Frequency of delirium and its associated factors among COVID-19 inpatients in Iran.

BACKGROUND AND AIM: Delirium has been presented as the leading cause of sudden change in the mental state of patients with coronavirus disease 2019 (COVID-19). Given that the delayed diagnosis of such a dysfunction is often associated with excess mortality, it seems essential to devote vastly more attention to this significant clinical characteristic. MATERIALS AND METHODS: This cross-sectional study was performed on 309 patients [viz. 259 cases hospitalized in general wards and 50 individuals admitted to the intensive care unit (ICU)]. For this purpose, a Demographic-Clinical Information Questionnaire, the Confusion Assessment Method (CAM), the Confusion Assessment Method for the ICU (CAM-ICU), the Richmond Agitation-Sedation Scale (RASS) and face-to-face interviews were completed by a trained senior psychiatry resident. The data analysis was further done with the SPSS Statistics V22.0 software package. RESULTS: Out of 259 patients admitted to the general wards and 50 cases in the ICU due to COVID-19, 41 (15.8%) and 11 (22%) individuals were diagnosed with delirium, respectively. As well, a significant relationship was observed between the incidence rate of delirium and age (p < 0.001), level of education (p < 0.001), hypertension (HTN) (p = 0.029), a history of stroke (p = 0.025), a history of ischemic heart disease (IHD) (p = 0.007), a history of psychiatric disorders, a history of cognitive impairment (p < 0.001), use of hypnotic and antipsychotic medications (p < 0.001) and a history of substance abuse (p = 0.023). Among 52 patients with delirium, only 20 cases had received psychiatric consultation by consultation-liaison psychiatry service for the possibility of delirium. CONCLUSION: In view of the high frequency of delirium among COVID-19 inpatients, their screening for this important mental state should be a priority in clinical settings.

Efficacy and safety of adding fluoxetine to the treatment regimen of hospitalized patients with non-critical COVID-19 pneumonia: A double-blind randomized, placebo-controlled clinical trial.

INTRODUCTION: Selective serotonin reuptake inhibitors are considered the drugs, whose effectiveness in viral pandemics has been studied. The aim of this study was to evaluate of adding fluoxetine to the treatment regimen of patients with COVID-19 pneumonia. METHODS: This study was a double-blind randomized placebo controlled clinical trial .36 patients in the fluoxetine and 36 patients in the placebo group were enrolled. Patients in the intervention group were first treated with fluoxetine 10 mg for 4 days and then the dose of 20 mg was continued for 4 weeks. Data analysis was conducted using SPSS V. 22.0. RESULTS: There was no statistically significant difference between the two groups in terms of clinical symptoms at the beginning of the study and also the score of anxiety and depression, oxygen saturation at the time of hospitalization, mid-hospitalization and discharge periods. The need for mechanical ventilator support (p = 1.00), the need for admission in the intensive care unit (ICU) (p = 1.00), rate for mortality (p = 1.00), and discharge with relative recovery (p = 1.00) were not significantly different between the two groups. The distribution of CRP within the study groups showed a significant decrease during different time periods (p = 0.001), and although there was no statistically significant difference between the two groups on the first day (p = 1.00) and at discharge (p = 0.585), mid-hospital CRP showed a significant decrease in the fluoxetine group (p = 0.032). CONCLUSION: Fluoxetine resulted in a faster reduction of patients' inflammation without association with depression and anxiety.

Non-effectiveness of Ivermectin on Inpatients and Outpatients With COVID-19; Results of Two Randomized, Double-Blinded, Placebo-Controlled Clinical Trials.

Background: Ivermectin which was widely considered as a potential treatment for COVID-19, showed uncertain clinical benefit in many clinical trials. Performing large-scale clinical trials to evaluate the effectiveness of this drug in the midst of the pandemic, while difficult, has been urgently needed. Methods: We performed two large multicenter randomized, double-blind, placebo-controlled clinical trials evaluating the effectiveness of ivermectin in treating inpatients and outpatients with COVID-19 infection. The intervention group received ivermectin, 0.4mg/kg of body weight per day for 3 days. In the control group, placebo tablets were used for 3 days. Results: Data for 609 inpatients and 549 outpatients were analyzed. In hospitalized patients, complete recovery was significantly higher in the ivermectin group (37%) compared to placebo group (28%; RR, 1.32 [95% CI, 1.04-1.66]; p-value = 0.02). On the other hand, the length of hospital stay was significantly longer in the ivermectin group with a mean of 7.98 ± 4.4 days compared to the placebo receiving group with a mean of 7.16 ± 3.2 days (RR, 0.80 [95% CI, 0.15-1.45]; p-value = 0.02). In outpatients, the mean duration of fever was significantly shorter (2.02 ± 0.11 days) in the ivermectin group versus (2.41 ± 0.13 days) placebo group with p value = 0.020. On the day seventh of treatment, fever (p-value = 0.040), cough (p-value = 0.019), and weakness (p-value = 0.002) were significantly higher in the placebo group compared to the ivermectin group. Among all outpatients, 7% in ivermectin group and 5% in placebo group needed to be hospitalized (RR, 1.36 [95% CI, 0.65-2.84]; p-value = 0.41). Also, the result of RT-PCR on day five after treatment was negative for 26% of patients in the ivermectin group versus 32% in the placebo group (RR, 0.81 [95% CI, 0.60-1.09]; p-value = 0.16). Conclusion: Our data showed, ivermectin, compared with placebo, did not have a significant potential effect on clinical improvement, reduced admission in ICU, need for invasive ventilation, and death in hospitalized patients; likewise, no evidence was found to support the prescription of ivermectin on recovery, reduced hospitalization and increased negative RT-PCR assay for SARS-CoV-2 5 days after treatment in outpatients. Our findings do not support the use of ivermectin to treat mild to severe forms of COVID-19. Clinical Trial Registration: www.irct.ir IRCT20111224008507N5 and IRCT20111224008507N4.

Evaluation of Antiphospholipid Antibodies in COVID-19 Patients with Coagulopathy.

Background: Due to the importance of recent published studies regarding the thrombotic events in COVID-19 patients, the purpose of this study was to evaluate the frequency of antiphospholipid antibodies in COVID-19 patients with coagulopathy. Materials and Methods: The present cross-sectional study was conducted on COVID-19 patients with coagulopathy admitted to Imam Khomeini Hospital in Sari, Iran, between June and September in 2020. Later on, the levels of anti-phospholipid antibodies (aPL-ab) and biochemical factors were measured. Results: This study was performed on 40 patients. Individuals who were positive for at least one of the aPL-ab were classified in the group of aPL-ab positive; according to which 29 patients (72.5%) had no positive aPL-ab and 11 patients (27.5%) had at least one positive aPL-ab. 8 patients were only positive for lupus anticoagulant (LA) assay, one patient had B2GPI- IgM, one patient had aCL-IgG and only one patient had two positive simultaneous tests for LA and aCL-IgG. Thrombotic events have been found in 7 patients (17.5%) of which, three patients with deep vein thrombosis, one patient with pulmonary embolism, two patients with stroke, and one patient with myocardial infarction. The values of aPTT for the screening of Lupus anticoagulant assay were significantly different between the two groups, although there was no significant difference between the two groups in the co-morbidities, disease severity, death and laboratory tests (P> 0.05). Conclusion: Despite the high incidence of thrombotic complications reported in COVID-19 patients in the current study, the levels of antiphospholipid antibodies had no significant correlation with the occurrence of thromboembolic events and disease outcome in COVID-19 patients with coagulopathy.

Occupational burnout in Iranian health care workers during the COVID-19 pandemic.

BACKGROUND AND AIM: Health care workers (HCWs), mostly frontliners, are encountering numerous physical and psychosocial stressors, and even managing some conflicts over the course of the novel coronavirus disease 2019 (COVID-19). In this respect, the present study was to investigate the prevalence rate of occupational burnout (OB) in such workers during this pandemic. MATERIALS AND METHODS: This cross-sectional study was conducted between April 6 and May 30, 2020, via an online survey in 31 provinces of Iran, on HCWs selected based on convenience sampling method. For data collection, a socio-demographic information form and the Maslach Burnout Inventory (MBI) was utilized. Descriptive statistics, Chi-square test, and multivariate regression analysis were also applied to test the research hypotheses. RESULTS: In total, 7626 HCWs participated in the present study. Accordingly, 73.2 and 26.8% of the workers were female and male, respectively. As well, 57.8% of the respondents were nurses and 14.4% of the cases were clinicians. Moreover, 44.8% of the participants had thus far worked in isolation wards and 40.3% of these individuals reported working for 4-8 hours with COVID-19 patients. The prevalence rate of OB was 18.3%. Besides, 34.2, 48.7, and 56.1% of the respondents had severe levels of emotional exhaustion (EE), higher depersonalization (DP), and decreased sense of personal accomplishment (PA), respectively. Besides, the HCWs at the age range of 20 to 30, having female gender, no children, and a bachelor's degree, and working in isolation wards showed the higher levels of OB with reference to the Chi-square test results (p < 0.001). Accordingly, the statistical test outcomes demonstrated that a history of physical illnesses (p = 0.001) and psychiatric disorders (p = 0.044) could be the best predictor of OB throughout the first peak of the COVID-19 pandemic. CONCLUSION: Regarding the high prevalence rate of OB among the HCWs and the remaining COVID-19 journey in Iran, health care managers are recommended to orient the required management and coping strategies toward improving mental health in these individuals.

Non-effectiveness of Ivermectin on Inpatients and Outpatients With COVID-19;Results of Two Randomized, Double-Blinded, Placebo-Controlled Clinical Trials

Background Ivermectin which was widely considered as a potential treatment for COVID-19, showed uncertain clinical benefit in many clinical trials. Performing large-scale clinical trials to evaluate the effectiveness of this drug in the midst of the pandemic, while difficult, has been urgently needed. Methods We performed two large multicenter randomized, double-blind, placebo-controlled clinical trials evaluating the effectiveness of ivermectin in treating inpatients and outpatients with COVID-19 infection. The intervention group received ivermectin, 0.4mg/kg of body weight per day for 3 days. In the control group, placebo tablets were used for 3 days. Results Data for 609 inpatients and 549 outpatients were analyzed. In hospitalized patients, complete recovery was significantly higher in the ivermectin group (37%) compared to placebo group (28%;RR, 1.32 [95% CI, 1.04–1.66];p-value = 0.02). On the other hand, the length of hospital stay was significantly longer in the ivermectin group with a mean of 7.98 ± 4.4 days compared to the placebo receiving group with a mean of 7.16 ± 3.2 days (RR, 0.80 [95% CI, 0.15–1.45];p-value = 0.02). In outpatients, the mean duration of fever was significantly shorter (2.02 ± 0.11 days) in the ivermectin group versus (2.41 ± 0.13 days) placebo group with p value = 0.020. On the day seventh of treatment, fever (p-value = 0.040), cough (p-value = 0.019), and weakness (p-value = 0.002) were significantly higher in the placebo group compared to the ivermectin group. Among all outpatients, 7% in ivermectin group and 5% in placebo group needed to be hospitalized (RR, 1.36 [95% CI, 0.65–2.84];p-value = 0.41). Also, the result of RT-PCR on day five after treatment was negative for 26% of patients in the ivermectin group versus 32% in the placebo group (RR, 0.81 [95% CI, 0.60–1.09];p-value = 0.16). Conclusion Our data showed, ivermectin, compared with placebo, did not have a significant potential effect on clinical improvement, reduced admission in ICU, need for invasive ventilation, and death in hospitalized patients;likewise, no evidence was found to support the prescription of ivermectin on recovery, reduced hospitalization and increased negative RT-PCR assay for SARS-CoV-2 5 days after treatment in outpatients. Our findings do not support the use of ivermectin to treat mild to severe forms of COVID-19. Clinical Trial Registration www.irct.ir IRCT20111224008507N5 and IRCT20111224008507N4.

Fiberoptic Bronchoscopic Findings in Patients Suffering from Emerging Pulmonary Lophomoniasis: A First Registry-Based Clinical Study.

Background: Lophomonas blattarum is an emerging protozoan agent that mainly infects the lower respiratory system, causing pulmonary lophomoniasis. The bronchoscopic findings in patients with pulmonary lophomoniasis have not been investigated yet. Accordingly, we assess the bronchoscopic findings of lophomoniasis in patients suffering from pulmonary lophomoniasis through a registry-based clinical study. Methods: In this retrospective study, of 480 patient candidates for bronchoscopy, 50 Lophomonas-positive patients were enrolled. Demographic data, relevant characteristics, and bronchoscopy findings of the patients were recorded and analyzed. Results: Overall, 50 (male = 32, female = 18) patients with an average age of 61.8 ± 13.3 years were examined. Nineteen patients (38%) had normal bronchoscopic findings, and 31 patients (62%) had abnormal bronchoscopic findings. According to the severity index, most (52%) of patients had mild severity, followed by moderate (30%) and severe (18%) cases. The highest involvement was in the right lung bronchus (46%), and the lowest was in the carina (8%). Furthermore, purulent and mucosal secretions in the right and left lung bronchus were the most abnormalities found in different anatomical locations. Conclusion: For the first time, the current study demonstrated that pulmonary lophomoniasis does not have pathognomonic bronchoscopic findings. However, each suspected patient must be checked for lophomoniasis, even with normal bronchoscopic findings, particularly in endemic areas.

First Co-morbidity of Lophomonas blattarum and COVID-19 Infections: Confirmed Using Molecular Approach.

INTRODUCTION: Lophomoniasis is caused by Lophomonas spp., a new emerging protozoan, which commonly affects the human lower respiratory tract. The Lophomonas parasite mostly lives commensally in the hindgut of cockroaches. CASE PRESENTATION: We present the case of a 33-year-old woman, 30 weeks pregnant, who had severe COVID-19. She was intubated upon admission and began the routine COVID-19 treatment. To rule out possible super infection dual with COVID-19, microscopic examination of the patient's mini-bronchoalveolar lavage (mini-BAL) specimen, revealed L. blattarum, which was identified by the SSU rRNA-PCR and sequencing approaches (accession number: MZ093069). According to that, the patient was treated successfully with metronidazole. CONCLUSION: To prevent serious complications, lophomoniasis should be listed in co-morbidity cases of COVID-19 infection during the COVID-19 pandemic worldwide. To the best of our knowledge, this is the first co-infection of Lophomonas blattarum and COVID-19 in the world which has been confirmed using a molecular approach.

First Co-morbidity of Lophomonas blattarum and COVID-19 Infections: Confirmed Using Molecular Approach

Introduction Lophomoniasis is caused by Lophomonas spp., a new emerging protozoan, which commonly affects the human lower respiratory tract. The Lophomonas parasite mostly lives commensally in the hindgut of cockroaches. Case Presentation We present the case of a 33-year-old woman, 30 weeks pregnant, who had severe COVID-19. She was intubated upon admission and began the routine COVID-19 treatment. To rule out possible super infection dual with COVID-19, microscopic examination of the patient's mini-bronchoalveolar lavage (mini-BAL) specimen, revealed L. blattarum, which was identified by the SSU rRNA-PCR and sequencing approaches (accession number: MZ093069). According to that, the patient was treated successfully with metronidazole. Conclusion To prevent serious complications, lophomoniasis should be listed in co-morbidity cases of COVID-19 infection during the COVID-19 pandemic worldwide. To the best of our knowledge, this is the first co-infection of Lophomonas blattarum and COVID-19 in the world which has been confirmed using a molecular approach.

Melatonin effects on sleep quality and outcomes of COVID-19 patients: An open-label, randomized, controlled trial.

This trial aims to evaluate the effectiveness of adding melatonin to the treatment protocol of hospitalized coronavirus disease 2019 (COVID-19) patients. This was an open-label, randomized controlled clinical trial in hospitalized COVID-19 patients. Patients were randomized into a treatment arm receiving melatonin plus standard care or a control arm receiving standard care alone. The trial's primary endpoint was sleep quality examined by the Leeds Sleep Evaluation Questionnaire (LSEQ). The trial's secondary endpoints were symptoms alleviation by Day 7, intensive care unit admission, 10-day mortality, white blood cell count, lymphocyte count, C-reactive protein status, and peripheral capillary oxygen saturation. Ninety-six patients were recruited and allocated to either the melatonin arm (n = 48) or control arm (n = 48). Baseline characteristics were similar across treatment arms. There was no significant difference in symptoms on Day 7. The mean of the LSEQ scores was significantly higher in the melatonin group (p < 0.001). There was no significant difference in laboratory data, except for blood oxygen saturation, which has improved significantly in the melatonin group compared with the control group (95.81% vs. 93.65% respectively, p = 0.003). This clinical trial study showed that the combination of oral melatonin tablets and standard treatment could substantially improve sleep quality and blood oxygen saturation in hospitalized COVID-19 patients.

Alkaline phosphatase and score of HRCT as indicators for predicting the severity of COVID-19.

BACKGROUND: The clinical symptoms, blood laboratory data, O2 saturation and high-resolution computed tomography (HRCT) findings are critical factors in diagnosis of COVID-19 infection. METHODS: In this study, 105 hospitalized patients suspected of having COVID-19 were evaluated. Finally, the laboratory and HRCT and related factors data of 83 confirmed cases by HRCT and RT-PCR were analyzed. To compare the median of quantitative variables in the two groups, the Mann-Whitney U test was used. Also, to determine the factors associated with the positiveness of the HRCT result, a univariate logistic model was fitted. Moreover, receiver operating characteristic (ROC) curves were constructed to test the ability of the final model to predict the positiveness of HRCT result. RESULTS: 61.40% of the patients had a comorbidity disease. 89.20% had fever, 92.00% cough, 91.40% dyspnea. Abnormal CRP was seen in 77.80% of the patients, followed by 66.70% lymphopenia, and 60.30% neutrophilia. Also, ALP (abnormal vs. normal) and score of HRCT assessment variables had a significant effect on the positiveness of HRCT findings. 87.95% had abnormal HRCT with 41% bilateral multi lobar patchy ground glass opacity (GGO). Moreover, there was a statistically significant association between the level of O2 saturation and HRCT results. CONCLUSION: Our findings showed that male patients with middle age and comorbidity disease were more susceptible to the COVID-19 infection. Additionally, clinical features, blood laboratory findings, O2 saturation and HRCT findings are critical factors in the prognosis of COVID-19 infection.

Apoptosis and immunophenotyping of peripheral blood lymphocytes in Iranian COVID-19 patients: Clinical and laboratory characteristics.

A novel member of human coronavirus, named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has been recently recognized in China and rapidly spread worldwide. Studies showed the decreasing of peripheral blood lymphocytes in a majority of patients. In this study, we have reported the clinical features, laboratory characteristics, the frequency of peripheral blood lymphocyte subpopulations, and their apoptosis pattern in Iranian coronavirus infectious disease (COVID-19) patients. Demographic and clinical data of 61 hospitalized confirmed cases with COVID-19 at Imam Khomeini Hospital were collected and analyzed. Peripheral blood mononuclear cells were isolated from all samples and the apoptosis pattern was evaluated using Annexin V/propidium iodide method. The frequency of lymphocyte subsets, including T-CD4+ , T-CD8+ , NK, B cells, and monocytes, was measured in all patients and 31 controls by flow cytometry. Our findings demonstrated that the percentage of lymphocytes, CD4+ , and CD8+ T cells were decreased in COVID-19 patients compared with the control group. Regarding the clinical severity, the number of lymphocytes, CD4+ , CD8+ T cells, and NK cells were also decreased in severe cases when compared with mild cases. Finally, our data have also indicated the increase in apoptosis of mononuclear cells from COVID-19 patients which was more remarkable in severe clinical cases. The frequency of immune cells is a useful indicator for prediction of severity and prognosis of COVID-19 patients. These results could help to explain the immunopathogenesis of SARS-CoV-2 and introducing novel biomarkers, therapeutic strategies, and vaccine candidates.

Cytokine profiling in Iranian patients with COVID-19; association with clinical severity.

BACKGROUND: SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is recognized for the first time in Wuhan, China. The cytokine storm is a known factor causing major clinical symptoms leading to death in COVID-19 patients. OBJECTIVE: To investigate and compare the serum levels of different cytokines in COVID-19 patients with different clinical severity. METHODS: Concentrations of serum cytokines, including IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, IFN-γ, and GM-CSF, were measured in 61 COVID-19 patients and 31 normal controls with ELISA. We investigated the correlation between the levels of these cytokines and clinical severity, CRP level, neutrophil and lymphocyte count in patients with COVID-19. RESULTS: Our data indicated that the levels of IL-1ß, IL-2, IL-4, IL-6, IL-8, TNF-α, IFN-γ, and GM-CSF, but not IL-10 were significantly increased in COVID-19 patients compared to normal controls. Statistical analysis showed that the level of IL-1ß, IL-2, IL-4, IL-6, IL-8, TNF-α, IFN-γ, and GM-CSF were higher in severe COVID-19 than those of mild cases. The concentrations of all mentioned cytokines were negatively associated with the absolute count of lymphocytes, and positively correlated with the CRP level and the absolute count of neutrophils. CONCLUSION: The current study suggests that high levels of various cytokines correlate with the disease severity and immunopathogenesis of COVID-19.