Steroid in the Treatment of Outpatient COVID-19: A Multicenter Randomized Controlled Trial.

Background: Early treatment of COVID-19 patients could reduce hospitalization and death. The effect of corticosteroids in the outpatient setting is still unknown. This study aimed to determine the effect of corticosteroids in the prevention of hospitalization of nonsevere cases. Materials and Methods: This study is a multicenter randomized controlled trial. Seventy five nonsevere COVID-19 patients presented between days 7 and 14 of their symptoms received either prednisolone or placebo. The primary outcome was hospitalization. The study protocol was registered in the Iranian Registry of Clinical Trials on December 2, 2020 (IRCT20171219037964N2). Results: Although the rate of hospitalization in the prednisolone group was higher than the placebo group (10.8% vs. 7.9%, respectively), it was not statistically significant (P value.,6). One patient in each group reported an adverse event and withdrew the medication. Conclusion: Considering the null effect of corticosteroids in the prevention of hospitalization in outpatient settings, it is suggested not to consider corticosteroids for outpatient treatment.

Thalidomide for the Treatment of COVID-19 Pneumonia: A Randomized Controlled Clinical Trial.

Background: Coronavirus disease 2019 has become a public health concern with a high number of fatalities. Thalidomide can target inflammatory mediators and decrease inflammation in SARS-CoV-2. Materials and Methods: An open-label, randomized controlled trial was conducted on patients with compatible lung high-resolution computed tomography scan for COVID-19 pneumonia and moderate involvement. Childbearing-age women were excluded. A total of 20 patients in the control group receiving usual treatment were compared with 26 patients in the case group who in addition to the same regimen also received thalidomide. The primary outcome was time for clinical recovery (TTCR) and intensive-care unit (ICU) admission. Results: From April 25 to August 8, 2020, based on the inclusion criteria, 47 patients were assigned to the study. Patients receiving thalidomide had a mean TTCR of days 5.5 (95% confidence interval [CI], 0.7-10.3), as compared with days 5.3 (95% CI, 1.7-8.9) with control (odds ratio 0.01; 95% CI, -1.58-1.59, P = 0.807). The incidence of ICU admission was 27% in the thalidomide group compared with 20% in the control group (odds ratio 3.89; 95% CI, 0.55-27.4, P = 0.425). The mean length of stay in hospital in both groups was 10 days. Progressive improvement in respiratory rate, fever, and O2 saturation during the study was seen in both groups without a significant difference between the thalidomide and control group (P > 0.05). Conclusion: This study investigated the effects of thalidomide to treat moderate COVID-19 clinical outcomes. The results established that this drug regimen did not add more effect to usual treatment for moderate COVID-19 pneumonia.

Favipiravir in the Treatment of Outpatient COVID-19: A Multicenter, Randomized, Triple-Blind, Placebo-Controlled Clinical Trial.

BACKGROUND: Finding effective outpatient treatments to prevent COVID-19 progression and hospitalization is necessary and is helpful in managing limited hospital resources. Repurposing previously existing treatments is highly desirable. In this study, we evaluate the efficacy of Favipiravir in the prevention of hospitalization in symptomatic COVID-19 patients who were not eligible for hospitalization. METHODS: This study was a triple-blind randomized controlled trial conducted between 5 December 2020 and 31 March 2021 in three outpatient centers in Isfahan, Iran. Patients in the intervention group received Favipiravir 1600 mg daily for five days, and the control group received a placebo. Our primary outcome was the proportion of hospitalized participants from day 0 to day 28. The outcome was assessed on days 3, 7, 14, 21, and 28 through phone calls. RESULTS: Seventy-seven patients were randomly allocated to Favipiravir and placebo groups. There was no significant difference between groups considering baseline characteristics. During the study period, 10.5% of patients in the Favipiravir group and 5.1% of patients in the placebo group were hospitalized, but there was no significant difference between them (p-value = 0.3). No adverse event was reported in the treatment group. CONCLUSIONS: Our study shows that Favipiravir did not reduce the hospitalization rate of mild to moderate COVID-19 patients in outpatient settings.

Positive Pressure Ventilation Treatment Based on Daytime and Night-time Titration in Patients with Obesity Hypoventilation Syndrome: A Randomized Controlled Trial.

Objectives The aim of the present study was to investigate the improvements of gas exchange and excessive daytime sleepiness in patients with obesity hypoventilation syndrome (OHS) in daytime and night-time split polysomnography (DSPSG and NSPSG). Materials and Methods In the present randomized controlled trial, patients with OHS were enrolled in two DSPSG (51 patients) and NSPSG (50 patients) groups in the Bamdad respiratory and sleep research center in Isfahan, Iran. In both groups, the diagnostic polysomnography (PSG) and titration were conducted in one session according to the guidelines of NSPSG. SpO2, PaCO2, and the Epworth Sleepiness Scale (ESS), were measured initially and 12 weeks after treatment. Furthermore, the PSG parameters and the type of treatments for the two groups were recorded and analyzed. Results A total of 101 OHS patients (age: 62.02 ± 12.4 year old; 61 females [60.4%]) were evaluated. There were no significant differences regarding BMI, gender, and AHI between groups ( p > 0.05). Primary SpO2, PaCO2, and ESS were not significantly different between the two groups. After 12 weeks of treatment by continuous positive airway pressure (CPAP) or bi-level positive airway pressure (BiPAP), there were significant improvement of SpO2, PaCO2, and ESS score ( p < 0.001). The amount of change of these variables was not different between groups. Among all variables, only the lower SpO2 and higher PaCO2 were associated with response to BiPAP. Discussion There were no significant differences in the number of changes of SpO2, PaCO2, and ESS by treatment in the DSPSG and NSPSG groups. Therefore, DSPSG may be considered as a valuable alternative method for the diagnosis and titration in OHS patients. Clinical Trials IRCT20170512033930N2.

Non Invasive Ventilation's Effectiveness (NIV) in Patients with Interstitial Lung Disease and Hypercapnic Respiratory Failure.

Background: The therapeutic options for patients with interstitial lung disease (ILD) are limited. On the other hand, the role of noninvasive ventilation (NIV) in ILD management is not clear. This study investigated the effect of nighttime NIV in hypercapnic ILD patients. Materials and Methods: In this unblinded randomized clinical trial, we included a total of 20 ILD patients admitted in a specialized center with hypoxia, PaCO2>45, and HCO3>27. Participants were randomly allocated into two groups; intervention (nighttime NIV plus standard treatment) and control (standard treatment). The severity of dyspnea and the quality of life (QoL) was evaluated at beginning of the trial and after 30 days through Modified medical research council (mMRC) dyspnea scale and the SF-36 health survey questionnaire. Paired or Wilcoxon Signed rank tests and independent samples t-test or Mann-Whiney U test were used for between and within groups analyses, respectively. Results: The mean age of 20 patients enrolled was 62.57±6.67 and 40% were male. Although, a clinical significant improvement of dyspnea was detected in NIV group (P=0.046) after intervention, it was not statistically different from control group. Significant improvement was observed in physical functioning (P<0.001), social functioning (P=0.004) and pain (P=0.003) detected after 30 days in NIV group and the observed improvement in QoL was significantly higher than control group for physical functioning (P=0.042) and general health (0.049). Conclusion: Our results suggest NIV treatment in patients with ILD and hypercapnic respiratory failure could be advised in order to improve physical functioning.

T-cell immunophenotyping in COVID-19 pneumonia.

The COVID-19 epidemic is currently a global threat that has affected many parts of the world. Some patients require intensive care unit admission due to severe symptoms in the course of the disease. The severity of symptoms in this disease varies from person to person. The effectiveness of the immune response against viral infections depends on the number and activity of T-cells, which play an important role in eliminating virus-infected cells. In this study, we report two patients with COVID-19 pneumonia, one with moderate symptoms and the other with severe symptoms. Although a decrease of absolute lymphocyte count was seen in both patients, a more significant decline reported in the ICU-admitted patient. Expression of activated markers, HLA-DR, CD38, on CD8-positive T-cells was shown in a patient with more severe disease. On the other hand, partial loss of CD7 in the severe case was also observed. Hence, besides of the above parameters that already mentioned in other studies, loss of pan T-markers could be considered as a potentially valuable test for predicting disease severity. We suggest evaluating the predictability of these tests in COVID-19 in larger studies. This study was approved by the Ethics Committee of Isfahan University of Medical Sciences (IR.MUI.MED.REC.1399.238).

Association of lymphocyte subsets with mortality in severe COVID-19 pneumonia patients.

BACKGROUND: Few studies have investigated the alterations in the T and B cell counts and related subgroups in pulmonary infections especially COVID-19. Here, we aimed to evaluate total T and B lymphocytes and T cell subgroup counts to find the possible correlation between number of these cells and severity and mortality in COVID-19 patients. METHODS: This study was performed on 40 patients with severe COVID-19 infection confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and chest HRCT in August 2020. By the time of admission, T lymphocytes profile in peripheral blood was investigated using multicolor flow cytometry. The total number of T lymphocytes, CD4+ T cells, CD8+ T cells, and B lymphocytes were calculated. Expression of CD2, CD3, CD5, and CD7 as pan T cell surface markers and expression of CD38 and HLA-DR as activated markers on T lymphocytes were also evaluated. RESULTS: Nine patients (22.5%) died during the study and 16 patients (40%) were admitted to ICU. Deceased patients demonstrated lower amounts of T cell count and CD4+ T cell count (with a marginal difference (p = 0.07)) compared with survived patients at the time of admission. The chance of mortality was significantly higher for patients with CD7 loss (OR = 14.89). A marginally significant relationship was also indicated between CD4<200/ml and mortality (OR = 8.65), but no other significant relationships were observed between variables and ICU admission. CONCLUSION: Altogether, CD7 loss on T lymphocytes and CD4+ T cell count below 200/ml revealed a significant relationship with mortality. Considering T lymphocytes and T cell subgroup count could have a predictive value for patients suffering from COVID-19.

Presentation of COVID-19 infection with bizarre behavior and encephalopathy: a case report.

BACKGROUND: Current studies show that patients with severe coronavirus disease 2019 (COVID-19) have neurological symptoms manifesting as acute cerebrovascular diseases, impaired consciousness, and skeletal muscle symptoms. Bizarre behavior is an unusual and unique presenting symptom of COVID-19 infection in our patient. CASE PRESENTATION: We report a case of COVID-19 infection in a middle aged Iranian man without underlying disease who presented with bizarre behavior. Results of brain imaging were normal, but COVID-19 pneumonia was detected on chest computed tomography scan. Given the respiratory problem and positive polymerase chain reaction (PCR) test for COVID-19, treatment with hydroxychloroquine was administered, and after 2 days all of the symptoms resolved. CONCLUSIONS: Encephalopathy and encephalitis may be a possible presentation of COVID-19. Clinicians and health care providers should consider the presence of COVID-19 with bizarre behavior during this COVID-19 pandemic.

Healthcare workers' sleep and mood disturbances during COVID-19 outbreak in an Iranian referral center.

PURPOSE: This study aimed to assess the frequency of sleep and mood disturbances, and their association with COVID-like symptoms in healthcare workers (HCWs) with and without positive Coronavirus RT-PCR in a corona referral center. METHODS: This study was a cross-sectional, anonymous survey of adult HCWs. Data collection was performed in May and June 2020, while governmental restrictions were in place. The participants completed the forms including six separate parts: personal and occupational information, Insomnia Severity Index (ISI), Generalized Anxiety Disorder-7 (GAD-7), Patient's Health Questionnaire (PHQ-9), Pittsburgh Sleep Quality Index (PSQI), and COVID-like symptoms and Coronavirus RT-PCR status. RESULTS: Among the 372 HCW participants, 245 (66%) were women and  mean age was 34.5 ± 7.1 years (age range 23 to 58). The mean scores of all questionnaires except ISI were significantly higher in the HCWs with positive Coronavirus RT-PCR than another group (PSQI, 9 ± 3.4 vs. 6.9 ± 3.1; GAD-7, 9.8 ± 3.6 vs. 7.9 ± 5.3; PHQ-9, 12.8 ± 6.1 vs. 9.5 ± 6.4, P < 0.05; and ISI, 13.8 ± 5.3 vs. 12.3 ± 6 P = 0.163). Positive association between COVID-like symptoms and sleep and mood disturbances was found in the group without a positive test result. Analysis of questionnaires showed higher scores in the group directly involved except for ISI (P < 0.001 and P = 0.053 respectively). CONCLUSIONS: During the COVID-19 pandemic, the HCWs in this sample experienced a high rate of sleep and mood disturbances. There was also a strong association between sleep and mood disturbances and COVID-like symptoms in the group without a positive RT-PCR result. With all this considered, effective psychological support for HCWs during crisis seems to be necessary.

Cardiac involvement according to echocardiographic findings in severe coronavirus disease 2019.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has led to considerable morbidity and mortality worldwide and myocardial injury has been one of the most common findings in the affected patients. However, published evidence of cardiac evaluation by imaging techniques including echocardiography is rare. We aimed to evaluate myocardial involvement by echocardiography in patients with severe COVID-19. METHODS: We studied 64 patients with severe COVID-19 who were admitted in the intensive care unit (ICU) in Khorshid Hospital, Isfahan, Iran, from February 20, 2020 until May 20, 2020. Demographic characteristics, laboratory tests, and electrocardiography (ECG) data were collected and transthoracic echocardiography (TTE) using a focused time-efficient echocardiography protocol was performed. RESULTS: Mean age of the participating patients was 66.40 ± 14.14 years (range: 34.0-92.0 years), and 35 patients (54.7%) were men. Reduced left ventricular (LV) systolic function was seen in 20 (32%) patients. Only 4 patients had LV ejection fraction (LVEF) less than 40%. Cardiac troponin I (cTn-I) was elevated (over 15 pg/ml) in 39 (60.9%) patients and was significantly associated with higher mortality in these patients (P = 0.05). In addition, dynamic ST and T wave changes and new bundle branch blocks had a significant association with adverse clinical outcome (P = 0.05 and P = 0.02, respectively). CONCLUSION: New LV systolic dysfunction (LVSD) in patients with severe COVID-19 was mild to moderate and not uncommon and had no significant adverse effect on the prognosis of these patients, although elevation of cardiac biomarkers could predict mortality and had an adverse effect on clinical outcome.

G6PD deficiency and aluminum phosphide poisoning.

Aluminum phosphide (ALP) poisoning is one of the fatal poisonings in the world. Hemolysis is a rare presentation of this poisoning. Here, we report an episode of hemolysis due to G6PD deficiency after ingestion of ALP and also the patient survived.

Comparison of the effects of pegylated granulocyte-colony stimulating factor and granulocyte-colony stimulating factor on cytopenia induced by dose-dense chemotherapy in breast cancer patients.

BACKGROUND: Myelosuppression is one of the frequent side effects of chemotherapy in breast cancer patients. Granulocyte-colony stimulating factor (G-CSF) and pegylated G-CSF are used for the prevention of neutropenia after chemotherapy. Pegylated G-CSF has longer half-life of action and can be used as a single dose in comparison to G-CSF. The aim of this study is to compare the grade of cytopenia and side effects between G-CSF and biosimilar pegylated G-CSF in breast cancer patients treated with dose-dense chemotherapy. MATERIALS AND METHODS: In the cross-over clinical trial study, 24 women with breast cancer were randomly divided into two groups and treated with dose-dense chemotherapy. The first group was treated with single dose of 6 mg biosimilar pegylated G-CSF 24 h after the first course of chemotherapy and the second course was followed by 300 µg daily injection of G-CSF for 6 days. The chemotherapy regimen was combination of doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2. The second group was treated with G-CSF after the first course and pegylated G-CSF after the second course. Cell blood count (CBC) and side effects were evaluated 1 and 2 weeks after both courses of chemotherapy. RESULTS: In this study, no significant carryover effect and treatment effect about the CBC parameters was found between pegylated G-CSF and G-CSF. Patients who were treated with biosimilar pegylated G-CSF had significantly higher side effects such as bone pain (P = 0.09) and gastrointestinal effects (P = 0.005) in comparison to G-CSF. CONCLUSION: G-CSF and biosimilar pegylated G-CSF are effective in reducing cytopenia in breast cancer patients treated with dose-dense chemotherapy, but side effects induced by pegylated G-CSF (Pegagen) are higher.

Metabolic syndrome in migraine headache: A case-control study.

BACKGROUND: The correlation of metabolic syndrome and migraine headache was evaluated in some previous studies. However there is no study that compared the prevalence of metabolic syndrome in the patients with and without migraine. Control of coincidental factors such as metabolic syndrome reduces therapeutic resistance in migrainous patients. The aim of this study was to compare prevalence of metabolic syndrome in patients with and without migraine headache. MATERIALS AND METHODS: 200 migrainous patients diagnosed according to International Headache Society and 200 healthy controls without migraine enrolled in this study. Metabolic syndrome was diagnosed according to ATP III criteria in these two groups and compared with each other. RESULTS: In this study, 17% (34) of migrainous patients and 15% (30) of healthy control without migraine had metabolic syndrome. (P = 0.585). Of the metabolic syndrome components, body mass index (P = 0.05) and waist circumference in migrainous (P = 0.03) were significantly more frequent. CONCLUSION: Our results demonstrate that metabolic syndrome and migraine headache had not significant correlation; however, higher body mass index and waist circumference as metabolic syndrome components had correlated with migraine headache.