This retrospective cohort study has demonstrated the efficacy and safety of oral administration of BAR for a 14-day period among hospitalized patients with COVID-19 infection, most of whom had severe or critical illnesses. Overall, BAR treatment was associated with an 88.5% reduction in the risk of mortality from any cause. Similar findings were observed in PSM analyses at ratios of 1:2 and 1:3. Furthermore, BAR treatment initiated 96 hours or more after hospital admission did not significantly lower the mortality rate compared to treatment initiated earlier. Therefore, patients with severe or critical COVID-19 illness may benefit from BAR treatment initiated within four days of hospital admission.
A meta-analysis was conducted to assess the efficacy and safety of BAR in the treatment of hospitalized adults with COVID-19. The results indicate that BAR has resulted in accelerated recovery and reduced hospitalization duration for COVID-19 patients, particularly excluding those in critical condition[22]. A prior study has documented the efficacy of BAR among patients with COVID-19 infection in a double-blind, randomized phase 3 trial. The objective of this study was to assess the efficacy in terms of the risk reduction for progression to severe COVID-19 infection[23]. The cumulative randomized evidence to date indicates that JAK inhibitors, primarily BAR, reduce mortality in hospitalized patients with COVID-19 by approximately one-fifth[18]. The exploratory trial was conducted across 18 hospitals in Argentina, Brazil, Mexico, and the USA to assess the efficacy and safety of BAR in combination with standard care for critically ill hospitalized adults with COVID-19 requiring invasive mechanical ventilation or extracorporeal membrane oxygenation. This study found that in critically ill hospitalized patients with COVID-19 receiving invasive mechanical ventilation or extracorporeal membrane oxygenation, treatment with BAR, in combination with standard care including corticosteroids, reduced mortality compared to placebo. This reduction in mortality aligns with the observed mortality reduction in less severely ill patients in the primary COV-BARRIER study population[24]. While a more recent randomized, double-blind phase 3 trial examined the efficacy and safety of BAR among hospitalized patients with severe or critical COVID-19 infection, the trial was prematurely terminated, rendering it underpowered to reach a definitive conclusion[15]. However, there is currently no definitive evidence regarding the effectiveness of BAR in complex scenarios such as severe or critical illness in China, where numerous variants of COVID-19 are prevalent and spreading extensively. Consequently, the efficacy of BAR among hospitalized patients with COVID-19 infection has largely remained uncertain. Our study encompassed a substantial number of hospitalized patients with COVID-19 infection, the majority of whom were afflicted with various sub-variants of the Omicron variant. Additionally, most of our study population experienced severe or critical illness. Moreover, our PSM analyses were conducted at ratios of 1:1, 1:2, and 1:3, which helped eliminate other confounding factors associated with severe or critical illness treated with BAR. Our findings are in line with currently reported results and offer significant guidance for the treatment of COVID-19 patients in China. However, it should be noted that the limitation of our study lies in the current absence of multicenter clinical trials in China. Currently, there have been several monoclonal antibodies, such as sotrovimab[25] and bamlanivimab[26] that have been demonstrated to markedly reduce the risk for progression to severe COVID-19 infection. Most of these require intravenous or subcutaneous administration in a medical facility or center. The oral administration of BAR may constitute an advantage for convenient administration, in the hospital and community settings, among COVID-19-infected patients.
No serious adverse events leading to treatment discontinuation were identified throughout our study. The most commonly reported adverse events included secondary infection caused by bacteria or influenza virus, as well as venous thromboembolism, which were deemed unrelated to BAR treatment by the site investigator. It is worth noting that COVID-19-infected patients with severe or critical illness may often exhibit compromised immunity, which can predispose them to secondary infections [27] or venous circulation dysregulation [28]. Our findings suggest that BAR may be safe for treating severe or critical COVID-19 infection. However, the concurrent use of BAR and corticosteroids may potentially increase the risk of adverse drug interactions, underscoring the need for monitoring adverse events closely.
Our study has several limitations. Firstly, the majority of patients were infected with the prevailing Omicron variant, raising uncertainty about whether BAR provides similar therapeutic benefits to COVID-19-infected patients associated with other emerging variants. Secondly, we did not collect blood or sputum samples for further immune response profiling, including cytokine production, after initiating BAR treatment. Therefore, we cannot elucidate the molecular mechanisms underlying the therapeutic benefits conferred by the anti-inflammatory effects.
In conclusion, BAR, when administered alongside corticosteroids, proved efficacious and safe for treating hospitalized COVID-19-infected patients with severe or critical illness. However, further validation is needed to determine the optimal time window for treatment initiation, which may be within 4 days after hospital admission.