Prognosis Of Coronavirus Disease 2019 Research Articles

Identification of novel drug targets for the risk and prognosis of COVID-19.

BackgroundSince the epidemic continues, there is a pressing need to improve our understanding of coronavirus disease 2019 (COVID-19). Mendelian randomization (MR) studies provide us with a method to explore the causality between circulating proteins and COVID-19 susceptibility and severity. We aim to find new perspectives on the pathological mechanism of the disease and possible drug targets for treatment based on this study.MethodsWe conducted a phenome-wide MR study to prioritize circulating proteins causally associated with COVID-19 susceptibility, which was defined as “patients tested positive for COVID-19 vs. population controls”, and severity, which was defined as “patients hospitalized with COVID-19 vs. population controls”. And we repeated the analysis for different definition of COVID-19 susceptibility, severity and control groups.ResultsAssociation of three circulating proteins with COVID-19 susceptibility and severity were demonstrated via our study. C-C motif chemokine 4 (OR =1.887, 95% CI: 1.608–2.165, P=8.04×10−6) and 2'-5'-oligoadenylate synthase 1 (OR =0.511, 95% CI: 0.266–0.757, P=8.51×10−8) were found respectively positively and negatively correlated with increased COVID-19 severity. Tissue factor, contrary to previous studies, was found associated with decreased COVID-19 susceptibility (OR =0.667, 95% CI: 0.484–0.850, P=1.47×10−5) and decreased COVID-19 severity (OR =0.459, 95% CI: 0.132–0.786, P=3.01×10−6).ConclusionsGenetic evidence supports C-C motif chemokine 4 as a risk factor for COVID-19 severity, and 2'-5'-oligoadenylate synthase 1 as a protective factor for COVID-19 severity. The causal association between tissue factor and COVID-19 is contrary to the previous studies, needing further analyses. Further research is warranted to assess the viability of C-C motif chemokine 4 and 2'-5'-oligoadenylate synthase 1 as well as their downstream pathways as drug targets for anti-inflammatory and anti-virus treatment in severe cases.

Assessment of some Physiological Biomarkers in COVID-19 Patients in Thi-Qar, Iraq.

It is believed that many biomarkers and factors could be linked to the prognosis of coronavirus disease 2019 (COVID-19). Therefore, this study aimed to evaluate the association of lactate dehydrogenase (LDH), D-Dimer, vitamin D, and ferritin statuses with the prognosis of COVID-19; moreover, it was attempted to investigate its prevalence according to age, employment status, body mass index (BMI), and place of residency in a population sample of hospitalized patients in Thi-Qar, Iraq. This study evaluated 200 COVID-19 patients and 100 controls. The BMI of all individuals was calculated, and such demographic characteristics as age, gender, place of residency, and occupational status were collected from all participants. Blood samples were taken and used to estimate D-Dimer, LDH, vitamin D, ferritin, oxygen, and pulse rate. The mean age of the patients approached the fifth decade, and 72% of the cases were more than 40 years of age. In addition, 60% of the patients were living in the countryside, and 52% of the participants were employed, compared to only 8% of the cases who were students. The BMI of the patients was obtained at 31.44±10.2 kg/m2; accordingly, 47% and 40% of the cases were obese and overweight, respectively, compared to only 12% of the patients who had normal weight (P˂0.05). There were significantly lower vitamin D levels in the patients; however, the concentrations of LDH, serum ferritin, and D-Dimer were significantly higher in the patients, compared to the control group (P˂0.05). Not only age and body weight but also employment status and place of residency maybe also the important risk factors for COVID-19 distribution. LDH, D-dimer, vitamin D, and ferritin statuses could be used as good biomarkers for this disease and its severity.

Nazal Polipli Hastalarda COVID-19 İnsidansının ve Prognozunun Değerlendirilmesi

Objective: Coronavirus disease 2019 (COVID-19) is a global pandemic infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Type 2 immune response accompanied by type 2 cytokines such as IL-4, IL-5, IL-13, and eosinophilic inflammation, may have a potential protective effect against COVID-19 in chronic rhinosinusitis patients with nasal polyps (CRS + P). In the study, it was aimed to investigation the prevalence and prognosis of COVID-19 in chronic rhinosinusitis patients with nasal polyps (CRS + P). Materials and Methods: Patients between the ages of 15-65 operated for CRS + P and were compared with the control group in terms of incidence and disease severity. Results: Covid RT-PCR test was positive in 5.04% of CRS + P patients. This rate was 8.96% in the control group, and the difference between both groups was statistically significant. When the two groups were compared in terms of disease severity, no significant difference was found. Conclusions: The incidence of COVID-19 was lower in patients with CRS + P. However, further prospective studies are needed to research the relationship between nasal polyp and COVID-19.

Multiple sclerosis in the era of COVID-19: disease course, DMTs and SARS-CoV2 vaccinations.

As of January 21st 2022, over 340 million are confirmed cases of coronavirus disease 2019 (COVID-19), including nearly 5.6 million deaths. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is neurotropic and affects the neural parenchyma through direct viral invasion from the nasal mucosa and postinfectious cytokine storm. Further challenges of SARS-CoV-2 infection are nowadays linked to variants of concern. Multiple sclerosis is an inflammatory and progressive degenerative disorder of the central nervous system commonly affecting young adults and potentially generating irreversible disability. Since the beginning of the SARS-CoV-2 pandemic, people with multiple sclerosis (pwMS) have been considered 'extra' vulnerable because of the immune-mediated nature of the disease, the disability status, and the immunomodulatory therapies potentially increasing the risk for viral infection. Today multiple sclerosis neurologists are faced with several challenges in the management of pwMS to both prevent SARS-CoV-2 infection and protection from disease worsening. We aimed to highlight today's most relevant facts about the complex management of pwMS in the COVID-19 era. The incidence of COVID-19 among pwMS does not differ from the general population. The prognosis of COVID-19 among pwMS is driven by older age, male sex, nonambulatory status, comorbidity as in the general population, as well as by corticosteroid treatment and B-cell depleting agents which decrease seropositivity from SARS-CoV-2 infection and immune responses to SARS-CoV-2 vaccination. Disease modifying treatments (DMTs) should be regularly continued in relation to SARS-CoV-2 vaccination, but an ad hoc timing is required with B-cell depleting agents. SARS-CoV-2 vaccination is recommended in pwMS with willingness improving through health education programs. Multiple sclerosis does not seem to worsen after SARS-Cov2 vaccination but COVID-19 may enhance disease activity.

Relationship between Selective IgA Deficiency and COVID-19 Prognosis.

The prevalence and mortality rates of coronavirus disease 2019 (COVID-19) widely vary among populations. Mucosal immunity is the first barrier to the pathogen's entry into the body. Immunoglobulin A (IgA) is the primary antibody responsible for mucosal immunity. We explored the relationship between selective IgA deficiency (SIgAD) and COVID-19 severity. We included 424 patients (203 women) with COVID-19. Eleven patients had SIgAD. Laboratory data of patients with SIgAD and normal IgA levels were compared. The relationship between SIgAD and severe COVID-19 infection was explored using logistic regression analysis. In the univariate logistic regression analysis, the risk of severe COVID-19 disease in patients with SIgAD was approximately 7.7-fold higher than that in other patients (odds ratio [OR], 7.789; 95% confidence interval [CI], 1.665-36.690, P = 0.008), while it was 4-fold (OR, 4.053; 95% CI, 1.182-13.903, P = 0.026) higher in the multivariate logistic regression analysis. Serum IgA levels were positively correlated with total lymphocyte counts and negatively correlated with C-reactive protein levels, which was a risk factor for severe COVID-19. In patients with SIgAD, the number of severe acute respiratory coronaviruses 2 that pass through mucosal membranes may be increased, leading to complications such as cytokine storm syndrome and acute respiratory distress syndrome.

Patients with hemodialysis-induced hypoxemia had a poor prognosis of COVID-19

BackgroundWe experienced that some hemodialysis (HD) patients with coronavirus disease 2019 (COVID-19) exacerbated hypoxemia during HD. Though HD-induced hypoxemia has been reported, there have been no reports of HD-induced hypoxemia in patients with COVID-19 and its effect on prognosis of COVID-19.MethodsEleven HD patients admitted with COVID-19 from August 2020 to April 2021 were classified into the patients whose oxygen demand increased by more than 3 L/min with mask during HD (worsened group, n = 5) and others (not-worsened group, n = 6). The background, laboratory findings, severity of COVID-19 and prognosis were compared between the two groups. In addition, blood gases were measured before and after dialysis among HD patients admitted with COVID-19 on April 2021 (n = 3).ResultsThere were no significant differences in backgrounds, except for a higher proportion of diabetes mellitus in worsened group (p = 0.04). Although laboratory findings were not significantly different on admission day, albumin and LDH levels 7 days after admission were significantly lower and higher in worsened group, respectively (p = 0.03 and < 0.01). The severity of COVID-19 and survival rate were significantly worse in worsened group (p = 0.01 and 0.03). The alveolar-arterial oxygen pressure difference (Aa-DO2) opened during HD in a patient with HD-induced hypoxemia, but did not open in patients without HD-induced hypoxemia.ConclusionsThere is a close relationship among HD-induced hypoxemia and poor prognosis of COVID-19. The HD-induced hypoxemia of patients with COVID-19 may be caused by ventilation/perfusion mismatching.

Predictive Factors For Severe And Critical Coronavirus Disease-19 In Young Adults

Predictive Factors For Severe And Critical Coronavirus Disease-19 In Young Adults Abstract Objective: Advanced age is associated with a poor prognosis in Coronavirus disease-2019 (COVID-19). The present study was conducted with the aim of investigating the predictive factors for disease severity in young adults. Materials and Methods: A total of 399 patients with COVID-19 aged under 60 who had been hospitalized at our hospital were retrospectively evaluated. Patients were stratified into mild, moderate, severe, and critical groups according to their respiratory rate, SpO2, and PaO2/FiO2 levels. The relationship between the signs and symptoms on hospital admission and the disease severity was evaluated. Results: The patients were classified as mild (n:112), moderate (n:192), severe and critical (n:95) according to disease severity. The mean age was 44. 43 of 399 patients were followed in the intensive care unit and 17 patients died. According to the binary logistic regression analysis, advanced age, hypertension, dyspnea on admission, elevated CRP, decreased lymphocyte and eosinophil count, presence of multiple bilateral ground glass appearance and consolidation were independently predicted the severity of disease. Conclusion: The signs and symptoms should be evaluated in detail also in young patients with COVID-19 and if risk factors are detected, they should be monitored more closely for predicting a poor prognosis.

Prevalence and Outcomes of Pancreatic Enzymes Elevation in Patients With COVID-19: A Meta-Analysis and Systematic Review.

Background:Although coronavirus disease 2019 (COVID-19) is considered to be a disease that mainly involves the respiratory system, an increasing number of studies have reported that COVID-19 patients had pancreatic enzymes (PE) elevation and even pancreatic injury. The study aims to determine the prevalence of PE elevation, and the relationship between elevated PE and prognosis in COVID-19 patients.MethodsA comprehensive literature search was conducted according to the PRISMA guideline in PubMed, Embase, Scopus, Web of Science, and Google Scholar for studies reporting PE elevation in patients with COVID-19 from 1st January 2020 to 24th November 2021.ResultsA total of 13 studies (24,353 participants) were included in our review. The pooled prevalence of PE elevation in COVID-19 patients was 24% (18%–31%), the pooled odds ratio (OR) of mortality was 2.5 (1.7–3.6), the pooled OR of ICU admission was 4.4 (2.8–6.8), and the pooled OR of kidney injury, respiratory failure and liver injury were 3.5 (1.6–7.4), 2.0 (0.5–8.7), and 2.3 (1.4–3.9) respectively. In addition, the subgroup analysis revealed that although PE elevated to > 3 × upper normal limit (ULN) was significantly related to the mortality (OR = 4.4, 2.1–9.4), it seemed that mild elevation of PE to 1–3 ULN also had a considerable risk of mortality (OR = 2.3, 1.5–3.5).ConclusionsPE elevation was a common phenomenon in patients with COVID-19, and was associated with poor clinical outcomes. However, due to the limited numbers of included studies, the result of our study still needed to be validated.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=295630, identifier: CRD42021295630.

Advance in research on application of endotoxin adsorption membrane in treatment of coronavirus disease 2019

The new type coronavirus disease 2019 (COVID-19) is a contagious disease of severe lung inflammation induced by 2019 novel coronavirus (2019-nCoV). The World Health Organization (WHO) nomenclature of the newly discovered coronavirus was 2019-nCoV and the disease caused by 2019-nCoV was named COVID-19 on January 12, 2020. After 2019-nCoV invasion into a human body, it can stimulate the human immune system and engender a large number of cytokines, triggering a cytokine storm, resulting in severe infection, acute lung injury, multiple organ dysfunction, etc. Therefore, theoretically, the removal of over-production of cytokines can avoid the occurrence of cytokine storm and reduce the incidence of severe critical COVID-19 and serious poor prognosis. In this review, the authors systematically reviewed the past published reports related to the occurrence of cytokine storm in sepsis resulting in deterioration of disease situation, and recently they analyzed the therapeutic effects of patients with severe critical COVID-19 using endotoxin adsorption membrane for treatment in the disease course, further providing the effective clinical evidence of applying endotoxin adsorption membrane for treatment of COVID-19.

Laboratory Biomarkers for Diagnosis and Prognosis in COVID-19.

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) causes a wide spectrum of clinical manifestations, with progression to multiorgan failure in the most severe cases. Several biomarkers can be altered in coronavirus disease 2019 (COVID-19), and they can be associated with diagnosis, prognosis, and outcomes. The most used biomarkers in COVID-19 include several proinflammatory cytokines, neuron-specific enolase (NSE), lactate dehydrogenase (LDH), aspartate transaminase (AST), neutrophil count, neutrophils-to-lymphocytes ratio, troponins, creatine kinase (MB), myoglobin, D-dimer, brain natriuretic peptide (BNP), and its N-terminal pro-hormone (NT-proBNP). Some of these biomarkers can be readily used to predict disease severity, hospitalization, intensive care unit (ICU) admission, and mortality, while others, such as metabolomic and proteomic analysis, have not yet translated to clinical practice. This narrative review aims to identify laboratory biomarkers that have shown significant diagnostic and prognostic value for risk stratification in COVID-19 and discuss the possible clinical application of novel analytic strategies, like metabolomics and proteomics. Future research should focus on identifying a limited but essential number of laboratory biomarkers to easily predict prognosis and outcome in severe COVID-19.

Impact of Pregnancy on Susceptibility and Severity of COVID-19: A Hospital-Based Prospective Observational Study.

Objective: Pregnancy is a transient state of immunosuppression. The objective of this study was to ascertain whether pregnant women are more susceptible to coronavirus disease 2019 (COVID-19) than non-pregnant women and the impact of pregnancy on the severity of COVID-19 and associated morbidity and mortality.Methods: A prospective observational study was performed at All India Institute of Medical Sciences (AIIMS) Rishikesh for a period of two months. A total of 42 and 33 COVID-19 positive women were included in the obstetric and non-obstetric cohorts respectively.Results: Baseline characteristics were similar in both groups. Approximately 48% of the obstetric cohort had no COVID-19-related symptoms. Whereas, 100% of the non-obstetric cohort was symptomatic and had a significantly higher number of patients presenting with fever, cough, and breathlessness. The obstetric cohort had a significantly higher incidence of mild disease (p=0.009). In the obstetric cohort, the mean gestational age was 32.59 ± 2.57 weeks, with patients spread across all trimesters. Most of the patients with severe disease were in their second trimester. There was no difference in intensive care unit (ICU) admission, duration of ICU stay, duration of hospital stay, and mortality among both groups. A significantly smaller number of patients in the obstetric cohort required ventilatory support (p=0.0002). The maternal mortality rate was 16.67%. All of them had severe diseases requiring ICU admission. The cause of death was attributed to severe COVID pneumonia with septic shock in all cases. The mortality rate was comparatively higher (27.27%) in the non-obstetric group.Conclusion: Pregnancy, unlike other immunocompromised conditions, does not seem to affect the prognosis of COVID-19 in terms of disease severity or mortality.

Geriatric Nutritional Risk Index assessment in elderly patients during the COVID-19 outbreak.

Background and AimsGlobally, coronavirus disease‐2019 (COVID‐19) is persistent in many countries and presents a major threat to public health. Critically, elderly individuals, especially those with underlying disease, poor nutritional and immune functions, are highly susceptible. Therefore, we analyzed the epidemiological features in elderly COVID‐19 patients.MethodsIn total, 126 patients were recruited in the Fifth Affiliated Hospital of Sun Yat‐sen University, China from January 2020 to March 2020 (including 103 confirmed COVID‐19 patients and 23 elderly suspected cases). Epidemiological, demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. We assessed nutritional risks in elderly patients by calculating the Geriatric Nutritional Risk Index (GNRI).ResultsWhen compared with young patients, elderly patients were more likely to have underlying comorbidities and received nutritional support and intensive care unit treatment. Elderly patients had significantly lower levels of the following: lymphocyte percentages, red blood cell counts, hemoglobin levels, and serum albumin values. When compared with suspected COVID‐19 elderly cases, elderly patients had significantly lower red blood cell counts and hemoglobin levels. The average GNRI of suspected cases and confirmed patients indicated no nutritional risk. There were no marked differences in GNRI values between groups.ConclusionNutritional risk assessments may provide valuable information for predicting a COVID‐19 prognosis, especially in elderly patients. Anemia prevention and management should be actively and timely provided. GNRI is a potentially prognostic factor for hospitalized elderly patients. Moreover, it is also important to follow up discharged patients for continuous nutritional observations.

Weight excess association with severity in children and adolescents with COVID-19: A systematic review.

Background & aimsConcomitantly to the coronavirus disease 2019 (COVID-19), in the child population there was already another pandemic wave in progress: childhood obesity. Numerous studies in adults have been carried out and describe obesity as an independent risk and prognostic factor for the severity of COVID-19. This study aims to systematically review the literature on the relation between weight excess and the severity of COVID-19 in children and adolescents.MethodsThis systematic review was developed following the PRISMA standards (Preferred Reporting Items for Systematic Review and Meta-Analysis). The literature search was performed in September 2020, in the following databases: MEDLINE (via PubMed), Embase, Scopus, The Cochrane Library (Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials (CENTRAL)), Web of Science, BVS/LILACS and SciELO. Registration on the PROSPERO platform (International Prospective Registry of Systematic Reviews) can be found under the registration number: CRD42021230686.ResultsOf the 667 selected articles, 11 were included according to all agreed criteria, most of them being unicentric and American. In assessing the risk of bias and quality, following the criteria of the Newcastle–Ottawa Scale, eight studies achieved scores higher than 7. Only 5 studies sought to assess obesity and its relation with worse outcomes (such as need for pediatric intensive care unit (PICU), mechanical ventilation (MV), tracheostomy, hospital readmission and mortality), and out of these, only one article demonstrated this comorbidity as a prognostic factor for worse evolution of the COVID picture.ConclusionsFew studies in the literature seek to assess excess weight and its relation with worse outcomes of COVID-19 in children and adolescents. Taking into account that there is already scientific evidence on this subject in adult patients, it is necessary to carry out more research in the pediatric age group.

A Study of Impacts of Artificial Intelligence on COVID-19 Prediction, Diagnosis, Treatment, and Prognosis

Following the identification of Coronavirus Disease 2019 (COVID-19) in Wuhan, China in December 2019, AI researchers have teamed up with a health specialist to combat the virus. This study explores the medical and non-medical areas of COVID-19 that AI has impacted: the prevalence of the AI technologies adopted across all stages of the pandemic, the collaboration networks of global AI researchers, and the open issues. 21,219 papers from ACM Digital, Science Direct and Google Scholar were examined. Adherence to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework and utilizing the PICO (population, intervention, comparison, and outcome) paradigm, guided the inclusion of researches in the review. Tables and graphs were utilized to display the results. Analysis revealed that AI has impacted 4 molecular, 4 clinical, and 7 societal areas of COVID-19. Deep Learning among other AI technologies was traced to all aspects of the pandemic. 2173 authors and co-authors were traced to these achievements, while 32 of the most connected 51 authors were affiliated with institutions in China, 18 to the United States, and 1 to Europe. The open issues identified had to do with the quality of datasets, AI model deployment, and privacy issues. This study demonstrates how AI may be utilized for COVID-19 diagnosis, prediction, medication and vaccine identification, prognosis, and contact person monitoring. This investigation began at the beginning of the epidemic and continued until the first batch of vaccinations received approval. The study provided collaboration opportunities for AI researchers and revealed open issues that will spike further research toward preparing the world for any future pandemic Keywords: Artificial Intelligence, COVID-19, Diagnosis, Prognosis, Contact Tracing

The red half-moon nail sign in a COVID-19 patient

Sir, Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic. Several cutaneous manifestations associated with COVID-19 have been reported, including chilblains or chilblain-like lesions, erythematous rash, viral exanthem, urticaria, livedo reticularis, acral ischemia, palpable purpura, and erythema multiforme. These were thought to be useful in the early diagnosis and triage of COVID-19 patients and their risk stratification [1]. However, there are limited reports on the nail manifestations of COVID-19, including several cases of Beau lines, leukonychia, orange discoloration, and onychomadesis [2]. An exceptionally rarely reported manifestation of COVID-19 is the red half-moon-nail sign [3,4]. A 46-year-old male presented to our outpatient clinic with transversal red bands surrounding the distal margin of the nail’s lunula on all of the fingernails, which the patient noticed a week previously (Fig. 1). One month before, with symptoms of fever, shortness of breath, and coughing present for three days, he had been given the diagnosis of COVID-19 following a positive nasopharyngeal swab polymerase chain reaction test. Computed tomography of the lungs revealed generalized ground-glass opacities and paraseptal emphysema in the upper lobes, and the patient was hospitalized for one week and treated with favipiravir for five days and was on oxygen therapy. He was discharged from the hospital one week later with partial remission of the respiratory symptoms. He also had hypertension, atherosclerotic heart disease, and Behçet’s disease, and had been using metoprolol, amlodipine, edoxaban, irbesartan, hydrochlorothiazide, and colchicine. After two weeks of follow-up, the bands remained present and became wider (Fig. 2). The red-half-moon sign was first described by Neri et al. as half-moon-shaped transversal red bands after SARS-CoV-2 infection. The patient was a sixty-year-old female and the bands appeared two weeks after the onset of symptoms of COVID-19. The patient was hospitalized and received oxygen therapy and several other treatments, including hydroxychloroquine and lopinavir/ritonavir. As in our patient, the bands remained present and became wider after one month of follow-up [3]. Mendez-Flores et al. reported a case of the red half-moon nail sign in a 37-year-old female with COVID-19. The patient noticed the changes two days after the COVID-19 symptoms appeared, and these lasted for one week before gradually returning to normal. The patient was managed at home and required no oxygen therapy [4]. The pathogenesis of the red half-moon sign is unknown. Neri et al. proposed that localized microvascular injury secondary to an inflammatory immune response and procoagulant state may play a role. It is thought that, because of the location, the distal subungual arcade’s capillary network may be affected in these cases [2,3]. We also agree that the red half-moon sign could be associated with microvascular injury or a procoagulant state connected to an inflammatory immune response. Recently, Natalello et al. reported nailfold capillaroscopy abnormalities in COVID-19 patients, including microvascular alterations in the nailfold capillary bed ranging from microthrombosis to altered capillary structures, according to the COVID-19 phase supporting this theory [5]. We also think that the persistence of the bands might be related to the severity of the disease, as both our and Neri et al.’s patients were hospitalized and had a more severe disease course than Mendez-Florez et al.’s patient. We think that, similarly to skin findings, nail findings may be a clue in the diagnosis and prognosis of COVID-19 as well as the pathogenesis of the disease, and clinicians should search for nail findings in COVID-19 patients.

Alterations of Urinary Microbial Metabolites and Immune Indexes Linked With COVID-19 Infection and Prognosis

Coronavirus disease 2019 (COVID-19) has evolved into an established global pandemic. Metabolomic studies in COVID-19 patients is worth exploring for further available screening methods. In our study, we recruited a study cohort of 350 subjects comprising 248 COVID-19 patients (161 non-severe cases, 60 asymptomatic cases, and 27 severe cases) and 102 healthy controls (HCs), and herein present data with respect to their demographic features, urinary metabolome, immunological indices, and follow-up health status. We found that COVID-19 resulted in alterations of 39 urinary, mainly microbial, metabolites. Using random forest analysis, a simplified marker panel including three microbial metabolites (oxoglutaric acid, indoxyl, and phenylacetamide) was constructed (AUC=0.963, 95% CI, 0.930-0.983), which exhibited higher diagnostic performance than immune feature-based panels between COVID-19 and HC groups (P<0.0001). Meanwhile, we observed that urine metabolic markers enabled discriminating asymptomatic patients (ASY) from HCs (AUC = 0.981, 95% CI, 0.946-0.996), and predicting the incidence of high-risk sequalae in COVID-19 individuals (AUC=0.931, 95% CI, 0.877-0.966). Co-expression network analysis showed that 13 urinary microbial metabolites (e.g., oxoglutaric acid) were significantly correlated with alterations of CD4+, CD3+, and CD8+ T-cells, as well as IFN-γ, IL-2 and IL-4 levels, suggesting close interactions between microbial metabolites and host immune dysregulation in COVID-19. Taken together, our findings indicate that urinary metabolites may have promising potential for screening of COVID-19 in different application scenarios, and provide a new entry point to understand the microbial metabolites and related immune dysfunction in COVID-19.

Lung Ultrasound Findings in COVID-19: A Descriptive Retrospective Study.

BackgroundPoint-of-care ultrasound (POCUS) is an indispensable tool in emergency medicine. With the emergence of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a need for improved diagnostic capabilities and prognostic indicators for patients who are symptomatic for COVID-19 has become apparent. POCUS has been demonstrated to be a useful diagnostic and prognostic tool in the emergency department (ED) in assessing other lung complications. Still, limited data regarding its utility in assessing COVID-19 are available. This study sought to evaluate whether POCUS findings in the ED were correlated with vital signs or laboratory abnormalities typically seen among patients with COVID-19.MethodsA retrospective study was conducted that included 39 patients who presented with COVID-19 and systemic inflammatory response syndrome (SIRS) to a large, urban tertiary care ED. The study population was limited to adults aged 18 and above who came to the ED with the primary complaint of respiratory symptoms, met SIRS criteria on admission, and had images of at least one anterior and one posterior intercostal space per lung and a minimum of four intercostal spaces. POCUS images were obtained by trained operators in the ED using portable ultrasound machines, recorded in an image database, and reviewed by ultrasound fellowship-trained emergency physicians. Clinical data (e.g., acute phase reactants and vital signs) were obtained through a chart review of patients’ electronic medical records.Results Both the percentage of intercostal spaces with B-lines and the percentage of merging B-lines were correlated with decreased oxygen saturation on presentation. No other statistically significant correlations were observed between these sonographic findings and other vital signs or acute phase reactants, nor between these clinical data and the percentage of intercostal spaces that were positive for the shred sign.ConclusionsWith the emergence of the COVID-19 pandemic, emergency medicine physicians are on the frontline of identifying and caring for patients affected by the virus. This study found that sonographic findings associated with interstitial pneumonitis, notably merging B-lines, and the overall percentage of intercostal spaces with B-lines, were clearly associated with worsening oxygen saturation, now thought to be one of the driving causes of morbidity and mortality in COVID-19. As ultrasound has become a ubiquitous and indispensable tool in the ED, this study demonstrated its utility in assessing and managing patients with COVID-19. Bedside ultrasound is a cheap, fast, and non-invasive tool that healthcare providers can use as an essential adjunct in addition to laboratory markers and other imaging modalities for the diagnosis and prognosis of COVID-19.

New laboratory evidence for the association between endothelial dysfunction and COVID-19 disease progression.

There is growing evidence that angiotensin‐converting enzyme 2 is highly expressed on endothelial cells, endothelial dysfunction plays a critical role in coronavirus disease 2019 (COVID‐19) progression, but laboratory evidence is still lacking. This study established a multicenter retrospective cohort of 966 COVID‐19 patients from three hospitals in Wuhan, China. We found that male (62.8% vs. 46.5%), old age [72 (17) vs. 60.5 (21)], and coexisting chronic diseases (88.5% vs. 60.0%) were associated with poor clinical prognosis in COVID‐19. Furthermore, the deteriorated patients exhibited more severe multiorgan damage, coagulation dysfunction, and extensive inflammation. Additionally, a cross‐sectional study including 41 non‐COVID‐19 controls and 39 COVID‐19 patients assayed endothelial function parameters in plasma and showed that COVID‐19 patients exhibited elevated vascular cell adhesion molecule‐1 (VCAM‐1) (median [IQR]: 0.32 [0.27] vs. 0.17 [0.11] μg/ml, p < 0.001), E‐selectin (21.06 [12.60] vs. 11.01 [4.63] ng/ml, p < 0.001), tissue‐type plasminogen activator (tPA) (0.22 [0.12] vs. 0.09 [0.04] ng/ml, p < 0.001), and decreased plasminogen activator inhibitor‐1 (0.75 [1.31] vs 6.20 [5.34] ng/ml, p < 0.001), as compared to normal controls. Moreover, VCAM‐1 was positively correlated with d‐dimer (R = 0.544, p < 0.001); tPA was positively correlated with d‐dimer (R = 0.800, p < 0.001) and blood urea nitrogen (R = 0.638, p < 0.001). Our findings further confirm the strong association between endothelial dysfunction and poor prognosis of COVID‐19, which offers a rationale for targeting endothelial dysfunction as a therapeutic strategy for COVID‐19.

Effect of Hyperglycemia on COVID-19 Outcomes: Vaccination Efficacy, Disease Severity, and Molecular Mechanisms.

Background/Aims: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive-stranded single-stranded RNA virus, a member of the subgenus Sarbecovirus (beta-CoV lineage B) and responsible for the coronavirus disease 2019 (COVID-19). COVID-19 encompasses a large range of disease severity, from mild symptoms to severe forms with Intensive Care Unit admission and eventually death. The severe forms of COVID-19 are usually observed in high-risk patients, such as those with type two diabetes mellitus. Here, we review the available evidence linking acute and chronic hyperglycemia to COVID-19 outcomes, describing also the putative mediators of such interactions. Findings/Conclusions: Acute hyperglycemia at hospital admission represents a risk factor for poor COVID-19 prognosis in patients with and without diabetes. Acute and chronic glycemic control are both emerging as major determinants of vaccination efficacy, disease severity and mortality rate in COVID-19 patients. Mechanistically, it has been proposed that hyperglycemia might be a disease-modifier for COVID-19 through multiple mechanisms: (a) induction of glycation and oligomerization of ACE2, the main receptor of SARS-CoV-2; (b) increased expression of the serine protease TMPRSS2, responsible for S protein priming; (c) impairment of the function of innate and adaptive immunity despite the induction of higher pro-inflammatory responses, both local and systemic. Consistently, managing acute hyperglycemia through insulin infusion has been suggested to improve clinical outcomes, while implementing chronic glycemic control positively affects immune response following vaccination. Although more research is warranted to better disentangle the relationship between hyperglycemia and COVID-19, it might be worth considering glycemic control as a potential route to optimize disease prevention and management.

Relationship of Computed Tomography Severity Score With Patient Characteristics and Survival in Hypoxemic COVID-19 Patients.

BackgroundComputed tomography (CT) scans and CT severity scores (CTSS) are widely used to assess the severity and prognosis in coronavirus disease 2019 (COVID-19). CTSS has performed well as a predictor in differentiating severe from non-severe cases. However, it is not known if CTSS performs similarly in hospitalized severe cases with hypoxia at admission.MethodsWe conducted a retrospective comparative study at a COVID-care center from Western India between 25th April and 31st May 2021, enrolling all consecutive severe COVID-19 patients with hypoxemia (peripheral oxygen saturation < 94%). Neutrophil-lymphocyte ratio (NLR), C-reactive protein (CRP), interleukin-6 (IL-6), lactate dehydrogenase (LDH), D-dimer, ferritin, and CT thorax were done within 24h of admission before being initiated on any anti-COVID-19 therapy. CTSS was calculated by visual assessment and categorized into three severity categories and was correlated with laboratory markers and overall survival (OS). Statistical analysis was done using John's Macintosh Project (JMP) 15.0.0 ver. 3.0.0 (Cary, North Carolina).ResultsThe median age of the study population (n-298) was 59 years (24-95) with a male preponderance (61.41%, n=183). The 15 and 30-day survivals were 67.64% and 59.90%, respectively. CTSS did not correlate with age, gender, time from vaccination, symptoms, or comorbidities but had a significant though weak correlation with LDH (p=0.009), D-dimer (p=0.006), and NLR (p=0.019). Comparing demographic and laboratory aspects using CT severity categories, only NLR (p=0.0146) and D-dimer (p=0.0006) had significant differences. The 15d-OS of mild, moderate, and severe CT categories were 88.62%, 70.39%, and 52.62%, respectively, while 30d-OS of three categories were 59.08%, 63.96%, and 49.12%, respectively.ConclusionAmong hospitalized severe COVID-19 patients with hypoxemia at admission, CT severity categories correlate well with outcomes but not inflammatory markers at admission.