The frequency of AmpC overproduction, OprD downregulation and OprM efflux pump expression in Pseudomonas aeruginosa: A comprehensive meta-analysis.

OBJECTIVES: Pseudomonas aeruginosa is a major opportunistic pathogen responsible for a wide range of infections. The emergence of antibiotic resistance in this pathogen poses a significant public health challenge. This study aims to conduct a comprehensive meta-analysis of studies conducted in Iran to determine the frequency of key antibiotic resistance mechanisms in Pseudomonas aeruginosa and their association with multidrug-resistant and extensively drug-resistant strains or pandrug-resistant strains. METHODS: Systematic database searches encompassing literature up to June 2023 were undertaken. The selected studies centered on OprD downregulation, efflux pump (mexAB-OprM, mexXY-OprM) expression, and AmpC overproduction. Extracted data were synthesised in a meta-analysis for pooled frequency determination of each resistance mechanism. RESULTS: In total, 24 studies were included. OprD downregulation exhibited a pooled frequency of 61%. Efflux pump component frequency ranged from 48% to 77.5%. AmpC overproduction was identified in 29.1% of isolates. Polymyxin B and colistin demonstrated lower antibiotic resistance rates, with pooled frequency of 1% and 1.6%, respectively. Conversely, resistance to other antibiotics ranged widely, with pooled frequency spanning 38.4% to 98.2%. CONCLUSIONS: This study underscores the concerning frequency of diverse antibiotic resistance mechanisms in Pseudomonas aeruginosa strains from Iran. Concurrent OprD downregulation, mexAB, mexXY, OprM expression, and AmpC overproduction highlight the urgent need for stringent infection control and prudent antibiotic usage to curb the dissemination of these resistant strains. PROSPERO: CRD42022379311.

Liposomal amphotericin for secondary prophylaxis: A systematic review and meta-analysis.

INTRODUCTION: This systematic review and meta-analysis aimed to determine the safety of liposomal amphotericin B (L-AMB) compared to other antifungal agents for secondary prophylaxis. METHOD: We conducted a comprehensive search across international databases and reference lists of articles to compile all relevant published evidence evaluating the efficacy and safety of L-AMB versus other antifungals (NLAMB) for secondary prophylaxis against invasive fungal infections. Pooled estimates were calculated after data transformation to evaluate mortality, breakthrough infections, and the frequency of adverse effects, including hypokalemia and nephrotoxicity. Comparisons of breakthrough fungal infection and mortality between the L-AMB and NLAMB groups were performed. RESULT: We identified 10 studies. The cumulative frequency of patients using L-AMB was 148, compared to 341 patients in the NLAMB group. The mortality rates in the L-AMB and NLAMB groups were 10% and 0%, respectively. However, based on the odds ratio, the mortality in the L-AMB group was lower than that in the NLAMB group. No significant difference was observed in breakthrough invasive fungal infections between the L-AMB and NLAMB groups. The frequencies of nephropathy and hypokalemia in the L-AMB group were 36% and 18%, respectively. CONCLUSION: Our findings indicate a lower incidence of mortality in the L-AMB group compared to the NLAMB group. No statistically significant difference was observed in the incidence of breakthrough infection between the two groups. L-AMB administration is associated with nephropathy and hypokalemia. However, the refusal to continue treatment due to adverse effects is not significantly high.

Prevalence of Dysglycemia, Dyslipidemia, and Metabolic Syndrome among Patients with HIV Infection: a Cross-sectional Study from Iran.

Background: Human immunodeficiency virus (HIV) resulted in considerable morbidity and mortality. Following antiretroviral therapy (ART), the life expectancy of HIV-infected patients increased; however, they were more at risk of developing chronic diseases such as endocrinopathies. This study aimed to determine the prevalence of dysglycemia, dyslipidemia, and metabolic syndrome among patients with HIV infection. Methods: This cross-sectional study was conducted on HIV-infected patients referring to Loghman Hakim Hospital (Tehran, Iran) between April 2020 and April 2021. We examined demographic features, medical history, and laboratory tests indicating the metabolic status of the patients. Eventually, collected data were processed using SPSS version 23. Results: The mean age of 68 confirmed HIV patients was 39.85±10.54 years and 64.7% were male. BMI (MD = 2.57, 95% CI = [0.25, 4.88], P = 0.035), cholesterol (MD = 22.73, 95% CI = [4.70, 40.76], P = 0.014), HDL (MD = 8.54, 95% CI = [2.06, 15.02], P = 0.011), and LDL of women was significantly higher than men (MD = 22.43, 95% CI = [7.60, 37.27], P = 0.004). Additionally, 30 patients (44.1%) suffered from metabolic syndrome. The prevalence of metabolic syndrome differed significantly between men (34.1%) and women (62.50%) (P = 0.024). Conclusion: Dysglycemia, dyslipidemia, and metabolic syndrome are common among HIV-infected patients. Thus, periodic evaluation of the patients can be advantageous in early diagnosis and timely treatment.

Mucormycosis, New Causative Agents, and New Susceptible Populations: Review of Cases in a Tertiary Care Hospital in Iran (2007-2021).

Background: Mucormycosis is an aggressive opportunistic fungal infection that afflicts patients with severe underlying immunosuppression, uncontrolled hyperglycemia and/or ketoacidosis, iron overload, and occasionally healthy patients who are inoculated with fungal spores through traumatic injuries. The epidemiology of mucormycosis has changed after the COVID-19 pandemic, with mucormycosis becoming the most common and the fatal coinfection. Methods: In a retrospective, cross-sectional study, 82 hospitalized patients with a definite diagnosis of mucormycosis were reported from 2007 to 2021 in a referral, tertiary care center in Tehran, Iran. Results: The number of post-COVID cases increased 4.6 times per year, with 41.5% of patients admitted during the two years of the pandemic. Mucormycosis was more common in women (57.3%), and the most common underlying diseases were diabetes (43.7%), both COVID-19 and diabetes (23.2%), cancer (11%), rheumatic diseases (7.3%), COVID-19 without other underlying diseases (6.1%), and transplantation (4.9%). Rhino-orbito-cerebral Mucormycosis (54.9%) followed by Sino-orbital infection (23.2%) was the most common presentation. There was a significant relationship between the use of immunosuppressive agents and the development of Mucormycosis (P<0.005) The average mortality was 41.5%, but this ratio decreased to 35% during the pandemic era. Conclusion: The COVID-19 pandemic caused a 4.6-fold increase in the number of mucormycosis patients, and there was a significant relationship between hyperglycemia, corticosteroid use, and mucormycosis. The death rate during the COVID-19 pandemic has decreased by 6.5%, and during the COVID period, the interval between the arrival of a patient with mucormycosis and the start of the correct treatment was significantly decreased.

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.

Evaluation of vancomycin pharmacokinetics in patients with augmented renal clearances: A randomized clinical trial.

Purpose: Vancomycin is a narrow therapeutic window glycopeptide antibiotic that acts against Gram-positive bacteria. As it is renally eliminated, therapeutic drug monitoring is recommended for vancomycin, especially in case of kidney function alteration. Augmented renal clearance (ARC), defined as a creatinine clearance of more than 130 ml/min, is a risk factor for sub-therapeutic concentrations of vancomycin. This study aimed to evaluate the vancomycin pharmacokinetics following the administration of two different regimens in ARC patients. Methods: A randomized clinical trial (IRCT20180802040665N1) was conducted on patients in need of vancomycin therapy. Eight hours of urine was collected and 56 patients divided into two groups with creatinine clearance of more than 130 ml/min were included in the study. The first group received 15 mg/kg of vancomycin every 12 h and the second group 15 mg/kg every 8 h. After four doses, the peak and trough concentrations were measured from two blood samples. The primary outcome was the percentage of patients who attainted AUC more than 400. The occurrence of acute kidney injury also was evaluated after seven days. Results: The mean age of patients in the every 12 h and every 8 h groups was 44.04 ± 16.55 and 42.86 ± 11.83 years, respectively. While neurosurgical issues were the most common causes of hospitalization, central nervous infections were the most common indications for vancomycin initiation. Urinary creatinine clearance was 166.94 ± 41.32 ml/min in the every 12 h group and 171.78 ± 48.56 ml/min in the every 8 h group. 46.42% of patients in the every 12 h group and 82.14% of patients in the every 8 h group attained AUC/MIC of more than 400 mg × hr/L. None of the patients in the every 12 h group reached more than 15 mcg/ml concentration. At the 7-day follow-up, 10.7% patients in the BD group and 28.6% patients in the TDS group developed acute kidney injury (p = 0.089). Conclusion: Administration of vancomycin at a dose of 15 mg/kg every 8 h is associated with higher pharmacokinetic attainment in ARC patients. The occurrence of acute kidney injury also was not significantly higher in this therapeutic regimen. AUC/MIC monitoring is necessary in this population.

Evaluation of the epidemiologic, clinical, radiologic, and treatment methods of patients with subacute and chronic meningitis.

BACKGROUND: Meningitis is known as a meningeal inflammation accompanied by pleocytosis in the cerebrospinal fluid (CSF), and can be classified into acute, subacute, and chronic meningitis based on symptoms duration of ≤ 5 days, ≥ 5 days and ≥ 4 weeks, respectively. Subacute and chronic meningitis are caused mainly by indolent infectious agents and noninfectious causes such as autoimmune, and neoplastic. In this study, we investigated the characteristics, diagnosis, and treatment of subacute and chronic meningitis. METHODS: We extracted the medical records of patients with chronic and subacute meningitis who were referred to three tertiary centers from Jun 2011 to Jun 2021. Initially, 2050 cases of meningitis were screened, and then 79 patients were included in the study. RESULTS: Headache (87.3%), nausea and vomiting (74.7%), fever (56.4%), and visual impairments (55.7%) were the most prevalent symptoms. The most common signs were nuchal rigidity (45.3%), altered mental status (26.9%), and papillary edema (37.5%). Brain computed tomography (CT) was normal in 68.6% of the patients while 22.9% of the cases had hydrocephalus. Brain magnetic resonance imaging (MRI) was normal in 60.0% of the patients. The most common abnormal MRI findings were leptomeningeal enhancement (16.0%) and hydrocephalus (16.0%). We had a 44.3% definite diagnosis with bacterial (n:25, 31.6%) and neoplastic (n:8, 10.1%) being the most prevalent etiologies. Mycobacterium tuberculosis (60%) and Brucella spp. (12%) were the most prevalent bacterial pathogens. CONCLUSIONS: The most common etiologies include infectious, neoplastic, and immunologic. Due to insidious presentation and uncommon etiologies, establishing a proper diagnosis, and providing timely targeted treatment for patients with subacute and chronic meningitis remains a challenge for clinicians.

Meningitis Caused by Cryptococcus neoformans in an Apparently Immunocompetent Patient.

Cryptococcal meningitis (CM), as a life-threatening opportunistic infection, often is among cases with cell-mediated immunodeficiencies, such as AIDS, hematologic malignancies, and solid organ transplant recipients. Cryptococcal meningitis in healthy individuals is uncommon, and its detection in immunocompetent cases may be tricky because the presentation is generally more indolent than the traditional meningitis presentation, leading to late diagnosis and potential sequels. We present a CM case in an immunocompetent Iranian male patient who was treated successfully.

Hematologic malignancies and COVID-19 infection: A monocenter retrospective study.

Introduction: Hematologic malignancies are risk factors for severe COVID-19 infection. Identification of risk factors correlated with mortality in these groups of patients is important in the assessment strategy. We studied the characteristics of patients with hematologic malignancies and COVID-19 and then analyzed the predictors of mortality. Methods: Eligible for the analysis were hospitalized patients with hematologic malignancies and confirmed COVID-19 infection observed between January 2020 and March 2021. Patients were categorized based on the type of malignancy and phase of the treatment. Results: A total of 194 COVID-19 infected patients with hematologic malignancies were included. The median age was 44 (15-81) years; 135 of them were males and 59 were females. Acute myeloid leukemia was the most frequent cancer type (43.8%). A total of 119 patients had severe COVID-19 and 61 patients were admitted to the intensive care unit. A total of 92 deaths occurred in all cases for an overall case-fatality rate of 47%. Male gender, preinduction and induction phase of the treatment, intensive care admission, low levels of oxygen saturation, Rhesus (RH) factor positivity, and higher fibrinogen level correlated with mortality. Conclusion: This study focuses on the epidemiology, risk factors, outcomes, and predictors of mortality of COVID-19 among patients with hematologic malignancies. Patients with hematologic malignancies are at high risk of mortality.

Delayed post-pneumonectomy empyema necessitans caused by Aspergillus flavus: An unusual report.

Post-pneumonectomy empyema (PPE), with or without bronchopleural fistula, is a challenging and serious entity with significant mortality and morbidity. PPE is usually caused by bacteria such as staphylococci, streptococci and also gram-negative rods. Among fungal pathogens, Aspergillus species is a very rare cause of this entity. Herein, we describe an unusual case of delayed post-pneumonectomy empyema necessitans caused by Aspergillus flavus in a 65-year-old man with favourable clinical outcome by combined surgical and antifungal therapy.

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 effect of sofosbuvir and daclatasvir in hospitalized COVID-19 patients: a randomized double-blind clinical trial (DISCOVER).

BACKGROUND: The combination of sofosbuvir and daclatasvir has shown preliminary efficacy for hospitalized patients with COVID-19 in four open-label studies with small sample sizes. This larger trial aimed to assess if the addition of sofosbuvir/daclatasvir to standard care improved clinical outcomes in hospitalized patients with COVID-19. METHODS: This was a placebo-controlled, double-blind, randomized clinical trial in adults hospitalized with COVID-19 at 19 hospitals in Iran. Patients were randomized to oral sofosbuvir/daclatasvir 400/60 mg once-daily or placebo in addition to standard of care. Patients were included if they had positive PCR or diagnostic chest CT, O2 saturation <95% and compatible symptoms. The primary outcome was hospital discharge within 10 days of randomization. Secondary outcomes included mortality and time to clinical events. The trial is registered on the Iran Registry of Clinical Trials under IRCT20200624047908N1. RESULTS: Between July and October 2020, 1083 patients were randomized to either the sofosbuvir/daclatasvir arm (n = 541) or the placebo arm (n = 542). No significant difference was observed in the primary outcome of hospital discharge within 10 days, which was achieved by 415/541 (77%) in the sofosbuvir/daclatasvir arm and 411/542 (76%) in the placebo arm [risk ratio (RR) 1.01, 95% CI 0.95-1.08, P = 0.734]. In-hospital mortality was 60/541 (11%) in the sofosbuvir/daclatasvir arm versus 55/542 (10%) in the placebo arm (RR 1.09, 95% CI 0.77-1.54, P = 0.615). No differences were observed in time to hospital discharge or time to in-hospital mortality. CONCLUSIONS: We observed no significant effect of sofosbuvir/daclatasvir versus placebo on hospital discharge or survival in hospitalized COVID-19 patients.

Emergence of carbapenem resistant Acinetobacter baumannii clonal complexes CC2 and CC10 among fecal carriages in an educational hospital.

Carbapenem-resistant Acinetobacter baumannii strains are increasing worldwide. In this study, samples were collected from hospital environments, extra hospital environments, and fecal carriages. 76% (89/117) of bacterial isolates were detected as A. baumannii strains. The imipenem resistance in the hospital environment, fecal carriages, extra hospital environments, and clinical isolates was 37.7% (17/45), 100% (9/9), 0% (0/45), and 92.9% (92/99), respectively. The blaVIM and blaOXA-23 were detected in 6.6% (3/45) and 2.2% (1/45) of strains isolated from hospital environments. Interestingly, strains isolated from fecal carriages had blaVIM, blaOXA-23, and blaIMP genes which resembled carbapenem resistance genes in clinical strains. The structure of clonal relatedness among all non-clinical isolates was as follows: CC2, 37% (33/89); CC1, 22.4% (20/89); CC3, 12.3% (11/89); CC25, 7.8% (7/89); CC10, 4.4% (4/89) and CC15, 2.2% (2/89). Comparison of clonal relatedness among clinical and non-clinical isolates indicated that widespread clones including CC2, CC3, and CC10 were common clonal complexes between two categories.

Acinetobacter endocarditis: a rare nosocomial infection of native heart valves.

Acinetobacter baumannii is an opportunistic bacterial pathogen predominantly associated with hospital-acquired infections. Here we present a case of infective endocarditis of native Mitral and Aorta valves caused by A. baumannii in a 73-year-old man. He underwent surgical excision and Pathologic specimen showed A. baumannii growth after 48 hours that was extensively drug-resistant (XDR). He was treated with colistin and tigecycline. Finally, he discharged with no important complication. To our best knowledge, it is the first case of Acinetobacter endocarditis has ever been reported in Iran. Although XDR A. baumannii is a life-threatening pathogen, proper and timely treatment can be life-saving.

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.

Adverse reaction of methylprednisolone pulse therapy: Acute respiratory distress syndrome.

Methylprednisolone pulse therapy has significant anti-inflammatory effects in multiple sclerosis. Acute respiratory distress syndrome as a probable adverse effect of methylprednisolone pulse therapy in MS patients should be considered.

Platelets in the perspective of COVID-19; pathophysiology of thrombocytopenia and its implication as prognostic and therapeutic opportunity.

Despite endorsed and exponential research to improve diagnostic and therapeutic strategies, efforts have not yet converted into a better prospect for patients infected with the novel coronavirus (2019nCoV), and still, the name of SARS-CoV-2 is coupled with numerous unanswered questions. One of these questions is concerning how this respiratory virus reduces the number of platelets (PLTs)? The results of laboratory examinations showed that about a quarter of COVID-19 cases experience thrombocytopenia, and more remarkably, about half of these patients succumb to the infection due to coagulopathy. These findings have positioned PLTs as a pillar in the management as well as stratifying COVID-19 patients; however, not all the physicians came into a consensus about the prognostic value of these cells. The current review aims to unravel the contributory role of PLTs s in COVID-19; and alsoto summarize the original data obtained from international research laboratories on the association between COVID-19 and PLT production, activation, and clearance. In addition, we provide a special focus on the prognostic value of PLTs and their related parameters in COVID-19. Questions on how SARS-CoV-2 induces thrombocytopenia are also responded to. The last section provides a general overview of the most recent PLT- or thrombocytopenia-related therapeutic approaches. In conclusion, since SARS-CoV-2 reduces the number of PLTs by eliciting different mechanisms, treatment of thrombocytopenia in COVID-19 patients is not as simple as it appears and serious cautions should be considered to deal with the problem through scrutiny awareness of the causal mechanisms.

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.

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.