Incidence and potential risk factors of human cytomegalovirus infection in patients with severe and critical coronavirus disease 2019.

BACKGROUND: Human cytomegalovirus (HCMV) infection occurs in immunosuppressed individuals and is known to increase mortality. Patients with coronavirus disease 2019 (COVID-19) are often treated with steroids, require intensive care unit (ICU) treatment, and may therefore be at risk for HCMV infection. However, which factors predispose severely ill patients with COVID-19 to HCMV infection and the prognostic value of such infections remain largely unexplored. This study aimed to examine the incidence and potential risk factors of HCMV infection in patients with severe or critical COVID-19 and evaluate the relationship between HCMV infection and mortality. METHODS AND FINDINGS: We used administrative claims data from advanced treatment hospitals in Japan to identify and analyze patients with severe or critical COVID-19. We explored potential risk factors for HCMV infection using multivariable regression models and its contribution to mortality in patients with COVID-19. Overall, 33,151 patients who progressed to severe or critical COVID-19 illness were identified. The incidence of HCMV infection was 0.3-1.7 % depending on the definition of HCMV infection. Steroids, immunosuppressants, ICU admission, and blood transfusion were strongly associated with HCMV infection. Furthermore, HCMV infection was associated with patient mortality independent of the observed risk factors for death. CONCLUSIONS: HCMV infection is a notable complication in patients with severe or critical COVID-19 who are admitted to the ICU or receive steroids, immunosuppressants, and blood transfusion and can significantly increase mortality risk.

Unchanged Faces of Acute Appendicitis: Exploring Presentation and Treatment Amidst the COVID-19 Pandemic.

Introduction The emergence of the COVID-19 pandemic necessitated the implementation of novel guidelines for managing appendicitis, prompting an evaluation of its effects on patient presentation and treatment at a district general hospital. Healthcare facilities worldwide have adapted protocols to meet the unique challenges of the pandemic, ensuring safe and efficient care. Our study assesses the pandemic's influence on patient demographics, clinical outcomes, surgical procedures, and adherence to guidelines among individuals undergoing emergency appendicitis surgery. Through this investigation, we aimed to determine whether significant deviations occurred in managing acute appendicitis amidst the pandemic. Methodology Consecutive adult patients (≥18 years) diagnosed with acute appendicitis were included in two cohorts for this retrospective analysis, comparing cases treated during the COVID-19 pandemic period (April to September 2020) with those treated one year prior. All patients underwent standardized assessments upon emergency department admission, including imaging studies and COVID-19 testing. Demographics, laboratory results, surgical details, and outcomes were compared between the pre- and post-pandemic groups, focusing on their overall management. Results The research involved a total of 172 individuals. During the pandemic (April to September 2020), 91 of these participants underwent surgery, which is more than the 81 individuals who had surgery during the same period the previous year (April to September 2019). Preoperative C-reactive protein levels were significantly higher in the pandemic group (P = 0.0455). The time from admission to surgery was shorter in the pandemic group (7.5 ± 4.6 vs. 5.8 ± 4.9; P = 0.0155). The overall operative and laparoscopic operative times were longer in the pandemic group (65 vs. 71 minutes, P = 0.391, and 55 vs. 62 minutes, P = 0.1424, respectively). However, these differences were not statistically significant. The number of patients presenting with complicated appendicitis was significantly higher in the pandemic group than in the nonpandemic group (44.4% vs. 61.4%; P = 0.034). The length of stay was shorter in the pandemic group (P = 0.53). Conclusions Our study suggests that surgery for acute appendicitis remains safe and feasible during the COVID-19 pandemic, with comparable outcomes. However, we noted an increase in the number of patients presenting with complicated appendicitis, possibly influenced by national pandemic guidelines in the United Kingdom. Despite this trend, our findings affirm the continued effectiveness of surgical management for acute appendicitis during the pandemic, highlighting the adaptability of healthcare systems in addressing emergent medical needs under challenging circumstances.

Immunogenicity and safety of a recombinant COVID-19 vaccine (ZF2001) as heterologous booster after priming with inactivated vaccine in healthy children and adolescents aged 3-17 years: an open-labeled, single-arm clinical trial.

Considering that neutralizing antibody levels induced by two doses of the inactivated vaccine decreased over time and had fallen to low levels by 6 months, and homologous and heterologous booster immunization programs have been implemented in adults in China. The booster immunization of recombinant COVID-19 vaccine (ZF2001) after priming with inactivated vaccine in healthy children and adolescents has not been reported. We performed an open-labeled, single-arm clinical trial to evaluate the safety and immunogenicity of heterologous booster immunization with ZF2001 after priming with inactivated vaccine among 240 population aged 3-17 years in China. The primary outcome was immunogenicity, including geometric mean titers (GMTs), geometric mean ratios (GMRs) and seroconversion rates of SARS-CoV-2 neutralizing antibodies against prototype SARS-CoV-2 and Omicron BA.2 variant at 14 days after vaccination booster. On day 14 post-booster, a third dose booster of the ZF2001 provided a substantial increase in antibody responses in minors, and the overall occurrence rate of adverse reactions after heterologous vaccination was low and all adverse reactions were mild or moderate. The results showed that the ZF2001 heterologous booster had high immunogenicity and good safety profile in children and adolescents, and can elicit a certain level of neutralizing antibodies against Omicron.Trial registration NCT05895110 (Retrospectively registered, First posted in ClinicalTrials.gov date: 08/06/2023).

Comparison of Neutralizing Activity between Vaccinated and Unvaccinated Hospitalized COVID-19 Patients Infected with Delta, Omicron BA.1, or Omicron BA.2 Variant.

BACKGROUND: Understanding the immune response to evolving viral strains is crucial for evidence-informed public health strategies. The main objective of this study is to assess the influence of vaccination on the neutralizing activity of SARS-CoV-2 delta and omicron infection against various SARS-CoV-2 variants. METHODS: A total of 97 laboratory-confirmed COVID-19 cases were included. To assess the influence of vaccination on neutralizing activity, we measured the neutralizing activity of SARS-CoV-2 delta or omicron (BA.1 or BA.2) infection against wild-type (WT), delta, BA.1, and BA.2, with the results stratified based on vaccination status. RESULTS: The neutralizing activity against the WT, delta, and omicron variants (BA.1 and BA.2) was significantly higher in the vaccinated patients than those in the unvaccinated patients. In the unvaccinated individuals infected with the delta variant, the decrease in binding to BA.1 and BA.2 was statistically significant (3.9- and 2.7-fold, respectively) compared to the binding to delta. In contrast, vaccination followed by delta breakthrough infection improved the cross-neutralizing activity against omicron variants, with only 1.3- and 1.2-fold decreases in BA.1 and BA.2, respectively. Vaccination followed by infection improved cross-neutralizing activity against WT, delta, and BA.2 variants in patients infected with the BA.1 variant, compared to that in unvaccinated patients. CONCLUSIONS: Vaccination followed by delta or BA.1 infection is associated with improved cross-neutralizing activity against different SARS-CoV-2 variants. The enhanced protection provided by breakthrough infections could have practical implications for optimizing vaccination strategies.

Photo-sensitive peptide inducing targeted cross-linking in a one-step and reagent-, enzyme- and antibody-free detection of SARS-Cov-2 marker protein.

Modern biosensing technology plays a crucial role in combating the spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). However, the associated assays remain costly, considering their extensive daily use. In response, we developed a simplified one-step SARS-CoV-2 protease assay that reduces both time and financial expenses. This approach eliminates the need for extra reagents, enzymes, or antibodies. The simplification involves a photo-sensitive Bengal red-tagged substrate peptide, allowing specific cross-linking upon protease-substrate recognition. This process forms a di-tyrosine product with a distinctive fluorescence signal readout, enabling the detection of SARS-CoV-2 in patient serum samples. This method anticipates a major reduction in assay costs in the near future.

Favipiravir Analogues as Inhibitors of SARS-CoV-2 RNA-Dependent RNA Polymerase, Combined Quantum Chemical Modeling, Quantitative Structure-Property Relationship, and Molecular Docking Study.

Our study was motivated by the urgent need to develop or improve antivirals for effective therapy targeting RNA viruses. We hypothesized that analogues of favipiravir (FVP), an inhibitor of RNA-dependent RNA polymerase (RdRp), could provide more effective nucleic acid recognition and binding processes while reducing side effects such as cardiotoxicity, hepatotoxicity, teratogenicity, and embryotoxicity. We proposed a set of FVP analogues together with their forms of triphosphate as new SARS-CoV-2 RdRp inhibitors. The main aim of our study was to investigate changes in the mechanism and binding capacity resulting from these modifications. Using three different approaches, QTAIM, QSPR, and MD, the differences in the reactivity, toxicity, binding efficiency, and ability to be incorporated by RdRp were assessed. Two new quantum chemical reactivity descriptors, the relative electro-donating and electro-accepting power, were defined and successfully applied. Moreover, a new quantitative method for comparing binding modes was developed based on mathematical metrics and an atypical radar plot. These methods provide deep insight into the set of desirable properties responsible for inhibiting RdRp, allowing ligands to be conveniently screened. The proposed modification of the FVP structure seems to improve its binding ability and enhance the productive mode of binding. In particular, two of the FVP analogues (the trifluoro- and cyano-) bind very strongly to the RNA template, RNA primer, cofactors, and RdRp, and thus may constitute a very good alternative to FVP.

Clinico-Demographic Profiles of Herpes Zoster Cases in Patients With and Without COVID-19 Infection During the Pandemic: A Retrospective Analysis of 32 Cases.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has multiple impacts on the human body. The immunological effect is one of the prominent ones, which is thought to be fundamental in many physical manifestations and disease severity. Herpes zoster (HZ) reactivation has been well-linked to immunity; immunocompromised states predispose a person to HZ. Studies have raised concerns about HZ incidences in COVID-19 patients; however, the clinical characteristics of the HZ cases among patients with and without COVID-19 are another area to be explored. METHODS: In this retrospective analysis, we compared the clinical and demographic characteristics of HZ cases presented to our outpatient department immediately before and during the early second wave of the COVID-19 pandemic (September 2020 to April 2021) in India. The cases were divided into two groups based on the history of COVID-19 infections. The clinico-demographic characteristics were then compared using an unpaired t-test, Fisher's exact test, and analysis of variance as applicable using InStat software; a two-sided p-value <0.05 was considered significant. RESULTS: During the period, 32 cases (17 HZ cases with a history of COVID-19; 15 HZ cases without) were detected. The age and gender distribution were indifferent statistically. Our analysis showed that multi-dermatomal and disseminated involvements were significantly higher in HZ cases having a history of COVID-19. CONCLUSION: The present retrospective analysis of 32 cases indicates that persons who suffered from COVID-19 and presented with HZ were likely to have a higher chance of multi-dermatomal and disseminated involvement. While our analysis cannot establish a true association between COVID-19 infection and HZ reactivation, which will require a large-scale study, clinicians might get a clue of the possible progression of the extent of HZ manifestations from our findings.

Risk factors for clinically significant diffuse parenchymal lung abnormalities persisting after severe COVID-19 pneumonia.

Background & objectives: The risk factors for clinically significant diffuse parenchymal lung abnormalities (CS-DPLA) persisting after severe coronavirus disease 2019 (COVID-19) pneumonia remain unclear. The present study was conducted to assess whether COVID-19 severity and other parameters are associated with CS-DPLA. Methods: The study participants included patients who recovered after acute severe COVID-19 and presented with CS-DPLA at two or six month follow up and control group (without CS-DPLA). Adults volunteers without any acute illness, chronic respiratory illness and without a history of severe COVID-19 were included as healthy controls for the biomarker study. The CS-DPLA was identified as a multidimensional entity involving clinical, radiological and physiological pulmonary abnormalities. The primary exposure was the neutrophil-lymphocyte ratio (NLR). Recorded confounders included age, sex, peak lactate dehydrogenase (LDH), advanced respiratory support (ARS), length of hospital stay (LOS) and others; associations were analyzed using logistic regression. The baseline serum levels of surfactant protein D, cancer antigen 15-3 and transforming growth factor-ß (TGF-ß) were also compared among cases, controls and healthy volunteers. Results: We identified 91/160 (56.9%) and 42/144 (29.2%) participants with CS-DPLA at two and six months, respectively. Univariate analyses revealed associations of NLR, peak LDH, ARS and LOS with CS-DPLA at two months and of NLR and LOS at six months. The NLR was not independently associated with CS-DPLA at either visit. Only LOS independently predicted CS-DPLA at two months [adjusted odds ratios (aOR) (95% confidence interval [CI]), 1.16 (1.07-1.25); P<0.001] and six months [aOR (95% CI) and 1.07 (1.01-1.12); P=0.01]. Participants with CS-DPLA at six months had higher baseline serum TGF-ß levels than healthy volunteers. Interpretation and conclusions: Longer hospital stay was observed to be the only independent predictor of CS-DPLA six months after severe COVID-19. Serum TGF-ß should be evaluated further as a biomarker.

Double Trouble Co-Infections: Understanding the Correlation Between COVID-19 and HIV Viruses.

A global outbreak of coronavirus disease 2019 (COVID-19), an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mounted a substantial threat to public health worldwide. It initially emerged as a mere outbreak in Wuhan, China, in December 2019 and quickly engulfed the entire world, evolving into a global pandemic, consuming millions of lives and leaving a catastrophic effect on our lives in ways unimaginable. The entire healthcare system was significantly impacted and HIV healthcare was not spared. In this article, we reviewed the effect of HIV on COVID-19 disease and the ramifications of the recent COVID-19 pandemic over HIV management strategies. Our review highlights that contrary to the instinctive belief that HIV should render patients susceptible to COVID-19 infection, the studies depicted mixed results, although comorbidities and other confounders greatly affected the results. Few studies showed a higher rate of in-hospital mortality due to COVID-19 among HIV patients; however, the use of antiretroviral therapy had no consequential effect. COVID-19 vaccination was deemed safe among HIV patients in general. The recent pandemic can destabilize the HIV epidemic control as it hugely impacted access to care and preventive services and led to a marked reduction in HIV testing. The collision of these two disastrous pandemics warrants the need to materialize rigorous epidemiological measures and health policies, but most importantly, brisk research in prevention strategies to mitigate the combined burden of the two viruses and to battle similar future pandemics.

[Reasons for allergology consultations prior to COVID-19 vaccination and their outcomes : Two-year experience of an allergy center in North Rhine-Westphalia]. / Gründe für allergologische Diagnostik und deren Ergebnisse im Kontext von COVID-19-Vakzinierungen : 2-jährige Erfahrung eines Allergiezentrums in Nordrhein-Westfalen.

BACKGROUND: To counteract the coronavirus disease 2019 (COVID-19) pandemic, several severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccines have been licensed since December 2020. Shortly after the start of the vaccination campaigns, occasional allergic reactions related to vaccines were described, thus, leading to concerns in many patients with a history of allergies. The aim of this work was to evaluate which anamnestic events represented a reason for an allergology work-up before COVID-19 vaccination. Furthermore, the results of the allergology diagnostics are described. METHODS: We performed a retrospective data analysis of all patients who presented at the Center for Dermatology, Allergology and Dermatosurgery of the Helios University Hospital Wuppertal during the years 2021 and 2022 for allergology work-up prior to COVID-19 vaccination. Demographic data, allergological history, reason for the consultation in the clinic and results of allergology diagnostic tests including reactions after vaccination were included. RESULTS: A total of 93 patients presented for allergology work-up with COVID-19 vaccines. In about half of the cases, the reasons for the presentation to the clinic were doubts and concerns about allergic reactions and side effects. In all, 26.9% (25/93) of the presented patients had not previously received a COVID-19 vaccine yet and 23.7% (22/93) of patients developed non-allergic reactions after prior COVID-19 vaccine (e.g., headache, chills, fever, malaise). Of the patients, 46.2% (43/93) were successfully vaccinated in the clinic due to a complex allergological history, while the remaining 53.8% (50/93) were subjected to outpatient vaccination in the vaccination practice. Only one patient with known chronic spontaneous urticaria developed a mild angioedema of the lips a few hours after vaccination; however, we do not consider this episode an allergic reaction to the vaccine due to the time delay. CONCLUSION: Allergic reactions after COVID-19 vaccines are rare, but many patients with a positive medical history of allergies are concerned about allergic reactions after COVID-19 vaccination. Thus, public work by practicing allergologists is important during vaccination campaigns to meet the concerns and fears of the population, especially of patients with allergies in their medical history.

Mitigating the risk of COVID-19 infection in the operating room: Using healthcare failure mode and effect analysis.

Context: The process of caring for patients requiring surgery exposes them to a high risk of COVID-19 infection during the pre-operative, operative, and post-operative phases, as these procedures are known to be modes of transmission for the virus. Objective: We conducted this study to prevent the risk of COVID-19 infection by identifying potential failure modes during the patient care process, determining critical activities, and defining mitigation measures to reduce transmission. Materials and methods: Through a quality and a priori risk management method, which is Healthcare Failure Mode and Effect Analysis (HFMEA), applied in the patient care process in the Central Operating Room of Mohammed VI University Hospital in Morocco. Results: We identified 38 potential failure modes in the patient care process during the three phases (preoperative, operative, and postoperative) that could increase the risk of COVID-19 infection. Of these, 61% are classified as critical, and we have identified all their possible causes. To reduce the risk of transmission, we have proposed 16 mitigation actions. Conclusion: The use of HFMEA has been effective in the new pandemic context, improving patient safety during the care process in the operating room and reducing the risk of COVID-19 infection.

Immune Thrombocytopenia and Cerebral Venous Sinus Thrombosis Following COVID-19 Vaccination: A Case Report.

Mass vaccination against coronavirus disease 2019 (COVID-19) has been safe and effective. The ongoing emergence of vaccine-induced complications has challenged the public trust in vaccination programs and, though uncommon, can lead to significant morbidity and mortality. Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a rare and fatal complication of the COVID-19 vaccine. We present a rare case of VITT in a young female who presented with worsening headache, body rash with deteriorating neurological deficit after 12 days of the second dose of the ChAdOx1 COVID-19 vaccine. Initial blood tests showed thrombocytopenia with deranged clotting time and D-dimer levels. Her computed tomography venogram showed thrombosis in the left transverse sinus, and she was diagnosed with a provisional diagnosis of VITT. She initially managed with dexamethasone, intravenous immunoglobulins, and apixaban to reverse the autoimmune process. Our case highlights the clinical course, diagnosis, and management of VITT, which will assist physicians in the timely recognition and adequate management of VITT.

Myocardial Injury on CMR in Patients With COVID-19 and Suspected Cardiac Involvement.

BACKGROUND: Myocardial injury in patients with COVID-19 and suspected cardiac involvement is not well understood. OBJECTIVES: The purpose of this study was to characterize myocardial injury in a multicenter cohort of patients with COVID-19 and suspected cardiac involvement referred for cardiac magnetic resonance (CMR). METHODS: This retrospective study consisted of 1,047 patients from 18 international sites with polymerase chain reaction-confirmed COVID-19 infection who underwent CMR. Myocardial injury was characterized as acute myocarditis, nonacute/nonischemic, acute ischemic, and nonacute/ischemic patterns on CMR. RESULTS: In this cohort, 20.9% of patients had nonischemic injury patterns (acute myocarditis: 7.9%; nonacute/nonischemic: 13.0%), and 6.7% of patients had ischemic injury patterns (acute ischemic: 1.9%; nonacute/ischemic: 4.8%). In a univariate analysis, variables associated with acute myocarditis patterns included chest discomfort (OR: 2.00; 95% CI: 1.17-3.40, P = 0.01), abnormal electrocardiogram (ECG) (OR: 1.90; 95% CI: 1.12-3.23; P = 0.02), natriuretic peptide elevation (OR: 2.99; 95% CI: 1.60-5.58; P = 0.0006), and troponin elevation (OR: 4.21; 95% CI: 2.41-7.36; P < 0.0001). Variables associated with acute ischemic patterns included chest discomfort (OR: 3.14; 95% CI: 1.04-9.49; P = 0.04), abnormal ECG (OR: 4.06; 95% CI: 1.10-14.92; P = 0.04), known coronary disease (OR: 33.30; 95% CI: 4.04-274.53; P = 0.001), hospitalization (OR: 4.98; 95% CI: 1.55-16.05; P = 0.007), natriuretic peptide elevation (OR: 4.19; 95% CI: 1.30-13.51; P = 0.02), and troponin elevation (OR: 25.27; 95% CI: 5.55-115.03; P < 0.0001). In a multivariate analysis, troponin elevation was strongly associated with acute myocarditis patterns (OR: 4.98; 95% CI: 1.76-14.05; P = 0.003). CONCLUSIONS: In this multicenter study of patients with COVID-19 with clinical suspicion for cardiac involvement referred for CMR, nonischemic and ischemic patterns were frequent when cardiac symptoms, ECG abnormalities, and cardiac biomarker elevations were present.

Clinical risk factors of adverse outcomes among women with COVID-19 in the pregnancy and postpartum period: a sequential, prospective meta-analysis.

OBJECTIVE: This sequential, prospective meta-analysis sought to identify risk factors among pregnant and postpartum women with COVID-19 for adverse outcomes related to disease severity, maternal morbidities, neonatal mortality and morbidity, and adverse birth outcomes. DATA SOURCES: We prospectively invited study investigators to join the sequential, prospective meta-analysis via professional research networks beginning in March 2020. STUDY ELIGIBILITY CRITERIA: Eligible studies included those recruiting at least 25 consecutive cases of COVID-19 in pregnancy within a defined catchment area. METHODS: We included individual patient data from 21 participating studies. Data quality was assessed, and harmonized variables for risk factors and outcomes were constructed. Duplicate cases were removed. Pooled estimates for the absolute and relative risk of adverse outcomes comparing those with and without each risk factor were generated using a 2-stage meta-analysis. RESULTS: We collected data from 33 countries and territories, including 21,977 cases of SARS-CoV-2 infection in pregnancy or postpartum. We found that women with comorbidities (preexisting diabetes mellitus, hypertension, cardiovascular disease) vs those without were at higher risk for COVID-19 severity and adverse pregnancy outcomes (fetal death, preterm birth, low birthweight). Participants with COVID-19 and HIV were 1.74 times (95% confidence interval, 1.12-2.71) more likely to be admitted to the intensive care unit. Pregnant women who were underweight before pregnancy were at higher risk of intensive care unit admission (relative risk, 5.53; 95% confidence interval, 2.27-13.44), ventilation (relative risk, 9.36; 95% confidence interval, 3.87-22.63), and pregnancy-related death (relative risk, 14.10; 95% confidence interval, 2.83-70.36). Prepregnancy obesity was also a risk factor for severe COVID-19 outcomes including intensive care unit admission (relative risk, 1.81; 95% confidence interval, 1.26-2.60), ventilation (relative risk, 2.05; 95% confidence interval, 1.20-3.51), any critical care (relative risk, 1.89; 95% confidence interval, 1.28-2.77), and pneumonia (relative risk, 1.66; 95% confidence interval, 1.18-2.33). Anemic pregnant women with COVID-19 also had increased risk of intensive care unit admission (relative risk, 1.63; 95% confidence interval, 1.25-2.11) and death (relative risk, 2.36; 95% confidence interval, 1.15-4.81). CONCLUSION: We found that pregnant women with comorbidities including diabetes mellitus, hypertension, and cardiovascular disease were at increased risk for severe COVID-19-related outcomes, maternal morbidities, and adverse birth outcomes. We also identified several less commonly known risk factors, including HIV infection, prepregnancy underweight, and anemia. Although pregnant women are already considered a high-risk population, special priority for prevention and treatment should be given to pregnant women with these additional risk factors.

Identification of a promising inhibitor from Illicium verum (star anise) against the main protease of SARS-CoV-2: insights from the computational study.

SARS-CoV-2, the causing agent of coronavirus disease (COVID-19), first broke out in Wuhan and rapidly spread worldwide, resulting in a global health emergency. The lack of specific drugs against the coronavirus has made its spread challenging to control. The main protease (Mpro) is a key enzyme of SARS-CoV-2 used as a key target in drug discovery against the coronavirus. Medicines derived from plant phytoconstituents have been widely exploited to treat various diseases. The present study has evaluated the potential of Illicium verum (star anise) phytoconstituents against Mpro by implementing a computational approach. We performed molecular docking and molecular dynamics simulation study with a set of 60 compounds to identify their potential to inhibit the main protease (Mpro) of SARS-CoV-2. DFT study and post dynamics free energy calculations were also performed to strengthen the findings. The identified four compounds by docking study exhibited the highest potential compared to other selected phytoconstituents. Further, density functional theory (DFT) calculation, molecular dynamics simulation and post dynamics MM-GBSA energy calculation predicted Verimol-G as a potential compound, which formed stable interactions through the catalytic dyad residues. The HOMO orbital energy (-0.250038) from DFT and the post dynamics binding free energy calculation (-73.33 Kcal/mol) correlate, suggesting Verimol-G is the best inhibitor compared to the other phytoconstituents. This compound also complies with the ADME properties of drug likeliness. Thus, based on a computational study, we suggest that Verimol G may be developed as a potential inhibitor against the main protease to combat COVID-19.Communicated by Ramaswamy H. Sarma.

Psicodrama público sp on-line durante a pandemia de covid-19 / Public psychodrama sp on-line during the covid-19 pandemic / Psicodrama público sp on-line durante la pandemia del covid-19

RESUMO O objetivo deste trabalho é apresentar reflexões sobre as sessões de Psicodrama Público SP On-line ocorridas entre agosto de 2020 e dezembro de 2021. O procedimento utilizado foi a análise qualitativa de entrevistas com a unidade funcional, o anfitrião e alguns participantes, gravadas após a realização dos psicodramas. Foram criadas quatro categorias a partir dos temas protagônicos apresentados. Foram identificados dois movimentos complementares: um em direção ao desequilíbrio e outro em direção à tentativa de restaurá-lo,além de uma retroalimentação entre as categorias e entre os períodos analisados. Observou-se que se instauraram novos processos de subjetivação no contexto grupal marcados pelos múltiplos sofrimentos vivenciados no período pandêmico da COVID-19, facilitados pela liberação da espontaneidade e criatividade.

ABSTRACT This paper aims to present reflections on the Psicodrama Público SP On-line sessions that took place between August 2020 and December 2021. The procedure used was the qualitative analysis of interviews, with the functional unit, the host and some participants, recorded after the realization of psychodramas. Four categories were created from the main themes presented. Two complementary movements were identified: one towards the imbalance and the other towards the attempt to restore it, in addition to a feedback between the categories and between the analyzed periods. It was observed that new processes of subjectivation were established in the group context marked by many sufferings in the pandemic period of COVID-19, facilitated by the release of spontaneity and creativity.

RESUMEN El objetivo de este trabajo es presentar reflexiones sobre las sesiones de Psicodrama Público SP On-line que se desarrollaron entre agosto de 2020 y diciembre de 2021. El procedimiento utilizado fue el análisis cualitativo de entrevistas, con la unidad funcional, el conductor y algunos participantes, grabadas después de la realización de psicodramas. Se crearon cuatro categorías a partir de los principales temas presentados. Se identificaron dos movimientos complementarios: uno hacia el desequilibrio y otro hacia el intento de restaurarlo, además de una retroalimentación entre las categorías y entre los periodos analizados. Se observó que se establecieron nuevos procesos de subjetivación en el contexto grupal marcado por los muchos sufrimientos en el período de pandemia por la COVID-19, facilitados por la liberación de la espontaneidad y la creatividad.

Risk factors of active upper gastrointestinal bleeding in patients with COVID-19 infection and the effectiveness of PPI prophylaxis.

BACKGROUND: Gastrointestinal (GI) bleeding is one of the most impactful complications in patients hospitalized from COVID-19 infection. Limited study has focused on patients with upper GI bleeding (UGIB). This study aimed to identify the risk factors of patients who were hospitalized from COVID-19 infection and developed UGIB as well as the effectiveness of proton pump inhibitor (PPI) prophylaxis in those patients. METHODS: This study was comprised of two phases. The first phase was the retrospective enrollment of patients who were admitted due to COVID-19 infection and developed UGIB between April and August 2021 to evaluate the associated factors of active UGIB. The second phase was a retrospective analysis after PPI prophylaxis protocol from September - October 2021 to assess the benefit of PPI use in those patients. RESULTS: Of 6,373 patients hospitalized, 43 patients (0.7%) had evidence of UGIB. The majority were male 28 (65.1%) with a mean age of 69.1 ± 11.8 years. Twenty-four of 43 patients (55.8%) needed mechanical ventilation, 35 patients (81.4%) received systemic corticosteroids, and 10 patients (23.3%) were taking anticoagulants for venous thromboembolic prophylaxis. Seven of 43 patients (16%) had active UGIB. There was no significant difference in the number of patients taking antiplatelets, anticoagulants, or steroids and the severity of COVID-19 infection between the two groups. An emergency endoscopy or endoscopic hemostasis were performed in 6/7 (85.7%) patients. The multivariate logistic regression analysis revealed two significant factors associated with active UGIB including higher of Glasgow-Blatchford score (GBS) per point (OR = 7.89; 95%CI 1.03-72.87; p = 0.04) and an absence of PPI use (OR 4.29; 95%CI 1.04-19.51; p = 0.04). After prescribing PPI as a prophylaxis, there was a slightly lower incidence of UGIB (0.6% vs 0.7%) in addition to an absence of active UGIB (0% vs 16%). CONCLUSION: Our study demonstrated that the absence of PPI and higher GBS were significant risk factors for active UGIB which required therapeutic endoscopy in patients with COVID-19 infection. We suggest that short-term PPI prophylaxis should be prescribed in those patients once they need hospitalization regardless of the severity of COVID-19 infection to minimize the severity of UGIB.

Immune checkpoint inhibitor therapy and elevated levels of C-reactive protein associated with COVID-19 aggravation in patients with lung cancer.

BACKGROUND: COVID-19 has become a significant health threat and a primary healthcare concern among the most vulnerable patients with cancer. Patients with COVID-19 who have lung cancer are at great risk and need careful monitoring if they are affected. This study aimed to investigate the clinical characteristics of COVID-19-positive patients with lung cancer and the risks associated with anticancer medication. METHODS: This study was a single-center, retrospective cohort study. Patients with lung cancer who presented with COVID-19 during hospitalization were divided into two groups: those who presented with respiratory failure and those who did not. The patient's background, clinical laboratory values, and anticancer drugs used for therapy were investigated to identify risk factors for respiratory failure. RESULTS: Thirty-one patients were included in the study; 18 (58.1%) were in the respiratory failure group and 13 (41.9%) were in the group without respiratory failure. In the respiratory failure group, there was a significant difference in using immune checkpoint inhibitor (ICI) use within 90 days (p = 0.025) and the level of C-reactive protein (CRP) level (p = 0.017). The analysis of the operating characteristic of the receiver revealed a cutoff value of 2.75 mg/dL for CRP (area under the curve = 0.744, sensitivity 0.611, specificity 0.923). CONCLUSIONS: A history of ICI within 90 days and elevated CRP (≥ 2.75 mg/dL) levels are potential factors leading to respiratory failure in COVID-19-affected patients undergoing chemotherapy for lung cancer.

Mortality risk factors in patients with SARS-CoV-2 infection and atrial fibrillation: Data from the SEMI-COVID-19 registry.

Introduction: Atrial fibrillation and associated comorbidities pose a risk factor for mortality, morbidity and development of complications in patients admitted for COVID-19. Objectives: To describe the clinical, epidemiological, radiological and analytical characteristics of patients with AF admitted for COVID-19 in Spain. Secondarily, we aim to identify those variables associated with mortality and poor prognosis of COVID-19 in patients with AF. Methods: Retrospective, observational, multicenter, nationwide, retrospective study of patients hospitalized for COVID-19 from March 1 to October 1, 2020. Data were obtained from the SEMI-COVID-19 Registry of the Spanish Society of Internal Medicine (SEMI) in which 150 Spanish hospitals participate. Results: Between March 1 and October 1, 2020, data from a total of 16,461 patients were entered into the SEMI-COVID-19 registry. 1,816 (11%) had a history of AF and the number of deaths among AF patients amounted to 738 (41%). Regarding clinical characteristics, deceased patients were admitted with a higher heart rate (88.38 vs 84.95; p > 0.01), with a higher percentage of respiratory failure (67.2% vs 20.1%; p < 0.01) and high tachypnea (58% vs 30%; p < 0.01). The comorbidities that presented statistically significant differences in the deceased group were: age, hypertension and diabetes with target organ involvement. There was also a higher prevalence of a history of cardiovascular disease in the deceased. On multivariate analysis, DOACs treatment had a protective role for mortality (OR:0,597) IC (0,402-0,888 ; p = 0.011). Conclusions: Previous treatment with DOACs and DOACs treatment during admission seem to have a protective role in patients with AF, although this fact should be verified in prospective studies.

Introducción: La fibrilación auricular y las comorbilidades asociadas a ella suponen un factor de riesgo de mortalidad, morbilidad y desarrollo de complicaciones en los pacientes ingresados por COVID-19. Objetivos: Describir las características clínicas, epidemiológicas, radiológicas y analíticas de los pacientes con FA ingresados por COVID-19 en España. De forma secundaria, se pretende identificar aquellas variables que se asocian con mortalidad y mal pronóstico de la COVID-19 en pacientes que presentan FA. Métodos: Estudio retrospectivo, observacional y multicéntrico de ámbito nacional de pacientes hospitalizados por COVID-19 desde el 1 de marzo al 1 de octubre de 2020. Los datos fueron obtenidos del Registro SEMI-COVID-19 de la Sociedad Española de Medicina Interna (SEMI) en el que participan 150 hospitales españoles. Resultados: De un total de 16.461 pacientes en el registro SEMI-COVID-19, 1.816 (11%) tenían antecedente de FA y el número de fallecidos entre los pacientes con FA ascendió a 738 (41%). En cuanto a la clínica, los pacientes fallecidos ingresaron con una frecuencia cardíaca mayor (88,38 vs 84,95; p > 0,01), con mayor porcentaje de insuficiencia respiratoria (67,2% vs 20,1%; p < 0,01) y mayor taquipnea (58% vs 30%; p < 0,09). En el análisis multivariante, el tratamiento con ACOD tuvo un papel protector para la mortalidad por infección por COVID 19 (OR:0,597; IC (0,402-0,888; p = 0.011). Conclusiones: El tratamiento previo con ACOD como el tratamiento con ACOD durante el ingreso parecen tener un papel protector en los pacientes con FA, aunque este hecho debería ser comprobado con estudios prospectivos.

COVID-19 Vaccine Clinical Trials: A Bird's Eye Perspective.

Several Phase-III clinical studies investigating vaccine safety and effectiveness have been published a year following the first breakout of the COVID-19 pandemic. These vaccine candidates were produced using a variety of vaccination technologies, including mRNA, recombinant protein, adenoviral vector, and inactivated virus-based platforms, by various research organizations and pharmaceutical firms. Despite many successful clinical studies, participants are restricted by trial inclusion and exclusion criteria, geographic location, and the current state of the virus epidemic. Many concerns remain, particularly for specific populations such as the elderly, women who are pregnant or nursing, and teenagers. Vaccine effectiveness against asymptomatic infection and particular viral variations, on the other hand, is still largely unclear. This review will focus on vaccination candidates that have completed Phase-III clinical trials and will examine the scientific evidence that has been gathered so far for these vaccine candidates for various subgroups of individuals and virus variations.