Association of County-Level Social Vulnerability with Chronic Respiratory Diseases Mortality in the United States.

RATIONALE: Chronic respiratory diseases, the third leading cause of death worldwide, have been associated with significant morbidity, mortality, and increased economic burden, which make a profound impact on individuals and communities. However, limited research has delineated complex relationships between specific sociodemographic disparities and chronic respiratory disease outcomes among US counties. OBJECTIVE: To assess the association of county-level sociodemographic vulnerabilities with chronic respiratory diseases mortality in the US. METHODS: Chronic respiratory diseases mortality data among US counties for 2014-2018 was obtained from the Centers for Disease Control and Prevention, Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) database. Social Vulnerability Index (SVI), including subindices of Socioeconomic Status, Household Composition & Disability, Minority Status & Language, and Housing Type & Transportation, is a composite, percentile-based measure developed by the CDC to evaluate county-level sociodemographic vulnerabilities to disasters. We examined county-level sociodemographic characteristics from the SVI and classified the percentile rank into quartiles, with higher quartile indicating greater vulnerability. The associations between chronic respiratory diseases mortality and overall SVI, its four subindices, and each county characteristic were analyzed by negative binomial regression. RESULTS: From 2014 to 2018, the age-adjusted mortality per 1,000,000 population attributed to chronic lower respiratory disease (CLRD) was 406.4 (95% CI: 405.5-407.3); chronic obstructive pulmonary disease (COPD), 393.7 (392.8-394.6); Asthma, 10.0 (9.9-10.2); interstitial lung disease (ILD), 50.5 (50.1-50.8); idiopathic pulmonary fibrosis (IPF), 37.0 (36.7-37.3); and Sarcoidosis, 5.3 (5.2-5.4). Counties in the higher quartile of overall SVI were significantly associated with greater diseases mortality (CLRD, incidence rate ratios: 4th versus 1st quartile, 1.43 [95% CI: 1.39-1.48]; COPD, 1.44 [1.39-1.49]; Asthma, 2.06 [1.71-2.48]; ILD, 1.07 [1.02-1.13]; IPF, 1.14 [1.06-1.22]; Sarcoidosis, 2.01 [1.44-2.81]). Additionally, higher mortality was also found in counties in the higher quartile of each subindex and most sociodemographic characteristics. CONCLUSIONS: Chronic respiratory diseases mortalities were significantly associated with county-level sociodemographic determinants as measured by the SVI in the US. These findings suggested sociodemographic determinants may add a considerable barrier to establishing health equity. Multilevel public health strategies and clinical interventions addressing inequitable outcomes of chronic respiratory diseases should be developed and targeted on areas with greater social vulnerability and disadvantage.

Impact of Global Climate Change on Pulmonary Health: Susceptible and Vulnerable Populations.

As fossil fuel combustion continues to power the global economy, the rate of climate change is accelerating, causing severe respiratory health impacts and large disparities in the degree of human suffering. Hotter and drier climates lead to longer and more severe wildland fire seasons, impairing air quality around the globe. Hotter temperatures lead to higher levels of ozone, and particles, causing the exacerbation of chronic respiratory diseases and premature mortality. Longer pollen seasons and higher pollen levels provoke allergic airway diseases. In arid regions, accelerated land degradation and desertification are promoting dust pollution and impairing food production and nutritional content that are essential to respiratory health. Extreme weather events and flooding impede healthcare delivery and can lead to poor indoor air quality due to mold overgrowth. Climate and human activities that harm the environment and ecosystem may also affect the emergence and spread of viral infections including Severe Acute Respiratory Syndrome-related Coronavirus 2 (SARS-CoV-2) and associated morbidity and mortality exacerbated by air pollution. Children and elderly are more susceptible to the adverse health effects of climate change. Geographical and socioeconomic circumstances along with a decreased capacity to adapt, collectively enhance the vulnerability to adverse effects of climate change. Successful mitigation of anthropogenic climate change is dependent on the commitment of energy-intensive nations to manage greenhouse gas emissions, as well as, societal support and response to aggravating factors. This review focuses on the respiratory health impacts of global climate change, with an emphasis on susceptible and vulnerable populations and low- and middle- income countries.

Results From a Phase 4, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Repository Corticotropin Injection for the Treatment of Pulmonary Sarcoidosis.

INTRODUCTION: Long-term treatment of pulmonary sarcoidosis with glucocorticoids has been associated with toxicity and other adverse events, highlighting the need for alternative therapies. The goal of this study was to evaluate the efficacy and safety of repository corticotropin injection (RCI, Acthar® Gel) in patients with pulmonary sarcoidosis and to validate endpoints for use in future clinical trials. METHODS: In this multicenter, randomized, placebo-controlled trial, subjects received subcutaneous RCI (80 U) twice weekly or matching placebo through 24 weeks in a double-blind treatment phase, followed by an optional 24-week open-label extension. Efficacy was measured by glucocorticoid tapering, pulmonary function tests, chest imaging, patient-reported outcomes, and a novel sarcoidosis treatment score (STS). Safety was assessed by adverse events, physical examinations, vital signs, clinical laboratory abnormalities, and imaging. The study was terminated early due to low enrollment caused by the COVID-19 pandemic, thereby precluding statistical analysis. RESULTS: Fifty-five subjects were randomized to receive either RCI (n = 27) or placebo (n = 28). Mean STS at week 24 showed greater improvement with RCI (1.4) compared with placebo (0.7). At week 48, those who remained on RCI had an STS of 1.8 compared with 0.9 in those who switched from placebo to RCI. More subjects in the RCI group discontinued glucocorticoids at week 24 compared to the placebo group. Glucocorticoid discontinuation was comparable at week 48 for those who switched from placebo to RCI and those who continued RCI. Similar trends in favor of RCI over placebo were observed with the other efficacy endpoints. No new or unexpected safety signals were identified. CONCLUSIONS: RCI was safe and well tolerated, with trends in efficacy data suggesting greater improvement with RCI compared to placebo in patients receiving standard-of-care therapy for pulmonary sarcoidosis. The study also provided validation of efficacy endpoints that may be used in larger trials for pulmonary sarcoidosis. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03320070.

Pulmonary sarcoidosis is a disease characterized by inflammation of the lungs. Standard treatments include glucocorticoids, which may have harmful side effects. This clinical trial investigated whether repository corticotropin injection (RCI, Acthar^® Gel) was safe and effective in patients who were already taking glucocorticoids to treat pulmonary sarcoidosis. Patients were randomly assigned to be in one of two treatment groups: RCI or placebo. In the first 24 weeks of the study, 27 patients were injected with RCI twice weekly, while 28 patients were injected with an inactive substance (placebo). Forty-seven patients continued into an optional phase of the study for an additional 24 weeks in which all patients received RCI twice weekly. A sarcoidosis treatment score and assessments of lung health, general health, and fatigue were used to determine whether RCI was effective. These assessments showed greater improvements with RCI compared to placebo. Patients who switched from placebo to RCI showed similar improvements to those who remained on RCI throughout the entire study. Patients receiving RCI were able to discontinue their use of glucocorticoids more quickly than those taking placebo, thus helping them to avoid the harmful side effects of the glucocorticoids. Side effects for RCI were mostly mild or moderate, and no new or unexpected safety concerns for RCI were seen throughout the study.

COVID-19 and Acute Kidney Injury: A Systematic Review.

Introduction: Acute kidney injury (AKI) has been associated with an increased mortality rate among hospitalized patients with Coronavirus disease 2019 (COVID-19). The current review aimed to evaluate the symptoms, complications, and treatments performed to manage AKI in patients with COVID-19. Methods: We searched PubMed/Medline, Web of Science, and Embase for the relevant scientific literature published up to February 1, 2022. The following keywords were used: "COVID-19", "SARS-CoV-2", and "Acute kidney injury". Results: Forty-four studies with a total number of 114 COVID-19 patients with AKI (Mean age: 53.6 years) were included in our systematic review. The most common comorbidities in patients with COVID-19 suffering from AKI were the history of diabetes, hypertension, and hyperlipidemia. Twelve out of the 44 included studies reported a history of chronic kidney disease (CKD) in this group of patients. Focal segmental glomerulosclerosis (FSGS) and acute tubular necrosis (ATN) were the most common pathological evidence. The average length of hospital stay was 19 days, and the average duration of need for mechanical ventilation was 3 days. Conclusions: The current systematic review shows that AKI frequently complicates the course of COVID-19 hospitalizations and is associated with increased severity of illness, prolonged duration of hospitalization, and poor prognosis. Given the extent of the adverse impact of AKI, early detection of comorbidities and renal complications is essential to improve the outcomes of COVID-19 patients.

Predicting COVID-19 cases using SARS-CoV-2 RNA in air, surface swab and wastewater samples.

Genomic footprints of pathogens shed by infected individuals can be traced in environmental samples, which can serve as a noninvasive method of infectious disease surveillance. The research evaluates the efficacy of environmental monitoring of SARS-CoV-2 RNA in air, surface swabs and wastewater to predict COVID-19 cases. Using a prospective experimental design, air, surface swabs, and wastewater samples were collected from a college dormitory housing roughly 500 students from March to May 2021 at the University of Miami, Coral Gables, FL. Students were randomly screened for COVID-19 during the study period. SARS-CoV-2 concentration in environmental samples was quantified using Volcano 2nd Generation-qPCR. Descriptive analyses were conducted to examine the associations between time-lagged SARS-CoV-2 in environmental samples and COVID-19 cases. SARS-CoV-2 was detected in air, surface swab and wastewater samples on 52 (63.4 %), 40 (50.0 %) and 57 (68.6 %) days, respectively. On 19 (24 %) of 78 days SARS-CoV-2 was detected in all three sample types. COVID-19 cases were reported on 11 days during the study period and SARS-CoV-2 was also detected two days before the case diagnosis on all 11 (100 %), 9 (81.8 %) and 8 (72.7 %) days in air, surface swab and wastewater samples, respectively. SARS-CoV-2 detection in environmental samples was an indicator of the presence of local COVID-19 cases and a 3-day lead indicator for a potential outbreak at the dormitory building scale. Proactive environmental surveillance of SARS-CoV-2 or other pathogens in multiple environmental media has potential to guide targeted measures to contain and/or mitigate infectious disease outbreaks within communities.

Predicting COVID-19 cases using SARS-CoV-2 RNA in air, surface swab and wastewater samples

Genomic footprints of pathogens shed by infected individuals can be traced in environmental samples, which can serve as a noninvasive method of infectious disease surveillance. The research evaluates the efficacy of environmental monitoring of SARS-CoV-2 RNA in air, surface swabs and wastewater to predict COVID-19 cases. Using a prospective experimental design, air, surface swabs, and wastewater samples were collected from a college dormitory housing roughly 500 students from March to May 2021 at the University of Miami, Coral Gables, FL. Students were randomly screened for COVID-19 during the study period. SARS-CoV-2 concentration in environmental samples was quantified using Volcano 2nd Generation-qPCR. Descriptive analyses were conducted to examine the associations between time-lagged SARS-CoV-2 in environmental samples and COVID-19 cases. SARS-CoV-2 was detected in air, surface swab and wastewater samples on 52 (63.4 %), 40 (50.0 %) and 57 (68.6 %) days, respectively. On 19 (24 %) of 78 days SARS-CoV-2 was detected in all three sample types. COVID-19 cases were reported on 11 days during the study period and SARS-CoV-2 was also detected two days before the case diagnosis on all 11 (100 %), 9 (81.8 %) and 8 (72.7 %) days in air, surface swab and wastewater samples, respectively. SARS-CoV-2 detection in environmental samples was an indicator of the presence of local COVID-19 cases and a 3-day lead indicator for a potential outbreak at the dormitory building scale. Proactive environmental surveillance of SARS-CoV-2 or other pathogens in multiple environmental media has potential to guide targeted measures to contain and/or mitigate infectious disease outbreaks within communities. Graphical Unlabelled Image

Association of COVID-19 Case-Fatality Rate With State Health Disparity in the United States.

Background: The disproportionate burden of COVID-19 pandemic has become a major concern in the United States (US), but the association between COVID-19 case-fatality rate (CFR) and factors influencing health outcomes at a state level has not been evaluated. Methods: We calculated COVID-19 CFR for three different waves using COVID Data Tracker from the Centers for Disease Control and Prevention. America's Health Rankings assesses the factors that influence health outcomes to determine state's health rankings. The association between COVID-19 CFR and state health disparities was analyzed by linear regression. Results: States with better rankings of Physical Environment were associated with lower CFR for the 1st wave (ß = 0.06%, R2 = 0.170, P = 0.003). There was a paradoxical association between the 2nd wave CFR and Clinical Care (ß = -0.04%, R2 = 0.112, P = 0.017) and Overall health rankings (ß = -0.03%, R2 = 0.096, P = 0.029). For the 3rd wave, states with better rankings of Overall health factors (ß = 0.01%, R2 = 0.179, P = 0.002), Social & Economic Factors (ß = 0.01%, R2 = 0.176, P = 0.002), Behaviors (ß = 0.01%, R2 = 0.204, P < 0.001), and Health Outcomes (ß = 0.01%, R2 = 0.163, P = 0.004) were associated with lower CFR. COVID-19 vaccination coverage was also associated with state health rankings (at least one dose: ß = -0.13%, R2 = 0.305, P < 0.001; fully vaccinated: ß = -0.06%, R2 = 0.120, P = 0.014). Conclusions: These findings suggested targeted public health interventions and mitigation strategies addressing health disparities are essential to improve inequitable outcomes of COVID-19 in the US.

COVID-19 in patients with and without acute kidney injury.

BACKGROUND AND OBJECTIVE: SARS-CoV-2 as the newest member of Beta-Coronaviruses can cause a complicated disease called COVID-19. This virus is able to penetrate a broad range of human cells, such as liver, heart, and kidney cells via ACE2-associated endocytosis. Heart involvement can result in kidney injuries; it is now testified that kidney congestion occurs following the cardio-renal syndrome. Acute Kidney Injury is one of the most critical damages to the kidney in a wide range of COVID-19-caused kidney injuries (which includes proteinuria, hematuria, etc.). Examination of AKI risk factors in COVID-19 patients can assist physicians to prevent its incidence. The final aim of this systematic review was to collate the condition and risk factors of AKI and non-AKI COVID-19 patients and to investigate AKI incidence in high-risk patients. METHOD: A complete and comprehensive survey was performed by reviewing original articles and case reports indexed in various databases such as PubMed/Medline, Embase, and WoS to find appropriate articles. The eligible articles then were selected by two authors and entered into the evaluation process. This systematic review conforms PRISMA statement. RESULTS: After searching for potentially relevant articles, 14 out of the initial 463 articles from 6 countries were selected and evaluated. All of eligible articles have investigated the rate of AKI incidence and its physio-pathological consequences in COVID-19 patients in all conditions (not only patients in critical condition). First, the initial differences between AKI and non-AKI patients were compared. As an instance, our study revealed that mean of White Blood cells (WBC) was much higher in AKI patients which can be responsible for the severe conditions. Then, other variations like differences in laboratory and imaging findings were compared between these two groups. Our outcomes demonstrated that the presence of diabetes mellitus (DM), hypertension (HTN), and male sex can be three significant risk factors in AKI incidence in COVID-19 patients. Fatality rate and treatment methods were also compared among these two groups. CONCLUSION: As one of kidney damages, AKI can worsen COVID-19 patients' status by causing conditions such as acidosis. Our study shows the common symptoms in AKI COVID-19 patients were fever, cough, and malaise. The results of our study can help physicians to arrange COVID-19 with AKI patients' treatment strategy precisely (Tab. 8, Fig. 1, Ref. 48).

Immunomodulatory LncRNA on antisense strand of ICAM-1 augments SARS-CoV-2 infection-associated airway mucoinflammatory phenotype.

Noncoding RNAs are important regulators of mucoinflammatory response, but little is known about the contribution of airway long noncoding RNAs (lncRNAs) in COVID-19. RNA-seq analysis showed a more than 4-fold increased expression of IL-6, ICAM-1, CXCL-8, and SCGB1A1 inflammatory factors; MUC5AC and MUC5B mucins; and SPDEF, FOXA3, and FOXJ1 transcription factors in COVID-19 patient nasal samples compared with uninfected controls. A lncRNA on antisense strand to ICAM-1 or LASI was induced 2-fold in COVID-19 patients, and its expression was directly correlated with viral loads. A SARS-CoV-2-infected 3D-airway model largely recapitulated these clinical findings. RNA microscopy and molecular modeling indicated a possible interaction between viral RNA and LASI lncRNA. Notably, blocking LASI lncRNA reduced the SARS-CoV-2 replication and suppressed MUC5AC mucin levels and associated inflammation, and select LASI-dependent miRNAs (e.g., let-7b-5p and miR-200a-5p) were implicated. Thus, LASI lncRNA represents an essential facilitator of SARS-CoV-2 infection and associated airway mucoinflammatory response.

SARS-CoV-2 cell entry beyond the ACE2 receptor.

BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) is known as the major viral entry site for SARS-CoV-2. However, viral tissue tropism and high rate of infectivity do not directly correspond with the level of ACE2 expression in the organs. It may suggest involvement of other receptors or accessory membrane proteins in SARSCoV-2 cell entry. METHODS AND RESULTS: A systematic search was carried out in PubMed/Medline, EMBASE, and Cochrane Library for studies reporting SARS-CoV-2 cell entry. We used a group of the MeSH terms including "cell entry", "surface receptor", "ACE2", and "SARS-CoV-2". We reviewed all selected papers published in English up to end of February 2022. We found several receptors or auxiliary membrane proteins (including CD147, NRP-1, CD26, AGTR2, Band3, KREMEN1, ASGR1, ANP, TMEM30A, CLEC4G, and LDLRAD3) along with ACE2 that facilitate virus entry and transmission. Expression of Band3 protein on the surface of erythrocytes and evidence of binding with S protein of SARS-CoV-2 may explain asymptomatic hypoxemia during COVID19 infection. The variants of SARS-CoV-2 including the B.1.1.7 (Alpha), B.1.617.1 (Kappa), B.1.617.2 (Delta), B.1.617.2+ (Delta+), and B.1.1.529 (Omicron) may have different potency to bond with these receptors. CONCLUSIONS: The high rate of infectivity of SARS-CoV-2 may be due to its ability to enter the host cell through a group of cell surface receptors. These receptors are potential targets to develop novel therapeutic agents for SARS-CoV-2.

Diagnostic Accuracy of Rapid Antigen Tests for COVID-19 Detection: A Systematic Review With Meta-analysis.

Introduction: Reverse transcription-polymerase chain reaction (RT-PCR) to detect SARS-CoV-2 is time-consuming and sometimes not feasible in developing nations. Rapid antigen test (RAT) could decrease the load of diagnosis. However, the efficacy of RAT is yet to be investigated comprehensively. Thus, the current systematic review and meta-analysis were conducted to evaluate the diagnostic accuracy of RAT against RT-PCR methods as the reference standard. Methods: We searched the MEDLINE/Pubmed and Embase databases for the relevant records. The QUADAS-2 tool was used to assess the quality of the studies. Diagnostic accuracy measures [i.e., sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratios (PLR), negative likelihood ratios (NLR), and the area under the curve (AUC)] were pooled with a random-effects model. All statistical analyses were performed with Meta-DiSc (Version 1.4, Cochrane Colloquium, Barcelona, Spain). Results: After reviewing retrieved records, we identified 60 studies that met the inclusion criteria. The pooled sensitivity and specificity of the rapid antigen tests against the reference test (the real-time PCR) were 69% (95% CI: 68-70) and 99% (95% CI: 99-99). The PLR, NLR, DOR and the AUC estimates were found to be 72 (95% CI: 44-119), 0.30 (95% CI: 0.26-0.36), 316 (95% CI: 167-590) and 97%, respectively. Conclusion: The present study indicated that using RAT kits is primarily recommended for the early detection of patients suspected of having COVID-19, particularly in countries with limited resources and laboratory equipment. However, the negative RAT samples may need to be confirmed using molecular tests, mainly when the symptoms of COVID-19 are present.

Effect of Androgen Suppression on Clinical Outcomes in Hospitalized Men With COVID-19: The HITCH Randomized Clinical Trial.

Importance: SARS-CoV-2 entry requires the TMPRSS2 cell surface protease. Antiandrogen therapies reduce expression of TMPRSS2. Objective: To determine if temporary androgen suppression induced by degarelix improves clinical outcomes of inpatients hospitalized with COVID-19. Design, Setting, and Participants: The Hormonal Intervention for the Treatment in Veterans With COVID-19 Requiring Hospitalization (HITCH) phase 2, placebo-controlled, double-blind, randomized clinical trial compared efficacy of degarelix plus standard care vs placebo plus standard care on clinical outcomes in men hospitalized with COVID-19 but not requiring invasive mechanical ventilation. Inpatients were enrolled at 14 Department of Veterans Affairs hospitals from July 22, 2020, to April 8, 2021. Data were analyzed from August 9 to October 15, 2021. Interventions: Patients stratified by age, history of hypertension, and disease severity were centrally randomized 2:1 to degarelix, (1-time subcutaneous dose of 240 mg) or a saline placebo. Standard care included but was not limited to supplemental oxygen, antibiotics, vasopressor support, peritoneal dialysis or hemodialysis, intravenous fluids, remdesivir, convalescent plasma, and dexamethasone. Main Outcomes and Measures: The composite primary end point was mortality, ongoing need for hospitalization, or requirement for mechanical ventilation at day 15 after randomization. Secondary end points were time to clinical improvement, inpatient mortality, length of hospitalization, duration of mechanical ventilation, time to achieve a temperature within reference range, maximum severity of COVID-19, and the composite end point at 30 days. Results: The trial was stopped for futility after the planned interim analysis, at which time there were 96 evaluable patients, including 62 patients randomized to the degarelix group and 34 patients in the placebo group, out of 198 initially planned. The median (range) age was 70.5 (48-85) years. Common comorbidities included chronic obstructive pulmonary disorder (15 patients [15.6%]), hypertension (75 patients [78.1%]), cardiovascular disease (27 patients [28.1%]), asthma (12 patients [12.5%]), diabetes (49 patients [51.0%]), and chronic respiratory failure requiring supplemental oxygen at baseline prior to COVID-19 (9 patients [9.4%]). For the primary end point, there was no significant difference between the degarelix and placebo groups (19 patients [30.6%] vs 9 patients [26.5%]; P = .67). Similarly, no differences were observed between degarelix and placebo groups in any secondary end points, including inpatient mortality (11 patients [17.7%] vs 6 patients [17.6%]) or all-cause mortality (11 patients [17.7%] vs 7 patents [20.6%]). There were no differences between degarelix and placebo groups in the overall rates of adverse events (13 patients [21.0%] vs 8 patients [23.5%) and serious adverse events (19 patients [30.6%] vs 13 patients [32.4%]), nor unexpected safety concerns. Conclusions and Relevance: In this randomized clinical trial of androgen suppression vs placebo and usual care for men hospitalized with COVID-19, degarelix did not result in amelioration of COVID-19 severity. Trial Registration: ClinicalTrials.gov Identifier: NCT04397718.

Diagnostic, Prognostic, and Therapeutic Roles of Gut Microbiota in COVID-19: A Comprehensive Systematic Review.

Introduction: The Coronavirus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2) emerged in late December 2019. Considering the important role of gut microbiota in maturation, regulation, and induction of the immune system and subsequent inflammatory processes, it seems that evaluating the composition of gut microbiota in COVID-19 patients compared with healthy individuals may have potential value as a diagnostic and/or prognostic biomarker for the disease. Also, therapeutic interventions affecting gut microbial flora may open new horizons in the treatment of COVID-19 patients and accelerating their recovery. Methods: A systematic search was conducted for relevant studies published from December 2019 to December 2021 using Pubmed/Medline, Embase, and Scopus. Articles containing the following keywords in titles or abstracts were selected: "SARS-CoV-2" or "COVID-19" or "Coronavirus Disease 19" and "gastrointestinal microbes" or "dysbiosis" or "gut microbiota" or "gut bacteria" or "gut microbes" or "gastrointestinal microbiota". Results: Out of 1,668 studies, 22 articles fulfilled the inclusion criteria and a total of 1,255 confirmed COVID-19 patients were examined. All included studies showed a significant association between COVID-19 and gut microbiota dysbiosis. The most alteration in bacterial composition of COVID-19 patients was depletion in genera Ruminococcus, Alistipes, Eubacterium, Bifidobacterium, Faecalibacterium, Roseburia, Fusicathenibacter, and Blautia and enrichment of Eggerthella, Bacteroides, Actinomyces, Clostridium, Streptococcus, Rothia, and Collinsella. Also, some gut microbiome alterations were associated with COVID-19 severity and poor prognosis including the increment of Bacteroides, Parabacteroides, Clostridium, Bifidobacterium, Ruminococcus, Campylobacter, Rothia, Corynebacterium, Megasphaera, Enterococcus, and Aspergillus spp. and the decrement of Roseburia, Eubacterium, Lachnospira, Faecalibacterium, and the Firmicutes/Bacteroidetes ratio. Conclusion: Our study showed a significant change of gut microbiome composition in COVID-19 patients compared with healthy individuals. This great extent of impact has proposed the gut microbiota as a potential diagnostic, prognostic, and therapeutic strategy for COVID-19. There is much evidence about this issue, and it is expected to be increased in near future.

Immunomodulatory agents for COVID-19 treatment: possible mechanism of action and immunopathology features.

The novel coronavirus pandemic has emerged as one of the significant medical-health challenges of the current century. The World Health Organization has named this new virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the first detection of SARS-CoV-2 in November 2019 in Wuhan, China, physicians, researchers, and others have made it their top priority to find drugs and cures that can effectively treat patients and reduce mortality rates. The symptoms of Coronavirus Disease 2019 (COVID-19) include fever, dry cough, body aches, and anosmia. Various therapeutic compounds have been investigated and applied to mitigate the symptoms in COVID-19 patients and cure the disease. Degenerative virus analyses of the infection incidence and COVID-19 have demonstrated that SARS-CoV-2 penetrates the pulmonary alveoli's endothelial cells through Angiotensin-Converting Enzyme 2 (ACE2) receptors on the membrane, stimulates various signaling pathways and causes excessive secretion of cytokines. The continuous triggering of the innate and acquired immune system, as well as the overproduction of pro-inflammatory factors, cause a severe condition in the COVID-19 patients, which is called "cytokine storm". It can lead to acute respiratory distress syndrome (ARDS) in critical patients. Severe and critical COVID-19 cases demand oxygen therapy and mechanical ventilator support. Various drugs, including immunomodulatory and immunosuppressive agents (e.g., monoclonal antibodies (mAbs) and interleukin antagonists) have been utilized in clinical trials. However, the studies and clinical trials have documented diverging findings, which seem to be due to the differences in these drugs' possible mechanisms of action. These drugs' mechanism of action generally includes suppressing or modulating the immune system, preventing the development of cytokine storm via various signaling pathways, and enhancing the blood vessels' diameter in the lungs. In this review article, multiple medications from different drug families are discussed, and their possible mechanisms of action are also described.

Machine-learning-based COVID-19 mortality prediction model and identification of patients at low and high risk of dying.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused by the SARS-Cov2 virus has become the greatest health and controversial issue for worldwide nations. It is associated with different clinical manifestations and a high mortality rate. Predicting mortality and identifying outcome predictors are crucial for COVID patients who are critically ill. Multivariate and machine learning methods may be used for developing prediction models and reduce the complexity of clinical phenotypes. METHODS: Multivariate predictive analysis was applied to 108 out of 250 clinical features, comorbidities, and blood markers captured at the admission time from a hospitalized cohort of patients (N = 250) with COVID-19. Inspired modification of partial least square (SIMPLS)-based model was developed to predict hospital mortality. Prediction accuracy was randomly assigned to training and validation sets. Predictive partition analysis was performed to obtain cutting value for either continuous or categorical variables. Latent class analysis (LCA) was carried to cluster the patients with COVID-19 to identify low- and high-risk patients. Principal component analysis and LCA were used to find a subgroup of survivors that tends to die. RESULTS: SIMPLS-based model was able to predict hospital mortality in patients with COVID-19 with moderate predictive power (Q2 = 0.24) and high accuracy (AUC > 0.85) through separating non-survivors from survivors developed using training and validation sets. This model was obtained by the 18 clinical and comorbidities predictors and 3 blood biochemical markers. Coronary artery disease, diabetes, Altered Mental Status, age > 65, and dementia were the topmost differentiating mortality predictors. CRP, prothrombin, and lactate were the most differentiating biochemical markers in the mortality prediction model. Clustering analysis identified high- and low-risk patients among COVID-19 survivors. CONCLUSIONS: An accurate COVID-19 mortality prediction model among hospitalized patients based on the clinical features and comorbidities may play a beneficial role in the clinical setting to better management of patients with COVID-19. The current study revealed the application of machine-learning-based approaches to predict hospital mortality in patients with COVID-19 and identification of most important predictors from clinical, comorbidities and blood biochemical variables as well as recognizing high- and low-risk COVID-19 survivors.

Drug-Induced Liver Injury in COVID-19 Patients: A Systematic Review.

Introduction: The severity of COVID-19 may be correlated with the risk of liver injury development. An increasing number of studies indicate that degrees of hepatotoxicity has been associated with using some medications in the management of COVID-19 patients. However, limited studies had systematically investigated the evidence of drug-induced liver injury (DILI) in COVID-19 patients. Thus, this study aimed to examine DILI in COVID-19 patients. Methods: A systematic search was carried out in PubMed/Medline, EMBASE, and Web of Science up to December 30, 2020. Search items included "SARS-CoV-2", "Coronavirus," COVID-19, and liver injury. Results: We included 22 related articles. Among included studies, there was five case report, five case series, four randomizes control trial (RCT), seven cohort studies, and one cross-sectional study. The drugs included in this systematic review were remdesivir, favipiravir, tocilizumab, hydroxychloroquine, and lopinavir/ritonavir. Among included studies, some studies revealed a direct role of drugs, while others couldn't certainly confirm that the liver injury was due to SARS-CoV-2 itself or administration of medications. However, a significant number of studies reported that liver injury could be attributable to drug administration. Discussion: Liver injury in COVID-19 patients could be caused by the virus itself or the administration of some types of drug. Intensive liver function monitoring should be considered for patients, especially patients who are treated with drugs such as remdesivir, lopinavir/ritonavir, and tocilizumab.

COVID-19 and cause of pregnancy loss during the pandemic: A systematic review.

INTRODUCTION: The association between Coronavirus Disease 2019 (COVID-19) and abortion has been debated since the beginning of the COVID-19 pandemic. We aimed to conduct this systematic review to understand better the potential effects of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) on fetal loss in infected mothers presented with abortion following this infection. METHODS: We included articles published in PubMed/Medline, Web of Science, clinicaltrials.gov, and Embase databases in 2019 and 2020 through a comprehensive search via appropriate keywords, including COVID-19 and abortion synonyms. All studies with the abortion data in COVID-19 confirmed pregnant females were collected. RESULTS: Out of 208 potentially relevant articles, 11 articles were eligible to include in the systematic review. The included reports were published because of the following reasons: (1) First-trimester miscarriage; (2) Late miscarriage; (3) complication of COVID-19 infection in pregnancy; (4) COVID-19 disease in artificial pregnancy. First-trimester abortion was found in 5 studies, and second-trimester abortion in 7 studies. Two patients acquired infection during the hospital stay while they were referred for abortion. Reports related to abortion in pregnant females with COVID-19 show that most miscarriages due to COVID-19 in the first trimester were due to placental insufficiency. CONCLUSIONS: There is an increased risk of abortion in mothers with a positive test result of SARS-CoV-2, which several case reports and case series have identified during the pandemic. Placental inflammation during the viral infection may result in fetal growth retardation and induce abortion. There has not been any consistent evidence of vertical transmission of the virus from mother to fetus, which requires further investigation.

COVID-19 and Cardiomyopathy: A Systematic Review.

Background: Cardiomyopathies (CMPs) due to myocytes involvement are among the leading causes of sudden adolescent death and heart failure. During the COVID-19 pandemic, there are limited data available on cardiac complications in patients with COVID-19, leading to severe outcomes. Methods: We conducted a systematic search in Pubmed/Medline, Web of Science, and Embase databases up to August 2020, for all relevant studies about COVID-19 and CMPs. Results: A total of 29 articles with a total number of 1460 patients were included. Hypertension, diabetes, obesity, hyperlipidemia, and ischemic heart disease were the most reported comorbidities among patients with COVID-19 and cardiomyopathy. In the laboratory findings, 21.47% of patients had increased levels of troponin. Raised D-dimer levels were also reported in all of the patients. Echocardiographic results revealed mild, moderate, and severe Left Ventricular (LV) dysfunction present in 17.13, 11.87, and 10% of patients, respectively. Conclusions: Cardiac injury and CMPs were common conditions in patients with COVID-19. Therefore, it is suggested that cardiac damage be considered in managing patients with COVID-19.