Long COVID among US adults from a population-based study: Association with vaccination, cigarette smoking, and the modifying effect of chronic obstructive pulmonary disease (COPD).

OBJECTIVE: Post-COVID Conditions (or Long COVID) have been widely reported, but population-based studies exploring the relationship between its risk factors are lacking. We examined the associations between Long COVID, chronic obstructive pulmonary disease [COPD], vaccination status, and cigarette smoking. We also tested for the modifying effect of COPD status. METHODS: Data from the 2022 US nationwide Behavioral Risk Factor Surveillance System (BRFSS) were analyzed. Our primary outcome was Long COVID (Yes/No) after a positive COVID-19 diagnosis. Predictor variables were COPD, coronary heart disease (CHD), diabetes, asthma, body mass index, cigarette smoking status, and number of COVID-19 vaccinations (0-4). Weighted multivariable logistic regression models were used and adjusted for sociodemographic factors. Regression models were used to explore the modifying effects of COPD status. RESULTS: The weighted prevalence of Long COVID among survivors (N = 121,379) was 21.8% (95%CI: 21.4, 22.3), with tiredness/fatigue (26.2% [95%:25.1, 27.2]) as the most common symptom. Respondents with COPD (aOR: 1.71 [95%CI: 1.45, 2.02]), current daily smokers (aOR: 1.23 [95%CI:1.01, 1.49]), and former smokers (aOR: 1.24 [95%CI:1.12, 1.38]) (vs. never established smokers) had higher odds of Long COVID. However, respondents who had received three (aOR: 0.75 [95%CI:0.65, 0.85]) and four (aOR: 0.71 [95%CI:0.58, 0.86]) vaccine doses (vs. no vaccine) had lower odds of Long COVID. COPD had a modifying effect on the relationship between cigarette smoking and Long COVID (p-value: 0.013). CONCLUSION: Our findings underscore a complex interaction between COPD, cigarette smoking, and Long COVID. Further, COVID-19 vaccination may be protective against Long COVID.

Long-term health consequences of COVID-19 in survivors hospitalised at a tertiary care hospital and their correlation with acute COVID-19 severity and associated risk factors.

OBJECTIVES: To determine post-COVID syndromes in the Indian population, correlating a wide spectrum of post-COVID manifestations with acute disease severity and associated risk factors. BACKGROUND: Post-COVID Syndrome (PCS) is defined as signs and symptoms that develop during or after acute COVID-19 infection. DESIGN OF STUDY: This is a prospective observational cohort with repetitive measurements. METHODS: The study followed RT-PCR confirmed COVID-19-positive survivors discharged from HAHC Hospital, New Delhi, for a period of 12 weeks. The patients were interviewed over the phone at 4 weeks and 12 weeks from the onset of symptoms for evaluation of clinical symptoms and health-related quality of life parameters. RESULTS: A total of 200 patients completed the study. At the baseline, 50% of the patients were categorised as severe based on their acute infection assessment. At 12 weeks after symptom onset, fatigue (23.5%), hair loss (12.5%) and dyspnea (9%) were the main persistent symptoms. The incidence of hair loss (12.5%), memory loss (4.5%) and brain fog (5%) were found to be increased as compared to the acute infection period. Severity of the acute COVID infection behaved as an independent predictor for the development of PCS, with high odds of experiencing persistent cough (OR = 13.1), memory loss (OR = 5.2) and fatigue (OR = 3.3). Further, 30% of subjects in the severe group experienced statistically significant fatigue at 12 weeks (p < .05). CONCLUSION: From the results of our study, it can be concluded that there is a huge disease burden of post-COVID Syndrome (PCS). The PCS comprised multisystem symptoms ranging from serious complaints of dyspnea, memory loss and brain fog to non-serious complaints of fatigue and hair loss. Severity of the acute COVID infection behaved as an independent predictor for the development of PCS. Our findings strongly recommend vaccination against COVID-19, for protection from disease severity as well as prevention of PCS. RELEVANCE TO CLINICAL PRACTICE: The findings of our study support the multidisciplinary approach required for the management of PCS with a team comprising of physicians, nurses, physiotherapists and psychiatrists working in close coordination for the rehabilitation of these patients. As nurses are considered the most trusted professionals in the community and the class of health workers associated with rehabilitation, focus should be given to educating them on PCS, which would prove to be an important strategy for efficient monitoring and long-term management of COVID-19 survivors.

Neutrophil Activation and Immune Thrombosis Profiles Persist in Convalescent COVID-19.

PURPOSE: Following a severe COVID-19 infection, a proportion of individuals develop prolonged symptoms. We investigated the immunological dysfunction that underlies the persistence of symptoms months after the resolution of acute COVID-19. METHODS: We analyzed cytokines, cell phenotypes, SARS-CoV-2 spike-specific and neutralizing antibodies, and whole blood gene expression profiles in convalescent severe COVID-19 patients 1, 3, and 6 months following hospital discharge. RESULTS: We observed persistent abnormalities until month 6 marked by (i) high serum levels of monocyte/macrophage and endothelial activation markers, chemotaxis, and hematopoietic cytokines; (ii) a high frequency of central memory CD4+ and effector CD8+ T cells; (iii) a decrease in anti-SARS-CoV-2 spike and neutralizing antibodies; and (iv) an upregulation of genes related to platelet, neutrophil activation, erythrocytes, myeloid cell differentiation, and RUNX1 signaling. We identified a "core gene signature" associated with a history of thrombotic events, with upregulation of a set of genes involved in neutrophil activation, platelet, hematopoiesis, and blood coagulation. CONCLUSION: The lack of restoration of gene expression to a normal profile after up to 6 months of follow-up, even in asymptomatic patients who experienced severe COVID-19, signals the need to carefully extend their clinical follow-up and propose preventive measures.

An immune-protein score combining TRAIL, IP-10 and CRP for predicting severe COVID-19 disease.

COVID-19 patients are oftentimes over- or under-treated due to a deficit in predictive management tools. This study reports derivation of an algorithm that integrates the host levels of TRAIL, IP-10, and CRP into a single numeric score that is an early indicator of severe outcome for COVID-19 patients and can identify patients at-risk to deteriorate. 394 COVID-19 patients were eligible; 29% meeting a severe outcome (intensive care unit admission/non-invasive or invasive ventilation/death). The score's area under the receiver operating characteristic curve (AUC) was 0.86, superior to IL-6 (AUC 0.77; p = 0.033) and CRP (AUC 0.78; p < 0.001). Likelihood of severe outcome increased significantly (p < 0.001) with higher scores. The score differentiated severe patients who further deteriorated from those who improved (p = 0.004) and projected 14-day survival probabilities (p < 0.001). The score accurately predicted COVID-19 patients at-risk for severe outcome, and therefore has potential to facilitate timely care escalation and de-escalation and appropriate resource allocation.

People exposed to proton-pump inhibitors shortly preceding COVID-19 diagnosis are not at an increased risk of subsequent hospitalizations and mortality: A nationwide matched cohort study.

AIMS: To assess whether exposure to proton-pump inhibitors (PPIs) shortly preceding COVID-19 diagnosis affected the risk of subsequent hospitalizations and mortality. METHODS: This population-based study embraced first COVID-19 episodes in adults diagnosed up to 15 August 2021 in Croatia. Patients were classified based on exposure to PPIs and burden of PPI-requiring morbidities as nonusers (no issued prescriptions, no recorded treatment-requiring conditions between 1 January 2019 and COVID-19 diagnosis), possible users (no issued prescriptions, but morbidities present; self-medication possible) and users (≥1 prescription within 3 months prior to the COVID-19 diagnosis; morbidities present). Subsets were mutually exactly matched for pre-COVID-19 characteristics. The contrast between users and possible users informed about the effect of PPIs that is separate of the effect of PPI-requiring conditions. RESULTS: Among 433 609 patients, users and possible users were matched 41 195 (of 55 098) to 17 334 (of 18 170) in the primary and 33 272 to 16 434 in the sensitivity analysis. There was no relevant difference between them regarding mortality (primary: relative risk [RR] = 0.93 [95% confidence interval 0.85-1.02; absolute risk difference [RD] = -0.34% [-0.73, 0.03]; sensitivity: RR = 0.88 [0.78-0.98]; RD = -0.45% [-0.80, -0.11]) or hospitalizations (primary: RR = 1.04 [0.97-1.13]; RD = 0.29% [-0.16, 0.73]; sensitivity: RR = 1.05 [0.97-1.15]; RD = 0.32% [-0.12, 0.75]). The risks of both were slightly higher in possible users or users than in nonusers (absolutely by ~0.4-1.6%) indicating the effect of PPI-requiring morbidities. CONCLUSION: Premorbid exposure to PPIs does not affect the risk of death or hospitalization in adult COVID-19 patients, but PPI-requiring morbidities seemingly slightly increase the risk of both.

COVID 19 infection clinical features in pediatric patients in Southwestern Iran: a cross-sectional, multi-center study.

With the SARS-CoV-2 pandemic, the impact of recent coronavirus, especially in children, cannot be ignored. In this study, we evaluated the SARS-CoV-2 infection rates and associated features in children less than 18 years of age in "Fars" and "Kohgiluyeh and Boyer Ahmad", provinces, Iran. 5943 children who were suspected cases to SARS-CoV-2 infection were enrolled in this study. Demographic and clinical data of SARS-CoV-2 patients were collected from 16 February 2020 to 20 June 2021. Underlying conditions were considered in this study as well. Among 5943 patients suspected COVID 19 cases, 13.51% were confirmed by real-time PCR assay. The female/male ratio was 1:1.3 with a mean age of 5.71 years. 11.2% of confirmed patients were transferred and admitted in Pediatric ICU. COVID 19 was significantly higher in children with malignancy and diabetes rather than those with other underlying diseases. Children of all ages were susceptible to COVID 19, and there is no significant difference between both sexes. Most of the COVID 19 cases were in 10-18 years old group. Among a number of children with different underlying diseases, children with malignancy had the highest rate of SARS-CoV-2 infection, followed by those with diabetes.

Peculiar weather patterns effects on air pollution and COVID-19 spread in Tokyo metropolis.

As a pandemic hotspot in Japan, between March 1, 2020-October 1, 2022, Tokyo metropolis experienced seven COVID-19 waves. Motivated by the high rate of COVID-19 incidence and mortality during the seventh wave, and environmental/health challenges we conducted a time-series analysis to investigate the long-term interaction of air quality and climate variability with viral pandemic in Tokyo. Through daily time series geospatial and observational air pollution/climate data, and COVID-19 incidence and death cases, this study compared the environmental conditions during COVID-19 multiwaves. In spite of five State of Emergency (SOEs) restrictions associated with COVID-19 pandemic, during (2020-2022) period air quality recorded low improvements relative to (2015-2019) average annual values, namely: Aerosol Optical Depth increased by 9.13% in 2020 year, and declined by 6.64% in 2021, and 12.03% in 2022; particulate matter PM2.5 and PM10 decreased during 2020, 2021, and 2022 years by 10.22%, 62.26%, 0.39%, and respectively by 4.42%, 3.95%, 5.76%. For (2021-2022) period the average ratio of PM2.5/PM10 was (0.319 ± 0.1640), showing a higher contribution to aerosol loading of traffic-related coarse particles in comparison with fine particles. The highest rates of the daily recorded COVID-19 incidence and death cases in Tokyo during the seventh COVID-19 wave (1 July 2022-1 October 2022) may be attributed to accumulation near the ground of high levels of air pollutants and viral pathogens due to: 1) peculiar persistent atmospheric anticyclonic circulation with strong positive anomalies of geopotential height at 500 hPa; 2) lower levels of Planetary Boundary Layer (PBL) heights; 3) high daily maximum air temperature and land surface temperature due to the prolonged heat waves (HWs) in summer 2022; 4) no imposed restrictions. Such findings can guide public decision-makers to design proper strategies to curb pandemics under persistent stable anticyclonic weather conditions and summer HWs in large metropolitan areas.

Risk factors of SARS-CoV-2 infection and complications from COVID-19 in lung cancer patients.

BACKGROUND: Identifying lung cancer patients at an increased risk of getting SARS-CoV-2-related complications will facilitate tailored therapy to maximize the benefit of anti-cancer therapy, while decreasing the likelihood of COVID-19 complications. This analysis aimed to identify the characteristics of lung cancer patients that predict for increased risk of death or serious SARS-CoV-2 infection. PATIENTS AND METHODS: This was a retrospective cohort study of patients with lung cancer diagnosed October 1, 2015, and December 1, 2020, and a diagnosis of COVID-19 between February 2, 2020, and December 1, 2020, within the Veterans Health Administration. Serious SARS-CoV-2 infection was defined as hospitalization, ICU admission, or mechanical ventilation or intubation within 2 weeks of COVID-19 diagnosis. For categorical variables, differences were assessed using Χ2 tests, while Kruskal-Wallis rank-sum test was used for continuous variables. Multivariable logistic regression models were fit relative to onset of serious SARS-CoV-2 infection and death from SARS-CoV-2 infection. RESULTS: COVID-19 infection was diagnosed in 352 lung cancer patients. Of these, 61 patients (17.3%) died within four weeks of diagnosis with COVID-19, and 42 others (11.9%) experienced a severe infection. Patients who had fatal or severe infection were older and had lower hemoglobin levels than those with mild or moderate infection. Factors associated with death from SARS-CoV-2 infection included increasing age, immune checkpoint inhibitor therapy and low hemoglobin level. CONCLUSIONS:  The mortality of lung cancer patients from COVID-19 disease in the present cohort was less than previously reported in the literature. The identification of risk factors associated with severe or fatal outcomes informs management of patients with lung cancer who develop COVID-19 disease.

Elevated level of serum human epididymis protein 4 (HE4) predicts disease severity and mortality in COVID-19 pneumonia.

BACKGROUND: We retrospectively analyzed serum level of human epididymis protein 4 (HE4) as a pulmonary inflammatory biomarker in patients with COVID-19 pneumonia in association with disease severity and outcome. METHODS: Ninety-nine (40 critically ill, 40 severe and 19 mild) COVID-19 patients and as controls 25 age- and sex-matched non-COVID-19 bacterial sepsis subjects were included. Serum HE4 was measured by an immunoassay (Architect® i1000SR, Abbott) in the baseline samples of all study participants obtained at intensive care unit (ICU) admission or during outpatient clinic visit and follow-up sera were available in case of 30 COVID-19 subjects with life-threating conditions. Associations were studied between serum HE4, routinely available laboratory parameters, clinical characteristics, and disease progression. RESULTS: Baseline HE4 level was significantly higher (P < 0.0001) in critically ill (524.7 [300.1-1153.0] pmol/L) than severe COVID-19 subjects (157.4 [85.2-336.9] pmol/L) and in mild SARS-CoV-2 infection (46.7 [39.1-57.2] pmol/L). Similarly increased HE4 concentrations were found in bacterial sepsis (1118.0 [418.3-1953.0] pmol/L, P = 0.056) compared to critically ill COVID-19 individuals. Serum HE4 levels significantly correlated with age, SOFA-score, inflammation-dependent biomarkers, and the degree of lung manifestation evaluated by chest CT examination in ICU COVID-19 individuals. Based on ROC-AUC curve analysis, baseline HE4 independently indicated the severity of COVID-19 with an AUC value of 0.816 (95% CI [0.723-0.908]; P < 0.0001), while binary logistic regression test found HE4 as an independent prognostic parameter for death (OR: 10.618 [2.331-48.354]; P = 0.002). Furthermore, COVID-19 non-survivors showed much higher baseline HE4 levels without a substantial change under treatment vs. survivors (P < 0.0001). Finally, pre-treatment HE4 level of ≥ 331.7 pmol/L effectively predicted a larger risk for mortality (Log-Rank P < 0.0001) due to severe COVID-19 pneumonia. CONCLUSION: Elevated serum HE4 level at ICU admission highly correlates with COVID-19 severity and predicts disease outcome.

Obesity increased the risk of SARS-CoV-2 positivity in children.

AIM: To determine the effects of obesity in childhood on SARS-CoV-2 infection. METHODS: A population-based, cross-sectional study combining the Israeli Growth Survey and COVID-19 data for children with at least one SARS-CoV-2 test from 16 February 2020 to 20 December 2021. Overweight and obesity status were based on body mass index and the Center for Disease Control criteria. Multivariate logistics regression was performed to validate reliability for weight categories at the age of approximately 6 years compared with weights at approximately 12 years. RESULTS: A total of 444 868 records for children with an overall positivity rate of 22% were studied. The mean age was 9.5 years. The odds ratios of children with obesity or overweight after controlling for sex at 6 years to test positive were 1.07-1.12 and 1.06-1.08 (depending on the model), respectively, compared to those with healthy range body mass index. CONCLUSION: Excess weight appears to increase the risk of SARS-CoV-2 infection. This finding should be considered for public health planning. For example, children with overweight and obesity should be prioritised for vaccination. Excess weight in childhood can be harmful at a young age and not only for long-term health.

SARS-CoV-2-specific B- and T-cell immunity in a population-based study of young Swedish adults.

BACKGROUND: Young adults are now considered major spreaders of coronavirus disease 2019 (COVID-19) disease. Although most young individuals experience mild to moderate disease, there are concerns of long-term adverse health effects. The impact of COVID-19 disease and to which extent population-level immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exists in young adults remain unclear. OBJECTIVE: We conducted a population-based study on humoral and cellular immunity to SARS-CoV-2 and explored COVID-19 disease characteristics in young adults. METHODS: We invited participants from the Swedish BAMSE (Barn [Children], Allergy Milieu, Stockholm, Epidemiology) birth cohort (age 24-27 years) to take part in a COVID-19 follow-up. From 980 participants (October 2020 to June 2021), we here present data on SARS-CoV-2 receptor-binding domain-specific IgM, IgA, and IgG titers measured by ELISA and on symptoms and epidemiologic factors associated with seropositivity. Further, SARS-CoV-2-specific memory B- and T-cell responses were detected for a subpopulation (n = 108) by ELISpot and FluoroSpot. RESULTS: A total of 28.4% of subjects were seropositive, of whom 18.4% were IgM single positive. One in 7 seropositive subjects was asymptomatic. Seropositivity was associated with use of public transport, but not with sex, asthma, rhinitis, IgE sensitization, smoking, or body mass index. In a subset of representative samples, 20.7% and 35.0% had detectable SARS-CoV-2 specific B- and T-cell responses, respectively. B- and T-cell memory responses were clearly associated with seropositivity, but T-cell responses were also detected in 17.2% of seronegative subjects. CONCLUSIONS: Assessment of IgM and T-cell responses may improve population-based estimations of SARS-CoV-2 infection. The pronounced surge of both symptomatic and asymptomatic infections among young adults indicates that the large-scale vaccination campaign should be continued.

Bayesian time-varying autoregressive models of COVID-19 epidemics.

The COVID-19 pandemic has highlighted the importance of reliable statistical models which, based on the available data, can provide accurate forecasts and impact analysis of alternative policy measures. Here we propose Bayesian time-dependent Poisson autoregressive models that include time-varying coefficients to estimate the effect of policy covariates on disease counts. The model is applied to the observed series of new positive cases in Italy and in the United States. The results suggest that our proposed models are capable of capturing nonlinear growth of disease counts. We also find that policy measures and, in particular, closure policies and the distribution of vaccines, lead to a significant reduction in disease counts in both countries.

Changes in Lymphocyte Subpopulations after Remdesivir Therapy for COVID-19: A Brief Report.

Remdesivir (RDV) has demonstrated clinical benefit in hospitalized COronaVIrus Disease (COVID)-19 patients. The objective of this brief report was to assess a possible correlation between RDV therapy and the variation in lymphocyte subpopulations. We retrospectively studied 43 hospitalized COVID-19 patients: 30 men and 13 women (mean age 69.3 ± 15 years); 9/43 had received RDV therapy. Six patients had no need for oxygen (severity group 0); 22 were on oxygen treatment with a fraction of inspired oxygen (FiO2) ≤ 50% (group 1); 7 on not-invasive ventilation (group 2); 3 on invasive mechanical ventilation (group 3); and 5 had died (group 4). Cytofluorimetric assessment of lymphocyte subpopulations showed substantial changes after RDV therapy: B lymphocytes and plasmablasts were significantly increased (p = 0.002 and p = 0.08, respectively). Cytotoxic T lymphocytes showed a robust reduction (p = 0.008). No changes were observed in CD4+-T cells and natural killers (NKs). There was a significant reduction in regulatory T cells (Tregs) (p = 0.02) and a significant increase in circulating monocytes (p = 0.03). Stratifying by disease severity, after RDV therapy, patients with severity 0-2 had significantly higher B lymphocyte and monocyte counts and lower memory and effector cytotoxic T cell counts. Instead, patients with severity 3-4 had significantly higher plasmablast and lower memory T cell counts. No significant differences for CD4+-T cells, Tregs, and NKs were observed. Our brief report showed substantial changes in the lymphocyte subpopulations analyzed between patients who did not receive RDV therapy and those after RDV treatment. Despite the small sample size, due to the retrospective nature of this brief report, the substantial changes in lymphocyte subpopulations reported could lead to speculation on the role of RDV treatment both on immune responses against the virus and on the possible downregulation of the cytokine storm observed in patients with more severe disease.

COVID-19 and the Use of Angiotensin II Receptor Blockers in Older Chronic Hypertensive Patients: Systematic Review and Meta-Analysis.

Angiotensin II-converting enzyme inhibitors (ACEIs) and selective angiotensin II receptor antagonists (ARAIIs) are widely used antihypertensive agents. Their use has generated controversy due to their possible influence on the health status of chronic patients infected with COVID-19. The objective of this work is to analyze the influence of COVID-19 on chronic hypertensive patients treated with ACEI and ARAII inhibitors. A systematic review and meta-analysis in the databases Pubmed, Pro-Quest and Scopus were carried out. The systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search equation descriptors were obtained from the Medical Subject Headings (MeSH) thesaurus. The search equation was: "Older AND hypertension AND (COVID-19 OR coronavirus) AND primary care" and its equivalent in Spanish. Nineteen articles were obtained, with n = 10,806,159 subjects. Several studies describe the COVID-19 association with ACEI or ARAII treatment in hypertension patients as a protective factor, some as a risk factor, and others without a risk association. In the case of ACEI vs. ARAII, the risk described for the former has an odds ratio (OR) of 0.55, and for ARAII, an OR of 0.59. Some authors talk about mortality associated with COVID-19 and ACEI with a half ratio (HR) of 0.97, and also associated ARAIIs with an HR of 0.98. It is recommended to maintain the use of the renin-angiotensin-aldosterone axis in the context of the COVID-19 disease.

Effects of Anti-COVID-19 Vaccination and Pre-Exposure Prophylaxis with Tixagevimab-Cilgavimab in Kidney and Liver Transplant Recipients.

Background and Objectives: Underpowered immune response to vaccines against SARS-CoV-2 was observed in solid organ transplant (SOT) recipients. A novel combination of monoclonal antibodies tixagevimab-cilgavimab (TGM/CGM) received authorization as pre-exposure prophylaxis (PrEP) in those with reduced response to vaccine. We aimed to evaluate the response rate to COVID-19 vaccination in kidney transplant (KT), compared to liver transplant (LT) recipients, and the efficacy and safety of PrEP with TGM/CGM. Material and Methods: Between March and November 2022, adult KT and LT recipients who had completed the vaccination schedule (3 doses) were tested for anti-SARS-CoV-2 antibodies titer. SOT recipients with anti-SARS-CoV-2 titer ≥ 100 IU/mL were considered protected against infection, while those with titer < 100 UI/mL were defined non-protected. Patients with inadequate response were invited to PrEP. Results: In total, 306 patients were enrolled [KT:197 (64.4%), LT:109 (35.6%)]. After the complete scheme of vaccination, 246 (80.3%) patients developed a protective titer, while 60 (19.6%) did not have a protective titer. KT recipients had a lower rate of protective anti-COVID-19 titer compared to LT patients [149 (75.6%) vs. 97 (89.0%), p = 0.004]. Recipients with non-protective anti-COVID-19 titer received mainly tacrolimus-based regimen associated with mycophenolate mofetil (MMF) (70%) e steroids (46.7%) as maintenance immunosuppression, while those treated with everolimus were associated with higher protective titer. Of 35 (58.3%) patients who received PrEP, within 12 months, 6 (17.1%) (all KT) developed pauci-symptomatic COVID-19 disease, while 15/25 (60%) of non-responders, who did not receive the prophylaxis, developed COVID-19 disease. After PrEP, hospitalization rate was lower (2.8% vs. 16%), and no adverse events, neither graft loss nor rejection, were observed. Conclusions: Despite complete COVID-19 vaccination, SOT recipients might be not protected from the SARS-CoV-2 infection, especially after KT. In non-protected SOT patients, the subsequent pre-exposure prophylaxis with combination of monoclonal antibodies (TGM/CGM) might be an efficacy and safe strategy to prevent COVID-19 severe disease and hospitalization.

Comparing the predictive values of procalcitonin/albumin ratio and other inflammatory markers in determining COVID-19 severity.

Objective: To examine the relationship between COVID-19 severity and procalcitonin/albumin ratio (PAR) and compare the PAR with oft-reported inflammatory markers, including procalcitonin, white blood cell (WBC), neutrophil/lymphocyte ratio (NLR) and C-reactive protein (CRP). Methods: In this retrospective research study conducted at Sanliurfa Training and Research Hospital during May to September 2020; total, 577 adult subjects diagnosed with COVID-19 were included and categorized into two groups based on place of hospitalization: the intensive care unit (ICU) group (n=151) and the general ward (GW) group (n=426). Laboratory test results and demographic characteristics of the subjects were recorded. Results: PAR, NLR, CRP, WBC, neutrophil and procalcitonin values were markedly higher in the ICU group than in the GW group. On the contrary, lymphocyte count and albumin level were markedly lower. PAR showed positive correlations with WBC, NLR, and CRP. Multivariate analysis showed that advanced age, presence of hypertension, elevated PAR, WBC, NLR, urea and lactate dehydrogenase levels were independent risk factors associated with the need for intensive care in COVID-19 subjects. Among them, the PAR showed the highest odds ratio (5.564) for ICU admission. Additionally, the area under the ROC curve of the PAR (0.888) was markedly greater than that of WBC (0.777), NLR (0.822), CRP (0.842) and procalcitonin (0.870). Conclusions: This study revealed that PAR was superior to procalcitonin, WBC, NLR and CRP in determining COVID-19 severity. PAR was an important predictor of ICU requirement in COVID-19 cases.

Investigation into Grief Experiences of the Bereaved During the Covid-19 Pandemic.

The objective of the current study was to investigate the grief experiences of people affected by COVID-19. The study adopted a qualitative design of descriptive phenomenology. Fifteen adults who had lost a family member during the COVID-19 pandemic were selected as the sample through the purposive sampling method until theoretical saturation was achieved. Data was collected using semi-structured interviews and the Colaizzi analysis method. Six main themes (i.e., unexpressed grief, psychosomatic reactions, negative emotions, family problems, and social and occupational problems) were extracted. Data analysis showed that complex disenfranchised grief is the pervasive consequence of the COVID-19 experience. According to the findings, participants experienced disenfranchised grief during the loss of their loved ones due to the COVID-19 disease, which was a complex, painful experience accompanied by negative emotions and family, work, and social tensions. This grief is accompanied by more severe and prolonged symptoms, making it difficult for the bereaved to return to normal life. In unexpressed grieving, there are intense feelings of grief, pain, separation, despair, emptiness, low self-esteem, bitterness, or longing for the presence of the deceased. This grief originated from the conditions of quarantine and physical distance on the one hand, which required the control of the outbreak of the COVID-19 disease, and on the other hand, the cultural-religious context of the Iranian people.

The Effects of Covid-19 on Financial-Economic and Performance Efficiency of Hospitals.

Background: During the pandemic of COVID-19, the function and performance of hospitals have been affected by various economic-financial and management aspects. The aim of the current study was to assess the process of therapeutic care delivery and also the economic-financial functions of the selected hospitals before and after COVID-19. Methods: This research is a descriptive-analytical study and a cross-sectional-comparative study in terms of time, and it was conducted in several selected teaching hospitals of Iran University of Medical Sciences. A purposeful and convenient sampling method was used. The data has been collected using the standard research tool (standard checklist of the Ministry of Health) in the two areas of financial-economic and healthcare performance (such as Data of financial and economic indicators such as direct and indirect costs, liquidity ratio and profitability index as well as key performance indicators of hospitals such as bed occupancy ratio (BOR; %), average length of stay (ALOS), bed turnover rate (BTR), bed turnover distance rate (BTIR) and hospital mortality rate (HMR), physician-to-bed ratio and nurse-to-bed ratio) of hospitals in two times before and after the outbreak of COVID-19 (time period 2018 to 2021). The data was collected from 2018 to 2021. Pearson/Spearman regression was used for the evaluation of the relationship between variables using SPSS 22. Results: This research showed the admission of COVID-19 patients caused a change in the indicators we evaluated. ALOS (-6.6%), BTIR (-40.7%), and discharge against medical advice (-7.0%) decreased from 2018 to 2021. BOR; % (+5.0%), occupy bed days (+6.6%), BTR (+27.5%, HMR (+50%), number of inpatients (+18.8%), number of discharges (+13.1%), number of surgeries (+27.4%), nurse-per-bed ratio (+35.9%), doctor-per-bed ratio (+31.0%) increased in the same period of time. The profitability index was correlated to all of the performance indicators except for the net death rate. Higher length of stay and turnover interval had a negative effect on the profitability index while higher bed turnover rate, bed occupancy ratio, bed day, number of inpatient admission, and number of surgery had a positive effect on the profitability index. Conclusion: It has been shown from the beginning of the COVID-19 pandemic, the performance indicators of the studied hospitals were negatively affected. As a consequence of the COVID-19 epidemic, many hospitals were not able to deal with the negative financial and medical outcomes of this crisis due to a significant decrease in income and a double increase in expenses.

Poor Antibody Response After Two Doses of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccine in Transplant Recipients.

A low anti-spike antibody response of 28.6% was observed 28 days after BNT162b2 vaccine second dose among 133 solid organ transplant recipients without previous coronavirus disease 2019 (COVID-19). No serious adverse events were recorded. Four severe COVID-19 cases were reported between or after the 2 doses. Our data suggest to change the vaccine strategy.

The Potential of Stilbene Compounds to Inhibit Mpro Protease as a Natural Treatment Strategy for Coronavirus Disease-2019.

COVID-19 disease has had a global impact on human health with increased levels of morbidity and mortality. There is an unmet need to design and produce effective antivirals to treat COVID-19. This study aimed to explore the potential ability of natural stilbenes to inhibit the Mpro protease, an acute respiratory syndrome coronavirus-2 (SARS-CoV-2) enzyme involved in viral replication. The binding affinities of stilbene compounds against Mpro were scrutinized using molecular docking, prime molecular mechanics-generalized Born surface area (MM-GBSA) energy calculations, and molecular dynamic simulations. Seven stilbene molecules were docked with Mpro and compared with GC376 and N3, antivirals with demonstrated efficacy against Mpro. Ligand binding efficiencies and polar and non-polar interactions between stilbene compounds and Mpro were analyzed. The binding affinities of astringin, isorhapontin, and piceatannol were -9.319, -8.166, and -6.291 kcal/mol, respectively, and higher than either GC376 or N3 at -6.976 and -6.345 kcal/mol, respectively. Prime MM-GBSA revealed that these stilbene compounds exhibited useful ligand efficacy and binding affinity to Mpro. Molecular dynamic simulation studies of astringin, isorhapontin, and piceatannol showed their stability at 300 K throughout the simulation time. Collectively, these results suggest that stilbenes such as astringin, isorhapontin, and piceatannol could provide useful natural inhibitors of Mpro and thereby act as novel treatments to limit SARS-CoV-2 replication.