (9.4%) had DD versus 2 of 128 controls (1.6%), p = 0.0007. Eight of 44 additional exposed children had DD on ASQ-3 testing. Fully, 20 of 172 exposed children (11.6%) and 2 of 128 control children (1.6%), p = 0.0006 had DD. In Rio, 12% of exposed children versus 2.6% of controls, p = 0.02 had DD. In LA, 5.7% of exposed children versus 0 controls, p = 0.12 had DD. Severe/critical maternal COVID-19 predicted below average neurodevelopment in the exposed cohort (OR 2.6, 95% CI 1.1–6.4). Children exposed to antenatal COVID-19 have a tenfold higher frequency of DD as compared to controls and should be offered neurodevelopmental follow-up.

#2691 Treatment naive membranous nephropathy patients treated with rituximab in COVID19 era

Abstract Background and Aims Standard of care of high-risk idiopathic membranous nephropathy patients is immunosuppressive treatment with cyclophosphamide and corticosteroids or rituximab. Our aim was to assess outcome and safety of rituximab therapy in COVID19 era in comparison to modified Ponticelli protocol. Method In this retrospective study all adult patients with biopsy proven membranous nephropathy treated with rituximab as a first line therapy from 2020 till 2022 were enrolled and compared with MN patients treated with modified Ponticelli protocol from 2013 till 2020. Renal outcome was defined as composite of partial and complete remission defined according KDIGO guidelines. Except otherwise stated, data are shown as N (%) or median with interquartile range (IQR) and accompanied p levels. Results During the COVID 19 era, between 2020 and 2022, 8 MN patients were treated with rituximab as a first line therapy. One was lost from follow up and one had allergic infusion reaction and therefore was excluded from further analysis. Ten patients were treated with modified Ponticelli protocol. There was no difference in age (60 vs. 59 years; p = 0.669), gender (M 57.1 vs. 60%), BMI (26.3 vs. 29.1cm/kg; p = 0.906), systolic (140. vs. 150 mmHg; p = 0.161) or diastolic (90 vs. 91.5 mmHg; p = 0.230) blood pressure between rituximab and cyclophosphamide treated group. Also, there was no difference in proteinuria between rituximab and cyclophosphamide treated group (16.2 (5.7–31.3) vs. 8.7 (6.5–12.5) g/dU; p = 0.201) Patients treated with cyclophosphamide had lower eGFR compared with patients treated with rituximab (51 (34-79) vs. 93 (72-98) ml/min/1,73 m²; p = 0.005). At 6 months follow up only 2 (28.6%) in rituximab group and 6 (60%) in cyclophosphamide group achieved outcome defined as composite of complete and partial remission. At one year follow up, there was no difference in outcome between groups and all patients from rituximab group compared to 8 patients (88.9%) from cyclophosphamide group accomplished composite favorable renal outcome (p = 398). At the end of follow up, one year after cyclophosphamide therapy eGFR was better (57 (43-96) vs. 51 (34-79) ml/min/1,73 m²). Rituximab was safe in our cohort. Three (50%) of patients acquired SARS CoV2 infection and there was no adverse outcome regarding COVID 19 disease. Conclusion Cyclophosphamide is faster than rituximab in accomplishing remission of nephrotic syndrome and improves deteriorated kidney function. Nevertheless, at 1 year follow up rituximab efficiency is proven to be excellent. Cyclophosphamide should be reserved for MN patients with nephrotic syndrome with reduced glomerular filtration rate.

Ethnomedicinal use of plants by Ain Chkef (North Central Morocco) community to boost immunity and overcome SARS COV-2 infection

Ethnomedicinal use of plants by Ain Chkef (North Central Morocco) community to boost immunity and overcome SARS COV-2 infection

Photostability and photodynamic antimicrobial profile of dye extracts from four (4) plants: prospects for eco-friendly low-cost food disinfection and topical biomedical applications.

In this study, photostability and photodynamic antimicrobial performance of dye extracts from Hibiscus sabdariffa (HS) calyces, Sorghum bicolor (SB) leaf sheaths, Lawsonia inermis (LI) leaves and Curcuma longa (CL) roots were investigated in Acetate-HCl (AH) Buffer (pH 4.6), Tris Base-HCl (TBH) Buffer (pH 8.6), distilled water (dH2O), and Phosphate Buffer Saline (PBS, pH 7.2) using Bacillus subtilis as model for gram positive bacteria, Escherichia coli as model for gram negative bacteria, phage MS2 as model for non-envelope viruses and phage phi6 as model for envelope viruses including SARS CoV-2 which is the causative agent of COVID-19. Our results showed that the photostability of the dye extracts is in the decreasing order of LI > CL > SB > HS. The dye extract-HS is photostable in dH2O but bleaches in buffers-AH, TBH and PBS. The rate of bleaching is higher in AH compared to in TBH and PBS. The bleaching and buffers affected the photodynamic and non-photodynamic antimicrobial activity of the dye extracts. The photodynamic antibacterial activity of the dye extracts is in the decreasing order of CL > HS > LI > SB while the non-photodynamic antibacterial activity is in the decreasing order of LI > CL > HS > SB. The non-photodynamic antiviral activity pattern observed is the same as that of non-photodynamic antibacterial activity observed. However, the photodynamic antiviral activity of the dye extracts is in the decreasing order of CL > LI > HS > SB. Given their performance, the dye extracts maybe mostly suitable for environmental applications including fresh produce and food disinfection, sanitation of hands and contact surfaces where water can serve as diluent for the extracts and the microenvironment is free of salts.

Design, Synthesis of Novel Pyrido[2,3-d] pyrimidine Derivatives as SARS-CoV-2 Mpro Inhibitors for COVID-19 Therapy

Some of the interesting pyrido[2,3-d] pyrimidines (3a, 3b), 4, (5a–d), (6a, b), 7–13, and (15a–c) based on uracil moiety were synthesized efficiently using a conventional method and ultrasonic irradiation. Heterocyclic scaffolds such as pyrido[2,3-d] pyrimidines are vital structural elements in drug discovery. Their interactions with different viral mechanistic pathways will be leveraged in future research to create heterocycle-based antivirals. Therefore, the purpose of this work is to demonstrate the anticipated contribution of heterocyclic scaffolds to the advancement and identification of SARS CoV-2 treatment, The newly synthesized compounds were characterized by spectral data, and screened for their binding activity toward the main protease of COVID-19 utilizing a molecular docking study, according to the outcome of our initial screening and docking study, the produced compounds 3a, 4, 6a, 13, 15b, and 15c achieved an evaluation in vitro using the SARS-CoV-2 Mpro utilizing the main protease assay, the results of the evaluation showed that the hydrazinylpyridopyrimidine 4 (IC50 value: 10.69 µM) and triazolopyrimidin 15c (IC50 value 8.723 µM) had the greatest inhibitory effects on SARS-CoV-2 Mpro. Additionally, this study was conducted to assess the inhibitory efficacy of the synthesized compounds 4 and 15c, which show moderate inhibition for the replication of SARS CoV-2. Additional molecular dynamics and docking simulations were performed to prove the binding mechanism of 15c.

Comparison of hematologic parameters as predictors of severity in COVID-19: A single-center cross-sectional study

COVID-19 disease was a global pandemic that marred humanity globally from 2019 end till early 2023. The diseases caused by the novel SARS cov2 virus had a wide array of presentations, from asymptomatic to mild illness to severe acute respiratory illness, with patients presenting with ‘happy hypoxia and sudden deterioration of clinical condition to multiorgan involvement and proven to be fatal in many cases. There was an effort to identify a point-of-care test to screen patients so as to predict the disease course; therefore, this study was designed to compare hematologic parameters to predict the severity of the disease. This study showed that TLC,dNLR, and NLR can be effectively used in diagnosing severe COVID-19.

SCARLET (Supplemental Citicoline Administration to Reduce Lung injury Efficacy Trial): study protocol for a single-site, double-blinded, placebo-controlled, and randomized Phase 1/2 trial of i.v. citicoline (CDP-choline) in hospitalized SARS CoV-2-infected patients with hypoxemic acute respiratory failure

BackgroundThe SARS CoV-2 pandemic has resulted in more than 1.1 million deaths in the USA alone. Therapeutic options for critically ill patients with COVID-19 are limited. Prior studies showed that post-infection treatment of influenza A virus-infected mice with the liponucleotide CDP-choline, which is an essential precursor for de novo phosphatidylcholine synthesis, improved gas exchange and reduced pulmonary inflammation without altering viral replication. In unpublished studies, we found that treatment of SARS CoV-2-infected K18-hACE2-transgenic mice with CDP-choline prevented development of hypoxemia. We hypothesize that administration of citicoline (the pharmaceutical form of CDP-choline) will be safe in hospitalized SARS CoV-2-infected patients with hypoxemic acute respiratory failure (HARF) and that we will obtain preliminary evidence of clinical benefit to support a larger Phase 3 trial using one or more citicoline doses.MethodsWe will conduct a single-site, double-blinded, placebo-controlled, and randomized Phase 1/2 dose-ranging and safety study of Somazina® citicoline solution for injection in consented adults of any sex, gender, age, or ethnicity hospitalized for SARS CoV-2-associated HARF. The trial is named “SCARLET” (Supplemental Citicoline Administration to Reduce Lung injury Efficacy Trial). We hypothesize that SCARLET will show that i.v. citicoline is safe at one or more of three doses (0.5, 2.5, or 5 mg/kg, every 12 h for 5 days) in hospitalized SARS CoV-2-infected patients with HARF (20 per dose) and provide preliminary evidence that i.v. citicoline improves pulmonary outcomes in this population. The primary efficacy outcome will be the SpO2:FiO2 ratio on study day 3. Exploratory outcomes include Sequential Organ Failure Assessment (SOFA) scores, dead space ventilation index, and lung compliance. Citicoline effects on a panel of COVID-relevant lung and blood biomarkers will also be determined.DiscussionCiticoline has many characteristics that would be advantageous to any candidate COVID-19 therapeutic, including safety, low-cost, favorable chemical characteristics, and potentially pathogen-agnostic efficacy. Successful demonstration that citicoline is beneficial in severely ill patients with SARS CoV-2-induced HARF could transform management of severely ill COVID patients.Trial registrationThe trial was registered at www.clinicaltrials.gov on 5/31/2023 (NCT05881135).Trial statusCurrently enrolling.

Effect of Early pregnancy associated protein-1 on Spike protein and ACE2 interactions: Implications in SARS Cov-2 vertical transmission

IntroductionSeveral factors influence transmission of 2019-nCoV from mother to fetus during pregnancy, thus the dynamics of vertical transmission is unclear. The role of cellular protective factors, namely a 90 KDa glycoprotein, Early pregnancy-associated protein (Epap-1), expressed by placental endothelial cells in women during early pregnancy would provide an insight into role of placental factors in virus transmission. Since viral spike protein binding to the ACE2 receptors of the host cells promotes virus invasion in placental tissue, an analysis of effects of Epap-1 on the Spike-ACE2 protein binding was studied. MethodsEpap-1 was isolated from MTP placental tissue. Molecular interaction of Epap-1 and variants of the spike was analyzed in silco. The interaction of Epap-1 with Spike and RBD were analyzed using ELISA and immunofluorescence studies. ResultsThe results in silico showed an interaction of Epap-1 with S-protein at RBD region involving K417, Y449, Y453, Y456, Y473, Q474, F486, Q498, N501 residues of spike with Y61, F287, I302, N303, N305, S334, N465, G467, N468 residues of Epap-1 leading to interference of S-protein and ACE2 interaction [1]. Further, the interaction is conserved among the variants. The studies in vitro confirm that Epap-1 affects S protein-ACE2 and RBD- ACE2 binding, thus suggesting that during early pregnancy, SARS CoV-2 infection may be protected by Epap-1 protein present in placental tissue. The results were further confirmed by pseudovirus expressing Spike and RBD in an infection assay. DiscussionEpap-1 interferes with Spike and RBD interaction with ACE2, suggesting a possible mechanism of the antiviral environment during pregnancy.

Self-regulated learning of anatomy during the COVID-19 lockdown period in a low-income setting.

In March 2020, universities in Zimbabwe temporarily closed and switched to remote learning to contain the spread of SARS Cov2 infections. The sudden change to distance learning gave autonomy to students to direct their own learning. To understand how the students at the University of Zimbabwe and Midlands State University adapted to emergency remote learning, focus group discussions and a self-administered questionnaire survey based on the self-regulated learning inventory were conducted to capture cognitive, motivational, and emotional aspects of anatomy learning during the COVID-19 pandemic. Thematic analysis was used to identify patterns among these students' lived experiences. Two coders analyzed the data independently and discussed the codes to reach a consensus. The results showed that students at the two medical schools cognitively and meta-cognitively planned, executed and evaluated self-regulated strategies in different ways that suited their environments during the COVID-19 lockdown. Several factors, such as demographic location, home setting/situation, socioeconomic background and expertise in using online platforms, affected the students' self-directed learning. Students generally adapted well to the constraints brought about by the lockdown on their anatomy learning in order to learn effectively. This study was able to highlight important self-regulated learning strategies that were implemented during COVID-19 by anatomy learners, especially those in low-income settings, and these strategies equip teachers and learners alike in preparation for similar future situations that may result in forced remote learning of anatomy.

EPIDEMIOLOGICAL FRAMEWORK OF MYOCARDITIS DURING SARS–COV–2 PANDEMIC AND VACCINATION CAMPAIGN

Abstract Rationale Myocarditis is an inflammatory condition of cardiomyocytes whose clinical course can be heterogeneous. Etiologies include infections (mostly viral), drugs or toxic exposures or auto–immunity, while few cases have been reported in association with vaccines (following, mainly, attenuated smallpox vaccine). Estimated prevalence is 2–22 cases/100000 people/year, with greater frequency in males aged 30–40. Since SARS–CoV–2 outbreak and vaccination campaigns there is growing interest in their association with myo–pericardial inflammatory conditions, with incidence reports of 1–5/100.000 and 1–5/1.000.000 respectively among vaccinated and unvaccinated subjects (as part of COVID–19) and relatively higher incidence in males after second (mRNA) vaccine administration. Study Design and Objective We designed this observational registry and included patients with CMR–confirmed myocarditis diagnosis admitted to Maggiore Hospital in Bologna from March 2017 to April 2023. Primary goal was to conduct an epidemiological analysis on myocarditis incidence in the era of SARS–CoV–2 and respective vaccination. Results We enrolled 48 patients, among which 37 were diagnosed during SARS–CoV–2 pandemic. 86% were male, and mean age at diagnosis was 31 years old; the vast majority did not show major modifiable CV risk factors (apart from cigarette smoking: 42%) or previous/comorbid CV conditions. Median LVEF (by CMR) at diagnosis was 56%, with 3 patients (6%) with LVEF &amp;lt; 47%. Median hsTnI and CRP peaks were respectively 7317 ng/L and 4,5 mg/dl. We reported 6 (12.5%) arrhythmic events during index hospitalization (1 patient had sustained VT and 5 had non–sustained VT). 8 out of 37 patients with myocarditis during SARS–CoV–2 outbreak reported previous COVID–19, with a median time of 130 days from infection, but only 1 had myocarditis as part of its clinical course. 16 patients had already received at least one SARS–CoV–2 vaccine dose (median: 2 doses) at diagnosis, with a median time of 117 days from dose administration (only two patients were diagnosed &amp;lt; 30 days from last administration). Conclusions Myocarditis epidemiology of our cohort seems to reflect available incidence data; furthermore, myocarditis as part of COVID–19 course or occurring shortly after vaccination appears to be an uncommon event. Our cohort consisted only of low or intermediate risk presentations. Data about diagnosis in the “COVID era” suggest a relative “underdiagnosis” in the previous period.

CORONARY INFLAMMATION ON CHEST COMPUTED TOMOGRAPHY AND COVID–19 MORTALITY

Abstract Aims The main factors associated with coronavirus disease–19 (COVID–19) mortality are age, comorbidities, pattern of inflammatory response and SARS–CoV–2 lineage involved in infection. However, the clinical course of the disease is extremely heterogeneous, and reliable biomarkers predicting adverse prognosis are lacking. Our aim was to elucidate the prognostic role of a novel marker of coronary artery disease inflammation, peri–coronary adipose tissue attenuation (PCAT), available from high–resolution chest computed tomography (HRCT), in COVID–19 patients with severe disease requiring hospitalization. Methods and Results Two distinct groups of patients, admitted to Parma University Hospital in Italy with COVID–19 in March 2020 and March 2021 (first and third wave peaks of COVID–19 pandemic in Italy, with prevalence of wild–type and B.1.1.7 SARS–CoV–2 lineage, respectively) were retrospectively enrolled. The primary endpoint was in–hospital mortality. Demographic, clinical, laboratory, HRCT data and coronary artery HRCT features (coronary calcium score and PCAT attenuation) were collected to establish which variables were associated with mortality. Among the 769 patients enrolled, 555 (72%) were discharged alive and 214 (28%) died. In multivariable logistic regression analysis age (p&amp;lt;0.001), number of chronic illnesses (p&amp;lt;0.001), smoking habit (p=0.006), P/F ratio (p=0.001), platelet count (p=0.002), blood creatinine (p&amp;lt;0.001), non–invasive mechanical ventilation (p&amp;lt;0.001), HRCT visual score (p&amp;lt;0.001) and PCAT (p&amp;lt;0.001), but not the calcium score, were independently associated with in–hospital mortality. Conclusion Coronary inflammation, measured with PCAT on HRCT, was independently associated with higher mortality in patients with severe COVID–19, while the pre–existent coronary atherosclerotic burden was not associated with adverse outcomes after adjustment for covariates.

THE CHALLENGING SCENARIO OF DYSPNEA IN THE ELDERLY: DUE MORE TO CONGESTION OR INFLAMMATION?

Abstract Introduction Elderly patients hospitalized due to acute heart failure often have a concomitant acute lung disease. Establishing the role of each disease in a clinical picture of acute cardiopulmonary syndrome can be challenging. A common thread of these diseases is inflammation; a hyperinflammatory response determines more serious symptoms and a worse prognosis. Purpose We evaluated the effectiveness of a treatment with dexamethasone in patients with acute cardiopulmonary syndrome and strong inflammatory response. Materials and Methods We evaluated 302 consecutive HFPEF (heart failure with preserved ejection fraction) patients ≥80 years of age, with concomitant symptoms attributable to acute bronchitis, pneumonia, or COPD exacerbation, hospitalized due to worsening dyspnoea, with an NT–proBNP ≥3,000 pg/ml, and a finding X–ray of lung congestion with or without a consolidation. Reactive C Protein (CRP) was measured. Patients with SARS–CoV–2, indication to corticosteroids for other clinical conditions or need for mechanical ventilation were excluded. The 112 patients with CRP&amp;gt;20 mg/dl were randomized into 2 groups: 56 patients were treated open–label with dexamethasone at a dose of 8 mg iv/day for a maximun of ten days, in addition to the usual therapies, while the same number of patients were treated with the usual therapy. In both groups antibiotics were administered based on procalcitonin guided protocl. Clinical recovery time, length of hospitalization, in–hospital mortality, need for a new hospitalization and mortality at one month were evaluated. Results The mean age of patients was 89±5 years in the dexamethasone group and 88±5 in the usual therapy group. The results are shown in Table 1. Patients treated with dexamethasone experienced a faster clinical recovery and a shorter length of hospitalization. No significant differences were found regarding either in–hospital mortality or need for rehospitalization and mortality at 30 days. Notably, PCT guided treatment led to an average reduction in duration of antibiotic therapy from 8 to 5 days. Conclusions Very elderly patients with acute cardiopulmonary syndrome and hyperinflammatory state have a favorable response to dexamethasone therapy added to the usual therapy in terms of clinical improvement and length of hospitalization. Our case history is small to evaluate a possible improvement in mortality. These findings need to be consolidated from double–blind randomized controlled trials.

MYOCARDIAL AND PERICARDIAL DISEASES INCIDENCE IN COVID

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS–CoV–2), also referred to as COVID–19, was declared a pandemic by the World Health Organization in March 2020. The manifestations of COVID–19 are widely variable and range from asymptomatic infection to multi–organ failure and death. Like other viral illnesses, acute myocarditis and/or pericarditis has been reported to be associated with COVID–19 infection. The guidelines for the diagnosis of COVID–19 introduced the echocardiogram for diagnosis of carditis in these patients. Purpose In our study we investigated the incidences of myocarditis and/or pericarditis in a consecutive series of 1540 Athletes undergo to agonostic certification that performed echocardiogram, and subdivided the incidence of carditis depend on the period and the possible subtype of the covid (alpha, beta, gamma, delta, epsilon). Methods From March 2020 to October 2022 we enrolled in this epidemiological evaluation 1540 patients that was affected by COVID. Every patients was admitted to ambulatory of sport medicine of 2 Italian centres on the major islands to perform a return to play agonist certificate. Overall, 69% males and 31%. females were enrolled with a mean age of 24.3 years (12–67 years). None presented a risk factor of a cardiac disease. Results The incidence of Echocardiographic abnormality was 3,2% in our population The kind and the incidence of alteration was showed in table 1, and consist in dilated cardiomiopathy (0,4%), regional cinetic dysfunction (0,4%), pericardial effusion (1,9%), aspecific alterations (0,2%). Based on the period we evaluated the incidence of the echocardiographic alterations during the seasons and in corralation of variant of COVID . The results was showed in figure 1. Conclusions Based on our evalution the incidence of echocardiographic findings in COVID was 3,2% in all period, with a progressive reduction long the time, from alpha variant to epsilon variant.

Phytoconstituents of Artemisia Annua as potential inhibitors of SARS CoV2 main protease: an in silico study

BackgroundIn November 2019, the world faced a pandemic called SARS-CoV-2, which became a major threat to humans and continues to be. To overcome this, many plants were explored to find a cure.MethodsTherefore, this research was planned to screen out the active constituents from Artemisia annua that can work against the viral main protease Mpro as this non-structural protein is responsible for the cleavage of replicating enzymes of the virus. Twenty-five biocompounds belonging to different classes namely alpha-pinene, beta-pinene, carvone, myrtenol, quinic acid, caffeic acid, quercetin, rutin, apigenin, chrysoplenetin, arteannunin b, artemisinin, scopoletin, scoparone, artemisinic acid, deoxyartemisnin, artemetin, casticin, sitogluside, beta-sitosterol, dihydroartemisinin, scopolin, artemether, artemotil, artesunate were selected. Virtual screening of these ligands was carried out against drug target Mpro by CB dock.ResultsQuercetin, rutin, casticin, chrysoplenetin, apigenin, artemetin, artesunate, sopolin and sito-gluside were found as hit compounds. Further, ADMET screening was conducted which represented Chrysoplenetin as a lead compound. Azithromycin was used as a standard drug. The interactions were studied by PyMol and visualized in LigPlot. Furthermore, the RMSD graph shows fluctuations at various points at the start of simulation in Top1 (Azithromycin) complex system due to structural changes in the helix-coil-helix and beta-turn-beta changes at specific points resulting in increased RMSD with a time frame of 50 ns. But this change remains stable after the extension of simulation time intervals till 100 ns. On other side, the Top2 complex system remains highly stable throughout the time scale. No such structural dynamics were observed bu the ligand attached to the active site residues binds strongly.ConclusionThis study facilitates researchers to develop and discover more effective and specific therapeutic agents against SARS-CoV-2 and other viral infections. Finally, chrysoplenetin was identified as a more potent drug candidate to act against the viral main protease, which in the future can be helpful.

Sequencing analysis of SARS-CoV-2 cases in Slovenian long-term care facilities to support outbreak control.

Residents of long-term care facilities (LTCFs) are at high risk of morbidity and mortality due to COVID-19, especially when new variants of concern (VOC) emerge. To provide intradisciplinary data in order to tailor public health interventions during future epidemics, available epidemiologic and genomic data from Slovenian LTCFs during the initial phases of the COVID-19 pandemic was analyzed. The first part of the study included SARS-CoV-2 reverse-transcription Real-Time PCR (rtRT-PCR) positive LTCF residents, from 21 facilities with COVID-19 outbreaks occurring in October 2020. The second part of the study included SARS-CoV-2 rtRT-PCR positive LTCF residents and staff between January and April 2021, when VOC Alpha emerged in Slovenia. Next-generation sequencing (NGS) was used to acquire SARS-CoV-2 genomes, and lineage determination. In-depth phylogenetic and mutational profile analysis were performed and coupled with available field epidemiological data to assess the dynamics of SARS-CoV-2 introduction and transmission. 370/498 SARS-CoV-2 positive residents as well as 558/699 SARS-CoV-2 positive residents and 301/358 staff were successfully sequenced in the first and second part of the study, respectively. In October 2020, COVID-19 outbreaks in the 21 LTCFs were caused by intra-facility transmission as well as multiple independent SARS-CoV-2 introductions. The Alpha variant was confirmed in the first LTCF resident approximately 1.5 months after the first Alpha case was identified in Slovenia. The data also showed a slower replacement of existing variants by Alpha in residents compared to staff and the general population. Multiple SARS CoV-2 introductions as well as intra-facility spreading impacted disease transmission in Slovenian LTCFs. Timely implementation of control measures aimed at limiting new introductions while controlling in-facility transmission are of paramount importance, especially as new VOCs emerge. Sequencing, in conjunction with epidemiological data, can facilitate the determination of the need for future improvements in control measures to protect LTCF residents from COVID-19 or other respiratory infections.

Glycosylated SARs Cov 2 interaction with plant lectins.

Lectins are non-immune carbohydrate-binding proteins/glycoproteins that are found everywhere in nature, from bacteria to human cells. They have also been a valuable biological tool for the purification and subsequent characterisation of glycoproteins due to their carbohydrate binding recognition capacity. Antinociceptive, antiulcer, anti-inflammatory activities and immune modulatory properties have been discovered in several plant lectins, with these qualities varying depending on the lectin carbohydrate-binding site. The Coronavirus of 2019 (COVID-19) is a respiratory disease that has swept the globe, killing millions and infecting millions more. Despite the availability of COVID-19 vaccinations and the vaccination of a huge portion of the world's population, viral infection rates continue to rise, causing major concern. Part of the reason for the vaccine's ineffectiveness has been attributed to repeated mutations in the virus's epitope determinant elements. The surface of the Coronavirus envelope is heavily glycosylated, with approximately sixty N-linked oligomannose, composite, and hybrid glycans covering the core of Man3GlcNAc2Asn. Some O-linked glycans have also been discovered. Many of these glyco-chains have also been subjected to multiple mutations, with only a few remaining conserved. As a result, numerous plant lectins with specificity for these viral envelope sugars have been discovered to interact preferentially with them and are being investigated as a potential future tool to combat coronaviruses such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by preventing viral attachment to the host. The review will discuss the possible applications of plant lectins as anti-coronaviruses including SARS-CoV-2, antinociceptive, anti-inflammation and its immune modulating effect.