Identification of immune cell infiltration and biomarkers in Alzheimer's disease and COVID-19 by integrated bioinformatics analysis and machine learning (preprint)

Background: Since its emergence in late 2019, COVID-19 has become a global epidemic, resulting in numerous infections, including a significant number of critically ill patients. Several studies have suggested a possible link between Alzheimer's disease (AD) and COVID-19. For instance, a Mendelian randomization study has proposed a causal relationship between Alzheimer's disease and COVID-19 in the pathogenic mechanism. However, there are limited studies exploring the common pathogenic genes and immune infiltration between the two. Therefore, we conducted this study to identify key genes in COVID-19 associated with Alzheimer's disease, evaluate their correlation with immune cell characteristics and metabolic pathways, and investigate potential novel biomarkers. Methods: Transcriptome analyses were used to identify common biomolecular markers of AD and COVID-19. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were performed on gene chip datasets (GSE213313, GSE5281, and GSE63060) from AD and COVID-19 patients to identify genes associated with both conditions. Common pathogenic molecular mechanisms were identified through Gene Ontology (GO) enrichment analyses. The core genes were then identified using machine learning methods. Subsequently, we evaluated the relationship between these core genes and common immune cells and metabolic pathways. Finally, our findings were validated through single-cell analysis. Results: The study identified 484 common differentially expressed genes (DEGs) by taking the intersection of genes between AD and COVID-19. The black module, containing 132 genes, showed the highest association between the two diseases according to WGCNA. GO enrichment analysis revealed that these genes mainly affect inflammation, cytokines, immune-related functions, and signaling pathways related to metal ions and cellular response to viruses. Additionally, a machine learning approach identified eight core genes. We identified links between these genes and immune cells and also found a strong association between EIF3H and oxidative phosphorylation. In addition, these results were further validated by single-cell analysis. Conclusion: This study identifies potential shared genes, signaling pathways, immune-related alterations, and changes in metabolic pathways that may collectively contribute to the pathogenesis of COVID-19 and Alzheimer's disease. These findings provide new targets for the diagnosis and treatment of both diseases.

SARS-CoV-2 disrupts host gene networks: unveiling key hub genes as potential therapeutic targets for COVID-19 management (preprint)

Background Although the end of COVID-19 as a public health emergency was declared on May 2023, still new cases of the infection are reported and the risk remains of new variants emerging that may cause new surges in cases and deaths. While clinical symptoms have been rapidly defined worldwide, the basic body responses and pathogenetic mechanisms acting in patients with SARS-CoV-2 infection over time until recovery or death require further investigation. The understanding of the molecular mechanisms underlying the development and course of the disease is essential in designing effective preventive and therapeutic approaches, and ultimately reducing mortality and disease spreading.Methods The current investigation aimed to identify the key genes engaged in SARS-CoV-2 infection and uncover their molecular implication in disease severity. To achieve this goal high-throughput RNA sequencing of peripheral blood samples collected from healthy donors and COVID-19 patients was performed. The resulting sequence data were processed using a wide range of bioinformatics tools to obtain detailed modifications within five transcriptomic phenomena: expression of genes and long non-coding RNAs, alternative splicing, allel-specific expression and circRNA production. The in silico procedure was completed with a functional analysis of the identified alterations.Results The transcriptomic analysis revealed that SARS-CoV-2 has a significant impact on multiple genes encoding ribosomal proteins (RPs). Results show that these genes differ not only in terms of expression but also manifest biases in alternative splicing and ASE ratios. The integrated functional analysis exposed that RPs mostly affected pathways and processes related to infection—COVID-19 and NOD-like receptor signaling pathway, SARS-CoV-2-host interactions and response to the virus. Furthermore, our results linked the multiple intronic ASE variants and exonic circular RNA differentiations with SARS-CoV-2 infection, suggesting that these molecular events play a crucial role in mRNA maturation and transcription during COVID-19 disease.Conclusions By elucidating the genetic mechanisms induced by the virus, the current research provides significant information that can be employed to create new targeted therapeutic strategies for future research and treatment related to COVID-19. Moreover, the findings highlight potentially promising therapeutic biomarkers for early risk assessment of critically ill patients.

Racial/ethnic disparities in COVID-19 clinical outcomes: A comparison between Asian ethnic subgroups (preprint)

Background Since the outbreak of COVID-19, general studies about relationship between COVID-19 clinical outcome and ethnicity have been performed on the overall ethnic groups, but studies on ethnic subgroups is limited.Methods We conducted a population-based retrospective cohort study on hospitalized patients with suspected/confirmed COVID-19 to evaluate whether ethnic background influences disease severity and clinical outcomes. Patients were categorized into three groups: mild, moderate, and severe to critical. Analyses were adjusted for socio-demographic and comorbidities.Results Among all hospitalized patients, in the unadjusted model, Afghans had a lower risk of severe to critical illness than Iranians (OR, 0.52; 95%CI, 0.41–0.64; P < 0.000). After adjusting for age, sex and comorbidities the risk remained lower in Afghans (OR, 0.69; 95%CI, 0.56–0.88; P < 0.003). But among positive cases was comparable even after full adjustment (OR, 0.86; 95%CI, 0.54–1.3; P < 0.547). Among all hospitalized patients, in the unadjusted model, the risk of death was comparable between Afghans and Iranians (OR, 1.037; 95%CI, 0.70–1.5; P < 0.003). After adjusting for age, sex and comorbidities, Afghans had a higher risk of death than Iranians (OR, 1.66; 95%CI, 1.08–2.55; P = 0.020). Similar results were observed in positive cases (OR, 2.34; 95%CI, 1.47–3.72; P = 0.000).Conclusions In this cohort study, Iranians represented more COVID-19-related symptoms and disease severity than Afghans; but mortality was higher in Afghans. The impact of COVID-19 may be different in various Asian ethnic groups

Rox Index Variation as Predictor of Outcomes in COVID-19 Patients. Calderón Hospital Quito (preprint)

Background: During the pandemic, Emergency departments were overcrowded with critically ill patients and confronted ethical dilemmas to assign respiratory support to them due to scarce resources. Quick tools to evaluate patients at admission were needed; many scores were used but inaccurate to predict outcomes. The Rox Index is an easy and fast score that reflects the respiratory status in acute respiratory failure patients, this score could predict the outcome of covid 19 patients. Hypothesis: The 24-hour difference in the Rox Index discriminate accurately the mortality and needs for mechanical ventilation of patients with covid-19. Methods: Study design: Prospective analytic study. Population: 204 Patients admitted to the emergency department from May to August 2020. Data were collected from the clinical records. The Rox Index was calculated at admission and 24h later, the difference was used to establish the outcome, a logistic regression model adjusting for age, sex, presence of comorbidities and disease severity to build and perform ROC analysis. Results: Difference in respiratory ROX Index between admission and 24h is a good predictor for death AUC 0.92 and for mechanic ventilation AUC: 0.75. Each decrease in one unit of the difference at 24h had an Odds Ratio for death risk: 1.48 (95%CI: 1.31-1.67) and for mechanic ventilation: 1.16 (95%IC: 1.1-1.23). Conclusion: The 24-hour variation of Rox Index has good predictive value and allows healthcare professionals to identify which patients will benefit from invasive treatment, especially in low resource settings where emergency physicians deal with survival.

Development and Evaluation of a Peer Equity Navigator Intervention for COVID-19 Vaccine Promotion and Uptake in African, Caribbean and Black Communities in Ottawa, Canada (preprint)

Background African, Caribbean and Black Communities (ACB) have experienced an increased burden of COVID-19 morbidity and mortality as well as significant barriers to COVID-19 vaccine acceptance and uptake. Addressing the complex issues of vulnerable populations, such ACB communities, requires a multipronged approach and innovation. Peer-led approaches framed within critical health literacy (CHL) and critical racial literacy (CRL) discourses, along with collaborative and participatory equity learning processes, increased community capacity, empowerment, and practice outcomes. They may contribute to long-term improvements in health and health equity.Methods We developed and evaluated a peer-equity navigator intervention to increase vaccine confidence and acceptance in ACB communities using a modified Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) Framework. The evaluation drew upon multiple data sources, including tracking data, surveys with community members, and a focus group with peer equity navigators (PENs).Results We found that an innovative, community-informed and peer-led model designed to increase awareness and agency among ACB communities was feasible, acceptable, and effective for over 1500 ACB community members between Sept 16, 2022 and Jan 28, 2023. Consistent with the partnership approach, 8 trained PENS conducted over 56 community events. Peer equity navigators (PENS) and community members reported high levels of engagement, appreciation for peer-led community-based approaches and increased vaccine literacy.Conclusions The PEN approach is a feasible, acceptable, and effective intervention for reaching and engaging ACB community members in health-promoting actions and behaviors.

COVID-19-associated acute renal failure in critically ill patients correlates with microthrombosis and renal loss of thrombomodulin (preprint)

Critically ill COVID-19 patients have a high degree of acute kidney injury which develops in up to 85% of patients. We have previously shown that circulating levels of angiopoietin-2 increased in critically ill COVID-19 patients correlated to kidney injury, coagulopathy, and mortality. Furthermore, our experiments showed a causal effect on coagulopathy from angiopoietin-2 binding and inhibition of thrombomodulin mediated anticoagulation. In the current study we hypothesize that renal microthrombi may be a mechanism for reduced renal function in critically ill COVID-19 patients, and that local dysregulation of thrombomodulin and angiopoietin-2 may be involved. To investigate our hypothesis, we utilized postmortem kidney tissue from seven COVID-19 patients treated at the intensive care unit. We evaluated kidney function, thrombosis, tubular injury, fibrosis, glomerulosclerosis, glomerular size as well as renal expression of thrombomodulin and angiopoietin-2. Proximity ligation assay was utilized to evaluate the presence of angiopoietin-2 binding to thrombomodulin. Normal kidney tissue came from the healthy part of six nephrectomies due to cancer. Our experiments show renal thrombosis in 6/7 COVID-19 patients, on average 14.7 (6.9-22.5) thrombi per mm2. Most COVID-19 kidneys had extensive kidney injury, especially tubular necrosis, but also glomerular enlargement, glomerulosclerosis, and tubulointerstitial fibrosis which in some cases most likely resulted from underlying disease. Thrombomodulin expression was reduced in glomeruli and peritubular capillaries in kidneys from COVID-19 patients, whereas no change was found for angiopoietin-2. In summary, our study describes a high degree of acute renal failure, renal microthrombosis, and loss of thrombomodulin in postmortem tissue from critically ill COVID-19 patients.

Impact of the COVID-19 Epidemic on Death Among Critically Ill Patients (preprint)

Backgrounds: The coronavirus disease 2019 (COVID-19) epidemic is a major public health problem worldwide. This study estimated the impact of SARS-CoV-2 in terms of the excess mortality from any cause during the COVID-19 epidemic in the Republic of Korea. Methods: The excess mortality, ICU admissions and hospital admissions during the COVID-19 epidemic was analyzed using the number of deaths over the past 5 years (2015–2019) in Korea. The numbers of total deaths and COVID-19–related deaths were counted from January 2020 through May 2022, using public data from the Korean Statistical Information Service (KOSIS) of Statistics Korea. Data of hospital admissions were obtained from Health Insurance Review and Assessment (HIRA) service and KOSIS of Statistics Korea. Results: These numbers were compared with nationwide mortality data from January 1, 2015, through December 2019. There were more than 24,000 reported deaths officially across Korea from January 2020 through May 2022. Excess mortality was observed nationwide in March, August, October, November, and December 2020; January, March, July, and August 2021; and October 2021 through May 2022, which was consistent with the epidemic waves in the country. There was a decline in ICU admissions, especially soon after the declaration of the COVID-19 epidemic. Conclusions: After 2021, significant excess mortality occurred at the national level despite decreasing COVID-19 case fatality rates and decreased admissions to intensive care units, which means there might be an another relevant factors on all-cause mortality aside from the direct effect of deaths from COVID-19.

Course of inflammation and infection markers differ in ICU patients with severe COVID-19 under casirivimab- and/or tocilizumab application: an observational study (preprint)

Background: The outcome and longitudinal course of inflammation and infection markers were unknown in COVID-19 patients on the ICU treated without (N) or with SARS-CoV-2 specific monoclonal antibodies (casirivimab / imdevimab, C) or antibodies against interleukin-6 (IL-6) receptors (tocilizumab, T), solely, or in combination of both (C + T).  Methods: In a retrospective observational study, in critically ill N, C, T, C+ T COVID-19 patients admitted to the ICU with the CoV-2 delta-variant between August 2021 and February 2022, 28-day mortality and 30-day time course of infection and inflammation markers were evaluated.  Results: Out of 95 patients with COVID-19, 29 patients were not treated (N), 17 with C, 16 with T, 33 with C + T. Mortality rates in N, C, T, and C + T, were 24%, 35%, 56%, and 24%, being higher in T compared to N and C + T (p = 0.05). Prolonged leukocyte, procalcitonin (PCT), C-reactive protein (CRP) and interleukin 6 (IL-6) elevations were detected in nonsurvivors compared to survivors in C + T within the first two weeks, IL-6 in the first days in T. In N, higher PCT, CRP, IL-6 and ferritin occured in nonsurvivors in the first days.  Conclusion: Sporadically measured IL-6 and CRP in T is less useful. Longlasting IL-6 receptor blockade may be deleterious in COVID-19. High IL-6 may hint at poor prognosis within the first days in T, leukocytes, PCT, CRP and IL-6 in the first two weeks in C + T, and PCT, CRP, IL-6 and ferritin within the first days in N.  Trial registration: ClinicalTrials.gov Identifier: NCT06233357, retrospectively registered, release date: January 31, 2024.

The relationship between omega-3 intake and the severity and symptoms of Covid-19 (preprint)

Background and Aims: Omega 3 polyunsaturated fatty acids (n3 PUFAs) may exert beneficial effects on the immune system of patients with viral infections. This paper aimed to examine the effect of n3 PUFA on severity and symptoms in critically ill patients with COVID 19Methods In a cross-sectional study, 250 COVID-19 patients between the ages of 18 and 65 were enrolled. To gauge dietary omega-3 consumption, a validated 168-item online food frequency questionnaire (FFQ) was used. The severity of COVID-19 was determined using the COVID-19 Treatment Guidelines, and symptoms were assessed using a common questionnaire. Crude and modified analyses were carried out. (Model 1: age, sex, and energy intake; Model 2: Model 1 + physical activity, supplements, corticosteroids, and antiviral drugs; Model 3: Model 2 + body mass index).Results The mean age of participants was 44.06 ± 11.84 years, and 46% of them had severe COVID-19. Patients at the highest tertile of dietary omega-3 intake had lower serum levels of inflammatory biomarkers, including CRP (10.25 ± 13.12 vs. 25.20 ± 24.89 mg/L, p < 0.001) and ESR (14.55 ± 15.02 vs. 29.13 ± 2.26 mm/hr, p < 0.001), than those at the lowest tertile. After controlling for potential confounders, we observed that a higher dietary omega-3 intake was associated with a lower odds of severe COVID-19 (OR: 0.42; 95% CI: 0.22–0.79).Conclusion We found that higher intake of dietary omega-3 was inversely associated with COVID-19 severity and symptoms.

Sustained mTOR inhibition with sirolimus improves respiratory outcomes in LAM patients with COVID-19 (preprint)

Background Lymphangioleiomyomatosis (LAM) is a rare lung disease that predominantly affects women and can lead to severe respiratory complications. The impact of COVID-19 on LAM patients, particularly regarding the use of mammalian target of rapamycin (mTOR) inhibitors, remains poorly understood. This study investigates the clinical outcomes of LAM patients with COVID-19 and evaluates the role of sustained mTOR inhibition in respiratory outcomes.Results Our cohort included 186 LAM patients with COVID-19. Prior to infection, 72.6% were on mTOR inhibitors, with 29.6% discontinuing therapy due to infection. The hospitalization rate was 1.1%, with no reported need for invasive ventilation or fatalities. Patients with FEV1 less than 70% predicted had a higher risk of dyspnea exacerbation and supplemental oxygen requirement. Continuation of mTOR inhibitor therapy was associated with a lower risk of SpO2 decline, especially among patients with impaired lung function. Vaccination status did not significantly affect the prognosis.Conclusions LAM patients with COVID-19 showed a low rate of severe illness and mortality, with impaired lung function correlating with worse respiratory outcomes. Continued mTOR inhibitor therapy during COVID-19 infection may improve respiratory outcomes, suggesting the importance of maintaining treatment during viral pandemics.

Machine Learning for COVID-19 Patient Management: Predictive Analytics and Decision Support (preprint)

Background: The global impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has profoundly affected economies and healthcare systems around the world, including Lebanon. While numerous meta-analyses have explored the systemic manifestations of COVID-19, few have linked them to patient history. Our study aims to fill this gap by using cluster analysis to identify distinct clinical patterns among patients, which could aid prognosis and guide tailored treatments. Methods. We conducted a retrospective cohort study at Beirut's largest teaching hospital on 556 patients with SARS-CoV-2. We performed cluster analyses using K-prototypes, KAMILA and LCM algorithms based on 26 variables, including laboratory results, demographics and imaging findings. Silhouette scores, concordance index and signature variables helped determine the optimal number of clusters. Subsequent comparisons and regression analyses assessed survival rates and treatment efficacy according to clusters. Results. Our analysis revealed three distinct clusters: "resilient recoverees" with varying disease severity and low mortality rates, "vulnerable veterans" with severe to critical disease and high mortality rates, and "paradoxical patients" with a late presentation but eventual recovery. Conclusions. These clusters offer insights for prognosis and treatment selection. Future studies should include vaccination data and various COVID-19 strains for a comprehensive understanding of the disease's dynamics.

Distinct histopathological features of post-COVID-19 cholangiopathy (preprint)

Background: Cholangiopathy has been described in survivors of severe COVID-19, presenting significant clinical parallels to the pre-pandemic condition of secondary sclerosing cholangitis in critically ill patients (SSC-CIP).  Aim: Herein, we examined the liver histopathology of individuals with persistent cholestasis following severe COVID-19.  Methods: Post-COVID-19 cholestasis liver samples were subjected to routine staining techniques and cytokeratin 7 immunostaining, and the portal and parenchymal changes were semi-quantitatively analyzed.  Results: All ten patients, five men, median age 56, interquartile range (IQR) 51–60, requiring mechanical ventilation. The median and IQR liver enzyme concentrations proximal to biopsy were in IU/L: ALP, 605 (390–1,105); GGT, 925 (776–2,169); ALT, 92 (86–110); AST, 90 (68–108); and bilirubin, 3 (1–6) mg/dL. Imaging revealed intrahepatic bile duct anomalies and biliary casts. Biopsies were performed at a median of 203 (150–249) days after molecular confirmation of infection. Portal and periportal fibrosis, moderate-to-severe ductular proliferation, and bile duct dystrophy were found in all patients, while hepatocyte biliary metaplasia was observed in all tested cases. Mild-to-severe parenchymal cholestasis and bile plugs were observed in nine and six cases. Mild swelling of the arteriolar endothelial cells was observed in five patients. A thrombus in a small portal vein branch and mild periductal fibrosis were observed in one case each. One patient developed multiple small biliary infarctions. Ductopenia was not observed in any patient.  Conclusions: The alterations were similar to those observed in SSC-CIP; however, pronounced swelling of endothelial cells, necrosis of the vessel walls, and thrombosis in small vessels were notable.

Clinical characteristics and analysis of risk factors for disease progression in patients on maintenance hemodialysis infected with SARS-CoV-2 omicron variant (preprint)

Objective:To summarize the clinical characteristics of patients on maintenance hemodialysis (MHD) with the novel coronavirus omicron variant and explore the risk factors for severe cases. Methods:We retrospectively analyzed the data of 158 patients on MHD from Zhongnan Hospital of Wuhan University between December 7, 2022 and January 31, 2023. We collected clinical data, described clinical characteristics, and analyzed the relationships between these factors and critical illness using univariate and multivariate logistic regression analyses. Results: The median age of the 158 patients was 63 (interquartile range: 52–71) years, and 128 (63.7%) were men. Fever (62.7%) and cough (60.1%) were the two most common symptoms. Hypertension (80.4%) was the most common comorbidity, followed by diabetes (31.0%), cardiovascular disease (22.8%), and cerebrovascular disease (15.2%). Unvaccinated patients constituted the majority of the enrolled patients (88.6%, 140/158), whereas only a small proportion (11.4%, 18/158) had been vaccinated (including fully vaccinated and partially vaccinated patients). Multivariate logistic regression analysis indicated that an elevated C-reactive protein (CRP) level (odds ratio [OR]: 1.03, 95% confidence interval [CI], 1.014–1.046], p<0.001) and a decreased platelet count (OR: 0.986, 95% CI, 0.986 (0.976–0.997), p=0.013) during hospitalization were risk factors for the severe group. Conclusions:This study demonstrated a high mortality rate among patients on MHD infected with omicron variant. Furthermore, advanced age, increased CRP levels, and decreased platelet count were predictors of critical illness.

Biological Effects of Corticosteroids on Pneumococcal Pneumonia in Mice and Humans (preprint)

Background: Streptococcus pneumoniae is the most common bacterial cause of community acquired pneumonia and the acute respiratory distress syndrome (ARDS). Some clinical trials have demonstrated a beneficial effect of corticosteroid therapy in community acquired pneumonia, COVID-19, and ARDS, but the mechanisms of this benefit remain unclear. The objective of this study was to investigate the effects of corticosteroids on the pulmonary biology of pneumococcal pneumonia in an observational cohort of mechanically ventilated patients and in a mouse model of bacterial pneumonia with Streptococcus pneumoniae. Methods: We studied gene expression with lower respiratory tract transcriptomes from a cohort of mechanically ventilated patients and in mice. We also carried out comprehensive physiologic, biochemical, and histological analyses in mice to identify the mechanisms of lung injury in Streptococcus pneumoniae with and without adjunctive steroid therapy. Results: Transcriptomic analysis identified pleiotropic effects of steroid therapy on the lower respiratory tract in critically ill patients with pneumococcal pneumonia, findings that were reproducible in mice. In mice with pneumonia, dexamethasone in combination with ceftriaxone reduced (1) pulmonary edema formation, (2) alveolar protein permeability, (3) proinflammatory cytokine release, (4) histopathologic lung injury score, and (5) hypoxemia but did not increase bacterial burden. Conclusions: The gene expression studies in patients and in the mice support the clinical relevance of the mouse studies, which replicate several features of pneumococcal pneumonia and steroid therapy in humans. In combination with appropriate antibiotic therapy in mice, treatment of pneumococcal pneumonia with steroid therapy reduced hypoxemia, pulmonary edema, lung permeability, and histologic criteria of lung injury, and also altered inflammatory responses at the protein and gene expression level. The results from these studies provide evidence for the mechanisms that may explain the beneficial effects of glucocorticoid therapy in patients with community acquired pneumonia from Streptococcus Pneumoniae.

Pulmonary fibrosis in critically ill patients with COVID-19: A multi-center retrospective cohort study in South Korea (preprint)

Background: Pulmonary fibrosis persists long after recovering from coronavirus disease 2019 (COVID-19) infection, thereby reducing quality of life and lung function. We aimed to evaluate the prevalence and risk factors for pulmonary fibrosis in patients with severe COVID-19 pneumonia requiring mechanical ventilation, a high-risk group for developing pulmonary fibrosis. Methods: Clinical data and chest computed tomography (CT) scans of patients with severe COVID-19 pneumonia requiring mechanical ventilation were retrospectively collected from nine hospitals in South Korea. Fibrotic-like changes on chest CT were visually assessed. Results: We included 125 patients with a mean age of 68.5 years, 60.8% men and 7.2% having underlying lung disease. Based on follow-up chest CT (the median interval: 38.0 days, interquartile range: 24.0–68.0 days), 94 (75.2%) patients exhibited fibrotic-like changes, with traction bronchiectasis and/or bronchiolectasis being the most common change (60.8%). Adjusted Cox regression analysis revealed as association between hemoglobin levels ≤9 g/dL and an increased risk of pulmonary fibrosis development (HR: 3.182, 95% Cl: 1.203–8.415, P=0.025). Among all patients, 17.6% died during hospitalization and 71.2% experienced complications, including intubation-related airway injury (12.8%), ventilator-associated pneumonia (44.8%), lung injury (11.2%), and hemodynamic disturbance (33.4%). In-hospital mortality (16.1% vs. 18.1%) and complications (67.7% vs. 72.3%) were similar between patients with and without fibrotic-like changes. Conclusion: Our study demonstrated that in patients with severe COVID-19 pneumonia requiring mechanical ventilation, chest CT revealed fibrotic-like changes in approximately three-fourths of patients. Low hemoglobin levels might be associated with pulmonary fibrosis in severe COVID-19 pneumonia.

Investigating the correlation between demographic data, laboratory results, intubation, and mortality rate in hospitalized COVID-19 patients: A retrospective study (preprint)

Background COVID-19 is a highly contagious infectious disease that rapidly escalated into a pandemic. This coronavirus pandemic has been associated with considerable morbidity and mortality. Multiple risk factors for severe, critical illness and death due to COVID-19 have been identified. This study investigated associations between demographic traits, laboratory test results, intubation status, and mortality among hospitalized COVID-19 patients.Methods In this cross-sectional descriptive study, 181 patients infected with COVID-19 who were admitted to Imam Reza Hospital in Tabriz, Iran, between March and September 2020 were reviewed using the census sampling method. Demographic data, laboratory results, and intubation history were extracted from the records. The data were analyzed using Chi-square, the independent samples t-test, Mann-Whitney U tests, and logistic regression using SPSS 27. P < 0.05 and the odds ratio with a 95% confidence interval were considered significant.Results Out of 181 patients infected with COVID-19, there were 110 (60.8%) males with a median age of 66 (16–96) years. There was a significant direct relationship between outcome and intubation, chest X-ray, CT-Scan, renal diseases, age, WBC, K, P, urea, Cr, and LDH, respectively (P < 0.0001, < 0.0001, 0.02, 0.01, < 0.0001, 0.002, 0.002, 0.008, < 0.0001, < 0.0001, and 0.008). In contrast, there was a significant inverse relationship between outcome and PH, HCO3, and SaO2 (P = 0.005, 0.002, and < 0.0001).Conclusion This study found that several factors increase the risk of mortality in patients infected with COVID-19, including intubation, abnormal lung CT and chest X-ray findings, underlying kidney disease, advanced age, and high levels of white blood cells, potassium, phosphorus, urea, creatinine, and lactate dehydrogenase. On the other hand, increased pH, bicarbonate, and oxygen saturation were protective factors against mortality. These results highlight important risk and protective factors for mortality in COVID-19 patients. The findings can inform clinical decision-making and resource allocation during future COVID-19 outbreaks and pandemics involving similar respiratory viruses.

Impact of mechanical power on mortality in ventilated critically ill patients. Retrospective study with continuous real-life data (preprint)

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

In-hospital survival of critically ill COVID-19 patients treated with glucocorticoids: a multicenter real-world data study (preprint)

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

AN INSIGHT ON THE MATERNAL & FETAL OUTCOME OF CRITICALLY ILL PREGNANT WOMEN DURING THE SECOND WAVE OF COVID-19 (preprint)

Objective: To assess and compare the Maternal and fetal outcomes of critically ill pregnant women infected with COVID – 19 cases of pneumonia who required admission to the intensive care unit. Design: A retrospective observational study Settings: Tertiary care hospital settings affiliated with an academic center in UAE. Patients and Methods: A total of 123 patients in their third trimester were included from 1 December 2020 to 31 March 2021 in the study with 30 cases of severe or critical COVID and 93 mild to moderate pregnant COVID patients. The maternal demographic, radiological, and biochemical profile of mothers was noted. Maternal and fetal outcomes were compared. Main outcomes Measured: Maternal and fetal outcomes were compared in severe and mild COVID cases. Result: A total of 30 (24.3%) patients were admitted in ICU and eight required invasive ventilation meaning, Severe COVID was significantly associated with higher mortality (20% vs 0% p-value <0.001), postpartum complications (50% vs 9.67% p-value<0.001) and increased overall hospital stay (p-value<0.001). Neonates born to severe COVID patients had significant higher chances of being born preterm (76.6% vs 35.7% p-value<0.001) and have low birth weight (46.6% vs 13.9% p-value=0.002). There were four cases of stillbirth, two cases of vertical transmission, and no neonatal deaths. Conclusion: Pregnant females with severe COVID have high mortality, peripartum complications; and increased hospital stay. The newborns born to such mothers may be premature, have low birth weights but have comparable mortality

Outcome of using Intravenous Immunoglobulin (IVIG) in critically ill COVID-19 patients’: a ‎retrospective, ‏multi-centric cohort study (preprint)

Abstract Background: To access the effect of Intravenous immunoglobulin ‎‎(IVIG) in critically ill corona virus disease 2019 (COVID-19) patients. Method: In this retrospective matched cohort study, records of three tertiary centers with large number of COVID-19 admissions were evaluated and used. Based on treatment options, ‎patients were divided into two groups, standard COVID-19 treatment (109 patients) and IVIG treatment (74 patients) patients. Also, the effect of IVIG in different dosages was evaluated. Patients with IVIG treatment were divided into three groups of ‎low (0.25 gr/kg), medium (0.5 gr/kg), and high (1 gr/kg) dose. Data analysis was performed using independent t-test and ‎One-way analysis of variance (ANOVA) to compare the ‎outcomes between two groups, including duration of hospitalization, intensive care unit (ICU) length of stay, and mortality rate.‎ Result: The duration of hospitalization in the IVIG group ‎were significantly longer than standard treatment (13.74 days vs. 11.10 days, p<0.05). There was not a significant difference between the two groups in ICU length of stay, number of intubated patients and duration of mechanical ventilation (P>0.05).‎ Also initial ‎outcomes in IVIG subgroups were compared separately with the standard ‎treatment group. The results indicated that only the duration of hospitalization ‎in the IVIG subgroup with medium dose is significantly longer than the standard ‎treatment group (P<0.01). Conclusion: Using IVIG is not beneficial for COVID-19 patients based on no remarkable differences in duration of hospitalization, ICU length of stay, duration of mechanical ventilation and even mortality rate.