The public health impact of poor sleep on severe COVID-19, influenza and upper respiratory infections.

BACKGROUND: Poor sleep is associated with an increased risk of infections and all-cause mortality but the causal direction between poor sleep and respiratory infections has remained unclear. We examined if poor sleep contributes as a causal risk factor to respiratory infections. METHODS: We used data on insomnia, influenza and upper respiratory infections (URIs) from primary care and hospital records in the UK Biobank (N ≈ 231,000) and FinnGen (N ≈ 392,000). We computed logistic regression to assess association between poor sleep and infections, disease free survival hazard ratios, and performed Mendelian randomization analyses to assess causality. FINDINGS: Utilizing 23 years of registry data and follow-up, we discovered that insomnia diagnosis associated with increased risk for infections (FinnGen influenza Cox's proportional hazard (CPH) HR = 4.34 [3.90, 4.83], P = 4.16 × 10-159, UK Biobank influenza CPH HR = 1.54 [1.37, 1.73], P = 2.49 × 10-13). Mendelian randomization indicated that insomnia causally predisposed to influenza (inverse-variance weighted (IVW) OR = 1.65, P = 5.86 × 10-7), URI (IVW OR = 1.94, P = 8.14 × 10-31), COVID-19 infection (IVW OR = 1.08, P = 0.037) and risk of hospitalization from COVID-19 (IVW OR = 1.47, P = 4.96 × 10-5). INTERPRETATION: Our findings indicate that chronic poor sleep is a causal risk factor for contracting respiratory infections, and in addition contributes to the severity of respiratory infections. These findings highlight the role of sleep in maintaining sufficient immune response against pathogens. FUNDING: Instrumentarium Science Foundation, Academy of Finland, Signe and Ane Gyllenberg Foundation, National Institutes of Health.

Identification of priority pathogens for aetiological diagnosis in adults with community-acquired pneumonia in China: a multicentre prospective study.

BACKGROUND: Community-acquired pneumonia (CAP) is a major public health challenge worldwide. However, the aetiological and disease severity-related pathogens associated with CAP in adults in China are not well established based on the detection of both viral and bacterial agents. METHODS: A multicentre, prospective study was conducted involving 10 hospitals located in nine geographical regions in China from 2014 to 2019. Sputum or bronchoalveolar lavage fluid (BALF) samples were collected from each recruited CAP patient. Multiplex real-time PCR and bacteria culture methods were used to detect respiratory pathogens. The association between detected pathogens and CAP severity was evaluated. RESULTS: Among the 3,403 recruited eligible patients, 462 (13.58%) had severe CAP, and the in-hospital mortality rate was 1.94% (66/3,403). At least one pathogen was detected in 2,054 (60.36%) patients, with two or more pathogens were co-detected in 725 patients. The ten major pathogens detected were Mycoplasma pneumoniae (11.05%), Haemophilus influenzae (10.67%), Klebsiella pneumoniae (10.43%), influenza A virus (9.49%), human rhinovirus (9.02%), Streptococcus pneumoniae (7.43%), Staphylococcus aureus (4.50%), adenovirus (2.94%), respiratory syncytial viruses (2.35%), and Legionella pneumophila (1.03%), which accounted for 76.06-92.52% of all positive detection results across sampling sites. Klebsiella pneumoniae (p < 0.001) and influenza viruses (p = 0.005) were more frequently detected in older patients, whereas Mycoplasma pneumoniae was more frequently detected in younger patients (p < 0.001). Infections with Klebsiella pneumoniae, Staphylococcus aureus, influenza viruses and respiratory syncytial viruses were risk factors for severe CAP. CONCLUSIONS: The major respiratory pathogens causing CAP in adults in China were different from those in USA and European countries, which were consistent across different geographical regions over study years. Given the detection rate of pathogens and their association with severe CAP, we propose to include the ten major pathogens as priorities for clinical pathogen screening in China.

Evaluation of peripheral lymphocyte subsets' alteration and IL6 serum level correlated with severity and outcome in corona virus disease 2019 (COVID-19)

Background: Coronavirus disease 2019 (COVID-19) has rapid spread worldwide and its pathogenesis is still not well understood. It's critical to identify the key immune inflammatory markers that may be correlated with COVID-19 severity. Objective: This study aimed to study the association of the peripheral lymphocyte subsets' alteration and IL-6 serum level with disease severity and outcome in COVID-19. Methodology: Samples from 30 COVID-19 patients were collected;one is EDTA anticoagulated for flowcytometric analysis of different lymphocyte subsets and the other for Interleukin-6 (IL6) serum level assessed by ELISA technique. Results: Absolute lymphocytic count (0.9 (0.5-1.4)× 103/µL), CD4+ T cells (217 (135.6-445.5) cells/µL), CD8+ T cells (160 (112-338) cells/µL) and natural killer (NK) cells (33.3 (18.2-99.5) cells/µL) were significantly reduced in severe COVID-19 patients with significantly elevated IL-6 serum levels 90 (70-120) (pg/mL) in severe patients. Lower T lymphocytes and NK subset counts with higher IL-6 levels were significantly associated with higher mortality. However, B cell count was not associated with severity or mortality. Il-6 levels, CD4+ and CD8+ T cells counts were considered best predictors of disease severity and mortality according to ROC curve analysis (with AUC 0.842, 0.884 and 0.773 respectively). Conclusion: Peripheral lymphocyte subsets as CD4+ T cells, CD8+ T cells and NK cells were significantly reduced in severe COVID-19 patients. CD4+ T cell count was the most significant biomarker for disease severity.Serum IL-6 levels were higher in severe illness. So, IL-6 can serve as a significant predictor of COVID-19 severity. As regard mortality and relation with lymphocytic count and lymphocytic subsets, total lymphocytic count and all T lymphocyte subsets CD4+, CD8+ and CD56+ cells count can be used as a significant predictor of death in COVID-19 patients. However, CD19+ cells counts had no relation with death. © 2020 The author (s). Published by Zagazig University.

Impact of TRIM5α and TRIM22 Genes Expression on the Clinical Course of Coronavirus Disease 2019.

OBJECTIVE: The innate immune response in humans involves a wide variety of factors, including the tripartite motif-containing 5α (TRIM5α) and 22 (TRIM22) as a cluster of genes on chromosome 11 that have exhibited antiviral activity in several viral infections. We analyzed the correlation of the expression of TRIM5α and TRIM22 with the severity of Coronavirus Disease 2019 (COVID-19) in blood samples of 330 patients, divided into two groups of severe and mild disease, versus the healthy individuals who never had contact with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). METHODS: The transcription level of TRIM5α and TRIM22 was determined by quantitative real-time polymerase chain reaction (qPCR). The laboratory values were collected from the patients' records. RESULTS: The expression of both genes was significantly lower in the severe group containing the hospitalized patients than in both the mild group and the control group. However, in the mild group, TRIM22 expression was significantly higher (p <0.0001) than in the control group while TRIM5α expression was not significantly different between these two groups. We found a relationship between the cycle threshold (Ct) value of patients and the expression of the aforementioned genes. CONCLUSION: The results of our study indicated that lower Ct values or higher RNA viral load might be associated with the downregulation of TRIM5α and TRIM22 and the severity of COVID-19. Additional studies are needed to confirm the results of this study.

A Systematic Review of Lung Autopsy Findings in Elderly Patients after SARS-CoV-2 Infection.

Although COVID-19 may cause various and multiorgan diseases, few research studies have examined the postmortem pathological findings of SARS-CoV-2-infected individuals who died. Active autopsy results may be crucial for understanding how COVID-19 infection operates and preventing severe effects. In contrast to younger persons, however, the patient's age, lifestyle, and concomitant comorbidities might alter the morpho-pathological aspects of the damaged lungs. Through a systematic analysis of the available literature until December 2022, we aimed to provide a thorough picture of the histopathological characteristics of the lungs in patients older than 70 years who died of COVID-19. A thorough search was conducted on three electronic databases (PubMed, Scopus, and Web of Science), including 18 studies and a total of 478 autopsies performed. It was observed that the average age of patients was 75.6 years, of which 65.4% were men. COPD was identified in an average of 16.7% of all patients. Autopsy findings indicated significantly heavier lungs, with an average weight of the right lung of 1103 g, while the left lung mass had an average weight of 848 g. Diffuse alveolar damage was a main finding in 67.2% of all autopsies, while pulmonary edema had a prevalence of between 50% and 70%. Thrombosis was also a significant finding, while some studies described focal and extensive pulmonary infarctions in 72.7% of elderly patients. Pneumonia and bronchopneumonia were observed, with a prevalence ranging from 47.6% to 89.5%. Other important findings described in less detail comprise hyaline membranes, the proliferation of pneumocytes and fibroblasts, extensive suppurative bronchopneumonic infiltrates, intra-alveolar edema, thickened alveolar septa, desquamation of pneumocytes, alveolar infiltrates, multinucleated giant cells, and intranuclear inclusion bodies. These findings should be corroborated with children's and adults' autopsies. Postmortem examination as a technique for studying the microscopic and macroscopic features of the lungs might lead to a better knowledge of COVID-19 pathogenesis, diagnosis, and treatment, hence enhancing elderly patient care.

Identification of Monocytes Associated with Severe COVID-19 in the PBMCs of Severely Infected patients Through Single-Cell Transcriptome Sequencing.

Understanding the immunological characteristics of monocytes-including the characteristics associated with fibrosis-in severe coronavirus disease 2019 (COVID-19) is crucial for understanding the pathogenic mechanism of the disease and preventing disease severity. In this study, we performed single-cell transcriptomic sequencing of peripheral blood samples collected from six healthy controls and 14 COVID-19 samples including severe, moderate, and convalescent samples from three severely/critically ill and four moderately ill patients. We found that the monocytes were strongly remodeled in the severely/critically ill patients with COVID-19, with an increased proportion of monocytes and seriously reduced diversity. In addition, we discovered two novel severe-disease-specific monocyte subsets: Mono 0 and Mono 5. These subsets expressed amphiregulin (AREG), epiregulin (EREG), and cytokine interleukin-18 (IL-18) gene, exhibited an enriched erythroblastic leukemia viral oncogene homolog (ErbB) signaling pathway, and appeared to exhibit pro-fibrogenic and pro-inflammation characteristics. We also found metabolic changes in Mono 0 and Mono 5, including increased glycolysis/gluconeogenesis and an increased hypoxia inducible factor-1 (HIF-1) signaling pathway. Notably, one pre-severe sample displayed a monocyte atlas similar to that of the severe/critical samples. In conclusion, our study discovered two novel severe-disease-specific monocyte subsets as potential predictors and therapeutic targets for severe COVID-19. Overall, this study provides potential predictors for severe disease and therapeutic targets for COVID-19 and thus provides a resource for further studies on COVID-19.

Characteristics and Management of Critically Ill Children with Sars-Cov-2 Infection a Case Series of a Referral Single-Centre Pediatric Intensive Care Unit

BACKGROUND AND AIM: The clinical manifestations of the pediatric population with Sars-Cov-2 infection vary and seem to be milder than adults. Although, seldom, children can manifest life-threatening respiratory disease. This study aims to present the experience of a single-center Pediatric Intensive Care Unit (PICU). METHOD(S): A retrospective review was performed between October 2020 and January 2022 in children, hospitalized with SARS-CoV-2 infection, in a referral PICU. The medical records of the patients were reviewed in terms of demographic characteristics, clinical and laboratory data. All patients, from birthday day to 16 years old, admitted with confirmed SARS-CoV-2 infection, with respiratory involvement, were included. RESULT(S): The data of 16 patients were analyzed, 9 (56%) were males, with median age 6 years. Comorbidities were ascertained in 5 patients, concerned mainly obesity (n=3), and neurological disorders (n=2). The mean duration of the hospitalization was 6,1 days. Twelve patients had an X-ray chest consistent with Covid-19. Six patients had cardiovascular involvement. Only three patients were supported with mechanical ventilation, two had co-morbidities. A mild prevalence of leukopenia was observed (n=8). Fifteen patients received corticosteroids, 12 Remdesivir and 6 immunomodulatory treatment. All patients received antibiotics. Two patients died, one was a newborn, without past medical history and the other had co-morbidities. CONCLUSION(S): This study highlights that there is a low but not negligible risk of a life-threatening disease which can be combined with the age and the co-morbidities of the patient. Additional studies are needed to evaluate clinical and laboratory findings so to analyze possible correlations.

Usage of ACE2 as a biomarker in patients with COVID-19 severe infection in relation with LDH

Background: Coronavirus disease (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus-2. Most of the people infected with the virus will have moderate respiratory illness and they recover without requiring special treatment. Aim: The aim of this study was to evaluate the role of ACE2 as a biomarker in patients with COVID-19 severe infection. Materials and methods: A case-control retrospective study included 90. subjects who were divided as the following : 60 COVID-19 patients who aged between 13-90 years with a positive real time -polymerase chain reaction (RT-PCR) for COVID-19,under monitoring the specialist doctor in terms of giving treatment and observing the clinical condition of the patient, patients with COVID-19 were divided in to 20 patients with severe symptoms who were admitted into the intensive care unit in the hospital, 20 patients with moderate symptoms who were admitted to the hospital ,and 20 patients with mild symptoms who were treated as an out patients. 30 individuals who were apparently healthy as a control group. Blood blood sample were collected from each patients fir determination of Serum Angiotensin Converting Enzyme 2 (ACE2) and LDH by ELISA. Results: The highest proportion of study group were aged ≥ 60years (55% and 40% respectively). According to gender the highest proportion of the study group were female s(51 % and 56.7% respectively), regarding the smoking status 28.3% of patient group and 50 % of control were current smokers, while the highest proportion of the patient group complained from severe COVID-19 infection . A significant difference p<0.05 in ACE2 levels between patient and control group so significant increase was observed in the level of the biomarkers (ACE2, LDH, ) with means (261.47pg/ml,495.28 iu/l, when measured in COVID-19 patients, in comparison with control group means ( 50.07 pg/ml, 288.16 iu/l,) respectively, which meaning that a positive correlations between ACE2 level and LDH ,Ferritin Conclusions: Present study revealed that ACE2 has a vital role in COVID-19 patients and in severity of systemic inflammation, , LDH, play an essential role in severity of COVID-19. © 2022, HIV Nursing. All rights reserved.

Identification of Neutrophil-Related Factor LCN2 for Predicting Severity of Patients With Influenza A Virus and SARS-CoV-2 Infection.

Background: Influenza and COVID-19 are respiratory infectious diseases that are characterized by high contagiousness and high mutation and pose a serious threat to global health. After Influenza A virus (IAV) and SARS-CoV-2 infection, severe cases may develop into acute lung injury. Immune factors act as an important role during infection and inflammation. However, the molecular immune mechanisms still remain unclear. We aimed to explore immune-related host factors and core biomarker for severe infection, to provide a new therapeutic target of host factor in patients. Methods: Gene expression profiles were obtained from Gene Expression Omnibus and the Seurat R package was used for data process of single-cell transcriptome. Differentially expressed gene analysis and cell cluster were used to explore core host genes and source cells of genes. We performed Gene Ontology enrichment, Kyoto Encyclopedia of Genes and Genomes analysis, and gene set enrichment analysis to explore potential biological functions of genes. Gene set variation analysis was used to evaluate the important gene set variation score for different samples. We conduct Enzyme-linked immunosorbent assay (ELISA) to test plasma concentrations of Lipocalin 2 (LCN2). Results: Multiple virus-related, cytokine-related, and chemokine-related pathways involved in process of IAV infection and inflammatory response mainly derive from macrophages and neutrophils. LCN2 mainly in neutrophils was significantly upregulated after either IAV or SARS-CoV-2 infection and positively correlated with disease severity. The plasma LCN2 of influenza patients were elevated significantly compared with healthy controls by ELISA and positively correlated with disease severity of influenza patients. Further bioinformatics analysis revealed that LCN2 involved in functions of neutrophils, including neutrophil degranulation, neutrophil activation involved in immune response, and neutrophil extracellular trap formation. Conclusion: The neutrophil-related LCN2 could be a promising biomarker for predicting severity of patients with IAV and SARS-CoV-2 infection and may as a new treatment target in severe patients.

C-Reactive protein role in assessing COVID-19 deceased geriatrics and survivors of severe and critical illness.

Numerous risk variables, including age, medical co-morbidities, and deranged inflammatory response, lead to higher mortality in a senior population with coronavirus disease 2019. C-reactive protein (CRP), an acute phase inflammatory protein secreted by the liver, was tested in the elderly, showing a diagnostic and prognostic role. However, recent research has shed light on new applications for CRP in geriatrics. It was used as a follow-up marker and as a therapeutic target. Early and accurate identification of patients' risks may mitigate the devastation of the invading virus in older cases and permit the implementation of a quick treatment plan for those most likely to deteriorate.

Persistent but dysfunctional mucosal SARS-CoV-2-specific IgA and low lung IL-1ß associate with COVID-19 fatal outcome: A cross-sectional analysis.

The role of the mucosal pulmonary antibody response in coronavirus disease 2019 (COVID-19) outcome remains unclear. Here, we found that in bronchoalveolar lavage (BAL) samples from 48 patients with severe COVID-19-infected with the ancestral Wuhan virus, mucosal IgG and IgA specific for S1, receptor-binding domain (RBD), S2, and nucleocapsid protein (NP) emerged in BAL containing viruses early in infection and persist after virus elimination, with more IgA than IgG for all antigens tested. Furthermore, spike-IgA and spike-IgG immune complexes were detected in BAL, especially when the lung virus has been cleared. BAL IgG and IgA recognized the four main RBD variants. BAL neutralizing titers were higher early in COVID-19 when virus replicates in the lung than later in infection after viral clearance. Patients with fatal COVID-19, in contrast to survivors, developed higher levels of mucosal spike-specific IgA than IgG but lost neutralizing activities over time and had reduced IL-1ß in the lung. Altogether, mucosal spike and NP-specific IgG and S1-specific IgA persisting after lung severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance and low pulmonary IL-1ß correlate with COVID-19 fatal outcome. Thus, mucosal SARS-CoV-2-specific antibodies may have adverse functions in addition to protective neutralization. Highlights: Mucosal pulmonary antibody response in COVID-19 outcome remains unclear. We show that in severe COVID-19 patients, mucosal pulmonary non-neutralizing SARS-CoV-2 IgA persit after viral clearance in the lung. Furthermore, low lung IL-1ß correlate with fatal COVID-19. Altogether, mucosal IgA may exert harmful functions beside protective neutralization.

Comparing the expression levels of tripartite motif containing 28 in mild and severe COVID-19 infection.

BACKGROUND: Tripartite motif-containing 28 (TRIM28) is an impressive regulator of the epigenetic control of the antiviral immune response. This study evaluated if the differential expression of TRIM28 correlates with the severity of coronavirus disease 2019 (COVID-19) infection. METHODS: A total of 330 COVID-19 patients, including 188 mild and 142 severe infections, and 160 healthy controls were enrolled in this study. Quantitative real-time polymerase chain reaction (qPCR) was used to determine the expression levels of TRIM28 in the studied patients. RESULTS: TRIM28 mRNA levels were significantly lower in both groups of patients versus the control group and in the severe group indicated further reduction in comparison to mild infection. The multivariate logistic regression analysis showed the mean age, lower levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), cholesterol, lower 25-hydroxyvitamin D, and PCR cycle threshold (Ct) value and higher levels of erythrocyte sedimentation rate (ESR) and differential expression of TRIM28 were linked to the severity of COVID-19 infection. CONCLUSION: The results of this study proved that the downregulation of TRIM28 might be associated with the severity of COVID-19 infection. Further studies are required to determine the association between the COVID-19 infection severity and TRIM family proteins.

The Incidence and Severity of COVID-19 in the Liverpool Severe Asthma Population Undergoing Biologic Therapy.

Background The coronavirus disease 2019 (COVID-19) infection can have a variable impact on patients. Various host factors have been identified that play a significant role in the risk of COVID-19 infection and its severity. Patients with severe asthma have been clinically vulnerable since the first wave of the pandemic and the resurgence of COVID-19 in the United Kingdom in January 2020. In addition, those on treatment with monoclonal antibodies (mAbs) have been identified as being vulnerable to COVID-19 infection and severity by the World Health Organization and the Department of Health. However, the evidence to support this notion is limited, and there has been contrary evidence to suggest severe asthma is protective against COVID-19. In this study, a retrospective review of severe asthma patients in the Liverpool population between 1st January 2020 and 31st January 2021 was conducted. This study aimed to determine the association between asthma severity and the risk of COVID-19 infection and/or its severity for patients on mAb treatment. Methodology We conducted a review of all patients from the Liverpool severe asthma database/spreadsheet who tested positive in the community and at the hospital. Admission records, primary records, emails, and microbiological data for Anglia ICE were reviewed at the Royal Liverpool and Aintree University Hospital. A COVID-19 diagnosis was predefined as a positive lateral flow test and a positive polymerase chain reaction test. The proportion of patients with COVID-19 pneumonia and severe COVID-19 disease requiring hospital admission and escalation to intensive care (observation, intubation, continuous positive airway pressure) was noted. Other patient characteristics were recorded including age, weight, body mass index (BMI), gender, smoking status (never, former, current smoker), bronchiectasis, and the forced expiratory volume. Results In total, 760 patients were identified to have severe asthma, of whom 59 (7.8%) tested positive for COVID-19 and 701 (92.2%) tested negative. A total of 244 (32%) patients were taking mAbs, and 516 (68%) were not on mAb treatment. Patients were more susceptible to COVID-19 on an mAb (13.5%) versus non-mAb (5%) (odds ratio (OR) = 2.95; 95% confidence interval (CI) = 1.72 to 5.05) . A larger proportion of severe asthma patients on mAb treatment testing positive for COVID-19 were current smokers and had a higher BMI. Furthermore, severe asthmatics taking mAbs did not have a higher risk of severe COVID-19 disease, hospitalisation, and intensive care admission. Conclusions In the Liverpool severe asthma population, patients undergoing mAb therapy had a higher incidence of COVID-19 compared to non-mAb groups; however, they were not at a higher risk of severe disease progression. These findings suggest that continuing biologic therapy in severe asthmatics with COVID-19 appears to be safe to prevent exacerbations.

The Impact of Hyper-Acute Inflammatory Response on Stress Adaptation and Psychological Symptoms of COVID-19 Patients.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces a significant inflammatory response that are amplified by persistent stress. The pathophysiology of mental illnesses is explored in terms of inflammatory processes. Thus, anxious, depressed, or psychotic episodes may occur as a result of metabolic and immunological imbalances, as a direct result of their effect on the central nervous system, or as a side effect of the COVID-19 medication protocols. As such, the primary objective of this research is to establish if the psychological profiles of COVID-19 patients change substantially according to illness severity. The secondary objective is to determine if particular biological inflammatory indicators are associated with anxiety, sadness, psychoticism, and paranoid ideation. A cross-sectional study was performed on 90 hospitalized patients admitted during a 3-month period in the COVID-19 unit. All patients received the COPE-60 and SCL-90R questionnaires. Clinical and paraclinical data were collected and the information was classified according to the severity of COVID-19.The hyper-acute inflammation encountered in patients with severe COVID-19 infection characterized 80.0% of patients using disengagement coping methods, significantly more than patients with mild or moderate SARS-CoV-2 infection severity (p-value = 0.012), respectively, 73.3% severe COVID-19 patients engaging in emotion-focused coping strategies based on the COPE-60 scale (p-value = 0.037). Additionally, it was determined that negative coping mechanisms (disengagement) and emotion-focused methods are independent risk factors for developing psychoticism symptoms following acute SARS-CoV-2 infection, based on the SCL-90 questionnaire (OR = 2.07; CI = 1.44-3.01), respectively (OR = 2.92; CI = 1.44-3.01). Elevated white blood cells and monocytes and inflammatory markers, such as fibrinogen, procalcitonin, IL-6, and D-dimers, were also identified as risk factors for psychoticism symptoms in multivariate analysis. It is particularly important to consider the constant mental-state evaluation in patients with severe COVID-19 that might benefit from early intervention before psychotic symptoms onset.

Administration of Parenteral Vitamin C in Patients With Severe Infection: Protocol for a Systematic Review and Meta-analysis.

BACKGROUND: Severe infections are characterized by inflammation and oxidative damage. Ascorbic acid (vitamin C) administration may attenuate oxidative damage and, in turn, reduce vascular endothelial injury in pulmonary and systemic vasculature. OBJECTIVE: We aim to describe a protocol for a living systematic review that will evaluate the effectiveness and safety of parenteral vitamin C administration in adults with severe infections, including those with COVID-19. METHODS: We searched Ovid MEDLINE, Embase, CINAHL, the Centers for Disease Control and Prevention COVID-19 database, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception to March 30, 2021, for randomized controlled trials evaluating parenteral vitamin C versus no parenteral vitamin C in hospitalized adults with severe infection. Eligible studies will include at least 1 arm involving any dose of parenteral vitamin C alone or in combination with other cointerventions and at least 1 arm not involving parenteral vitamin C. The primary outcomes of interest will include in-hospital, 30-day, and 90-day mortality. Title and abstract screening, full-text screening, data extraction, and risk of bias evaluation via a modified Risk of Bias 2.0 tool will be conducted independently and in pairs. We will perform random effects modeling for meta-analyses, in which study weights will be generated by using the inverse variance method. We will assess certainty in effect estimates by using the Grading of Recommendations Assessment, Development and Evaluation methodology. Meta-analyses will be updated iteratively as new trial evidence becomes available. RESULTS: Among the 1386 citations identified as of March 30, 2021, a total of 17 eligible randomized controlled trials have been identified as of September 2021. We are in the process of updating the search strategy and associated data analyses. CONCLUSIONS: The results will be of importance to critical care physicians and hospitalists who manage severe infection and COVID-19 in daily practice, and they may directly inform international clinical guidance. Although our systematic review will incorporate the most recent trial evidence, ongoing trials may change our confidence in the estimates of effects, thereby necessitating iterative updates in the form of a living review. TRIAL REGISTRATION: PROSPERO CRD42020209187; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=209187. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/33989.

Prevalence, Demographics, and Risk of Severe Acute COVID-19.

BACKGROUND: Our goal was to assess the demographics, risk factors, and hospital admission and length of stay (LOS) among patients with acute COVID-19 and to identify whether age, smoking status, race, risk factors, and sex significantly affect the severity of illness according to hospitalization or admission to the intensive care unit (ICU). Severity was defined as admission to the hospital or ICU. METHODS: This retrospective cohort chart review included patients who received care from March 13 to August 17, 2020, at a single academic medical center. Age, COVID-19 risk factors, sex, race, smoking history, and hospital LOS were analyzed with hospital admission and ICU admission. Categorical variables were summarized. RESULTS: The chart review assessed 1,697 adult patients with various degrees of severity of COVID-19 illness: 23 patients had been admitted to the hospital, and 7 had been admitted to the ICU. Older age and more COVID-19 risk factors, as defined by the Centers for Disease Control and Prevention, were significantly associated with hospital admissions, and longer LOS was statistically associated with ICU admission. CONCLUSIONS: Severe COVID-19 infection was associated with older age and more risk factors. Current smoking status, sex, and race were not significantly different between hospitalized patients with severe COVID-19 infection who were admitted to the ICU and those who were not admitted to the ICU.

Newly Diagnosed Diabetes in Patients with COVID-19: Different Types and Short-Term Outcomes.

A great global concern is currently focused on the coronavirus disease 2019 (COVID-19) pandemic and its associated morbidities. The goal of this study was to determine the frequency of newly diagnosed diabetes mellitus (DM) and its different types among COVID-19 patients, and to check the glycemic control in diabetic cases for three months. After excluding known cases of DM, 570 patients with confirmed COVID-19 were studied. All participants were classified as non-diabetic or newly discovered diabetic. According to hemoglobin A1c (HbA1c) and fasting insulin, newly discovered diabetic patients were further classified into pre-existing DM, new-onset type 1 DM, and new-onset type 2 DM. Glycemic control was monitored for three months in newly diagnosed diabetic patients. DM was diagnosed in 77 patients (13.5%); 12 (2.1%) with pre-existing DM, 7 (1.2%) with new-onset type 1 DM, and 58 (10.2%) with new-onset type 2 DM. Significantly higher rates of severe infection and mortality (p < 0.001 and p = 0.046) were evident among diabetic patients. Among survived diabetic patients (n = 63), hyperglycemia and the need for anti-diabetic treatment persisted in 73% of them for three months. COVID-19 was associated with a new-onset of DM in 11.4% of all participants and expression of pre-existing DM in 2.1% of all participants, both being associated with severe infection. COVID-19 patients with newly diagnosed diabetes had high risk of mortality. New-onset DM persisted for at least three months in more than two-thirds of cases.

Severe COVID-19 in the intensive care unit: a case series.

BACKGROUND: Coronavirus disease 2019 (COVID-19) was first identified in Indonesia in March 2020, and the number of infections has grown exponentially. The situation is at its worst, overwhelming intensive care unit (ICU) resources and capacity. CASE PRESENTATION: This is a single-center observational case study of 21 confirmed COVID-19 patients admitted to the ICU from March 20, 2020, to April 31, 2020. Demographics, baseline comorbidities, clinical symptoms, laboratory tests, electrocardiogram (ECG) and chest imaging were obtained consecutively during patient care. We identified 21 patients with confirmed COVID-19 severe infection in our ICU. The mean (± standard deviation) age of the patients was 54 ± 10 years; 95% were men, with shortness of breath (90.6%) the most common symptom. Hypertension was identified as a comorbidity in 28.6% of patients. The most common reason for admission to the ICU was hypoxemic respiratory failure, with 80% (17 patients) requiring mechanical ventilation. Half of the patients (10) died between day 1 and day 18, with septic shock as the primary cause of death. Of the 11 surviving patients, five were discharged home, while six were discharged from the ICU but remained in the hospital ward. Even then, the median length of ICU stay amongst survivors was 18 days. CONCLUSIONS: To date, there are no known effective antiviral agents or specific therapy to treat COVID-19. As severe systemic inflammatory response and multiple organ failure seems to be the primary cause of death, supportive care in maintaining oxygenation and hemodynamic stability remain the mainstay goals in treating critically ill COVID-19 patients.