Deferoxamine in the management of COVID-19 adult patients admitted to ICU: a prospective observational cohort study.

COVID-19 infection is associated with high mortality, and despite extensive studying the scientific society is still working to find a definitive treatment. Some experts postulated a beneficial role of Deferoxamine. Aim: The aim of this study was to compare the outcomes of COVID-19 adult patients admitted to the ICU who received deferoxamine to those who received standard of care. Methods: Prospective observational cohort study, in the ICU of a tertiary referral hospital in Saudi Arabia to compare all-cause hospital mortality between COVID-19 patients who received deferoxamine and standard of care. Results: A total of 205 patients were enrolled, with an average age of 50.1±14.3, 150 patients received standard of care only, and 55 patients received deferoxamine additionally. Hospital mortality was lower in deferoxamine group (25.5 vs. 40.7%, 95% CI=1.3-29.2%; P=0.045). Clinical status score upon discharge was lower in deferoxamine group (3.6±4.3 vs. 6.2±4, 95% CI: 1.4-3.9; P<0.001), as was the difference between discharge score and admission score (indicating clinical improvement). More patients admitted with mechanical ventilation were successfully extubated in the deferoxamine group (61.5 vs. 14.3%, 95% CI: 15-73%; P=0.001), with a higher median ventilator-free days. There were no differences between groups in adverse events. Deferoxamine group was associated with hospital mortality [odds ratio=0.46 (95% CI: 0.22-0.95); P=0.04]. Conclusions: Deferoxamine may have mortality and clinical improvement benefits in COVID-19 adults admitted to ICU. Further powered and controlled studies are required.

Tocilizumab Outcomes in Critically Ill COVID-19 Patients Admitted to the ICU and the Role of Non-Tocilizumab COVID-19-Specific Medical Therapeutics.

BACKGROUND: Tocilizumab is a monoclonal antibody proposed to manage cytokine release syndrome (CRS) associated with severe COVID-19. Previously published reports have shown that tocilizumab may improve the clinical outcomes of critically ill patients admitted to the ICU. However, no precise data about the role of other medical therapeutics concurrently used for COVID-19 on this outcome have been published. OBJECTIVES: We aimed to compare the overall outcome of critically ill COVID-19 patients admitted to the ICU who received tocilizumab with the outcome of matched patients who did not receive tocilizumab while controlling for other confounders, including medical therapeutics for critically ill patients admitted to ICUs. METHODS: A prospective, observational, multicenter cohort study was conducted among critically ill COVID-19 patients admitted to the ICU of 14 hospitals in Saudi Arabia between 1 March 2020, and October 31, 2020. Propensity-score matching was utilized to compare patients who received tocilizumab to patients who did not. In addition, the log-rank test was used to compare the 28 day hospital survival of patients who received tocilizumab with those who did not. Then, a multivariate logistic regression analysis of the matched groups was performed to evaluate the impact of the remaining concurrent medical therapeutics that could not be excluded via matching 28 day hospital survival rates. The primary outcome measure was patients' overall 28 day hospital survival, and the secondary outcomes were ICU length of stay and ICU survival to hospital discharge. RESULTS: A total of 1470 unmatched patients were included, of whom 426 received tocilizumab. The total number of propensity-matched patients was 1278. Overall, 28 day hospital survival revealed a significant difference between the unmatched non-tocilizumab group (586; 56.1%) and the tocilizumab group (269; 63.1%) (p-value = 0.016), and this difference increased even more in the propensity-matched analysis between the non-tocilizumab group (466.7; 54.6%) and the tocilizumab group (269; 63.1%) (p-value = 0.005). The matching model successfully matched the two groups' common medical therapeutics used to treat COVID-19. Two medical therapeutics remained significantly different, favoring the tocilizumab group. A multivariate logistic regression was performed for the 28 day hospital survival in the propensity-matched patients. It showed that neither steroids (OR: 1.07 (95% CI: 0.75-1.53)) (p = 0.697) nor favipiravir (OR: 1.08 (95% CI: 0.61-1.9)) (p = 0.799) remained as a predictor for an increase in 28 day survival. CONCLUSION: The tocilizumab treatment in critically ill COVID-19 patients admitted to the ICU improved the overall 28 day hospital survival, which might not be influenced by the concurrent use of other COVID-19 medical therapeutics, although further research is needed to confirm this.

Effect of Tocilizumab on "Ventilator Free Days" Composite Outcome in SARS-CoV-2 Patients: A Retrospective Competing Risk Analysis.

Background: SARS-CoV-2 infection demonstrates a wide range of severity. More severe cases demonstrate a cytokine storm with elevated serum interleukin-6, hence IL-6 receptor antibody tocilizumab was tried for the management of severe cases. Aims: Effect of tocilizumab on ventilator-free days among critically ill SARS-CoV-2 patients. Method: Retrospective propensity score matching study, comparing mechanically ventilated patients who received tocilizumab to a control group. Results: 29 patients in the intervention group were compared to 29 controls. Matched groups were similar. Ventilator-free days were more numerous in the intervention group (SHR 2.7, 95% CI: 1.2 - 6.3; p = 0.02), ICU mortality rate was not different (37.9% versus 62%, p = 0.1), actual ventilator-free periods were significantly longer in tocilizumab group (mean difference 4.7 days; p = 0.02). Sensitivity analysis showed a significantly lower hazard ratio of death in tocilizumab group (HR 0.49, 95% CI: 0.25 - 0.97; p = 0.04). There was no difference in positive cultures among groups (55.2% in tocilizumab group versus 34.5% in the control; p = 0.1). Conclusion: Tocilizumab may improve the composite outcome of ventilator-free days at day 28 among mechanically ventilated SARS-CoV-2 patients; it is associated with significantly longer actual ventilator-free periods, and insignificantly lower mortality and higher superinfection.

Long-term outcomes of patients with COVID-19 treated with helmet noninvasive ventilation or usual respiratory support: follow-up study of the Helmet-COVID randomized clinical trial.

PURPOSE: To evaluate whether helmet noninvasive ventilation compared to usual respiratory support reduces 180-day mortality and improves health-related quality of life (HRQoL) in patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia. METHODS: This is a pre-planned follow-up study of the Helmet-COVID trial. In this multicenter, randomized clinical trial, adults with acute hypoxemic respiratory failure (n = 320) due to coronavirus disease 2019 (COVID-19) were randomized to receive helmet noninvasive ventilation or usual respiratory support. The modified intention-to-treat population consisted of all enrolled patients except three who were lost at follow-up. The study outcomes were 180-day mortality, EuroQoL (EQ)-5D-5L index values, and EQ-visual analog scale (EQ-VAS). In the modified intention-to-treat analysis, non-survivors were assigned a value of 0 for EQ-5D-5L and EQ-VAS. RESULTS: Within 180 days, 63/159 patients (39.6%) died in the helmet noninvasive ventilation group compared to 65/158 patients (41.1%) in the usual respiratory support group (risk difference - 1.5% (95% confidence interval [CI] - 12.3, 9.3, p = 0.78). In the modified intention-to-treat analysis, patients in the helmet noninvasive ventilation and the usual respiratory support groups did not differ in EQ-5D-5L index values (median 0.68 [IQR 0.00, 1.00], compared to 0.67 [IQR 0.00, 1.00], median difference 0.00 [95% CI - 0.32, 0.32; p = 0.91]) or EQ-VAS scores (median 70 [IQR 0, 93], compared to 70 [IQR 0, 90], median difference 0.00 (95% CI - 31.92, 31.92; p = 0.55). CONCLUSIONS: Helmet noninvasive ventilation did not reduce 180-day mortality or improve HRQoL compared to usual respiratory support among patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia.

Favipiravir Efficacy And Safety For The Treatment Of Severe Coronavirus Disease 2019: A Retrospective Study.

BACKGROUND: Corona virus disease is caused by the enveloped, single stranded RNA virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) becoming the deadliest disease of the century. Its global outbreak has led researchers to develop drugs or vaccines to prevent the spread of the disease. Favipiravir is an approved orally administered antiviral drug that selectively inhibits RNA-dependent RNA polymerase, used off-label to treat COVID-19. Objectives: The purpose of this study was to assess the efficacy and safety of this drug for severe COVID-19 infection. METHODS: This was an observational retrospective study, carried out at the ICU of King Saud Medical City (KSMC) from June 2020 to August 2020. Including a total of one thousand six hundred and ninety-nine patients (n=1699). Categorized into a treatment group (193 patients) who received Favipiravir along with standard care, and non-treatment group (1506 patients) who received standard care only. RESULTS: ICU all-cause mortality was similar in both groups i.e., (Treated group 38.3% Vs Untreated group 39.4%, 95% CI of difference: -6.6% to +8.4%; p = 0.8). The subgroup analysis of survivors as compared to deceased in the treatment group showed that survivors had significantly lower age, international normalising ratio (INR), blood urea nitrogen (BUN), and creatinine. The mean ICU length of stay (LOS) was shorter for survivors compared to deceased (11.2± 8.03 Vs 16.7±9.8 days respectively), while hospital LOS was almost similar between the two groups. Advanced age (OR 1.03 [95% CI: 1.01-1.06]; p=0.004), higher INR and BUN were significantly associated with increased odds of mortality. Comparison of lab investigations at day 1 and day 10 in the treatment group (regardless of outcome) showed that there was a significant increase in Alanine transaminase (ALT), alkaline phosphatase (ALK), and Bilirubin, while an insignificant trend of increase in Aspartate transaminase (AST) and creatinine was recorded. CONCLUSIONS: In this study, Favipiravir showed better therapeutic responses in patients with severe COVID-19 infection, in terms of average duration of stay in the intensive care unit and was well tolerated in the younger age, but showed no mortality benefit. However, elevated levels of inflammatory markers, including increased ALT, AST, BUN, bilirubin, and creatinine, needs to be carefully examined.

Helmet noninvasive ventilation for COVID-19 patients (Helmet-COVID): statistical analysis plan for a randomized controlled trial.

BACKGROUND: Noninvasive respiratory support is frequently needed for patients with acute hypoxemic respiratory failure due to coronavirus disease 19 (COVID-19). Helmet noninvasive ventilation has multiple advantages over other oxygen support modalities but data about effectiveness are limited. METHODS: In this multicenter randomized trial of helmet noninvasive ventilation for COVID-19 patients, 320 adult ICU patients (aged ≥14 years or as per local standards) with suspected or confirmed COVID-19 and acute hypoxemic respiratory failure (ratio of arterial oxygen partial pressure to fraction of inspired oxygen < 200 despite supplemental oxygen with a partial/non-rebreathing mask at a flow rate of 10 L/min or higher) will be randomized to helmet noninvasive ventilation with usual care or usual care alone, which may include mask noninvasive ventilation, high-flow nasal oxygen, or standard oxygen therapy. The primary outcome is death from any cause within 28 days after randomization. The trial has 80% power to detect a 15% absolute risk reduction in 28-day mortality from 40 to 25%. The primary outcome will be compared between the helmet and usual care group in the intention-to-treat using the chi-square test. Results will be reported as relative risk  and 95% confidence interval. The first patient was enrolled on February 8, 2021. As of August 1, 2021, 252 patients have been enrolled from 7 centers in Saudi Arabia and Kuwait. DISCUSSION: We developed a detailed statistical analysis plan to guide the analysis of the Helmet-COVID trial, which is expected to conclude enrollment in November 2021. TRIAL REGISTRATION: ClinicalTrials.gov NCT04477668 . Registered on July 20, 2020.

Early Versus Late DNR Orders and its Predictors in a Saudi Arabian ICU: A Descriptive Study.

Background: Practices of Do-Not-Resuscitate (DNR) orders show discrepancies worldwide, but there are only few such studies from Saudi Arabia. Objective: To describe the practice of DNR orders in a Saudi Arabian tertiary care ICU. Methods: This retrospective study included all patients who died with a DNR order at the ICU of King Saud Medical City, Riyadh, Saudi Arabia, between January 1 to December 31, 2021. The percentage of early DNR (i.e., ≤48 hours of ICU admission) and late DNR (>48 hours) orders were determined and the variables between the two groups were compared. The determinants of late DNR were also investigated. Results: A total of 723 cases met the inclusion criteria, representing 14.9% of all ICU discharges and 63% of all ICU deaths during the study period. The late DNR group comprised the majority of the cases (78.3%), and included significantly more patients with acute respiratory distress syndrome (ARDS), community acquired pneumonia (CAP), acute kidney injury, and COVID-19, and significantly fewer cases of readmissions and malignancies. Septic shock lowered the odds of a late DNR (OR = 0.4, 95% CI: 0.2-0.9;P= 0.02), while ARDS (OR = 3.3, 95% CI: 2-5.4;P < 0.001), ischemic stroke (OR = 2.5, 95% CI: 1.1-5.4;P= 0.02), and CAP (OR = 2, 95% CI: 1.3-3.1;P= 0.003) increased the odds of a late DNR. Conclusion: There was a higher frequency of late DNR orders in our study compared to those reported in several studies worldwide. Cases with potential for a favorable outcome were more likely to have a late DNR order, while those with expected poorer outcomes were more likely to have an early DNR order. The discrepancies highlight the need for clearer guidelines to achieve consistency.

Thromboprophylaxis and clinical outcomes in moderate COVID-19 patients: A comparative study.

BACKGROUND: Many thrombotic complications are linked to coronavirus disease 2019 (COVID-19). Antithrombotic treatments are important for prophylaxis against these thrombotic events. OBJECTIVES: This study was designed to compare enoxaparin and rivaroxaban as prophylactic anticoagulants in moderate cases of COVID-19 in terms of efficacy, safety, and clinical outcomes. METHODS: The study involved 124 patients with moderate COVID-19 (pneumonia without hypoxia) divided into two groups. The first group (G1) comprised 66 patients who received enoxaparin subcutaneously at a dose of 0.5 mg/kg every 12 h until discharge from the hospital. The second group (G2) comprised 58 patients who received oral rivaroxaban at a dose of 10 mg once daily until discharge from the hospital. The outcomes evaluated in this study were as follows: intermediate care unit (IMCU) duration, the number of patients transferred from the IMCU to the intensive care unit (ICU), ICU duration, the total length of hospital stay, in-hospital mortality, and thrombotic and bleeding complications. RESULTS: No significant differences in IMCU duration (p = 0.39), ICU duration (p = 0.96), and total length of hospital stay (p = 0.73) were observed between the two groups. The percentage of patients requiring ICU admission after hospitalization was 21.2% in G1 and 22.4% in G2 (p = 0.87). The mortality rate was 12.1% in G1 and 10.3% in G2 (p = 0.76). The proportion of patients who had thrombotic complications was 9.1% in G1 and 12.1% in G2 (p = 0.59). The incidence of mild bleeding was 3% in G1 and 1.7% in G2 (p = 0.64). CONCLUSION: Either enoxaparin or rivaroxaban may be used as thromboprophylaxis agents in managing patients with moderate COVID-19. Either medication has no clear advantage over the other.

"Ventilator-free days" composite outcome in patients with SARS-CoV-2 infection treated with tocilizumab: A retrospective competing risk analysis.

BACKGROUND: SARS-CoV-2 infection demonstrates a wide range of severity, with more severe cases presenting with a cytokine storm with elevated serum interleukin-6; hence, the interleukin-6 receptor antibody tocilizumab was used for the management of severe cases. OBJECTIVE: To explore the effect of tocilizumab on ventilator-free day composite outcomes among critically ill patients with SARS-CoV-2 infection. METHODS: This retrospective propensity score-matching study compared mechanically ventilated patients who received tocilizumab to a control group. RESULTS: Twenty-nine patients in the intervention group were compared to 29 controls. The matched groups were similar. The ventilator-free days composite outcome was higher in the intervention group (sub-distribution hazard ratio 2.7, 95% confidence interval [CI]: 1.2-6.3; p = 0.02), the mortality rate in the intensive care unit was not different (37.9% vs 62%, p = 0.1), and actual ventilator-free days were significantly longer in the tocilizumab group (mean difference 4.7 days; p = 0.02). Sensitivity analysis showed a significantly lower hazard ratio for death in the tocilizumab group (HR 0.49, 95% CI: 0.25-0.97; p = 0.04). Positive cultures were not significantly different among the groups (55.2% vs 34.5% in the tocilizumab and control groups, respectively; p = 0.1). CONCLUSIONS: Tocilizumab may improve the composite outcome of ventilator-free days at day 28 among mechanically ventilated patients with SARS-CoV-2 infection. It is associated with significantly longer actual ventilator-free days, insignificantly lower mortality, and higher superinfection.

Machine learning decision tree algorithm role for predicting mortality in critically ill adult COVID-19 patients admitted to the ICU.

BACKGROUND: Coronavirus disease-19 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is currently a major cause of intensive care unit (ICU) admissions globally. The role of machine learning in the ICU is evolving but currently limited to diagnostic and prognostic values. A decision tree (DT) algorithm is a simple and intuitive machine learning method that provides sequential nonlinear analysis of variables. It is simple and might be a valuable tool for bedside physicians during COVID-19 to predict ICU outcomes and help in critical decision-making like end-of-life decisions and bed allocation in the event of limited ICU bed capacities. Herein, we utilized a machine learning DT algorithm to describe the association of a predefined set of variables and 28-day ICU outcome in adult COVID-19 patients admitted to the ICU. We highlight the value of utilizing a machine learning DT algorithm in the ICU at the time of a COVID-19 pandemic. METHODS: This was a prospective and multicenter cohort study involving 14 hospitals in Saudi Arabia. We included critically ill COVID-19 patients admitted to the ICU between March 1, 2020, and October 31, 2020. The predictors of 28-day ICU mortality were identified using two predictive models: conventional logistic regression and DT analyses. RESULTS: There were 1468 critically ill COVID-19 patients included in the study. The 28-day ICU mortality was 540 (36.8 %), and the 90-day mortality was 600 (40.9 %). The DT algorithm identified five variables that were integrated into the algorithm to predict 28-day ICU outcomes: need for intubation, need for vasopressors, age, gender, and PaO2/FiO2 ratio. CONCLUSION: DT is a simple tool that might be utilized in the ICU to identify critically ill COVID-19 patients who are at high risk of 28-day ICU mortality. However, further studies and external validation are still required.

External Validation of 4C ISARIC Mortality Score in Critically ill COVID-19 Patients from Saudi Arabia.

Background: ISARIC mortality score is a risk stratification tool that helps predict the in-hospital mortality of COVID-19 patients. However, this tool was developed and validated in a British population, and thus, the external validation of this tool in local populations is important. Objectives: External validation of the ISARIC mortality score in COVID-19 patients from a large Saudi Arabian intensive care unit (ICU). Methods: This is a retrospective study that included all adult patients with COVID-19 admitted to the ICU of King Saud Medical City, Riyadh, Saudi Arabia, from March 2020 to June 2021. Patients who were pregnant or had pulmonary tuberculosis/human immunodeficiency virus were excluded along with patients with missing variables. Data were collected to calculate the ISARIC mortality score and then fitting receiver operator characteristic curve against patients' outcome. Results: A total of 1493 critically ill COVID-19 patients were included. The mortality was 38%, the area under the curve of the score was 0.81 (95% confidence interval [CI]: 0.79-0.83, P < 0.001) and the cutoff value correctly classified 72.7% of the cohort. The cutoff value of >9 had sensitivity of 70.5% (95% CI: 66.6-74.3); specificity, 73.97% (95% CI: 71-76.8); positive predictive value, 62.4% (95% CI: 59.5-65.2) and negative predictive value, 80.2% (95% CI: 78.2-82.4). Conclusion: The ISARIC score was found to have excellent predictive ability for mortality in critically ill COVID-19 patients in our Saudi Arabian cohort. A cutoff score of >9 was the optimal criterion.

Comparison of severity of immunized versus non-immunized COVID-19 patients admitted to ICU: A prospective observational study.

BACKGROUND: Vaccines against COVID-19 show high efficacy, yet, infection is still being detected among immunized patients, although with blunted severity. The purpose of this study was to assess the severity of COVID-19 infection among immunized versus non-immunized COVID-19 patients admitted to ICU. METHOD: A prospective observational cohort study, including all COVID-19 patients admitted to intensive care unit between January 1st, 2021 and June 30th, 2021 were eligible for inclusion. A comparison of severity upon hospitalization of immunized versus non-immunized patients on a 7-level ordinal scale was conducted, using ordinal logistic regression. RESULTS: 592 patients were enrolled, 524 (88.5%) non-immunized, 63 (10.6%) partially immunized, and 5 (0.9%) fully immunized, partially and fully immunized patients were grouped together. Majority of immunized patients (86.7%) were symptomatic before 21 days of immunization. Non-immunized group had fewer patients in the lower severity categories, while more patients in the higher severity categories compared to immunized group. At least one dose of immunization was associated with reduction of odds of moving up severity scale (OR = 0.2 [95% CI: 0.15-0.4]; p < 0.001) in a well fitted ordinal logistic regression model. At least one dose of immunization was associated with lower adjusted odds of 30 day all-cause mortality (OR = 0.45 [95% CI: 0.23-0.89]; p = 0.02). Non-immunized group had higher mortality rate (43.9% versus 29.4% [95% CI: 1.5 to 25.8]; p = 0.02). CONCLUSION: Most COVID-19 patients admitted to ICU were non-immunized, most of the partially immunized patients got infected before immunity could develop, and fully immunized patients were likely non-responders. At least one dose of immunization significantly decreases severity of the disease across all ordinal severity categories, and is significantly associated with lower 30 day all-cause mortality. Accordingly, immunization status may have to be considered when deciding on disposition of COVID-19 patients at the point of triage.

Helmet Non-Invasive Ventilation for COVID-19 Patients (Helmet-COVID): study protocol for a multicentre randomised controlled trial.

INTRODUCTION: Non-invasive ventilation (NIV) delivered by helmet has been used for respiratory support of patients with acute hypoxaemic respiratory failure due to COVID-19 pneumonia. The aim of this study was to compare helmet NIV with usual care versus usual care alone to reduce mortality. METHODS AND ANALYSIS: This is a multicentre, pragmatic, parallel randomised controlled trial that compares helmet NIV with usual care to usual care alone in a 1:1 ratio. A total of 320 patients will be enrolled in this study. The primary outcome is 28-day all-cause mortality. The primary outcome will be compared between the two study groups in the intention-to-treat and per-protocol cohorts. An interim analysis will be conducted for both safety and effectiveness. ETHICS AND DISSEMINATION: Approvals are obtained from the institutional review boards of each participating institution. Our findings will be published in peer-reviewed journals and presented at relevant conferences and meetings. TRIAL REGISTRATION NUMBER: NCT04477668.

Tocilizumab in the treatment of rapidly evolving COVID-19 pneumonia and multifaceted critical illness: A retrospective case series.

BACKGROUND: COVID-19 associated critical illness characterized by rapidly evolving acute respiratory failure (ARF) can develop, especially on the grounds of hyperinflammation. AIM AND METHODS: A case-series of 61 patients admitted to our intensive care unit (ICU) between August 12 and September 12, 2020 with confirmed COVID-19 pneumonia and rapidly evolving ARF requiring oxygen support therapy and/or mechanical ventilation was retrospectively analyzed. We examined whether intravenous administration of tocilizumab, a monoclonal interleukin-6 receptor antibody, was associated with improved outcome. All patients received empiric antivirals, dexamethasone 6 mg/day for 7 days, antibiotics, and prophylactic anticoagulation. Tocilizumab was administered at a dosage of 8 mg/kg [two consecutive intravenous infusions 12 h apart]. Outcome measures such as mortality on day-14, ICU length of stay, and rate of nosocomial acquired bacterial infections were also analyzed. Results: Patients were males (88.2%) aged 51 [interquartile range (IQR): 42.5-58.75)], with admission Acute Physiology and Chronic Health Evaluation (APACHE) 4 score of 53 (IQR: 37.75-72.5), and had more than one comorbidity (62.3%). On admission, twenty nine patients (47.5%) were mechanically ventilated, and thirty two patients (52.5%) were receiving oxygen therapy. No serious adverse effects due to tocilizumab therapy were recorded. However, twelve patients (19.6%) developed nosocomial acquired infections. ICU length of stay was 13 (IQR: 9-17) days, and mortality on day-14 was 24.6%. Six patients were shifted to other hospitals but were followed-up. The overall mortality on day-30 was 31.1%. Non-mechanically ventilated patients had higher survival rates compared to mechanically ventilated patients although results were not significant [hazards ratio = 2.6 (95% confidence intervals: 0.9-7.7), p = 0.08]. Tocilizumab did not affect the mortality of critically ill COVID-19 patients. CONCLUSION: Tocilizumab could be an adjunct safe therapy in rapidly evolving COVID-19 pneumonia and associated critical illness.

Ribavirin and Interferon Therapy for Critically Ill Patients With Middle East Respiratory Syndrome: A Multicenter Observational Study.

BACKGROUND: The objective of this study was to evaluate the effect of ribavirin and recombinant interferon (RBV/rIFN) therapy on the outcomes of critically ill patients with Middle East respiratory syndrome (MERS), accounting for time-varying confounders. METHODS: This is a retrospective cohort study of critically ill patients with laboratory-confirmed MERS from 14 hospitals in Saudi Arabia diagnosed between September 2012 and January 2018. We evaluated the association of RBV/rIFN with 90-day mortality and MERS coronavirus (MERS-CoV) RNA clearance using marginal structural modeling to account for baseline and time-varying confounders. RESULTS: Of 349 MERS patients, 144 (41.3%) patients received RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-ß1a; none received rIFN-ß1b). RBV/rIFN was initiated at a median of 2 days (Q1, Q3: 1, 3 days) from intensive care unit admission. Crude 90-day mortality was higher in patients with RBV/rIFN compared to no RBV/rIFN (106/144 [73.6%] vs 126/205 [61.5%]; P = .02]. After adjusting for baseline and time-varying confounders using a marginal structural model, RBV/rIFN was not associated with changes in 90-day mortality (adjusted odds ratio, 1.03 [95% confidence interval {CI}, .73-1.44]; P = .87) or with more rapid MERS-CoV RNA clearance (adjusted hazard ratio, 0.65 [95% CI, .30-1.44]; P = .29). CONCLUSIONS: In this observational study, RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-ß1a) therapy was commonly used in critically ill MERS patients but was not associated with reduction in 90-day mortality or in faster MERS-CoV RNA clearance.