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.

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.

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.

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 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.

Blood Purification Techniques, Inflammatory Mediators and Mortality in COVID-19 Patients.

BACKGROUND: Inflammatory mediators are an important component in the pathophysiology of the coronavirus disease 2019 (COVID-19). This study aimed to assess the effects of reducing inflammatory mediators using hemoperfusion (HP) and continuous renal replacement therapy (CRRT) on the mortality of patients with COVID-19. MATERIALS AND METHODS: Twelve patients with confirmed diagnosis of COVID-19 were included. All patients had acute respiratory distress syndrome (ARDS). Patients were divided into three groups, namely, HP, CRRT and HP+CRRT. The primary outcome was mortality and the secondary outcomes were oxygenation and reduction in inflammatory mediators at the end of the study. RESULTS: Patients were not different at baseline in demographics, inflammatory cytokine levels, and the level of acute phase reactants. Half of the patients (3 out of 6) in the HP+CRRT group survived along with the survival of one patient (1 out of 2) in the HP group. All four patients in the CRRT group died. Serum creatinine (SCr), Interleukin-1 (IL1), Interleukin-6 (IL6), Interleukin-8 (IL8), partial pressure of oxygen (PaO2), O2 saturation (O2 sat), and hemodynamic parameters improved over time in HP+CRRT and CRRT groups, but no significant difference was observed in the HP group (All Ps > 0.05). CONCLUSION: Combined HP and CRRT demonstrated the best result in terms of mortality, reduction of inflammatory mediators and oxygenation. Further investigations are needed to explore the role of HP+CRRT in COVID-19 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.

Favipiravir Effects on the Control of Clinical Symptoms of Hospitalized COVID-19 Cases: An Experience with Iranian Formulated Dosage Form.

Coronavirus disease -19 (COVID-19) pandemic, caused by SARS-CoV-2, has gradually spread worldwide, becoming a major public health event. This situation requires designing a novel antiviral agent against the SARS-CoV-2; however, this is time-consuming and the use of repurposed medicines may be promising. One such medicine is favipiravir, primarily introduced as an anti-influenza agent in east world. The aim of this study was to evaluate the efficacy and safety of favipiravir in comparison with lopinavir-ritonavir in SARS-CoV-2 infection. In this randomized clinical trial, 62 patients were recruited. These patients had bilateral pulmonary infiltration with peripheral oxygen saturation lower than 93%. The median time from symptoms onset to intervention initiation was seven days. Favipiravir was not available in the Iranian pharmaceutical market, and it was decided to formulate it at the research laboratory of School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. The patients received favipiravir tablet at a dose of 1600 mg orally twice a day for day one and then 600 mg orally twice a day for days 2 to 6. In the second group, the patients received lopinavir-ritonavir combination tablet at a dose of 200/50 mg twice a day for seven days. Fever, cough, and dyspnea were improved significantly in favipiravir group in comparison with lopinavir-ritonavir group on days four and five. Mortality rate and ICU stay in both groups were similar, and there was no significant difference in this regard (P = 0.463 and P = 0.286, respectively). Chest X-ray improvement also was not significantly different between the two groups. Adverse drug reactions occurred in both groups, and impaired liver enzymes were the most frequent adverse effect. In conclusion, early administration of oral favipiravir may reduce the duration of clinical signs and symptoms in patients with COVID-19 and hospitalization period. The mortality rate also should be investigated in future clinical trials.

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.

IgM-enriched immunoglobulin in COVID-19: Case series of 15 severely ill SARS-CoV-2-infected patients.

The healthcare system in Iran, like most around the world, is managing thousands of patients hospitalised with COVID-19. In Iran, in-hospital mortality is in the region of 25%, rising to 50-60% in patients admitted to intensive care. Hyperinflammation, characterised by cytokine storm, appears to be a hallmark of severe COVID-19 and to date only the anti-inflammatory drug dexamethasone has been shown to reduce mortality in those hospitalised with the disease. There is a sound scientific rationale behind the use of IgM-enriched immunoglobulin in the management of patients with severe COVID-19. It has been used successfully in the management of hyperinflammation in patients with sepsis and has led to improved radiographic scores in patients with severe cases of severe acute respiratory syndrome coronavirus (SARS-CoV) infection. Recently the successful treatment of a patient with COVID-19 with IgM-enriched immunoglobulin was reported. Here we report the outcome of a further 15 patients hospitalised with COVID-19 treated with IgM-enriched immunoglobulin. Improvements in computed tomography (CT) score were observed in nine patients, indicating that further clinical studies into the use of IgM-enriched immunoglobulin in the treatment of severe COVID-19 are warranted.

Symptom Prediction and Mortality Risk Calculation for COVID-19 Using Machine Learning.

Background: Early prediction of symptoms and mortality risks for COVID-19 patients would improve healthcare outcomes, allow for the appropriate distribution of healthcare resources, reduce healthcare costs, aid in vaccine prioritization and self-isolation strategies, and thus reduce the prevalence of the disease. Such publicly accessible prediction models are lacking, however. Methods: Based on a comprehensive evaluation of existing machine learning (ML) methods, we created two models based solely on the age, gender, and medical histories of 23,749 hospital-confirmed COVID-19 patients from February to September 2020: a symptom prediction model (SPM) and a mortality prediction model (MPM). The SPM predicts 12 symptom groups for each patient: respiratory distress, consciousness disorders, chest pain, paresis or paralysis, cough, fever or chill, gastrointestinal symptoms, sore throat, headache, vertigo, loss of smell or taste, and muscular pain or fatigue. The MPM predicts the death of COVID-19-positive individuals. Results: The SPM yielded ROC-AUCs of 0.53-0.78 for symptoms. The most accurate prediction was for consciousness disorders at a sensitivity of 74% and a specificity of 70%. 2,440 deaths were observed in the study population. MPM had a ROC-AUC of 0.79 and could predict mortality with a sensitivity of 75% and a specificity of 70%. About 90% of deaths occurred in the top 21 percentile of risk groups. To allow patients and clinicians to use these models easily, we created a freely accessible online interface at www.aicovid.net. Conclusion: The ML models predict COVID-19-related symptoms and mortality using information that is readily available to patients as well as clinicians. Thus, both can rapidly estimate the severity of the disease, allowing shared and better healthcare decisions with regard to hospitalization, self-isolation strategy, and COVID-19 vaccine prioritization in the coming months.

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.

No clinical benefit of high dose corticosteroid administration in patients with COVID-19: A preliminary report of a randomized clinical trial.

The aim of this study was to evaluate the clinical effects of dexamethasone administration in patients with mild to moderate acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19). The study included 50 patients who were randomly assigned to the dexamethasone group or control group. Dexamethasone was administered at a dose of 20 mg/day from day 1-5 and then at 10 mg/day from day 6-10. The need for invasive mechanical ventilation, death rate, duration of clinical improvement, length of hospital stay, and radiological changes in the computed tomography scan were assessed. The results revealed that 92% and 96% of patients in the dexamethasone and control groups, respectively, required noninvasive ventilation (P = 0.500). Among them, 52% and 44% of patients in the dexamethasone and control groups, respectively, required invasive mechanical ventilation (P = 0.389). At the end of the study, 64% of patients in the dexamethasone group and 60% of patients in the control group died (P = 0.500); the remaining patients were discharged from the hospital during the 28-day follow-up period. The median length of hospital stay was 11 days in the dexamethasone group and 6 days in the control group (P = 0.036) and the median length of hospital stay was 7 days in the dexamethasone group and 3 days in the control group (P < 0.001). No significant differences were observed in the other outcomes. This study showed that corticosteroid administration had no clinical benefit in patients with COVID-19-induced mild to moderate ARDS.

Efficacy and safety of Tocilizumab in severe and critical COVID-19: A Systematic Review and Meta-Analysis.

OBJECTIVES: Currently published papers and clinical guidelines regarding the effects of tocilizumab in severe and critical COVID-19 are contradictory. The aim of this meta-analysis was to combine the results of clinical studies of different designs to investigate the efficacy and safety of tocilizumab in severely-to-critically ill COVID-19 patients. METHODS: A systematic search was performed in PubMed, Embase, CENTRAL, ClinicalTrials.gov, Scopus, and preprint servers up to 26 December 2020. Since a substantial heterogeneity was expected, a random-effects model was applied to calculate the pooled effect size (ES) and 95% confidence interval (CI) for each study outcome. RESULTS: Forty-five comparative studies involving 13,189 patients and 28 single-arm studies involving 1,770 patients were analyzed. The risk of mortality (RR of 0.76 [95%CI 0.65 to 0.89], P < 0.01) and intubation (RR of 0.48 [95%CI 0.24 to 0.97], P = 0.04) were lower in tocilizumab patients compared with controls. We did not find any significant difference in secondary infections, length of hospital stay, hospital discharge before day 14, and ICU admission between groups. CONCLUSION: Tocilizumab can improve clinical outcomes and reduce mortality rates in severe to critical COVID-19 patients. Large-scale randomized controlled trials are still required to improve the statistical power of meta-analysis.

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.

Evaluating the effects of Intravenous Immunoglobulin (IVIg) on the management of severe COVID-19 cases: A randomized controlled trial.

BACKGROUND: The newly discovered coronavirus has turned into coronavirus disease 2019 (COVID-19) pandemic and it rages at an unprecedented rate. Considering the findings of previous studies on the use of Intravenous Immunoglobulin (IVIg) for treating severe H1N1 infection and the satisfying results for reducing viral load and mortality, this study aimed to investigate the potential usefulness of IVIg for the management of severe cases. METHODS: In this randomized controlled trial, 84 patients were included: 52 in the IVIg group and 32 in the control group. The intervention group received IVIg at a dose of 400 mg/kg, IV, daily for three days. Both groups received hydroxychloroquine, lopinavir/ritonavir and supportive care. The demographic data, mortality rate, the need for mechanical ventilation, length of stay in hospital and in Intensive Care Unit (ICU), and imaging findings were recorded and compared in terms of the mentioned factors. RESULTS: The mean time from admission to IVIg initiation was 3.84 ± 3.35 days. There was no significant difference between the two groups in terms of mortality rate (P-value = 0.8) and the need for mechanical ventilation (P-value = 0.39). The length of hospital stay was significantly lower for the control group than that of the intervention group (P-value = 0.003). There was a significant positive relationship between the time from hospital admission to IVIg initiation and the length of stay in the hospital and ICU among the survivors (P-value < 0.001 and =0.01, respectively). CONCLUSIONS: Our findings did not support the use of IVIg in combination with hydroxychloroquine and lopinavir/ritonavir in treatment of severe COVID-19 cases.

Combination therapy of IFNß1 with lopinavir-ritonavir, increases oxygenation, survival and discharging of sever COVID-19 infected inpatients.

Interferon Beta-1a (IFN-ß1-a), an immunomodulatory mediator with antiviral effects, has shown in vivo and in vitro activities especially on coronavirus including SARS-CoV-2. COVID-19 defined as the disease caused by infection with SARS-CoV-2. The virus has been illustrated inhibits the production of IFN-ß1-a from inflammatory cells. We conducted a retrospective study of all adult confirmed COVID-19 hospitalized patients who received combination of three doses of 12 million international units of IFN-ß1-a and Lopinavir 400 mg and Ritonavir 100 mg every 12 h (case group) for 14 days besides standard care and age- and sex- matched COVID-19 patients with receiving lopinavir/ritonavir (control group) at Masih Daneshvari Hospital as a designated hospital for COVID-19 between Feb 19 and Apr 30, 2020. Multivariate analysis was done to determine the impact of IFN-ß1-a on outcome and all-cause mortality. 152 cases in IFN-ß1-a group and 304 cases as control group were included. IFN-ß1-a group stayed at hospital longer and required noninvasive ventilation more than control group (13 vs. 6 days, p = 0.001) and (34% vs. 24%, p = 0.04), respectively. During treatment, 57 (12.5%) patients died. The death rate in case and control groups was 11% and 13% respectively. In multivariate analysis, not receiving IFN-ß1-a (HR 5.12, 95% CI: 2.77-9.45), comorbidity (HR 2.28, 95% CI: 1.13-4.60) and noninvasive ventilation (HR 2.77, 95% CI: 1.56-4.93) remained significantly associated with all-cause mortality. In this study, risk of death decreased by using IFN-ß1-a in COVID-19 patients. More clinical study will be necessary to measure efficacy of IFN-ß1-a in COVID-19 treatment.