A Randomized Clinical Trial of the Efficacy and Safety of Interferon ß-1a in Treatment of Severe COVID-19.

To the best of our knowledge, there is no published study on the use of interferon ß-1a (IFN ß-1a) in the treatment of severe COVID-19. In this randomized clinical trial, the efficacy and safety of IFN ß-1a were evaluated in patients with severe COVID-19. Forty-two patients in the interferon group received IFN ß-1a in addition to the national protocol medications (hydroxychloroquine plus lopinavir-ritonavir or atazanavir-ritonavir). Each 44-µg/ml (12 million IU/ml) dose of interferon ß-1a was subcutaneously injected three times weekly for two consecutive weeks. The control group consisted of 39 patients who received only the national protocol medications. The primary outcome of the study was time to reach clinical response. Secondary outcomes were duration of hospital stay, length of intensive care unit stay, 28-day mortality, effect of early or late administration of IFN on mortality, adverse effects, and complications during the hospitalization. Between 29 February and 3 April 2020, 92 patients were recruited, and a total of 42 patients in the IFN group and 39 patients in the control group completed the study. As the primary outcome, time to the clinical response was not significantly different between the IFN and the control groups (9.7 ± 5.8 versus 8.3 ± 4.9 days, respectively, P = 0.95). On day 14, 66.7% versus 43.6% of patients in the IFN group and the control group, respectively, were discharged (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.05 to 6.37). The 28-day overall mortality was significantly lower in the IFN than the control group (19% versus 43.6%, respectively, P = 0.015). Early administration significantly reduced mortality (OR, 13.5; 95% CI, 1.5 to 118). Although IFN did not change the time to reach the clinical response, adding it to the national protocol significantly increased discharge rate on day 14 and decreased 28-day mortality. (This study is in the Iranian Registry of Clinical Trials under identifier IRCT20100228003449N28.).

Intravenous magnesium sulfate for prevention of vancomycin plus piperacillin-tazobactam induced acute kidney injury in critically ill patients: An open-label, placebo-controlled, randomized clinical trial.

BACKGROUND: Recent studies have shown an increased risk of acute kidney injury (AKI) induced by vancomycin + piperacillin-tazobactam (VPT) combination. In this study, the efficacy of intravenous magnesium sulfate in prevention of VPT induced AKI in critically ill patients admitted to the ICU has been evaluated. METHODS: In an open-label, placebo-controlled, randomized clinical trial, 72 adults (≥ 18 years old) who had indications to receive VPT as empiric therapy were assigned to the magnesium or control group in 1:1 ratio. Concomitant with VPT, intravenous infusion of magnesium sulfate was started for patients in the magnesium group. The target serum level of magnesium was defined 3 mg/dl. Patients in the control group received normal saline as placebo. The target serum level of magnesium was defined 1.9 mg/dl in this group. The study's primary outcome was incidence of AKI during and up to 48 h after the treatment course. Escalation and de-escalation of VPT regimen, duration of hospitalization, length of ICU stay and 28-day mortality were secondary outcomes. RESULTS: Thirty patients in each group completed the examination. Five patients in the magnesium group and 11 patients in the control group experienced AKI (p = 0.072). De-escalation of VPT regimen was done approximately in 60% of patients. Duration of hospitalization and length of ICU stay were not statistically different between the groups. Finally, 28-day mortality was 23.33% in each group. Although the incidence of AKI was not statistically different between the groups in unadjusted logistic regression model, it became significant after adjusting for confounding factors [unadjusted model (OR = 0.34; 95% CI: 0.10-1.16, p = 0.084), adjusted model: (OR = 0.26; 95% CI: 0.07-0.96, p = 0.04)]. CONCLUSIONS: Administration of magnesium sulfate with the target serum levels around 3 mg/dL reduced the incidence of AKI in critically ill patients who were receiving VPT as empric therapy.

Distinguishing repeated polymerase chain reaction positivity from re-infections in COVID-19.

BACKGROUND: Possibility of reinfection with SARS-CoV-2 changes our view on herd immunity and vaccination and can impact worldwide quarantine policies. We performed real-time polymerase chain reaction (RT-PCR) follow-up studies on recovered patients to assess possible development of reinfections and re-positivity. METHODS: During a 6-month period, 202 PCR-confirmed recovering COVID-19 patients entered this study. Follow-up RT-PCR tests and symptom assessment were performed 1 month after the initial positive results. Patients who tested negative were tested again 1 and 3 months later. The serum IgG and IgM levels were measured in the last follow-up session. RESULTS: In the first two follow-up sessions, 82 patients continued their participation, of which four patients tested positive. In the second follow-up 44 patients participated, three of whom tested positive. None of the patients who tested positive in the first and second follow-up session were symptomatic. In the last session, 32 patients were tested and four patients were positive, three of them were mildly symptomatic and all of them were positive for IgG. CONCLUSIONS: A positive RT-PCR in a recovering patient may represent reinfection. While we did not have the resources to prove reinfection by genetic sequencing of the infective viruses, we believe presence of mild symptoms in the three patients who tested positive over 100 days after becoming asymptomatic, can be diagnosed as reinfection. The immune response developed during the first episode of infection (e.g., IgG or T-cell mediated responses that were not measured in our study) may have abated the symptoms of the reinfection, without providing complete protection.

Safety and effectiveness of high-dose vitamin C in patients with COVID-19: a randomized open-label clinical trial.

BACKGROUND: Vitamin C is an essential water-soluble nutrient that functions as a key antioxidant and has been proven to be effective for boosting immunity. In this study, we aimed to assess the efficacy of adding high-dose intravenous vitamin C (HDIVC) to the regimens for patients with severe COVID-19 disease. METHODS: An open-label, randomized, and controlled trial was conducted on patients with severe COVID-19 infection. The case and control treatment groups each consisted of 30 patients. The control group received lopinavir/ritonavir and hydroxychloroquine and the case group received HDIVC (6 g daily) added to the same regimen. RESULTS: There were no statistically significant differences between two groups with respect to age and gender, laboratory results, and underlying diseases. The mean body temperature was significantly lower in the case group on the 3rd day of hospitalization (p = 0.001). Peripheral capillary oxygen saturations (SpO2) measured at the 3rd day of hospitalization was also higher in the case group receiving HDIVC (p = 0.014). The median length of hospitalization in the case group was significantly longer than the control group (8.5 days vs. 6.5 days) (p = 0.028). There was no significant difference in SpO2 levels at discharge time, the length of intensive care unit (ICU) stay, and mortality between the two groups. CONCLUSIONS: We did not find significantly better outcomes in the group who were treated with HDIVC in addition to the main treatment regimen at discharge. Trial registration irct.ir (IRCT20200411047025N1), April 14, 2020.

Safety and effectiveness of azithromycin in patients with COVID-19: An open-label randomised trial.

As no specific pharmacological treatment has been validated for use in coronavirus disease 2019 (COVID-19), we aimed to assess the effectiveness of azithromycin (AZM) in these patients at a referral centre in Iran. An open-label, randomised controlled trial was conducted on patients with laboratory-confirmed COVID-19. A total of 55 patients in the control group receiving hydroxychloroquine (HCQ) and lopinavir/ritonavir (LPV/r) were compared with 56 patients in the case group who in addition to the same regimen also received AZM. Patients with prior cardiac disease were excluded from the study. Furthermore, patients from the case group were assessed for cardiac arrythmia risk based on the American College of Cardiology (ACC) risk assessment for use of AZM and HCQ. The main outcome measures were vital signs, SpO2 levels, duration of hospitalisation, need for and length of intensive care unit admission, mortality rate and results of 30-day follow-up after discharge. Initially, there was no significant difference between the general conditions and vital signs of the two groups. The SpO2 levels at discharge were significantly higher, the respiratory rate was lower and the duration of admission was shorter in the case group. There was no significant difference in the mortality rate between the two groups. Patients who received AZM in addition to HCQ and LPV/r had a better general condition. HCQ+AZM combination may be beneficial for individuals who are known to have a very low underlying risk for cardiac arrhythmia based on the ACC criteria.