Dysfunction In Coronavirus Disease 2019 Patients Research Articles

Effect of Corona Virus on Olfactory & Gustatory Functions (Systematic Review Study)

Abstract Background Because of the rapid spreading of severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) infection, the Coronavirus disease 2019 (COVID-19) outbreak was characterized as a pandemic by the WHO on March 11, 2020. Materials and Methods Following the PRISMA statement guidelines, we conducted this systematic review and meta-analysis according to the Cochrane handbook of systematic reviews of intervention. We searched PubMed, Scopus, Cochrane, and Web of Science, Embase, and Science Direct till December 2021 with relevant keywords. We included the whole clinical studies assessing olfactory and/or gustatory dysfunctions (OGD) in patients with COVID-19, studies including patients with a confirmed diagnosis of COVID-19 by a positive result of RT-PCR were included, studies that assessed the OGD by either subjective evaluation were also included, studies written in English languages only, all of the studies must have been written in English as a full-text manuscript, double or single-arm designs. Results A total of 12 studies were finally included for the final qualitative and quantitative analysis illustrating the association and the relationship between COVID-19 infection and olfactory and gustatory functions. The mean age of the participants was 49.12 years. The pooled analysis of the included studies showed a significant association of positive results between OGD and COVID-19 infection. Also, the analysis showed a significant association of positive results between either isolated olfactory or gustatory dysfunction and COVID-19 infection. Regarding the association between gustatory dysfunction in COVID-19 patients versus (Acute respiratory infection) ARI patients with no detectable virus, the analysis showed a significant difference between COVID-19 patients and ARI patients with no detectable virus regarding the gustatory dysfunction meaning there is a high association between gustatory dysfunction and COVID-19 patients other than ARI patients with no detectable virus. Finally, the pooled analysis of the included studies showed a significant difference between COVID-19 patients and ARI patients with other respiratory viruses (ORV) in terms of OGD. Conclusion Based on the available evidence, there are regional and chronological differences in the prevalence rates of olfactory and gustatory dysfunction. Future studies, particularly those that document the temporal relationship in the onset of these 2 symptoms, are needed.

Prevalence and Prognostic Factors Associated with Early Recovery of Olfactory Dysfunction in COVID-19 Patients.

The prevalence of smell dysfunction, along with its risk factors, has been evaluated in previous literature; however, little has been established regarding its relation to other factors such as disease severity, history of coronavirus disease-2019 (COVID-19) vaccinations, and medical treatment for COVID-19 infection. These factors may impact the overall recovery of olfaction in COVID-19 patients. This study investigated the prevalence of early olfactory recovery from COVID-19 infection and its associated factors. This study was a prospective cohort study on 348 COVID-19 patients with a new onset of anosmia or hyposmia. Smell sensation scores on the olfactory self-assessment test were collected at baseline and every week until 6 weeks of follow-up. The primary outcome was the prevalence of early olfactory recovery. The secondary outcomes were analyzing factors associated with early olfactory recovery and the median time to complete recovery of smell loss. The prevalence of early olfactory recovery was 63.1% (95% CI: 0.58-0.68), and significant associated factors in multivariate analysis included patients without allergic rhinitis (OR 2.22, 95% CI: 1.12-4.40, P = 0.023) and no alteration of taste perception (OR 1.62, 95% CI: 1.02-2.57, P = 0.042). The median time to complete recovery from smell loss was 2 weeks. The present study found that the prevalence of early olfactory recovery within 2 weeks was 63.1%. The median time to olfactory recovery was also 2 weeks. Patients without allergic rhinitis and taste alteration had a significantly better chance of early recovery of olfactory function.

Temporal patterns of organ dysfunction in COVID-19 patients hospitalized in the intensive care unit: A group-based multitrajectory modeling analysis

BackgroundThe course of organ dysfunction (OD) in Corona Virus Disease 2019 (COVID-19) patients is unknown. Herein, we analyze the temporal patterns of OD in intensive care unit-admitted COVID-19 patients. MethodsSequential organ failure assessment scores were evaluated daily within 2 weeks of admission to determine the temporal trajectory of OD using group-based multitrajectory modeling (GBMTM). ResultsA total of 392 patients were enrolled with a 28-day mortality rate of 53.6%. GBMTM identified four distinct trajectories. Group 1 (mild OD, n = 64), with a median APACHE II score of 13 (IQR 9-21), had an early resolution of OD and a low mortality rate. Group 2 (moderate OD, n = 140), with a median APACHE II score of 18 (IQR 13-22), had a 28-day mortality rate of 30.0%. Group 3 (severe OD, n = 117), with a median APACHR II score of 20 (IQR 13-27), had a deterioration trend of respiratory dysfunction and a 28-day mortality rate of 69.2%. Group 4 (extremely severe OD, n = 71), with a median APACHE II score of 20 (IQR 17-27), had a significant and sustained OD affecting all organ systems and a 28-day mortality rate of 97.2%. ConclusionsFour distinct trajectories of OD were identified, and respiratory dysfunction trajectory could predict nonpulmonary OD trajectories and patient prognosis.

Liver dysfunction and clinical outcomes of unvaccinated COVID-19 patients with and without chronic hepatitis B

BackgroundLiver dysfunction is common during coronavirus disease 2019 (COVID-19), while its clinical impact and association with chronic hepatitis B (CHB) remain uncertain. We aimed to investigate liver dysfunction in COVID-19 patients and its impacts on those with/without CHB. MethodsWe conducted a retrospective cohort study of COVID-19 patients at National Taiwan University Hospital, stratified according to hepatitis B surface antigen (HBsAg) serostatus, with demographics, laboratory data, and hospitalization course reviewed, and clinical outcomes compared through multivariable analyses. ResultsWe enrolled 109 COVID-19 patients unvaccinated against SARS-CoV-2 by August 2021. The HBsAg-positive group (n = 34) had significantly higher alanine aminotransferase (ALT) (26 vs. 16 U/L, P = 0.034), platelet (224 vs. 183 k/μL, P = 0.010) and longer hospitalizations (17 vs. 13 days, P = 0.012) compared with HBsAg-negative group (n = 75), while percentages of hepatitis (2-fold ALT elevation), oxygen supplementation, ventilators usage, COVID-specific treatment, intensive care unit (ICU) admission and mortality were comparable. Older age (odds ratio [OR]: 1.04, 95 % confidence interval [CI]: 1.00–1.08, P = 0.032) and higher aspartate aminotransferase (AST) (OR: 1.08, 95 % CI: 1.004–1.16, P = 0.038) were associated with oxygen supplementation according to multivariable analyses. Higher AST predicted ICU admission (OR: 1.11, 95 % CI: 1.03–1.19, P = 0.008). Oxygen usage (OR: 5.64, 95 % CI: 1.67–19.09, P = 0.005) and shock (OR: 5.12, 95 % CI: 1.14–22.91, P = 0.033) were associated with liver dysfunction. ConclusionsCHB patients had higher ALT levels and longer hospitalizations during COVID-19. Higher AST levels predict severe COVID-19 and ICU admission.

Mechanisms of gastrointestinal barrier dysfunction in COVID-19 patients.

Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a major global public health event, resulting in a significant social and economic burden. Although COVID-19 was initially characterized as an upper respiratory and pulmonary infection, recent evidence suggests that it is a complex disease including gastrointestinal symptoms, such as diarrhea, nausea, and vomiting. Moreover, it remains unclear whether the gastrointestinal symptoms are caused by direct infection of the gastrointestinal tract by SARS-CoV-2 or are the result of systemic immune activation and subsequent dysregulation of homeostatic mechanisms. This review provides a brief overview of the mechanisms by which SARS-CoV-2 disrupts the integrity of the gastrointestinal barrier including the mechanical barrier, chemical barrier, microbial barrier, and immune barrier.

Insight into the liver dysfunction in COVID-19 patients: Molecular mechanisms and possible therapeutic strategies.

As of June 2022, more than 530 million people worldwide have become ill with coronavirus disease 2019 (COVID-19). Although COVID-19 is most commonly associated with respiratory distress (severe acute respiratory syndrome), meta-analysis have indicated that liver dysfunction also occurs in patients with severe symptoms. Current studies revealed distinctive patterning in the receptors on the hepatic cells that helps in viral invasion through the expression of angiotensin-converting enzyme receptors. It has also been reported that in some patients with COVID-19, therapeutic strategies, including repurposed drugs (mitifovir, lopinavir/ritonavir, tocilizumab, etc.) triggered liver injury and cholestatic toxicity. Several proven indicators support cytokine storm-induced hepatic damage. Because there are 1.5 billion patients with chronic liver disease worldwide, it becomes imperative to critically evaluate the molecular mechanisms concerning hepatotropism of COVID-19 and identify new potential therapeutics. This review also designated a comprehensive outlook of comorbidities and the impact of lifestyle and genetics in managing patients with COVID-19.

Biomarkers of endothelial dysfunction are associated with poor outcome in COVID-19 patients: A systematic review and meta-analysis.

Numerous studies have linked coronavirus disease 2019 (COVID-19) with endothelial dysfunction and reported elevated levels of endothelial biomarkers in this disease. We conducted a systematic review and meta-analysis of the published evidence in this respect. A systematic literature search of PubMed and Scopus databases was performed to find studies investigating biomarkers of endothelial dysfunction in COVID-19 patients. Pooled standardized mean differences and their 95% confidence intervals were calculated for each biomarker using random effect model. 74 studies with 7668 patients were included. In comparison to patients with good outcome, those with poor outcome had higher levels of von Willebrand factor (vWF) (SMD: 0.83, 95% CI: 0.59-1.07, p<0.00001), vWF:ADAMTS13 (1.23, (0.77-1.7), p<0.00001), angiopoietin-2 (Ang-2) (1.06 (0.6-1.51), p<0.0001), E-selectin (1.09 (0.55-1.63), p<0.0001), P-selectin (0.59 (0.24-0.94), p=0.001), syndecan-1 (0.99 (0.6-1.37), p<0.00001), mid-regional pro-adrenomedullin (MR-proADM) (1.52 (1.35-1.68), p<0.00001), vascular endothelial growth factor (0.27 (0.02-0.53), p=0.03), soluble fms-like tyrosine kinase-1 (sFLT-1) (1.93 (0.65-3.21), p=0.03) and lower levels of ADAMTS13 antigen (-0.69 (-0.9 to -0.47) p<0.00001) and activity (-0.84 (-1.06 to -0.61) p<0.0000). Plasminogen activator inhibitor-1 and tissue plasminogen activator levels were not different between the two groups (p<0.05). There were elevated levels of endothelial dysfunction biomarkers in COVID-19 patients with poor outcome, indicating their possible role in disease severity and prognosis. In particular, MR-proADM, vWF, syndecan-1 and sFLT-1 showed a significant association with poor outcome in these patients.

COVID-19 Metabolomic-Guided Amino Acid Therapy Protects from Inflammation and Disease Sequelae.

The outbreak of coronavirus disease 2019 (COVID-19) has caused a worldwide pandemic since 2019. Ametabolic disorder is a contributing factor to deaths from COVID-19. However, the underlying mechanism of metabolic dysfunction in COVID-19 patients and the potential interventions are not elucidated. Here targeted plasma metabolomic is performed, and the metabolite profiles among healthy controls, andasymptomatic, moderate, and severe COVID-19 patients are compared. Among the altered metabolites, arachidonic acid and linolenic acid pathway metabolites are profoundly up-regulated in COVID-19 patients. Arginine biosynthesis, alanine, aspartate, and glutamate metabolism pathways are significantly disturbed in asymptomatic patients. In the comparison of metabolite variances among the groups, higher levels of l-citrulline and l-glutamine are found in asymptomatic carriers and moderate or severe patients at theremission stage. Furthermore, l-citrulline and l-glutamine combination therapy is demonstrated to effectively protect mice from coronavirus infection and endotoxin-induced sepsis, and is observed to efficiently prevent the occurrence of pulmonary fibrosis and central nervous system damage. Collectively, the data reveal the metabolite profile of asymptomatic COVID-19 patients and propose a potential strategy for COVID-19 treatment.

Microvascular Dysfunction in COVID-19 Patients with Acute Coronary Syndrome.

Coronavirus disease 2019 (COVID-19) is considered to deteriorate endothelial function through hyperinflammation. We aimed to investigate microvascular dysfunction using the angiographic parameters thrombolysis in myocardial infarction frame count (TFC) and myocardial blush grade (MBG), in COVID-19 patients with acute coronary syndrome (ACS). One hundred and sixty-five patients presented with ACS (62.4% ST elevated myocardial infarction) and underwent percutaneous coronary intervention between March 1 and June 30, 2020, were enrolled in the study. The polymerase chain reaction test was performed in case of suggestive symptoms or typical computerized tomography findings. Twenty-six patients (15.7%) were tested positive for COVID-19. Significantly higher values were observed in TFC in patients with COVID-19 (p<0.001), whereas COVID-19 patients had significantly lower MBGs (Grade 0 and 1) (p<0.001). Peak troponin-I value was also higher in the COVID-19 group (27335 vs. 15959 ng/dL, p=0.006). Mortality risk was higher in COVID-19 patients (38.4% vs. 7.2%, p<0.001). TFC and ejection fraction may predict in-hospital mortality among COVID-19 patients with ACS according to logistic regression results. In correlation analysis, TFC correlated positively with C-reactive protein (r=0.340, p<0.001) and peak troponin-I value (r=0.369, p<0.001). COVID-19 is associated with slow coronary flow and microvascular impairment in ACS.

Autonomic dysfunction in COVID-19 patients receiving mechanical ventilation: A cross-sectional study

Coronavirus disease 2019 (COVID-19) can damage cardiac tissue by increasing troponin levels and inducing arrhythmias, myocarditis, and acute coronary syndrome. To analyze the impact of COVID-19 on cardiac autonomic control in mechanically ventilated intensive care unit (ICU) patients. This cross-sectional analytical study of ICU patients of both sexes receiving mechanical ventilation was conducted in a tertiary hospital. Patients were divided into COVID-19-positive (COVID(+)) and COVID-19-negative (COVID(-)) groups. Clinical data were collected and heart rate variability (HRV) records obtained using a heart rate monitor. The study sample comprised 82 subjects: 36 (44%) in the COVID(-) group (58.3% female; median age, 64.5 years) and 46 (56%) in the COVID(+) group (39.1% females; median age, 57.5 years). The HRV indices were lower than the reference values. An intergroup comparison identified no statistically significant differences in the mean normal-to-normal (NN) interval, standard deviation of the NN interval, or root mean square of successive differences in NN intervals. The COVID(+) group had an increased low frequency (P = 0.05), reduced high frequency (P = 0.045), and increased low frequency/high frequency (LF/HF) ratio (P = 0.048). There was a weak positive correlation between LF/HF and length of stay in the COVID(+) group. Patients who received mechanical ventilation had lower overall HRV indices. COVID(+) patients who received mechanical ventilation had lower vagal HRV components. These findings likely indicate clinical applicability, as autonomic control impairments are associated with a greater risk of cardiac death.

Prevalence and risk factors of erectile dysfunction in COVID-19 patients: a systematic review and meta-analysis.

Studies have found that erectile dysfunction (ED) may be a short-term or long-term complication in coronavirus disease 2019 (COVID-19) patients, but no relevant studies have completed a pooled analysis of this claim. The purpose of the review was to comprehensively search the relevant literature, summarize the prevalence of ED in COVID-19 patients, assess risk factors for its development, and explore the effect of the COVID-19 infection on erectile function. Medline, Embase, and the Cochrane Library was performed from database inception until April 14, 2022. Heterogeneity was analyzed by χ2 tests and I2 was used as a quantitative test of heterogeneity. Subgroup analyses, meta-regression, and sensitivity analyses were used to analyze sources of heterogeneity. Our review included 8 studies, 4 of which functioned as a control group. There were 250,606 COVID-19 patients (mean age: 31-47.1years, sample size: 23-246,990). The control group consisted of 10,844,200 individuals (mean age: 32.76-42.4years, sample size 75-10,836,663). The prevalence of ED was 33% (95% CI 18-47%, I2 = 99.48%) in COVID-19 patients. The prevalence of ED based on the international coding of diseases (ICD-10) was 9% (95% CI 2-19%), which was significantly lower than the prevalence of ED diagnosed based on the International Index of Erectile Function (IIEF-5) (46%, 95% CI 22-71%, I2 = 96.72%). The pooling prevalence of ED was 50% (95% CI 34-67%, I2 = 81.54%) for articles published in 2021, significantly higher than that for articles published in 2022 (17%, 95% CI 7-30%, I2 = 99.55%). The relative risk of developing ED was 2.64times in COVID-19 patients higher than in non-COVID-19 patients (RR: 2.64, 95% CI 1.01-6.88). The GRADE-pro score showed that the mean incidence of ED events in COVID-19 patients was 1,333/50,606 (2.6%) compared with 52,937/844,200 (0.4%) in controls; the absolute impact of COVID-19 on ED was 656/100,000 (ranging from 4/100,000 to 2352/100,000). Anxiety (OR: 1.13, 95% CI 1.03-1.26, I2 = 0.0%) in COVID-19 patients was a risk factor for ED. COVID-19 patients have a high risk and prevalence of ED, mainly driven by anxiety. Attention should be paid to patient's erectile functioning when treating COVID-19.

Olfactory dysfunction in COVID-19: pathology and long-term implications for brain health.

Decreased smell function is related to brain health, future mortality, and quality of life. Most people inflicted with the SARS-CoV-2 virus evidence some measurable smell dysfunction during its acute phase, although many are unaware of the loss. Long-term deficits occur in up to 30% of COVID-19 cases, although total anosmia is relatively rare. This review explores what is presently known about the nature and pathophysiology of olfactory dysfunction due to the SARS-CoV-2 virus, including reversible inflammation within the olfactory cleft, downregulation of olfactory receptor proteins, and long-lasting peripheral and central damage to olfactory structures. It also addresses the question as to whether long-term smell loss might increase the likelihood of future development of cognitive and neurological deficits.

Changes in the Intranetwork and Internetwork Connectivity of the Default Mode Network and Olfactory Network in Patients with COVID-19 and Olfactory Dysfunction.

Olfactory dysfunction (OD) is a common symptom in coronavirus disease 2019 (COVID-19) patients. Moreover, many neurological manifestations have been reported in these patients, suggesting central nervous system involvement. The default mode network (DMN) is closely associated with olfactory processing. In this study, we investigated the internetwork and intranetwork connectivity of the DMN and the olfactory network (ON) in 13 healthy controls and 22 patients presenting with COVID-19-related OD using independent component analysis and region of interest functional magnetic resonance imaging (fMRI) analysis. There was a significant correlation between the butanol threshold test (BTT) and the intranetwork connectivity in ON. Meanwhile, the COVID-19 patients with OD showed significantly higher intranetwork connectivity in the DMN, as well as higher internetwork connectivity between ON and DMN. However, no significant difference was found between groups in the intranetwork connectivity within ON. We postulate that higher intranetwork functional connectivities compensate for the deficits in olfactory processing and general well-being in COVID-19 patients. Nevertheless, the compensation process in the ON may not be obvious at this stage. Our results suggest that resting-state fMRI is a potentially valuable tool to evaluate neurosensory dysfunction in COVID-19 patients.

Correlation Between Coronavirus Disease 2019 and Olfactory Dysfunction

A great number of patients with Coronavirus Disease 2019 (COVID-19) experience olfactory dysfunction, typically of a short duration and with a high incidence rate, during the early stages of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This kind of olfactory dysfunction appears more likely in young people and women. This study presents a review of the clinical features and pathogenic mechanism of the olfactory dysfunction related to SARS-CoV-2 infection, aiming to provide a clinical reference for the diagnosis, differential diagnosis, treatment, and prevention of olfactory dysfunction in COVID-19 patients.

Endothelial dysfunction in COVID-19 patients assessed with Endo-PAT2000.

It has been widely reported that the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) attaches human cells by using the Angiotensin Converting Enzyme 2 (ACE2) receptor, but vascular impairment described during coronavirus disease 2019 (COVID-19) infection is primarily due to the direct involvement of the endothelial cells by the virus or secondarily to the inflammatory host response is currently unknown. We therefore aimed to demonstrate in vivo the presence of endothelial dysfunction in six COVID-19 patients without cardiovascular risk factors or pre-existing cardiac condition, using the Endo-PAT 2000, a device able to measure endothelial vasodilation function in a rapid and non-invasive way. Four patients were positive for endothelial dysfunction, with RHI values between 1.13-1.56 (average value 1.32, normal values >1.67); in one of the two negative patients the reported RHI value was slightly above the cutoff (1.72). Our findings confirm that COVID-19 patients are at higher risk of developing endothelial dysfunction. In addition, our results demonstrate that endothelial impairment may occur even in the absence of cardiovascular risk factors.

Effects of Air Pollution on Chemosensory Dysfunction in COVID-19 Patients.

BackgroundIn some patients, coronavirus disease 2019 (COVID-19) is accompanied by loss of smell and taste, and this has been reportedly associated with exposure to air pollutants. This study investigated the relationship between the occurrence of chemosensory dysfunction in COVID-19 patients and air pollutant concentrations in Korea.MethodsInformation on the clinical symptom of chemosensory dysfunction, the date of diagnosis, residential area, age, and sex of 60,194 confirmed COVID-19 cases reported to the Korea Disease Control and Prevention Agency from January 20 to December 31, 2020 was collected. In addition, the daily average concentration of air pollutants for a week in the patients’ residential area was collected from the Ministry of Environment based on the date of diagnosis of COVID-19. A binomial logistic regression model, using age and gender, standardized smoking rate, number of outpatient visits, 24-hour mean temperature and relative humidity at the regional level as covariates, was used to determine the effect of air pollution on chemosensory dysfunction.ResultsSymptoms of chemosensory dysfunction were most frequent among patients in their 20s and 30s, and occurred more frequently in large cities. The logistic analysis showed that the concentration of particulate matter 10 (PM10) and 2.5 (PM2.5) up to 2 days before the diagnosis of COVID-19 and the concentration of sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3) at least 7 days before the diagnosis of COVID-19 affected the development of chemosensory dysfunction. In the logistic regression model adjusted for age, sex, standardized smoking rate, number of outpatient visits, and daily average temperature and relative humidity, it was found that an increase in the interquartile range of PM10, PM2.5, SO2, NO2, and CO on the day of diagnosis increased the incidence of chemosensory dysfunction 1.10, 1.10, 1.17, 1.31, and 1.19-fold, respectively. In contrast, the O3 concentration had a negative association with chemosensory dysfunction.ConclusionHigh concentrations of air pollutants such as PM10, PM2.5, SO2, NO2, and CO on the day of diagnosis increased the risk of developing chemosensory dysfunction from COVID-19 infection. This result underscores the need to actively prevent exposure to air pollution and prevent COVID-19 infection. In addition, policies that regulate activities and products that create high amounts of harmful environmental wastes may help in promoting better health for all during COVID-19 pandemic.

Can Perinephric Fat Stranding be used as a Predictor of Renal Dysfunction in COVID-19 Patients? A Retrospective Study

Introduction: High Resolution Computed Tomography (HRCT) of the chest is often performed in patients with Coronavirus Disease 2019 (COVID-19) to assess the severity of lung involvement. Multiorgan dysfunction is a well-known complication of COVID-19 infection. Bilateral Perinephric Fat Stranding (PFS) is often observed in cases of COVID-19 infection while reporting the chest Computed Tomography (CT) scans, which might represent associated acute kidney injury. It is still not known whether a correlation exists between the severity of COVID-19 infection and presence of PFS or renal dysfunction. Aim: To determine the association between PFS, Computed Tomography Severity Index (CTSI) and serum creatinine levels in patients with COVID-19 infection. Materials and Methods: This retrospective cohort study was conducted in Department of Radiology, Nizam’s Institute of Medical Sciences, Hyderabad, Telangana, India, from April 2021 to June 2021. A total of 90 COVID-19 positive patients of all ages and gender, who underwent HRCT of chest were included in the study. The chest scans were retrospectively reviewed for severity of lung involvement using a CTSI. The cases were divided equally into two groups A (n=45) and B (n=45). Group A included cases showing PFS on CT and group B included cases with no evidence of PFS. Serum creatinine levels (obtained within 24 hrs of the scan) of all patients were noted and analysed to determine any possible association between the PFS, CTSI and serum creatinine levels. Analysis was done using Mann-Whitney U test, for continuous variables and Chi-square test was used for categorical data. Results: The mean age of patients (p-value=0.047) and the male to female ratio (p-value&lt;0.001) was significantly higher in group A than in group B. Statistically significant association was found between PFS and serum creatinine (W=1375.500, p-value=0.003) PFS as an indicator of renal dysfunction had a sensitivity of 73.3%, specificity of 54.7%, Positive Predictive Value (PPV) of 24.4%, Negative Predictive Value (NPV) of 91.1% and a diagnostic accuracy of 57.8%. with an odds ratio of 3.32. Conclusion: Presence of PFS at imaging can serve as a useful screening tool for detecting underlying renal dysfunction in patients with COVID-19 infection.

Protective Effects of Meldonium in Experimental Models of Cardiovascular Complications with a Potential Application in COVID-19.

Right ventricular (RV) and left ventricular (LV) dysfunction is common in a significant number of hospitalized coronavirus disease 2019 (COVID-19) patients. This study was conducted to assess whether the improved mitochondrial bioenergetics by cardiometabolic drug meldonium can attenuate the development of ventricular dysfunction in experimental RV and LV dysfunction models, which resemble ventricular dysfunction in COVID-19 patients. Effects of meldonium were assessed in rats with pulmonary hypertension-induced RV failure and in mice with inflammation-induced LV dysfunction. Rats with RV failure showed decreased RV fractional area change (RVFAC) and hypertrophy. Treatment with meldonium attenuated the development of RV hypertrophy and increased RVFAC by 50%. Mice with inflammation-induced LV dysfunction had decreased LV ejection fraction (LVEF) by 30%. Treatment with meldonium prevented the decrease in LVEF. A decrease in the mitochondrial fatty acid oxidation with a concomitant increase in pyruvate metabolism was noted in the cardiac fibers of the rats and mice with RV and LV failure, respectively. Meldonium treatment in both models restored mitochondrial bioenergetics. The results show that meldonium treatment prevents the development of RV and LV systolic dysfunction by enhancing mitochondrial function in experimental models of ventricular dysfunction that resembles cardiovascular complications in COVID-19 patients.

Long-lasting olfactory dysfunction in COVID-19 patients

ObjectivesOlfactory dysfunction (OD) is a common symptom of Coronavirus Disease 2019 (COVID-19). Although many patients have been reported to regain olfactory function within the first month, long-term observation reports vary. Therefore, we aimed to assess the course of chemosensory function in patients diagnosed with COVID-19 within 3–15 months after the infection.MethodsOne hundred and two patients (71 females and 31 males; mean age 38.8 years) diagnosed with laboratory-confirmed COVID-19 and subjective OD participated in this single-center study 111–457 days after onset of OD. Patients first performed chemosensory tests at home, followed by psychophysical testing (Sniffin’ Sticks (TDI), 27-item Candy Smell Test (CST), Taste Strips Test (TST)) in the clinic. Questionnaires regarding importance of olfaction (IOQ) and olfactory-specific quality of life (QOD) were applied at both timepoints.ResultsAfter a mean 216 days (SD 73; range 111–457) between OD onset and follow-up testing, the mean Sniffin’ Sticks (TDI) score was 27.1 points (SD 5.8; range 4.25–38.5): 4.0% were anosmic, 72.5% hyposmic, and 23.5% normosmic. At follow-up testing, 73.5% of patients reported improvement, 5.9% deterioration, and 20.6% no change in OD. Moreover, full recovery of self-perceived smell, flavor, and taste was not observed. According to questionnaires, the individual importance of smell did not change, but participants showed improvement in OD-related quality of life (p < 0.001) and had increased parosmia scores (p = 0.014) at follow-up.ConclusionOur results show that long-lasting OD after SARS-CoV-2 infection is a common symptom. The majority of patients had OD in the range of hyposmia, which was confirmed by comprehensive smell tests.

Erythrocytes induce vascular dysfunction in COVID-19

BackgroundVascular injury has been implicated as a major cause of clinical complications in patients with coronavirus disease 2019 (COVID-19). Autopsy studies have revealed destruction of the endothelial cell lining, which might explain cardiovascular alterations arising from the infection. However, data demonstrating endothelial dysfunction during ongoing infection are sparse, and the underlying mechanisms are still largely unknown. Red blood cells (RBCs) are affected by COVID-19 with alterations in their structure and function, possibly contributing to vascular injury via increased oxidative stress.PurposeTo determine the presence of endothelial dysfunction in patients with COVID-19 and to explore the RBC as a possible mediator of such dysfunction.MethodsThe study was performed on 17 patients hospitalized for moderate COVID-19 infection and age- and sex-matched healthy subjects. Inclusion criteria of the COVID-19 patients were PCR-verified SARS-CoV2 infection, pulmonary infiltrates on x-ray, oxygen demand during hospital stay and ≤ one cardiovascular co-morbidity. Microvascular endothelial function in vivo was assessed with a pulse amplitude tonometry device on each index finger at baseline and during reactive hyperemia and expressed as reactive hyperemia index (RHI). RBCs from COVID-19 patients (C19-RBCs) and healthy subjects (H-RBCs) were incubated with isolated rat aortic segments for evaluation of endothelium-dependent and -independent relaxation.ResultsCOVID-19 patients displayed profound impairment in endothelial function in vivo with RHI 1.56 (1.30–1.81, median and interquartile range) compared to healthy subjects 2.36 (1.97–2.79, p<0.001). C19-RBCs induced severe impairment in both endothelium-dependent (27% maximal relaxation) and -independent relaxations (54%) compared to H-RBCs (67% and 95% relaxation, respectively). Further, C19-RBCs induced upregulation of vascular arginase 1 (∼2 fold increase compared to H-RBCs) and markers of oxidative stress (∼6 fold). Consequently, inhibition of vascular arginase or superoxide attenuated the impairment in endothelial function induced by C19-RBCs. C19-RBCs were characterized by increased production of reactive oxygen species (∼1.4 fold) and reduced export of the nitric oxide metabolite nitrate. Following pre-incubation with interferon-γ, but not interleukin-6 or tumor necrosis factor-α, H-RBCs induced impairment in endothelial function.ConclusionsThis study demonstrates the presence of marked endothelial dysfunction in an otherwise mainly healthy patient group hospitalized for COVID-19, and clearly implicates a central role of the RBC as a mediator of endothelial injury through enhancement of reactive oxygen species and arginase. These data shed light on a new pathological mechanism underlying vascular dysfunction in COVID-19 patients and may lay the foundation for future therapeutic developments.Funding AcknowledgementType of funding sources: Foundation. Main funding source(s): Swedish Heart and Lung foundationSwedish Research Council