Clinical outcomes of different therapeutic options for COVID-19 in two Chinese case cohorts: A propensity-score analysis

Abstract

Background: The timing of administration of agents and use of combination treatments in COVID-19 remain unclear. We assessed the effectiveness of therapeutics in cohorts in Hong Kong SAR and Anhui, China. Methods: We conducted propensity-score analysis of 4771 symptomatic patients from Hong Kong between 21st January and 6th December 2020, and 648 symptomatic patients from Anhui between 1st January and 27th February 2020. We censored all observations as at 13st December 2020. Time from hospital admission to discharge, and composite outcome of death, invasive mechanical ventilation or intensive care unit admission across 1) all therapeutic options including lopinavir-ritonavir, ribavirin, umifenovir, interferon-alpha-2b, interferon-beta-1b, corticosteroids, antibiotics, and Chinese medicines, and 2) four interferon-beta-1b combination treatment groups were investigated. Findings: Interferon-beta-1b was associated with an improved composite outcome (OR=0.55, 95%CI 0.38, 0.80) and earlier discharge (À8.8 days, 95%CI À9.7, À7.9) compared to those not administered interferonbeta-1b. Oral ribavirin initiated within 7 days from onset was associated with lower risk of the composite outcome in Hong Kong (OR=0.51, 95%CI 0.29, 0.90). Lopinavir-ritonavir, intravenous ribavirin, umifenovir, corticosteroids, interferon-alpha-2b, antibiotics or Chinese medicines failed to show consistent clinical benefit. Interferon-beta-1b co-administered with ribavirin was associated with improved composite outcome (OR=0.50, 95%CI 0.32, 0.78) and earlier discharge (À2.35 days, 95%CI À3.65, À1.06) compared to interferonbeta-1b monotherapy. Interpretation: Our findings support the early administration of interferon-beta-1b alone or in combination with oral ribavirin for COVID-19 patients.

The role of type I interferon in the treatment of COVID‐19

“…The study further demonstrated that coadministration of IFNβ−1b with ribavirin brings better clinical outcomes, including higher survival rate, lower mechanical ventilation, and intensive care requirements, and shorter length of stay, especially when administered in the early phases of the disease. 113 The efficacy of PEGylated IFNα−2b in addition to the standard care was studied against the standard care only group; the findings supported the effectiveness of PEG IFN-α2b in rapid viral clearance and improving clinical status on Day 15 as patients who received PEG IFN-α2b required oxygen supplementation for a shorter period than those who only received standard care treatments. 114 A recent publication has reported the beneficial impact of adding PEGylated interferon to ruxolitinib treatment by describing the case of an elderly woman with primary myelofibrosis, who was persistently tested positive for COVID-19, as ruxolitinib is known to have an immunosuppressive impact on innate immunity signaling and, most importantly interferon receptors.…”

“…A more recent publication, which has assessed different medications in treating COVID‐19 in two Chinese case cohorts, supported the therapeutic effect of IFNβ−1b in terms of earlier discharge. The study further demonstrated that coadministration of IFNβ−1b with ribavirin brings better clinical outcomes, including higher survival rate, lower mechanical ventilation, and intensive care requirements, and shorter length of stay, especially when administered in the early phases of the disease 113 …”

“…57 A recent propensity-score analysis study suggested that administering IFNα−2b beyond 7 days after symptoms onset can turn the antiviral effects into pro-inflammatory ones. 113 The IFN administration route might be another determinant factor in evaluating its efficacy; some studies have suggested IFN aerosols or nebulizers as a possible solution since they can be directly and noninvasively delivered to the lungs and reach a higher local concentration than the intramuscular form. 96 A recent clinical trial was carried out on Chinese medical staff exposed to COVID-19 at low-or high-risk levels, they were both receiving IFN-α nasal drops (2) IFN significantly improved the discharge rate by day 14.…”

Current utilization of interferon alpha for the treatment of coronavirus disease 2019: A comprehensive review

“… [179] In contrast, a retrospective study showed that no matter whether the treatment was initiated within 7 days of symptom onset or not, there was no difference between the IFNα (n=494) and non-IFNα (n=152) groups in terms of the time from admission to discharge, intensive care unit (ICU) admission, invasive mechanical ventilation, or mortality. [137] …”

Clofazimine: another potential magic bullet for the treatment of COVID-19?

“…The novelty of the virus is the driving force for numerous clinical trials taking place in an attempt to discover appropriate therapeutic agents. 1 Many pharmacological agents have shown promising results, including clofazimine. 2 3 More recently, a prospective open-label randomised controlled clinical trial of dual therapy with interferon beta-1b and clofazimine for patients infected with COVID-19 is being conducted.…”