The Role of Anxiety and Cortisol in Outcomes of Patients With Covid-19

Introduction: The outbreak due to Coronavirus Disease 2019 (COVID-19) is n global public health emergency and challenges psychological resilience. The central nervous system, endocrine system, and immune system are complex interacting systems. Cortisol has been implicated as the cause of a wide range of mental and physical health disorders;however, the impact of cortisol on outcomes in patients with COVID-19 is not clear.Methods: The current study enrolled patients with COVID-19 (onset of disease within 7 days of the first symptom) to evaluate the serum concentration of cortisol and levels of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS) to investigate a possible relationship between cortisol, depression, and anxiety levels and outcomes of patients with COVID-19.Results: A total of 30 patients with COVID-19 were studied. The levels of cortisol and HADS score in patients who died of Covid-19 were significantly higher in comparison with surviving patients (P<0.017 and P<0.001 respectively). We also found that the HADS score was positively correlated with serum cortisol levels (r= 0.842, P=0.004).Conclusion: Our findings showed that stress and anxiety are associated with patients' outcomes. Psychological interventions can improve the mental health of vulnerable groups during the COVID-19 epidemic.

Hospital-treated intentional self-poisoning events and in-hospital mortality in Tehran before and during the COVID-19 pandemic.

Hospital-treated intentional self-poisoning is common. The possibility of changed (increased) suicidal behaviors during the COVID-19 pandemic has been raised. To compare frequencies in self-poisoning events (SPEs) and the proportions with in-hospital mortality, in the year prior to and following the official onset of the COVID-19 pandemic, in a population of hospital-treated self-poisoning patients in Iran. All self-poisoned patients admitted to Loghman-Hakim Hospital, a clinical toxicology specialty hospital in Tehran, were included. The frequency of SPEs was compared between the one-year periods immediately before and after the onset of COVID-19 pandemic using Poisson regression. Differences in proportions of in-hospital mortality were also compared using logistic regression. A total of 14,478 patients with 15,391 SPEs (8,863 [61.2%] females) were evaluated in the study. There was no difference in the overall frequency of SPEs (relative risk [RR] of 0.99 [CI95% 0.96-1.03]), but a small increase in males (RR 1.07; 1.02-1.13) and a minor decrease in females (RR 0.95; 0.91-0.99). In total, 330 patients died (2.3% of all SPEs). There was no difference in overall in-hospital mortality odds ratio (OR: 0.98 [0.79-1.22]), in females (OR = 1.14 [0.80-1.60]) or males (OR = 0.92 [0.69-1.23]). There was no change in the frequency of SPEs and no difference in the in-hospital mortality proportions, suggesting that the COVID-19 pandemic had little or no effect on these aspects of suicidal behavior in Iran. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-022-03248-y.

An interrupted time series analysis of hospital admissions due to alcohol intoxication during the COVID-19 pandemic in Tehran, Iran.

The COVID-19 outbreak affected mental health globally. One of the major concerns following the COVID-19 pandemic was increased incidence of risky behaviors including alcohol consumption. This study evaluates the trend of alcohol poisoning in Loghman-Hakim Hospital (LHH), the main referral center of poisoning in Tehran, during the 2-year period from 1 year prior to 1 year after the onset (February 23rd, 2020) of the COVID-19 epidemic in Iran. All patients admitted with alcohol intoxication from February 23rd, 2019 to February 22nd, 2021 were evaluated and patient data extracted from LHH electronic hospital records. Alcohols were categorized as toxic (methyl alcohol) and non-toxic (ethyl alcohol). Of 2483 patients admitted, 796/14,493 (5.49%) and 1687/13,883 (12.15%) had been hospitalized before and after the onset of the COVID-19 epidemic in Iran, respectively. In total, 140 patients did not survive, of whom 131 (93.6%) were confirmed to have methanol intoxication. Mortality was significantly higher during the outbreak (127 vs 13; P < 0.001; OR: 4.90; CI 95%: 2.75 to 8.73). Among the patients, 503 were younger than age 20. Trend of alcohol intoxication showed increases in children (57 vs 17) and adolescents (246 vs 183) when compared before and after the COVID-19 epidemic outbreak. A total of 955 patients were diagnosed with methanol toxicity which occurred more frequently during the COVID-19 era (877 vs 78; P < 0.001; OR: 10.00; CI 95%: 7.75 to12.82). Interrupted time series analysis (April 2016-February 2021) showed that in the first month of the COVID-19 epidemic (March 2020), there was a significant increase in the alcohol intoxication rate by 13.76% (P < 0.02, CI = [2.42-24.91]). The trend of alcohol intoxication as well as resulting mortality increased in all age groups during the COVID-19 epidemic in Iran, indicating urgent need for the prevention of high-risk alcohol use as well as improved treatment.

Umifenovir in hospitalized moderate to severe COVID-19 patients: A randomized clinical trial.

INTRODUCTION: The effectiveness of umifenovir against COVID-19 is controversial; therefore, clinical trials are crucial to evaluate its efficacy. METHODS: The study was conducted as a single-center, randomized, open-label clinical trial. Eligible moderate-severe hospitalized patients with confirmed SARS-Cov-2 infection were randomly segregated into intervention and control groups. The intervention group were treated with lopinavir/ritonavir (400 mg/100 mg bid for 10-14 days) + hydroxychloroquine (400 mg single dose) + interferon-ß1a (Subcutaneous injections of 44 µg (12,000 IU) on days 1, 3, 5) + umifenovir (200 mg trice daily for 10 days), and the control group received lopinavir/ritonavir (same dose) + hydroxychloroquine (same dose) + interferon-ß1a (same dose). RESULTS: Of 1180 patients with positive RT-PCRs and positive chest CT scans, 101 patients were finally included in the trial; 50 were assigned to receive IFNß1a + hydroxychloroquine + lopinavir/ritonavir group and 51 were managed to treat with IFNß1a + hydroxychloroquine + lopinavir/ritonavir + umifenovir. Since all patients received the intended treatment as scheduled, the analysis just included as the ITT population. Time to clinical improvement (TTCI) did not hold a statistically significant difference between intervention and control groups (median, 9 days for intervention group versus 7 days for the control group; P: 0.22). Besides, Hazard Ratio for TTCI in the Cox regression model was 0.75 (95% CI: 0.45-1.23, P:0.25) which also confirmed that there was no statistically significant difference between the treatment group and the control group. The mortality was not statistically significant between the two groups (38% in controls vs 33.3% treatment group). CONCLUSIONS: Our findings shed new lights on the facts that additional umifenovir has not been found to be effective in shortening the duration of SARS-CoV-2 in severe patients and improving the prognosis in non-ICU patients and mortality. TRIAL REGISTRATION: The trial was confirmed by the Ethics in Medical Research Committee of the Shahid Beheshti University of Medical Sciences. signed informed consents were obtained from all the participants or their legally authorized representatives. This trial has been registered as ClinicalTrials.gov, NCT04350684.

Role of interferon therapy in severe COVID-19: the COVIFERON randomized controlled trial.

Type 1 Interferons (IFNs) have been associated with positive effects on Coronaviruses. Previous studies point towards the superior potency of IFNß compared to IFNα against viral infections. We conducted a three-armed, individually-randomized, open-label, controlled trial of IFNß1a and IFNß1b, comparing them against each other and a control group. Patients were randomly assigned in a 1:1:1 ratio to IFNß1a (subcutaneous injections of 12,000 IU on days 1, 3, 6), IFNß1b (subcutaneous injections of 8,000,000 IU on days 1, 3, 6), or the control group. All three arms orally received Lopinavir/Ritonavir (400 mg/100 mg twice a day for ten days) and a single dose of Hydroxychloroquine 400 mg on the first day. Our utilized primary outcome measure was Time To Clinical Improvement (TTCI) defined as the time from enrollment to discharge or a decline of two steps on the clinical seven-step ordinal scale, whichsoever came first. A total of 60 severely ill patients with positive RT-PCR and Chest CT scans underwent randomization (20 patients to each arm). In the Intention-To-Treat population, IFNß1a was associated with a significant difference against the control group, in the TTCI; (HR; 2.36, 95% CI 1.10-5.17, P-value = 0.031) while the IFNß1b indicated no significant difference compared with the control; HR; 1.42, (95% CI 0.63-3.16, P-value = 0.395). The median TTCI for both of the intervention groups was five days vs. seven days for the control group. The mortality was numerically lower in both of the intervention groups (20% in the IFNß1a group and 30% in the IFNß1b group vs. 45% in the control group). There were no significant differences between the three arms regarding the adverse events. In patients with laboratory-confirmed SARS-CoV-2 infection, as compared with the base therapeutic regiment, the benefit of a significant reduction in TTCI was observed in the IFNß1a arm. This finding needs further confirmation in larger studies.Trial Registration Number: ClinicalTrials.gov, NCT04343768. (Submitted: 08/04/2020; First Online: 13/04/2020) (Registration Number: NCT04343768).

Post-mortem Histopathologic Findings of Vital Organs in Critically Ill Patients with COVID-19.

BACKGROUND: The scientific evidence concerning pathogenesis and immunopathology of the coronavirus disease 2019 (COVID-19) is rapidly evolving in the literature. To evaluate the different tissues obtained by biopsy and autopsy from five patients who expired from severe COVID-19 in our medical center. METHODS: This retrospective study reviewed five patients with severe COVID-19, confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and imaging, to determine the potential correlations between histologic findings with patient outcome. RESULTS: Diffuse alveolar damage (DAD) and micro-thrombosis were the most common histologic finding in the lung tissues (4 of 5 cases), and immunohistochemical (IHC) findings (3 of 4 cases) suggested perivascular aggregation and diffuse infiltration of alveolar walls by CD4+ and CD8+ T lymphocytes. Two of five cases had mild predominantly perivascular lymphocytic infiltration, single cell myocardial necrosis and variable interstitial edema in myocardial samples. Hypertrophic cardiac myocytes, representing hypertensive cardiomyopathy was seen in one patient and CD4+ and CD8+ T lymphocytes were detected on IHC in two cases. In renal samples, acute tubular necrosis was observed in 3 of 5 cases, while chronic tubulointerstitial nephritis, crescent formation and small vessel fibrin thrombi were observed in 1 of 5 samples. Sinusoidal dilation, mild to moderate chronic portal inflammation and mild mixed macro- and micro-vesicular steatosis were detected in all liver samples. CONCLUSION: Our observations suggest that clinical pathology findings on autopsy tissue samples could shed more light on the pathogenesis, and consequently the management, of patients with severe COVID-19.

The Role of Anxiety and Cortisol in Outcomes of Patients With Covid-19.

INTRODUCTION: The outbreak due to Coronavirus Disease 2019 (COVID-19) is n global public health emergency and challenges psychological resilience. The central nervous system, endocrine system, and immune system are complex interacting systems. Cortisol has been implicated as the cause of a wide range of mental and physical health disorders; however, the impact of cortisol on outcomes in patients with COVID-19 is not clear. METHODS: The current study enrolled patients with COVID-19 (onset of disease within 7 days of the first symptom) to evaluate the serum concentration of cortisol and levels of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS) to investigate a possible relationship between cortisol, depression, and anxiety levels and outcomes of patients with COVID-19. RESULTS: A total of 30 patients with COVID-19 were studied. The levels of cortisol and HADS score in patients who died of Covid-19 were significantly higher in comparison with surviving patients (P<0.017 and P<0.001 respectively). We also found that the HADS score was positively correlated with serum cortisol levels (r= 0.842, P=0.004). CONCLUSION: Our findings showed that stress and anxiety are associated with patients' outcomes. Psychological interventions can improve the mental health of vulnerable groups during the COVID-19 epidemic.