Efficacy of Hemoperfusion in Severe and Critical Cases of COVID-19.

INTRODUCTION: Uncontrolled overproduction of inflammatory mediators is predominantly observed in patients with severe COVID-19. The excessive immune response gives rise to multiple organ dysfunction. Implementing extracorporeal therapies may be useful in omitting inflammatory mediators and supporting different organ systems. We aimed to investigate the effectiveness of hemoperfusion in combination with standard therapy in critically ill COVID-19 patients. METHOD: We conducted a single-center, matched control retrospective study on patients with confirmed SARS-CoV-2 infection. Patients were treated with hemoperfusion in combination with standard therapy (hemoperfusion group) or standard treatment (matched group). Hemoperfusion or hemoperfusion and continuous renal replacement therapies were initiated in the hemoperfusion group. The patients in the matched group were matched one by one with the hemoperfusion group for age, sex, oxygen saturation (SPO2) at the admission, and the frequency of using invasive mechanical ventilation during hospitalization. Two types of hemoperfusion cartridges used in this study were Jafron© (HA330) and CytoSorb® 300. RESULT: A total of 128 COVID-19-confirmed patients were enrolled in this study; 73 patients were allotted to the matched group and 55 patients received hemoperfusion. The median SPO2 at the admission day in the control and hemoperfusion groups was 80% and 75%, respectively (p value = 0.113). The mortality rate was significantly lower in the hemoperfusion group compared to the matched group (67.3% vs. 89%; p value = 0.002). The median length of ICU stay was statistically different in studied groups (median, 12 days for hemoperfusion group vs. 8 days for the matched group; p < 0.001). The median final SPO2 was statistically higher in the hemoperfusion group than in the matched group, and the median PaCO2 was lower. CONCLUSION: Among critically ill COVID-19 patients, based on our study, the use of hemoperfusion may reduce the mortality rate and improve SPO2 and PaCO2.

Study of the effects of interferon ß-1a on hospitalized patients with COVID-19: SBMU Taskforce on the COVIFERON study.

Interferons are an essential part of the innate immune system and have antiviral and immunomodulatory functions. We studied the effects of interferon ß-1a on the outcomes of severe cases of coronavirus disease 2019 (COVID-19). This retrospective study was conducted on hospitalized COVID-19 patients in Loghman-Hakim hospital from February 20, 2020 to April 20, 2020, Tehran, Iran. Patients were selected from two groups, the first group received interferon ß-1a in addition to the standard treatment regimen, and the second group received standard care. The clinical progression of two groups during their hospital admission was compared. We studied a total number of 395 hospitalized COVID-19 patients. Out of this number, 111 patients (33.5%) died (31.3% of the interferon ß-1a group and 34.1% of the control group). The mortality rate indicated no statistically significant difference between groups (p-value = 0.348), however for patients who were hospitalized for more than a week, the rate of mortality was lower in the interferon ß-1a group (p-value = 0.014). The median hospital stay was statistically longer for patients treated by interferon ß-1a (p-value < 0.001). The results of this study showed that interferon ß-1a can improve the outcomes of hospitalized patients with severe COVID-19, but more adequately-powered randomized controlled trials should be conducted.

Evaluation of the prophylactic effect of hydroxychloroquine on people in close-contact with patients with COVID-19.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has caused significant mortality worldwide. The disease attacks the lung tissue and may lead to acute respiratory distress syndrome. An in vitro study showed that hydroxychloroquine (HCQ) has a prophylactic effect against COVID-19 due to its anti-inflammatory effects. The present study aimed to evaluate the prophylactic effect of HCQ on individuals in close contact with patients with COVID-19. METHOD: In this quasi-trial study, we prescribed HCQ for 7 days to all people who had close contact with a patient with COVID-19. All contacts underwent a nasal swab in two steps, and those positive for COVID-19 were excluded from the study. After 14 days of follow-up, the clinical and laboratory manifestations of COVID-19 were evaluated. RESULTS: A total of 113 participants completed the study. The HCQ group comprised 51 (45.13%) contacts, and 62 (54.86%) contacts were allocated to the control group. According to the results of clinical examination and real-time polymerase chain reaction test, 8 (12.90%) contacts in the control group were reported to have contracted COVID-19. In the HCQ group, 7 (13.72%) contacts were confirmed to have contracted COVID-19. There was no relationship between HCQ use and age, sex, underlying disorders, and laboratory data (all p > 0.05). In terms of HCQ side effects, five participants experienced gastrointestinal and cutaneous side effects that subsided on discontinuation of HCQ. CONCLUSION: The current study showed that HCQ had no prophylactic effect with regard to COVID-19 prevention.

The Interval between External Ventricular Drain (EVD) Implantation and Time to Mobilization in Patients at the Neurosurgery ICU.

AIM: Neurosurgerypatients with external ventricular drain (EVD) who are admitted to ICU often remains at rest due to increased intracranial pressure and it leads to prolonged ICU and hospital LOS, mechanical ventilator (MV) duration, and other adverse effects. So, we aim to describe the interval between EVD implantation and time to mobilization in patients with EVD at the neurosurgery ICU. MATERIAL AND METHODS: A retrospective descriptive study was performed on 131 neurosurgery patients with SAH or ICH admitted to the ICU who underwent EVD. Patients who met the inclusion criteria were evaluated for time to mobilization, level of mobilization, ICU and hospital LOS, duration on MV, and some other factors. RESULTS: Of the 131 patients, 67 survived and 61 started to mobilize in different levels of dangling (26.22%), standing (44.26%), and walking (29.5%). The mean days of time EVD implantation to mobilization was 10.15. Based on the results mean of the days of ICU LOS in patients was 14.56, duration on MV was 7.13, Time to ICU discharge from EVD removal was 7.08, and hospital LOS was 16.98. Also, 7 patients (10.44%) developed DVT and 3 of them (4.47) developed PE. CONCLUSION: Prolonged immobility of patients with EVD has deleterious consequences such as PE and DVT In addition, leads to an increased duration on MV, ICU LOS, and hospital LOS. Therefore, designing an appropriate and standard mobilization protocol and training nursing staff in order to help patients mobilize safely, can greatly reduce the mentioned complications, reduce postoperative care and empower patients.

The Efficacy of High-Dose Pulse Therapy vs. Low-Dose Intravenous Methylprednisolone on Severe to Critical COVID-19 Clinical Outcomes: A Randomized Clinical Trial.

Background: It remains unclear which formulation of the corticosteroid regimen has the optimum efficacies on COVID-19 pneumonia. Objectives: The aim of this study was to compare the clinical outcomes of 2 different regimens in the treatment of acute respiratory distress syndrome (ARDS) caused by COVID-19: Methylprednisolone at a dose of 1 mg/kg every 12 hours (low-dose group) and 1000 mg/day pulse therapy for 3 days following 1 mg/kg methylprednisolone every 12 hours (high-dose group). Methods: In this randomized clinical trial, patients with mild to moderate ARDS due to COVID-19 were randomly assigned to receive either low-dose (n = 47) or high-dose (n = 48) intravenous methylprednisolone regimens. Two groups were matched for age, gender, body mass index (BMI), comorbidities, leukocytes, lymphocytes, neutrophil/lymphocyte, platelet, hemoglobin, and inflammatory markers (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], and ferritin). Both regimens were initiated upon admission and continued for 10 days. The clinical outcome and secondary complications were evaluated. Results: Evaluating in-hospital outcomes, no difference was revealed in the duration of intensive care unit (ICU) stays (5.4 ± 4.6 vs. 4.5 ± 4.9; P = 0.35), total hospital stays (8 ± 3.1 vs. 6.9 ± 3.4; P = 0.1), requirement rate for invasive ventilation (29.2% vs. 36.2%; P = 0.4) or non-invasive ventilation (16.6% vs 23.4%; P = 0.4), and hemoperfusion (16.6% vs 11.3%; P = 0.3) between the low- and high-dose groups. There was no significant difference in fatality due to ARDS (29.2% vs. 38.3%; P = 0.3) and septic shock (4.2% vs. 6.4%; P = 0.3) between the low- and high-dose groups. Patients in the high-dose group had significantly higher bacterial pneumonia co-infection events compared with those in the low-dose group (18.7% vs 10.6%; P = 0.01). Conclusions: The use of adjuvant pulse therapy with intravenous methylprednisolone did not result in improved in-hospital clinical outcomes among patients with mild to moderate ARDS due to COVID-19. A higher risk of bacterial pneumonia should be considered in such cases as receiving a higher dose of steroids.

Altered serum and cerebrospinal fluid TNF-α, caspase 3, and IL 1ß in COVID-19 disease.

Background: We evaluated the levels of the tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and caspase-3 in the cerebrospinal fluid (CSF) and serum of COVID-19 patients to improve our knowledge about underlying mechanisms caused by this virus in central nervous system involvement. Case Presentation: This case series study included six COVID-19 patients from March 26, 2020, to April 17, 2020, and six healthy control patients. CSF and serum levels of TNF-α, IL-1ß, and caspase-3 have been assayed using monoclonal antibodies-based ELISAs.Patients with COVID-19 had significantly higher level of IL-1ß, TNF-α, and caspase-3 in serum (239.16±35.73 pg/ml, 100.50±12.49 pg/ml, 3.58±0.11pg/ml, p < 0.001) and CSF (146.66±17.55 pg/ml, 63.16±14.68 pg/ml,3.22±0.03pg/ml, p<0.001), respectively as compared to control. In addition, our results showed that these biomarkers were significantly higher in serum compared with CSF of the COVID-19 patients (p<0.001). Conclusion: This study provides essential information for understanding the pathogenesis of COVID-19 infection and sheds light on the potential mechanisms of virus transmission. The obtained data could be useful for designing new prevention and treatment strategies for COVID-19.

The Predictive Power of Near-Infrared Spectroscopy in Improving Cognitive Problems in Patients Undergoing Brain Surgeries: A Systematic Review.

One of the main objectives in neurosurgical procedures is the prevention of cerebral ischemia and hypoxia leading to secondary brain injury. Different methods for early detection of intraoperative cerebral ischemia and hypoxia have been used. Near-infrared spectroscopy (NIRS) is a simple, non-invasive method for monitoring cerebral oxygenation increasingly used today. The aim of this study was to systematically review the brain monitoring with NIRS in neurosurgery. The search process resulted in the detection of 324 articles using valid keywords on the electronic databases, including Embase, PubMed, Scopus, Web of Science, and Cochrane Library. Subsequently, the full texts of 34 studies were reviewed, and finally 11 articles (seven prospective studies, three retrospective studies, and one randomized controlled trial) published from 2005 to 2020 were identified as eligible for systematic review. Meta-analysis was not possible due to high heterogeneity in neurological and neurosurgical conditions of patients, expression of different clinical outcomes, and different standard reference tests in the studies reviewed. The results showed that NIRS is a non-invasive cerebral oximetry that provides continuous and measurable cerebral oxygenation information and can be used in a variety of clinical settings.

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.

An investigation into the beneficial effects of high-dose interferon beta 1-a, compared to low-dose interferon beta 1-a in severe COVID-19: The COVIFERON II randomized controlled trial.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has been a serious obstacle in front of public health. Interferon-beta 1a (IFN-ß 1a) has been used to treat patients with COVID-19. We aimed to compare the effectiveness of high-dose IFN-ß 1a compared to low dose IFN-ß 1a in severe COVID-19 cases. METHODS: In this randomized, controlled, and clinical trial, eligible patients with confirmed SARS-CoV-2 infections were randomly assigned to receive one of the two following therapeutic regimens: The intervention group was treated with high-dose IFN-ß 1a (Recigen) (Subcutaneous injections of 88 µg (24 million IU) on days 1, 3, 6) + lopinavir /ritonavir (Kaletra) (400 mg/100 mg twice a day for 10 days, orally) and the control group was treated with low-dose IFN-ß 1a (Recigen) (Subcutaneous injections of 44 µg (12 million IU) on days 1, 3, 6) + lopinavir /ritonavir (Kaletra) (400 mg/100 mg twice a day for 10 days, orally). RESULT: A total of 168 COVID- 19 confirmed patients underwent randomization; 83 were assigned to the intervention group and 85 were assigned to the control group. Median Time To Clinical Improvement (TTIC) for cases treated with low-dose IFN-ß1a was shorter than that for cases treated with high-dose IFN-ß1a (6 vs 10 days; P = 0.018). The mortality rates in intervention and control group were 41% and 36.5%, respectively. CONCLUSION: The use of high-dose IFN-ß 1a did not improve TTCI in hospitalized patients with moderate to severe COVID-19. Also, it did not have any significant effect on mortality reduction compared with treating with low-dose IFN-ß 1a. TRIAL REGISTRATION: This trial has been registered as ClinicalTrials.gov, NCT04521400.

Clinical and Epidemiological Characteristics of Coronavirus Disease 2019 in Iran: a Hospital-Based Observational Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been pandemic and has caused a great burden on almost all countries across the world. Different perspectives of this novel disease are poorly understood. This study sought to investigate the clinical and epidemiological characteristics of COVID-19 to efficiently assist the health system of Iran to conquer the outbreak. MATERIALS AND METHODS: This retrospective observational study was performed on 394 patients with a diagnosis of COVID-19. The patients should have a history of hospitalization at Loghman-Hakim hospital, Tehran, Iran, for 10 weeks, beginning from the first official report of the disease in Iran. In the subsequent step, the baseline demographic and clinical and paraclinical information of the patients was documented. Finally, the patients were assessed if they had exhibited any morbidity or mortality. RESULTS: The epidemiological examination of the COVID-19 population suggested a bell diagram pattern for the hospitalization rate, in which the 4th week of the study was the peak. The highest rate of secondary adverse events due to the virus was observed at the 6th and 7th weeks of the study course. On another note, clinical evaluations resulted in identifying specific abnormalities, such as bilateral opacity in chest computed tomography scans or low oxygen saturation in laboratory data. CONCLUSION: This study provides evidence concerning the clinical and epidemiological characteristics of COVID-19 in the first phase of the virus outbreak in Iran. Further studies comparing the disease features in the subsequent phases with findings of this study can pave the way for additional information in this regard.

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).