Severe COVID-19 is associated with hyperactivation of the alternative complement pathway.

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) is characterized by impaired type I interferon activity and a state of hyperinflammation leading to acute respiratory distress syndrome. The complement system has recently emerged as a key player in triggering and maintaining the inflammatory state, but the role of this molecular cascade in severe COVID-19 is still poorly characterized. OBJECTIVE: We aimed at assessing the contribution of complement pathways at both the protein and transcriptomic levels. METHODS: To this end, we systematically assessed the RNA levels of 28 complement genes in the circulating whole blood of patients with COVID-19 and healthy controls, including genes of the alternative pathway, for which data remain scarce. RESULTS: We found differential expression of genes involved in the complement system, yet with various expression patterns: whereas patients displaying moderate disease had elevated expression of classical pathway genes, severe disease was associated with increased lectin and alternative pathway activation, which correlated with inflammation and coagulopathy markers. Additionally, properdin, a pivotal positive regulator of the alternative pathway, showed high RNA expression but was found at low protein concentrations in patients with a severe and critical disease, suggesting its deposition at the sites of complement activation. Notably, low properdin levels were significantly associated with the use of mechanical ventilation (area under the curve = 0.82; P = .002). CONCLUSION: This study sheds light on the role of the alternative pathway in severe COVID-19 and provides additional rationale for the testing of drugs inhibiting the alternative pathway of the complement system.

Mortality and Clinical Outcomes among Patients with COVID-19 and Diabetes.

Background Diabetes mellitus (DM) is a decisive risk factor for severe illness in coronavirus disease 2019 (COVID-19). India is home to a large number of people with DM, and many of them were infected with COVID-19. It is critical to understand the impact of DM on mortality and other clinical outcomes of COVID-19 infection from this region. Aims The primary objective of our study was to analyze the mortality rate in people with DM infected with COVID-19. The secondary objectives were to assess the effect of various comorbidities on mortality and study the impact of DM on other clinical outcomes. Methods This is a retrospective study of COVID-19 infected patients admitted to a tertiary care hospital in north India in the early phase of the pandemic. Results Of the 1211 cases admitted, 19 were excluded because of incomplete data, and 1192 cases were finally considered for analysis. DM constituted 26.8% of total patients. The overall mortality rate was 6.1%, and the rate was 10.7% in the presence of diabetes (p < 0.01, OR 2.55). In univariate analysis, increased age, chronic kidney disease (CKD), coronary artery disease (CAD), stroke, and cancer were associated with mortality. On multiple logistic regression, the independent predictors of mortality were CAD, CKD, and cancer. Breathlessness and low SpO2 at presentation, extensive involvement in CXR, and elevated ANC/ALC ratio were also significantly associated with mortality. Conclusions The presence of comorbidities such as DM, hypertension, CAD, CKD, and cancer strongly predict the risk of mortality in COVID-19 infection. Early triaging and aggressive therapy of patients with these comorbidities can optimize clinical outcomes.

Clinical outcomes in patients infected with different SARS-CoV-2 variants at one hospital during three phases of the COVID-19 epidemic in Marseille, France.

OBJECTIVES: To compare the demographics, clinical characteristics and severity of patients infected with nine different SARS-CoV-2 variants, during three phases of the COVID-19 epidemic in Marseille. METHODS: A single centre retrospective cohort study was conducted in 1760 patients infected with SARS-CoV-2 of Nextstrain clades 20A, 20B, and 20C (first phase, February-May 2020), Pangolin lineages B.1.177 (we named Marseille-2) and B.1.160 (Marseille-4) variants (second phase, June-December 2020), and B.1.1.7 (alpha), B.1.351 (beta), P.1 (gamma) and A.27 (Marseille-501) variants (third phase, January 2021-today). Outcomes were the occurrence of clinical failures, including hospitalisation, transfer to the intensive-care unit, and death. RESULTS: During each phase, no major differences were observed with regards to age and gender distribution, the prevalence of chronic diseases, and clinical symptoms between variants circulating in a given phase. The B.1.177 and B.1.160 variants were associated with more severe outcomes. Infections occurring during the second phase were associated with a higher rate of death as compared to infections during the first and third phases. Patients in the second phase were more likely to be hospitalised than those in the third phase. Patients infected during the third phase were more frequently obese than others. CONCLUSION: A large cohort study is recommended to evaluate the transmissibility and to better characterise the clinical severity of emerging variants.

Therapeutic interventions of remdesivir in diabetic and nondiabetic COVID-19 patients: A prospective observational study conducted on Pakistani population.

We aimed to investigate the interventions of remdesivir in both diabetic and nondiabetic individuals who were suffering from a severe infection of novel coronavirus disease (COVID-19). In this study, we aimed to explore the relationship between therapeutic effectiveness of remdesivir and complications of diabetes mellitus by observing the recovery period among diabetic and nondiabetic patients associated with COVID-19 infection. A total of 850 COVID-19 patients were recruited for this study, out of which 48% were diabetic and 52% were nondiabetics. The results of this study indicated that nondiabetic individuals administered with remdesivir recovered from COVID-19 within 10 days showing a 95% confidence interval (p < 0.01), while the diabetic individuals recovered in 15 days. Nondiabetic patients administered with remdesivir exhibited higher chances of clinical improvement at 15th day than those who were associated with diabetes. Remdesivir administration improved the levels of various biochemical parameters, such as C-reactive protein, lactate dehydrogenase, d-Dimer, and ferritin both in diabetic and nondiabetic patients. However, a significant improvement (p < 0.01) was seen in the level of biochemical parameters among nondiabetic patients as compared to that of diabetic patients administered with remdesivir treatment. In the end, it was concluded that remdesivir could be considered as a possible therapeutic agent in the treatment of COVID-19 both in diabetic and nondiabetic situations. However, diabetic patients showed a delayed recovery as compared with that of nondiabetic patients, in which the recovery rate was high.

Wharton's Jelly Mesenchymal Stem Cell-Derived Extracellular Vesicles Reduce SARS-CoV2-Induced Inflammatory Cytokines Under High Glucose and Uremic Toxin Conditions.

Cytokine storm is recognized as one of the factors contributing to organ failures and mortality in patients with COVID-19. Due to chronic inflammation, COVID-19 patients with diabetes mellitus (DM) or renal disease (RD) have more severe symptoms and higher mortality. However, the factors that contribute to severe outcomes of COVID-19 patients with DM and RD have received little attention. In an effort to investigate potential treatments for COVID-19, recent research has focused on the immunomodulation functions of mesenchymal stem cells (MSCs). In this study, the correlation between DM and RD and the severity of COVID-19 was examined by a combined approach with a meta-analysis and experimental research. The results of a systematic review and meta-analysis suggested that the odd of mortality in patients with both DM and RD was increased in comparison to those with a single comorbidity. In addition, in the experimental research, the data showed that high glucose and uremic toxins contributed to the induction of cytokine storm in human lung adenocarcinoma epithelial cells (Calu-3 cells) in response to SARS-CoV Peptide Pools. Of note, the incorporation of Wharton's jelly MSC-derived extracellular vesicles (WJ-EVs) into SARS-CoV peptide-induced Calu-3 resulted in a significant decrease in nuclear NF-κB p65 and the downregulation of the cytokine storm under high concentrations of glucose and uremic toxins. This clearly suggests the potential for WJ-EVs to reduce cytokine storm reactions in patients with both chronic inflammation diseases and viral infection.

Immune Interaction Map of Human SARS-CoV-2 Target Genes: Implications for Therapeutic Avenues.

There exists increasing evidence that people with preceding medical conditions, such as diabetes and cancer, have a higher risk of infection with SARS-CoV-2 and are more vulnerable to severe disease. To get insights into the possible role of the immune system upon COVID-19 infection, 2811 genes of the gene ontology term "immune system process GO: 0002376" were selected for coexpression analysis of the human targets of SARS-CoV-2 (HT-SARS-CoV-2) ACE2, TMPRSS2, and FURIN in tissue samples from patients with cancer and diabetes mellitus. The network between HT-SARS-CoV-2 and immune system process genes was analyzed based on functional protein associations using STRING. In addition, STITCH was employed to determine druggable targets. DPP4 was the only immune system process gene, which was coexpressed with the three HT-SARS-CoV-2 genes, while eight other immune genes were at least coexpressed with two HT-SARS-CoV-2 genes. STRING analysis between immune and HT-SARS-CoV-2 genes plotted 19 associations of which there were eight common networking genes in mixed healthy (323) and pan-cancer (11003) tissues in addition to normal (87), cancer (90), and diabetic (128) pancreatic tissues. Using this approach, three commonly applicable druggable connections between HT-SARS-CoV-2 and immune system process genes were identified. These include positive associations of ACE2-DPP4 and TMPRSS2-SRC as well as a negative association of FURIN with ADAM17. Furthermore, 16 drugs were extracted from STITCH (score <0.8) with 32 target genes. Thus, an immunological network associated with HT-SARS-CoV-2 using bioinformatics tools was identified leading to novel therapeutic opportunities for COVID-19.

Decreased in-hospital mortality associated with aspirin administration in hospitalized patients due to severe COVID-19.

Hypercoagulability and thrombosis caused by coronavirus disease 2019 (COVID-19) are related to the higher mortality rate. Because of limited data on the antiplatelet effect, we aimed to evaluate the impact of aspirin add-on therapy on the outcome of the patients hospitalized due to severe COVID-19. In this cohort study, patients with a confirmed diagnosis of severe COVID-19 admitted to Imam Hossein Medical Center, Tehran, Iran from March 2019 to July 2020 were included. Demographics and related clinical data during their hospitalization were recorded. The mortality rate of the patients was considered as the primary outcome and its association with aspirin use was assessed. Nine hundred and ninety-one patients were included, of that 336 patients (34%) received aspirin during their hospitalization and 655 ones (66%) did not. Comorbidities were more prevalent in the patients who were receiving aspirin. Results from the multivariate COX proportional model demonstrated a significant independent association between aspirin use and reduction in the risk of in-hospital mortality (0.746 [0.560-0.994], p = 0.046). Aspirin use in hospitalized patients with COVID-19 is associated with a significant decrease in mortality rate. Further prospective randomized controlled trials are needed to assess the efficacy and adverse effects of aspirin administration in this population.

Rare case of endogenous Klebsiella endophthalmitis associated with emphysematous prostatitis in a patient with diabetes, cirrhosis and COVID-19.

A 35-year-old Hispanic man presented with fever, chills, dysuria, diarrhoea, scleral icterus, tachycardia and tachypnea. He was found to be COVID-19 positive, CT of the pelvis revealed prostatic abscess, and urine culture grew Klebsiella pneumoniae Additionally, he was found to have diabetes and cirrhosis. During treatment, the patient developed vision loss, and was diagnosed with endogenous Klebsiella endophthalmitis. The patient was treated with intravenous antibiotics, pars plana vitrectomy, intravitreal antibiotics and cystoscopy/suprapubic catheter placement. On follow-up, the patient has had the suprapubic catheter removed, and successfully passed a voiding trial, but suffers permanent vision loss in both eyes.

Effects of a DPP-4 Inhibitor and RAS Blockade on Clinical Outcomes of Patients with Diabetes and COVID-19.

BACKGROUND: Dipeptidyl peptidase-4 inhibitor (DPP-4i) and renin-angiotensin system (RAS) blockade are reported to affect the clinical course of coronavirus disease 2019 (COVID-19) in patients with diabetes mellitus (DM). METHODS: As of May 2020, analysis was conducted on all subjects who could confirm their history of claims related to COVID-19 in the National Health Insurance Review and Assessment Service (HIRA) database in Korea. Using this dataset, we compared the short-term prognosis of COVID-19 infection according to the use of DPP-4i and RAS blockade. Additionally, we validated the results using the National Health Insurance Service (NHIS) of Korea dataset. RESULTS: Totally, data of 67,850 subjects were accessible in the HIRA dataset. Of these, 5,080 were confirmed COVID-19. Among these, 832 subjects with DM were selected for analysis in this study. Among the subjects, 263 (31.6%) and 327 (39.3%) were DPP4i and RAS blockade users, respectively. Thirty-four subjects (4.09%) received intensive care or died. The adjusted odds ratio for severe treatment among DPP-4i users was 0.362 (95% confidence interval [CI], 0.135 to 0.971), and that for RAS blockade users was 0.599 (95% CI, 0.251 to 1.431). These findings were consistent with the analysis based on the NHIS data using 704 final subjects. The adjusted odds ratio for severe treatment among DPP-4i users was 0.303 (95% CI, 0.135 to 0.682), and that for RAS blockade users was 0.811 (95% CI, 0.391 to 1.682). CONCLUSION: This study suggests that DPP-4i is significantly associated with a better clinical outcome of patients with COVID-19.

Clinical Manifestations and Outcomes in Disease-Modifying Antirheumatic Drug-Naive Adult Patients with Chronic Chikungunya Arthritis.

Most studies on chronic chikungunya virus (CHIKV) arthritis include patients treated with disease-modifying antirheumatic drugs (DMARDs), likely altering the expression of clinical manifestations and outcome. Therefore, we sought to evaluate the clinical features and correlates in DMARD-naive patients with chronic CHIKV arthritis. We conducted a case-control study in adult patients with serologically confirmed CHIKV infection in Puerto Rico. Demographic features, clinical manifestations, comorbidities, disease activity (per Clinical Disease Activity Index [CDAI]), functional status (per Health Assessment Questionnaire Disability Index [HAQ-DI]), and pharmacologic treatment were ascertained. Patients with and without chronic CHIKV arthritis were compared. Furthermore, a sub-analysis was performed among patients with chronic CHIKV who presented with mild disease activity versus moderate-to-high disease activity at study visit. In total, 61 patients were studied; 33 patients had chronic arthritis and 28 had resolved arthritis. Patients with chronic arthritis had significantly more diabetes mellitus, chronic back pain, and fever, tiredness, and myalgias on the acute phase. The mean (SD) HAQ score was 0.95 (0.56), and 57.6% had moderate-to-high disease activity. Patients with moderate-to-high disease activity had higher scores in overall HAQ-DI and HAQ-DI categories (dressing and grooming, arising, hygiene, reaching, and activities) than in those with mild activity. In conclusion, in this group of DMARD-naive patients with chronic CHIKV arthritis, nearly 58% had moderate-to-high disease activity and had substantial functional disability. Diabetes mellitus, chronic back pain, and some manifestations on acute infection were associated with chronic CHIKV arthritis.

HCV Seroprevalence among HIV Patients and Associated Comorbidities at One Primary Health Facility in Rwanda.

Hepatitis C virus (HCV) and HIV have emerged as major viral infections within the past two decades, and their coinfection poses a big challenge with a significant impact in terms of morbidity and mortality associated with liver disease and renal failure. The current study aimed at assessing the prevalence of HCV infection and associated comorbidities among HIV patients at one primary health facility in Rwanda. In total, 417 HIV-positive patients were recruited and included in the study from January 1, 2019 up to June 30, 2019. All participants were screened for HCV infection by using the SD Bioline HCV antibody rapid test. In addition, underlying medical conditions were also recorded as comorbidities. Among 417 participants, 52 exhibited HCV-positive results (12.5%). The group of 41- to 50- and 51- to 60-year-olds had higher prevalence of HIV/HCV coinfection than other age-groups with 3.6% and 4.6%, respectively. Furthermore, five underlying medical conditions were found as comorbidities among the study participants. Those with HIV/HCV coinfection showed higher comorbidities than those with mono-infection including liver toxicity, P value 0.005; tuberculosis, P value 0.005; renal failure, P value 0.003; hypertension, P value 0.001; and diabetes mellitus, P value 0.001. The relative risk ratio of having comorbidities in those groups was 4.09. To conclude, the prevalence of HCV/HIV coinfection is high, and there was a statistical significant association of having comorbidities in HIV/HCV-coinfected group compared with the group of HIV mono-infection, which suggests more intervention in this vulnerable group of patients.

First results of the "Lean European Open Survey on SARS-CoV-2-Infected Patients (LEOSS)".

PURPOSE: Knowledge regarding patients' clinical condition at severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection is sparse. Data in the international, multicenter Lean European Open Survey on SARS-CoV-2-Infected Patients (LEOSS) cohort study may enhance the understanding of COVID-19. METHODS: Sociodemographic and clinical characteristics of SARS-CoV-2-infected patients, enrolled in the LEOSS cohort study between March 16, 2020, and May 14, 2020, were analyzed. Associations between baseline characteristics and clinical stages at diagnosis (uncomplicated vs. complicated) were assessed using logistic regression models. RESULTS: We included 2155 patients, 59.7% (1,287/2,155) were male; the most common age category was 66-85 years (39.6%; 500/2,155). The primary COVID-19 diagnosis was made in 35.0% (755/2,155) during complicated clinical stages. A significant univariate association between age; sex; body mass index; smoking; diabetes; cardiovascular, pulmonary, neurological, and kidney diseases; ACE inhibitor therapy; statin intake and an increased risk for complicated clinical stages of COVID-19 at diagnosis was found. Multivariable analysis revealed that advanced age [46-65 years: adjusted odds ratio (aOR): 1.73, 95% CI 1.25-2.42, p = 0.001; 66-85 years: aOR 1.93, 95% CI 1.36-2.74, p < 0.001; > 85 years: aOR 2.38, 95% CI 1.49-3.81, p < 0.001 vs. individuals aged 26-45 years], male sex (aOR 1.23, 95% CI 1.01-1.50, p = 0.040), cardiovascular disease (aOR 1.37, 95% CI 1.09-1.72, p = 0.007), and diabetes (aOR 1.33, 95% CI 1.04-1.69, p = 0.023) were associated with complicated stages of COVID-19 at diagnosis. CONCLUSION: The LEOSS cohort identified age, cardiovascular disease, diabetes and male sex as risk factors for complicated disease stages at SARS-CoV-2 diagnosis, thus confirming previous data. Further data regarding outcomes of the natural course of COVID-19 and the influence of treatment are required.

An Assessment on Impact of COVID-19 Infection in a Gender Specific Manner.

Coronavirus disease 2019 (COVID-19) is caused by novel coronavirus Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was first time reported in December 2019 in Wuhan, China and thereafter quickly spread across the globe. Till September 19, 2020, COVID-19 has spread to 216 countries and territories. Severe infection of SARS-CoV-2 cause extreme increase in inflammatory chemokines and cytokines that may lead to multi-organ damage and respiratory failure. Currently, no specific treatment and authorized vaccines are available for its treatment. Renin angiotensin system holds a promising role in human physiological system specifically in regulation of blood pressure and electrolyte and fluid balance. SARS-CoV-2 interacts with Renin angiotensin system by utilizing angiotensin-converting enzyme 2 (ACE2) as a receptor for its cellular entry. This interaction hampers the protective action of ACE2 in the cells and causes injuries to organs due to persistent angiotensin II (Ang-II) level. Patients with certain comorbidities like hypertension, diabetes, and cardiovascular disease are under the high risk of COVID-19 infection and mortality. Moreover, evidence obtained from several reports also suggests higher susceptibility of male patients for COVID-19 mortality and other acute viral infections compared to females. Analysis of severe acute respiratory syndrome coronavirus (SARS) and Middle East respiratory syndrome coronavirus (MERS) epidemiological data also indicate a gender-based preference in disease consequences. The current review addresses the possible mechanisms responsible for higher COVID-19 mortality among male patients. The major underlying aspects that was looked into includes smoking, genetic factors, and the impact of reproductive hormones on immune systems and inflammatory responses. Detailed investigations of this gender disparity could provide insight into the development of patient tailored therapeutic approach which would be helpful in improving the poor outcomes of COVID-19. Graphical abstract.

Use of DPP4 inhibitors in Italy does not correlate with diabetes prevalence among COVID-19 deaths.

In a nationwide study of 3818 charts from patients with fatal COVID-19, we found that geographical differences in Dipeptidyl peptidase 4 (DPP4) inhibitors use did not correlate with diabetes prevalence among COVID-19 deaths, thus not supporting the hypothesis of a clinically relevant involvement of DPP4 inhibition in COVID-19 development and progression.

Prevalence of comorbidities among individuals with COVID-19: A rapid review of current literature.

INTRODUCTION: On February 11, 2020 WHO designated the name "COVID-19" for the disease caused by "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2), a novel virus that quickly turned into a global pandemic. Risks associated with acquiring the virus have been found to most significantly vary by age and presence of underlying comorbidity. In this rapid literature review we explore the prevalence of comorbidities and associated adverse outcomes among individuals with COVID-19 and summarize our findings based on information available as of May 15, 2020. METHODS: A comprehensive systematic search was performed on PubMed, Medline, Scopus, Embase, and Google Scholar to find articles published until May 15, 2020. All relevant articles providing information on PCR tested COVID-19 positive patient population with clinical characteristics and epidemiological information were selected for review and analysis. RESULTS: A total of 27 articles consisting of 22,753 patient cases from major epicenters worldwide were included in the study. Major comorbidities seen in overall population were CVD (8.9%), HTN (27.4%), Diabetes (17.4%), COPD (7.5%), Cancer (3.5%), CKD (2.6%), and other (15.5%). Major comorbidity specific to countries included in the study were China (HTN 39.5%), South Korea (CVD 25.6%), Italy (HTN 35.9%), USA (HTN 38.9%), Mexico, (Other 42.3%), UK (HTN 27.8%), Iran (Diabetes 35.0%). Within fatal cases, an estimated 84.1% had presence of one or more comorbidity. Subgroup analysis of fatality association with having comorbidity had an estimated OR 0.83, CI [0.60-0.99], p<0.05. CONCLUSIONS: Based on our findings, hypertension followed by diabetes and cardiovascular diseases were the most common comorbidity seen in COVID-19 positive patients across major epicenters world-wide. Although having one or more comorbidity is linked to increased disease severity, no clear association was found between having these risk factors and increased risk of fatality.

Comparison of the clinical characteristics and outcomes of hospitalized adult COVID-19 and influenza patients - a prospective observational study.

BACKGROUND: We compared the clinical characteristics, findings, and outcomes of hospitalized patients with coronavirus disease 2019 (COVID-19) or influenza to detect relevant differences. METHODS: From December 2019 to April 2020, we recruited all eligible hospitalized adults with respiratory infection to a prospective observational study at a tertiary care hospital in Finland. Influenza and SARS-CoV-2 infections were confirmed by RT-PCR. Follow-up lasted for 3 months from admission. RESULTS: We included 61 patients, of whom 28 were COVID-19 and 33 influenza patients with median ages of 53 and 56 years. Majority of both COVID-19 and influenza patients were men (61% vs. 67%) and had at least one comorbidity (68% vs. 85%). Pulmonary diseases and current smoking were less common among COVID-19 than influenza patients (5 [18%] vs. 15 [45%], p=.03 and 1 [4%] vs. 10 [30%], p=.008). In chest X-ray at admission, ground-glass opacities (GGOs) and consolidations were more frequent among COVID-19 than influenza patients (19 [68%] and 7 [21%], p<.001). Severe disease and intensive care unit (ICU) admission occurred more often among COVID-19 than influenza patients (26 [93%] vs. 19 [58%], p=.003 and 8 [29%] vs. 2 [6%], p=.034). COVID-19 patients were hospitalized longer than influenza patients (six days [IQR 4-21] vs. 3 [2-4], p<.001). CONCLUSIONS: Bilateral GGOs and consolidations in chest X-ray may help to differentiate COVID-19 from influenza. Hospitalized COVID-19 patients had more severe disease, required longer hospitalization and were admitted to ICU more often than influenza patients, which has important implications for public health policies.

The Urgent Need for Recommending Physical Activity for the Management of Diabetes During and Beyond COVID-19 Outbreak.

Diabetes is the second most prevalent non-communicable chronic diseases (NCDs) in patients with coronavirus disease 2019 (COVID-19) and is highly associated with increased incidence of disease severity and mortality. Individuals with diabetes and poor glycemic control have an even worse prognosis. Despite of the need/effectiveness of social distancing measures (i.e.: home confinement, quarantine and/or lockdown) during COVID-19 outbreak, preliminary findings showed an increase in negative behaviors during COVID-19 home confinement (i.e.: ~33.5% reduction in physical activity, ~28.6% (~3.10h) increase in sedentary behavior (i.e.: daily sitting, reclining and lying down time), and more unhealthy food consumption and meal pattern), which may have important clinical implications. For example, we estimated that this reduction in physical activity can increase the cases of type 2 diabetes (from ~7.2% to ~9.6%; ~11.1 million cases per year) and all-cause mortality (from ~9.4% to ~12.5%; ~1.7 million deaths per year) worldwide. Few weeks of reduction in physical activity levels result in deleterious effects on several cardiometabolic (i.e.: glycemic control, body composition, inflammatory cytokines, blood pressure, vascular function…) and functional parameters (i.e.: cardiorespiratory/muscle fitness, balance, agility…). In contrast, physical activity and exercise are important tools for preventing and treating diabetes and others NCDs. Home-based exercise programs are useful, safe and effective for the management of diabetes, and could be widely used during COVID-19 outbreak. In this context, there is an urgent need for recommending physical activity/exercise, during and beyond COVID-19 outbreak, for improving the management of diabetes, as well as to prevent the increase in global burden of COVID-19, diabetes and others NCDs.

Effects of underlying morbidities on the occurrence of deaths in COVID-19 patients: A systematic review and meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19), the most hectic pandemic of the era, is increasing exponentially and taking thousands of lives worldwide. This study aimed to assess the prevalence of pre-existing comorbidities among COVID-19 patients and their mortality risks with each category of pre-existing comorbidity. METHODS: To conduct this systematic review and meta-analysis, Medline, Web of Science, Scopus, and CINAHL databases were searched using pre-specified search strategies. Further searches were conducted using the reference list of the selected studies, renowned preprint servers (eg, medRxiv, bioRxiv, SSRN), and relevant journals' websites. Studies written in the English language included if those were conducted among COVID-19 patients with and without comorbidities and presented survivor vs non-survivor counts or hazard/odds of deaths or survivors with types of pre-existing comorbidities. Comorbidities reported in the selected studies were grouped into eight categories. The pooled likelihoods of deaths in each category were estimated using a fixed or random-effect model, based on the heterogeneity assessment. Publication bias was assessed by visual inspection of the funnel plot asymmetry and Egger's regression test. Trim and Fill method was used if there any publication bias was found. RESULTS: A total of 41 studies included in this study comprised of 27 670 samples. The most common pre-existing comorbidities in COVID-19 patients were hypertension (39.5%), cardiovascular disease (12.4%), and diabetes (25.2%). The higher likelihood of deaths was found among COVID-19 patients who had pre-existing cardiovascular diseases (odds ratio (OR) = 3.42, 95% confidence interval (CI) = 2.86-4.09), immune and metabolic disorders (OR = 2.46, 95% CI = 2.03-2.85), respiratory diseases (OR = 1.94, 95% CI = 1.72-2.19), cerebrovascular diseases (OR = 4.12, 95% CI = 3.04-5.58), any types of cancers (OR = 2.22, 95% CI = 1.63-3.03), renal (OR = 3.02, 95% CI = 2.60-3.51), and liver diseases (OR = 2.35, 95% CI = 1.50-3.69). CONCLUSIONS: This study provides evidence that COVID-19 patients with pre-existing comorbidities had a higher likelihood of death. These findings could potentially help health care providers to sort out the most susceptible COVID-19 patients by comorbidities, take precautionary measures during hospitalization, assess susceptibility to death, and prioritize their treatment, which could potentially reduce the number of fatalities in COVID-19.

Proinflammatory cytokines are associated with prolonged viral RNA shedding in COVID-19 patients.

Since December 2019, Coronavirus Disease 2019 (COVID-19) has emerged as a global pandemic. We aimed to investigate the clinical characteristics and analyzed the risk factors for prolonged viral RNA shedding. We retrospectively collected data from 112 hospitalized COVID-19 patients in a single center in Wuhan, China. Factors associated with prolonged viral RNA shedding (≥28 days) were investigated. Forty-nine (43.8%) patients had prolonged viral RNA shedding. Patients with prolonged viral shedding were older and had a higher rate of hypertension. Proinflammatory cytokines, including interleukin-2R (IL-2R) and tumor necrosis factor-α (TNF-α), were significantly elevated in patients with prolonged viral shedding. Multivariate analysis revealed that hypertension, older age, lymphopenia and elevated serum IL-2R were independent risk factors for prolonged viral shedding. This comprehensive investigation revealed the distinct characteristics between patients with or without prolonged viral RNA shedding. Hypertension, older age, lymphopenia and high levels of proinflammatory cytokines may be correlated with prolonged viral shedding.