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.

Effect of one-shot cognitive behavioral therapy on insomnia and heart rate variability of health care workers at the time of COVID-19 pandemic: a randomized controlled trial.

OBJECTIVES: The emergence of sleep disturbances in response to major stressful events has been previously documented. Heart rate variability (HRV) is an objective marker that provides insight into autonomic nervous system dynamics. The aim of the present study was to examine the preliminary effectiveness of a one-shot session of cognitive behavioral therapy for insomnia (CBT-I) for frontline healthcare providers with acute insomnia. METHODS: This study was conducted from 2020 to 2021 on healthcare workers with insomnia. The healthcare workers were randomly allocated to receive either one-shot cognitive behavioral therapy or routine care. Insomnia severity index (ISI) and heart rate variability were assessed before and 1 month after the interventions. RESULTS: Among 57 patients (n = 31 in the intervention group and n = 26 in the control group), mean (± SD) age of both groups were 34.6 (± 9.5) and 36.6 (± 6.9), respectively. Most participants in both groups were female (81% and 65% in the intervention and control groups, respectively; p-value = 0.10). Insomnia severity index score decreased in the intervention group from 13.3 to 6.7 (p < 0.001). The change before and after the intervention was significant between the two groups for HF-normalized unit (high-frequency power band [0.15-0.40 Hz] in the normalized unit) and LF/HF (the ratio of low frequency to high frequency). HF-normalized unit increased in the intervention group (35.8 ± 21.5 vs. 45.6 ± 19.8 before and after the intervention, respectively), and decreased in the control group (43.9 ± 16.5 vs. 39.8 ± 18.5, before and after the intervention, respectively). CONCLUSION: The findings suggest that a single-shot session of cognitive behavioral therapy for insomnia is effective in managing acute insomnia symptoms in healthcare workers.

Secondary Bacterial Infection and Clinical Characteristics in Patients With COVID-19 Admitted to Two Intensive Care Units of an Academic Hospital in Iran During the First Wave of the Pandemic.

Data on the prevalence of bacterial co-infections and secondary infection among adults with COVID-19 admitted to the intensive care unit (ICU) are rare. We aimed to determine the frequency of secondary bacterial infection, antibiotic use, and clinical characteristics in patients admitted to the ICU with severe SARS-CoV-2 pneumonia. This was a retrospective cohort study of adults with severe COVID-19 admitted to two ICUs from March 6 to September 7, 2020 in an academic medical center in Isfahan, Iran. To detect COVID-19, reverse transcription real-time polymerase chain reaction was performed and also typical pattern of CT scan was used for the diagnosis of COVID-19. Data collection included the age, gender, main symptoms, history of underlying disease, demographics, hospital stay, outcomes, and antibiotic regimen of the patient. Antimicrobial susceptibility testing was carried out according to the CLSI guidelines. During the study period, 553 patients were referred to the both ICUs for COVID-19 with severe pneumonia. Secondary bacterial infection was detected in 65 (11.9%) patients. The median age was 69.4 (range 21-95) years; 42 (63.6%) were men. Notably, 100% (n = 65) of the patients with superinfection were prescribed empirical antibiotics before first positive culture, predominantly meropenem (86.2%) with a median duration of 12 (range 2-32) days and levofloxacin (73.8%) with a median duration of nine (range 2-24) days. Most prevalent causative agents for secondary bacterial infection were Klebsiella pneumoniae (n = 44) and Acinetobacter baumannii (n = 33). Most patients with secondary bacterial infection showed extensive drug-resistance. The mortality among patients who acquired superinfections was 83% against an overall mortality of 38.1% in total admitted COVID-19 patients. We found a high prevalence of carbapenem-resistant Gram-negative bacilli in COVID-19 patients admitted to our ICUs, with a high proportion of K. pneumoniae followed by A. baumannii. These findings emphasize the importance of implementation of strict infection control measures and highlight the role of antimicrobial stewardship during a pandemic.

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.

Risk Factors for the Mortality in Hospitalized Patients with COVID-19: A Brief Report.

The cumulative rate of death of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has necessitated better recognizing the risk factors of the disease and the COVID-19-induced mortality. This cross-sectional study aimed to determine the potential risk factors that predict COVID-19-related mortality concentrating on the initial recorded laboratory tests. We extracted admission's medical records of a total of 136 deaths related to COVID-19 and 272 discharged adult inpatients (≥18 years old) related to four referral centers from February 24th to April 12th, 2020, in Isfahan, Iran, to figure out the relationship between the laboratory findings and mortality beyond demographic and clinical findings. We applied the independent sample t test and a chichi square test with SPSS software to compare the differences between the survivor and non-survivor patients. A P value of less than 0.05 was considered significant. Our results showed that greater length of hospitalization (P≤0.001), pre-existing chronic obstructive pulmonary disease (P≤0.001), high pulse rate, hypoxia (P≤0.001), and high computed tomography scan score (P<0.001), in addition to high values of some laboratory parameters, increase the risk of mortality. Moreover, high neutrophil/lymphocyte ratio (OR, 1.890; 95% CI, 1.074-3.325, P=0.027), increased creatinine levels (OR, 15.488; 95% CI, 0.801-299.479, P=0.07), and elevated potassium levels (OR, 13.400; 95% CI, 1.084-165.618, P=0.043) independently predicted in-hospital death related to COVID-19 infection. These results emphasized the potential role of impaired laboratory parameters for the prognosis of fatal outcomes in adult inpatients.

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.

Absolute mortality risk assessment of COVID-19 patients: the Khorshid COVID Cohort (KCC) study.

BACKGROUND: Already at hospital admission, clinicians require simple tools to identify hospitalized COVID-19 patients at high risk of mortality. Such tools can significantly improve resource allocation and patient management within hospitals. From the statistical point of view, extended time-to-event models are required to account for competing risks (discharge from hospital) and censoring so that active cases can also contribute to the analysis. METHODS: We used the hospital-based open Khorshid COVID Cohort (KCC) study with 630 COVID-19 patients from Isfahan, Iran. Competing risk methods are used to develop a death risk chart based on the following variables, which can simply be measured at hospital admission: sex, age, hypertension, oxygen saturation, and Charlson Comorbidity Index. The area under the receiver operator curve was used to assess accuracy concerning discrimination between patients discharged alive and dead. RESULTS: Cause-specific hazard regression models show that these baseline variables are associated with both death, and discharge hazards. The risk chart reflects the combined results of the two cause-specific hazard regression models. The proposed risk assessment method had a very good accuracy (AUC = 0.872 [CI 95%: 0.835-0.910]). CONCLUSIONS: This study aims to improve and validate a personalized mortality risk calculator based on hospitalized COVID-19 patients. The risk assessment of patient mortality provides physicians with additional guidance for making tough decisions.

Hemoperfusion in patients with severe COVID-19 respiratory failure, lifesaving or not?

BACKGROUND: The new coronavirus outbreak quickly filled hospital beds and stunned the world. Intensive care is required for 5% of patients, and the mortality rate for critically ill patients is 49%. The "cytokine storm" is considered as the main cause of pathogenesis for coronavirus disease-19 (COVID-19)-related respiratory failure, hemoperfusion may be a modality for treatment of disease. MATERIALS AND METHODS: Thirty-seven an patients with positive real-time polymerase chain reaction for SARStions2 in an upper respiratory tract sample or typical chest computed tomography lesion were eligible for this case-control study. Patients meeting the criteria for hemoperfusion including clinical and laboratory indices, were evaluated for outcomes such as hospitalization length and mortality. Patients were divided into three groups, i.e., patients who received hemoperfusion without a need for mechanical ventilation (MV), patients who received hemoperfusion before MV, and patients who received hemoperfusion after MV. RESULTS: Among 37 patients with COVID-19 respiratory failure, 32% were female with a mean age of 55.54 (standard deviation 14.1) years. There was no statistically significant difference between the three groups in terms of length of hospital stay and intensive care unit (ICU) stay (P-tayns: 0.593 and 0.243, respectively, confidence interval [CI]: 95%). Heart rate, respiratory rate, PaO2/FIO2, high-sensitivity C-reactive protein, and ferritin significantly improved after the application of hemoperfusion in all groups (P < 0.05, CI: 95%). CONCLUSION: It seems that applying hemoperfusion in the inflammatory phase of the disease, especially before the intubation, reduce the need for MV. However, hemoperfusion does not have any impacts on the duration of hospital and ICU stay.

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.

A one-year hospital-based prospective COVID-19 open-cohort in the Eastern Mediterranean region: The Khorshid COVID Cohort (KCC) study.

The COVID-19 is rapidly scattering worldwide, and the number of cases in the Eastern Mediterranean Region is rising. Thus, there is a need for immediate targeted actions. We designed a longitudinal study in a hot outbreak zone to analyze the serial findings between infected patients for detecting temporal changes from February 2020. In a hospital-based open-cohort study, patients are followed from admission until one year from their discharge (the 1st, 4th, 12th weeks, and the first year). The patient recruitment phase finished at the end of August 2020, and the follow-up continues by the end of August 2021. The measurements included demographic, socio-economics, symptoms, health service diagnosis and treatment, contact history, and psychological variables. The signs improvement, death, length of stay in hospital were considered primary, and impaired pulmonary function and psychotic disorders were considered main secondary outcomes. Moreover, clinical symptoms and respiratory functions are being determined in such follow-ups. Among the first 600 COVID-19 cases, 490 patients with complete information (39% female; the average age of 57±15 years) were analyzed. Seven percent of these patients died. The three main leading causes of admission were: fever (77%), dry cough (73%), and fatigue (69%). The most prevalent comorbidities between COVID-19 patients were hypertension (35%), diabetes (28%), and ischemic heart disease (14%). The percentage of primary composite endpoints (PCEP), defined as death, the use of mechanical ventilation, or admission to an intensive care unit was 18%. The Cox Proportional-Hazards Model for PCEP indicated the following significant risk factors: Oxygen saturation < 80% (HR = 6.3; [CI 95%: 2.5,15.5]), lymphopenia (HR = 3.5; [CI 95%: 2.2,5.5]), Oxygen saturation 80%-90% (HR = 2.5; [CI 95%: 1.1,5.8]), and thrombocytopenia (HR = 1.6; [CI 95%: 1.1,2.5]). This long-term prospective Cohort may support healthcare professionals in the management of resources following this pandemic.