The effects of combination-therapy of tocilizumab and baricitinib on the management of severe COVID-19 cases: a randomized open-label clinical trial.

Background: Tocilizumab and baricitinib are considered standard treatments for hospitalized COVID-19 patients with an inflammatory status. However, the effects of co-administering these medications aiming for more rapid patient recovery are controversial among practitioners. The potential benefits include the rapid improvement of patients and regulation of the immune system, and the potential risks include the increased chance of serious adverse events, including infections. This study aimed to investigate the effects of co-administering these two medications on the 28-day mortality rate, other efficacy parameters, and safety issues. Methods: In this randomized open-label trial, 68 patients were recruited. The study was conducted at Dr. Masih Daneshvari Hospital during 6 months (from 21 March 2022 to 23 August 2022). Severely ill patients aged between 18 and 100 years old with confirmed COVID-19 were enrolled. The primary outcomes included the need for invasive mechanical ventilation and a 28-day mortality rate. Secondary outcomes included the need for non-invasive mechanical ventilation, the need for admission to the intensive care unit (ICU), the length of hospital stay, and the need for a second dose of tocilizumab. Safety assessments were also performed for 28 days. The data were collected from the patients' medical records, which included age, gender, and comorbidities. Results: The 28-day mortality rate or the need for mechanical ventilation was not statistically different among the two groups (p-value = 0.49 for both outcomes). The need for non-invasive mechanical ventilation, the need for admission to the ICU, or the need for a second dose of tocilizumab and the length of hospital stay was not affected either (p-value = 1; 0.1; 0.49 and 0.9, respectively). One patient developed thrombosis in the combination group. No adverse events related to infectious complications were recorded in any groups. Conclusion: This study showed no beneficial effects of combining tocilizumab and baricitinib in managing severe COVID-19 cases. However, the need for ICU admission was meaningfully lower in the combination group. Studies with larger sample sizes are needed to confirm these results. Clinical Trial Registration: Identifier: RCT20151227025726N30M.

Efficacy of intravenous immunoglobulins (IVIG) in COVID-19 patients: a systematic review and meta-analysis.

Background and purpose: Though controversial, many clinical trials have been conducted to evaluate the efficacy of intravenous immunoglobulins (IVIG) in COVID-19 cases. Therefore, a systematic review and meta-analysis have been performed to evaluate the efficacy of IVIG in the treatment of COVID-19 patients. Experimental approach: A systematic search was performed in electronic databases and preprint servers up to November 20, 2021. Since substantial heterogeneity was expected, a random-effects model was applied to pool effect size from included studies to calculate the standardized mean differences (SMDs) for the continuous variables and relative risks (RRs) for the dichotomous variable with 95% confidence intervals (CIs). Findings/Results: Five randomized clinical trials and seven cohort studies were analyzed among the 12 eligible studies with a total of 2,156 patients. The pooled RR of mortality was 0.77 (CI 0.59-1.01, P-value = 0.06), and of mechanical ventilation was 1.50 (CI 0.29-7.83; P-value = 0.63) in the IVIG group compared with the standard care group. The pooled SMD of hospital length of stay was 0.84 (CI -0.43-2.11; P-value = 0.20) and of ICU length of stay was -0.07 (CI -0.92-0.78; P-value = 0.86) in the IVIG group compared with the standard care group. Conclusion and implications: This meta-analysis found that the IVIG therapy was not statistically different from the standard care group. Mortality, ICU admission, mechanical ventilation, length of hospital stay, and length of ICU stay were not significantly improved among IVIG recipients. However, statistical indifference is not equal to clinical indifference.

Evaluation of noscapine-licorice combination effects on cough relieving in COVID-19 outpatients: A randomized controlled trial.

Background: As February 2023, SARS-CoV-2 is still infecting people and children worldwide. Cough and dyspnea are annoying symptoms almost present in a large proportion of COVID-19 outpatients, and the duration of these symptoms might be long enough to affect the patients' quality of life. Studies have shown positive effects for noscapine plus licorice in the previous COVID-19 trials. This study aimed to assess the effects of the combination of noscapine and licorice-for relieving cough in outpatients with COVID-19. Methods: This randomized controlled trial was conducted on 124 patients at the Dr. Masih Daneshvari Hospital. Participants over 18 years of age with confirmed COVID-19 and cough were allowed to enter the study if the onset of symptoms was less than 5 days. The primary outcome was to assess the response to treatment over 5 days using the visual analogue scale. Secondary outcomes included the assessment of cough severity after 5 days using Cough Symptom Score, as well as the cough-related quality of life and dyspnea relieving. Patients in the noscapine plus licorice group received Noscough® syrup 20 mL every 6 h for 5 days. The control group received diphenhydramine elixir 7 mL every 8 h. Results: By day five, 53 (85.48%) patients in the Noscough® group and 49 (79.03%) patients in the diphenhydramine group had response to treatment. This difference was not statistically significant (p-value = 0.34). The presence of dyspnea was significantly lower in the Noscough® group versus diphenhydramine at day five (1.61% in the Noscough® group vs. 12.9% in the diphenhydramine group; p-value = 0.03). The cough-related quality of life and severity also significantly favored Noscough® syrup (p-values <0.001). Conclusion: Noscapine plus licorice syrup was slightly superior to diphenhydramine in relieving cough symptoms and dyspnea in the COVID-19 outpatients. The severity of cough and cough-related quality of life were also significantly better in the noscapine plus licorice syrup. Noscapine plus licorice may be a valuable treatment in relieving cough in COVID-19 outpatients.

Evaluating the efficacy of inhaled amikacin as an adjunct to intravenous combination therapy (ceftazidime and amikacin) in pediatric cystic fibrosis pulmonary exacerbation.

Background: Pseudomonas aeruginosa is the most common microorganism found in the sputum culture of Cystic fibrosis (CF) patients causing the pulmonary destruction. Aminoglycosides have a low diffuse rate from lipid membranes, and respiratory system secretions. Regarding the burden of pulmonary exacerbation caused by the pseudomonas aeruginosa in cystic fibrosis patients in the long term and the limited number of clinical trials focused on appropriate treatment strategies, the present study evaluated the concurrent inhaled and intravenous aminoglycoside antibiotics for pulmonary exacerbation caused by the pseudomonas aeruginosa as a safe and effective treatment in children. Method: This study was a blinded, randomized clinical trial phase conducted in a tertiary referral pediatric teaching hospital from May 2021 to May 2022. The patients were randomly allocated to receive intravenously administered ceftazidime and Amikacin alone or with inhaled Amikacin. Forced expiratory volume (FEV1), Amikacin via the level, kidney function tests, audiometry, inflammatory markers (erythrocyte sedimentation rate and C-reactive protein), hospital stay, and bacterial eradication rate were compared in two therapy groups. Results: the average FEV1 has increased by 47% in Neb + group compared to Neb- group following treatment. Hospital stay was lower in Neb + group. No renal toxicity or ototoxicity was observed in both therapy groups. Pseudomonas aeruginosa eradication rate Neb- and Neb + groups were 44% and 69%, respectively (p-value = 0.15). Conclusion: Concurrent inhaled and intravenous Amikacin is safe and effective to treat Pseudomonas aeruginosa exacerbation in CF patients. Moreover, co-delivery antibiotics' route treatment increased the eradication rate. Although not statistically significant, never the less, it is clinically relevant. The intervention reduced the length of hospitalization in this group. Clinical Trial Registration: clinicaltrials.gov, identifier [IRCT20120415009475N10].

Effectiveness of different vaccine platforms in reducing mortality and length of ICU stay in severe and critical cases of COVID-19 in the Omicron variant era: A national cohort study in Iran.

Various severe acute respiratory syndrome coronavirus 2 vaccines with different platforms have been administered worldwide; however, their effectiveness in critical cases of COVID-19 has remained a concern. In this national cohort study, 24 016 intensive care unit (ICU) coronavirus disease-2019 (COVID-19) admissions were included from January to April 2022. The mortality and length of ICU stay were compared between the vaccinated and unvaccinated patients. A total of 9428 (39.25%) patients were unvaccinated, and 14 588 (60.75%) patients had received at least one dose of the vaccine. Compared with the unvaccinated, the first, second, and third doses of vaccine resulted in 8%, 20%, and 33% lower risk of ICU mortality in the adjusted model, with risk ratio (RR): 0.92, 95% confidence interval (CI): 0.84-1.001, RR: 0.80, 95% CI: 0.77-0.83, and RR: 0.67, 95% CI: 0.64-0.71, respectively. The mean survival time was significantly shorter in the unvaccinated versus the fully vaccinated patients (hazard ratio [HR]: 0.84, 95% CI: 0.80-0.88); p < 0.001). All vaccine platforms successfully decreased the hazard of ICU death compared with the unvaccinated group. The duration of ICU stay was significantly shorter in the fully vaccinated than in unvaccinated group (MD, -0.62, 95% CI: -0.82 to -0.42; p < 0.001). Since COVID-19 vaccination in all doses and platforms has been able to reduce the risk of mortality and length of ICU-stay, universal vaccination is recommended based on vaccine availability.

Evaluating the Effects of Agomelatine on Polysomnography Parameters in Patients with Obstructive Sleep Apnea.

PURPOSE: Obstructive sleep apnea (OSA) is a common serious sleep disorder. Melatonin-based drugs such as agomelatine may have beneficial effects on patients with sleep disorders. This study aimed to evaluate agomelatine effects on polysomnography parameters in patients with OSA. METHODS: In this randomized, parallel, and single-blind study, seventy patients 18 years of age or older with obstructive sleep apnea who were referred to the sleep clinic were evaluated. The patients were randomly assigned into agomelatine and control groups. Patients in the agomelatine group received 50 mg agomelatine, one hour before sleep, for three consecutive nights prior to the polysomnography test, while the patients in the control group did not receive agomelatine. Sleep test parameters were compared between the two groups. RESULTS: Three parameters in the agomelatine versus control group showed significant differences. They were the median and interquartile range of the total sleep time, 397 [326.5-437.4] vs. 287.5 [184-393.1; p, 0.004] minuets, sleep efficiency percentage, 75.6 [71-87.4] vs. 65.1 [50.8-80.1; p, 0.005] and the wakening percentage, 7.5 [12.01-27.6] vs. 8.8[18.3-49; p, 0.004] agomelatine vs. control group. Other polysomnography parameters revealed no significant differences between the two groups. CONCLUSIONS: Agomelatine administration in patients with OSA may improve total sleep time, sleep efficiency percentage and the percentage of patients' awakening.

Evaluating the efficacy and safety of rivaroxaban as a warfarin alternative in chronic thromboembolic pulmonary hypertension patients undergoing pulmonary endarterectomy: A randomized clinical trial.

BACKGROUND AND AIM: Chronic thromboembolic pulmonary hypertension (CTEPH) is caused by the obstruction of the main pulmonary artery due to thrombosis and vascular remodeling. Regarding the need for anticoagulant therapy in CTEPH patients, this study aimed to compare rivaroxaban with warfarin in terms of its efficacy and safety in patients undergoing endarterectomy surgery. METHODS: The study was a parallel clinical trial in patients who underwent endarterectomy following CTEPH. A total of 96 patients were randomly selected and assigned to two groups: warfarin-treated (control) and rivaroxaban-treated (intervention). Patients were clinically assessed for re-thrombosis, re-admission, bleeding, and mortality in the first, third, and sixth months after surgery. RESULTS: There was no significant difference in the occurrence of thrombosis between the two groups within the first, third-, and sixth-months post-surgery (p=0.52, 1, 0.38 respectively). Moreover, the mortality rate (p=0.9), bleeding rate (p=0.06), and re-admission rate (p=0.15) showed no significant differences between the two groups. CONCLUSION: Rivaroxaban may be as effective as warfarin in treating CTEPH patients after endarterectomy in the short term and can be used as an anticoagulant in these patients. However, studies with long-term follow-ups are needed to consolidate the strategy of treating these patients with rivaroxaban.

Effect of bromhexine in hospitalized patients with COVID-19.

BACKGROUND: Bromhexine is a potent inhibitor of transmembrane serine protease 2 and appears to have an antiviral effect in controlling influenza and parainfluenza infection; however, its efficacy in COVID-19 is controversial. METHODS: A group of hospitalized patients with confirmed COVID-19 pneumonia were randomized using 1:1 allocation to either standard treatment lopinavir/ritonavir and interferon beta-1a or bromhexine 8 mg four times a day in addition to standard therapy. The primary outcome was clinical improvement within 28 days, and the secondary outcome measures were time to hospital discharge, all-cause mortality, duration of mechanical ventilation, the temporal trend in 2019-nCoV reverse transcription-polymerase chain reaction positivity and the frequency of adverse drug events within 28 days from the start of medication. RESULTS: A total of 111 patients were enrolled in this randomized clinical trial and data from 100 patients (48 patients in the treatment arm and 52 patients in the control arm) were analyzed. There was no significant difference in the primary outcome of this study, which was clinical improvement. There was no significant difference in the average time to hospital discharge between the two arms. There were also no differences observed in the mean intensive care unit stay, frequency of intermittent mandatory ventilation, duration of supplemental oxygenation or risk of death by day 28 noted between the two arms. CONCLUSION: Bromhexine is not an effective treatment for hospitalized patients with COVID-19. The potential prevention benefits of bromhexine in asymptomatic postexposure or with mild infection managed in the community remain to be determined.

The roles of dipeptidyl peptidase-4 inhibitors in prognosis of COVID-19 infection in patients with type 2 diabetes mellitus.

Background: COVID-19 is responsible for the latest pandemic. Dipeptidyl peptidase-4 (DPP-4) is one of the cellular receptors of interest for coronavirus. The aim of this study was to assess the roles of DPP-4 inhibitors in prognosis of COVID-19 infection in patients with type 2 diabetes mellitus. Materials and Methods: retrospective cohort study was performed in 2020 in military medical centers affiliated to AJA University of Medical Sciences in Tehran on 220 patients with type 2 diabetes mellitus who were admitted in medical centers with COVID-19 infection. We collected demographic data of patients including age, gender, drug history, usage of DPP-4 inhibitors, clinical presentations at the time of the first visit, and the disease outcome including hospitalization duration and need for respiratory assist. Results: The study population consisted of 133 males (60.5%) and 87 females (39.5%), with a mean age of 66.13 ± 12.3 years. Forty-four patients (20%) consumed DPP-4 inhibitors (sitagliptin and linagliptin). Patients who were treated with DPP-4 inhibitors required less oxygen (O2) therapies compared to other cases (76.7% vs. 88.6%, P = 0.04). Patients who were treated with DPP-4 inhibitors had significantly lower hospitalization duration compared to other cases (6.57 ± 2.3 days vs. 8.03 ± 4.4 days, respectively, P = 0.01). There were no significant differences between the two groups of patients regarding survival rates (P = 0.55). Age was a predictive factor for survival (odds ratio, 1.13; 95% confidence interval, 1.04-1.23; P = 0.004). Conclusion: DPP-4 inhibitors could significantly decrease hospitalization days in patients with type 2 diabetes mellitus who were hospitalized for COVID-19. However, DPP-4 inhibitor usage showed no statistically significant impact on survival. Age was the important prognostic factor.

National Research Institute of Tuberculosis and Lung Disease (NRITLD) Protocol for the Treatment of Patients with COVID-19.

More than a year after the onset of the coronavirus disease pandemic in 2019, the disease remains a major global health issue. During this time, health organizations worldwide have tried to provide integrated treatment guidelines to control coronavirus disease 2019 (COVID-19) at different levels. However, due to the novel nature of the disease and the emergence of new variants, medical teams' updating medical information and drug prescribing guidelines should be given special attention. This version is an updated instruction of the National Research Institute of Tuberculosis and Lung Disease (NRITLD) in collaboration with a group of specialists from Masih Daneshvari Hospital in Tehran, Iran, which is provided to update the information of caring clinicians for the treatment and care of COVID-19 hospitalized patients.

The Possible Role of Bruton Tyrosine Kinase Inhibitors in the Treatment of COVID-19: A Review.

BACKGROUND: Coronavirus disease 2019 (COVID-19), an acute, sometimes severe respiratory illness caused by a novel coronavirus has led to a vast pandemic with an astonishing spread rate. Its treatment is unknown, its mortality is significant, and its socioeconomic complications are uncontrollable. Although there is still little known about the pathogenesis of the disease, severe cases of COVID-19 are usually associated with cytokine release syndrome and high serum levels of inflammatory cytokines, which are believed to be a major cause of mortality in these patients. Different pathways cause inflammation and the release of cytokines. One of these pathways is the Bruton tyrosine kinase (BTK) pathway, which is essential for the production of several anti-inflammatory cytokines. Theoretically, the inhibition of BTK signaling can reduce cytokine levels and subsequent anti-inflammatory effects. OBJECTIVE: This review aims to investigate the role of the BTK pathway in the pathogenesis of COVID-19 and the possible effects of its inhibition in the treatment of this disease. METHODS: This narrative review provides information regarding the use of BTK inhibitors in patients with COVID-19 and discusses whether clinicians should consider these medications while managing their patients based on the literature. Data were gathered using the PubMed, Scopus, and Web of Science databases. RESULTS: Some data support the use of BTK inhibitors for treating COVID-19. CONCLUSIONS: It is recommended that patients continue their medications in this class if they develop COVID-19 and were receiving these agents before the disease developed. The use of BTK inhibitors might enable patients to experience less severe immune responses to the COVID-19. Well-designed studies are needed to evaluate the effectiveness of BTKis in the management of COVID-19. (Curr Ther Res Clin Exp. 2022; 82:XXX-XXX) © 2022 Elsevier HS Journals.

Study of the Effects of Melatonin on Sleep Disorders in Pulmonary Sarcoidosis Patients.

Background: The symptoms of pulmonary sarcoidosis may lead to fatigue, excessive daytime sleepiness, poor sleep quality, and a decrease in quality of life in these patients. Objectives: This study was designed to evaluate the effects of oral melatonin on sleep disorders of patients with pulmonary sarcoidosis. Methods: A randomized, single-blinded clinical trial was conducted on patients with pulmonary sarcoidosis. Eligible patients were randomly allocated into melatonin and control groups. Patients in the melatonin group were given 3 mg melatonin one hour before bedtime for three months. Sleep quality, daytime sleepiness, fatigue status, and quality of life were assessed applying General Sleep Disturbance Scale (GSDS), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Fatigue Assessment Scale (FAS), and the Patient-Reported Outcomes Measurement Information System (PROMIS), respectively, as well as the 12-item Short Form Survey (SF-12) scores at the baseline and three months after treatment. Results: There was a significant change in the GSDS (P < 0.001), PSQI (P < 0.001), ESS (P = 0.002), and FAS (P < 0.001) scores, which were decreased, compared to those of the control group. After intervention¸ global physical health and global mental health raw scores were improved comparing to the control group (P = 0.006, P = 0.02, respectively). The 12-item Short Form Survey evaluation showed that there was a significant difference between the melatonin (3.38 ± 4.61) and control (0.55 ± 7.25) groups in PCS-12 score after three months of therapy (P = 0.02). Conclusions: Our findings showed that supplemental melatonin could significantly improve sleep problems, quality of life, and excessive daytime sleepiness in sarcoidosis patients.

Hemoptysis Resolution with Rituximab in Behçet's Disease: A Case Report.

Behçet's disease (BD) is a multisystem, progressive, and inflammatory disorder of unknown etiology. Vasculitis is believed to underlie various clinical manifestations of BD and is known to be one of the main causes of death due to BD, in cases of large vessel involvement. The current study is done in order to examine the effects of rituximab on the patient's debilitating clinical manifestations, as a result of not responding to the standard treatment regimens. The present case is a 28-year-old female patient with BD associated vasculitis. She was referred to the respiratory referral center, chiefly complaining of intermittent episodes of massive hemoptysis. She had also recurrent oral and genital ulcers, and difficulty in walking, despite considering the common treatment approaches for BD. Our patient received two courses of rituximab in combination with intravenous methylprednisolone. Over six months follow-up period from the date of treatment initiation with rituximab, symptoms of BD such as recurrent hemoptysis and aphthous ulcers were reduced in both frequency and severity. Lower limb weakness and difficulty in walking were improved as well. To summarize, rituximab appears to be an effective alternative for treatment-resistant vasculitis in BD patients.

Remdesivir associated sinus bradycardia in patients with COVID-19: A prospective longitudinal study.

Background: Remdesivir is effective against SARS-Cov-2 with little evidence of its adverse effect on the cardiac system. The aim of the present study is investigating the incidence of bradycardia in COVID-19 patients treated with Remdesivir. Methods: This prospective longitudinal study was conducted in a tertiary center on COVID-19 patients for Remdesivir therapy. The objectives were to investigate the incidence of sinus bradycardia, and also the association between their demographics, underlying diseases, and the disease severity with developing bradycardia in COVID-19 patients treated with Remdesivir. Results: Of 177 patients, 44% were male. The mean (±standard deviation) age of patients was 49.79 ± 15.16 years old. Also, 33% were hospitalized due to more severe symptoms. Oxygen support was required for all hospitalized subjects. A total of 40% of the patients had comorbidities, with the most common comorbidity being hypertension. The overall incidence of bradycardia (heart rate<60 bpm) in patients receiving Remdesivir was 27%, of whom 70% had extreme bradycardia (heart rate <50 bpm). There was also a statistically significant reduction in heart rate after five doses of Remdesivir compared to the baseline heart rates. In the multivariable model, none of the covariates including age above 60 years, female sex, CRP>50 mg/L, O2 saturation<90%, underlying cardiovascular disease, hypertension and diabetes mellitus, and beta-blockers were associated with Remdesivir-induced bradycardia. No association was found between the COVID-19 severity indicators and bradycardia. Conclusion: As sinus bradycardia is a prevalent adverse cardiac effect of Remdesivir, it is recommended that all COVID-19 patients receiving Remdesivir, be evaluated for heart rate based on examination; and in the case of bradyarrhythmia, cardiac monitoring should be performed during administration to prevent adverse drug reactions.

The Effect of acetyl-L-carnitine, Alpha-lipoic Acid, and Coenzyme Q10 Combination in Preventing Anti-tuberculosis Drug-induced Hepatotoxicity: A Randomized, Double-blind, Placebo-controlled Clinical Trial.

Drug-induced liver injury (DILI) is one of the most serious adverse effects of anti-tuberculosis (TB) drugs. A suggested mechanism of this adverse effect is mitochondrial dysfunction (MDF). The purpose of this study was an evaluation of the possible preventive effects of the combination of acetyl-L-carnitine (ALCAR), alpha-lipoic acid (ALA), and coenzyme Q10 (CoQ10), as mitochondrial nutrients (MNs), against anti-TB DILI. In this clinical trial, patients who met the inclusion criteria were randomly assigned to either experimental (n = 44) or placebo (n = 43) groups. The experimental group received capsules containing CoQ10 (200 mg) + ALA (250 mg) + ALCAR (250 mg) orally twice daily for two weeks, and the placebo group received oral placebo capsules with the same interval and duration. The mean serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBil) at the end of the first and second weeks as well as the incidence of DILI during the intervention were recorded and compared between the two groups. At the end of the study, the mean serum levels of AST and ALT in the experimental group were significantly lower than the placebo group (36.27 ± 36.43 vs. 86.02 ± 97.23 and 28.41 ± 27.41 vs. 78.80 ± 118.28, respectively, P = 0.003 for both). Also, the incidence of anti-TB DILI was significantly lower in the experimental group than the placebo group (6.8% vs. 25.6%, P = 0.017). In conclusion, using the combination of ALCAR, ALA, and CoQ10 may provide an effective strategy in preventing anti-TB DILI.

Combined Therapy of Ciclosporin Plus Favipiravir in the Management of Patients with Severe COVID-19, not Responding to Dexamethasone: A non-Controlled Prospective Trial.

BACKGROUND: Regarding the COVID-19 pandemic, potential therapeutic agents are being evaluated almost every day. Ciclosporin, a calcineurin inhibitor, is characterized by beneficial antiviral and immunomodulatory effects. The present study aimed to evaluate the efficacy of ciclosporin in managing COVID-19. METHODS: This study was a prospective non-controlled clinical trial carried out on 20 patients. Confirmed COVID-19 patients received two doses of ciclosporin (10 mg/kg and 5 mg/kg injections) 24 h apart. Mortality rate and the lengths of intensive care unit (ICU) and hospital stays were assessed for all 20 patients. RESULTS: The mortality rate and the need for mechanical ventilation were calculated as 50%. The percentage of ICU admission was 70%. The lengths of ICU and hospital stays were 8.13 ± 6.81 and 14.25 ± 8.55 days, respectively. The levels of ferritin and white blood cells were significantly higher after injecting the second dose of ciclosporin. Seven patients (35%) had radiologically improved lungs after ciclosporin therapy. CONCLUSION: It seems that the protocol of two doses of ciclosporin in combination with favipiravir does not have favorable effects among COVID-19 patients that do not respond to dexamethasone. Controlled trials are needed to confirm the results.

Evaluation of adalimumab effects in managing severe cases of COVID-19: A randomized controlled trial.

BACKGROUND: COVID-19, which is a disease caused by the SARS-CoV-2 virus, has spread around the world since late 2019. Studies have found associations between the rising levels of TNF-α and severe COVID-19 cases. Hence, TNF-α blocking can possibly be a favorable intervention in modifying COVID-19. To this end, in order to manage pneumonia caused by COVID-19, adalimumab may potentially be considered as a potential therapeutic agent. The present study aimed to investigate the potential therapeutic role of adalimumab in treating COVID-19 cases in combination therapy with remdesivir and dexamethasone. METHODS: Among the 68 patients who were included in the current randomized controlled trial, 34 were assigned to the adalimumab group and the remaining 34 were assigned to the control group. Adalimumab at a dose of 40 mg, subcutaneous for once, was used for the intervention group. Both the intervention and control groups received remdesivir, dexamethasone, and supportive care. The data gathered to make comparisons of the groups included demographic information, the rate of mortality, mechanical ventilation requirement, length of stay in hospital and Intensive Care Unit (ICU), and imaging findings. RESULTS: There was no significant difference between the two groups in the terms of mortality rate (P-value = 1) and mechanical ventilation requirement (P-value = 1). The length of hospital and ICU stay as well as radiologic changes were not affected either (P-value = 1, 0.27, and 0.53, respectively). CONCLUSIONS: Our findings did not support the use of adalimumab in combination with remdesivir and dexamethasone in the treatment of severe COVID-19 cases.