A combination treatment of IFN-α2b and IFN-γ accelerates viral clearance and control inflammatory response in COVID-19: Preliminary results of a randomized controlled trial

Abstract

Early studies with combination treatments of a type I IFN and IFN- revealed synergistic inhibition of SARS CoV replication in vitro [9][10][11][12]. IFN- is a critical regulator linking the innate and adaptive immune responses [13] Moreover, combination treatments with antivirals that target different stages of the virus replicative cycle [14-16] and IFN-2b and IFN- may synergize further to accelerate viral clearance. Accordingly, we conducted a phase II randomized clinical trial to evaluate whether a combination of IFN-2b and IFN-, in addition to standard of care would offer a therapeutic advantage in COVID-19 cases, promoting faster viral clearance and preventing progression to severe disease. Methods Study design and patientsAdult (19-82 yrs), PCR(+) confi rmed SARS-CoV-2 infected cases were enrolled in this open-labeled, single center, prospective, randomized and controlled clinical trial

Administration of HeberFERON in Patients with Persistent Oropharyngeal SARS-CoV-2 Wuhan/D614G Strain Viral Shedding

“…Our sample size is small, and the timing of Viral dissemination is determinant in the establishment of severe disease [44]. Therefore, the shortening of time to virus clearance as has been demonstrated by Idelis, et al for HeberFERON [32] and the results from this study, will impact favorable in the disease outcome in COVID-19 infected patients, even in the era of vaccines. Depletion of antiviral defenses related to immune response [45] and insuffi cient activation of the IFN system [46] are key points of innate immune failure to control viral persistence.…”

“…It was found that after 5 days of therapy 25% of patients had clear the virus from oral swabs [40]. Recently, Idelsi EM, et al [32] found that with the use of HeberFERON the time to reach the negativization of the SARS-CoV-2 measured by RT-PCR was 3 days in a 50% of a cohort SARS-CoV-2 asymptomatic or mild to moderate symptomatic patients.…”

“…Patient diagnosis for SARS-CoV-2 was undertaken using a single swab with oropharyngeal sampling and defi ned as positive if they had two consecutive positive results, by RT-PCR targeting amplifi cations of E and /or RdRP genes, the details are provided by Idelis, et al [32]. Patients positive at diagnosis for SARS-CoV-2 were treated with 3.0 million international units (MIU) IFN-2b (Heberon Alpha R), thrice a week, intramuscularly and lopinavir-ritonavir 200/50 mg every 12 h and Chloroquine (KCh) 250 mg every 12 h. Those that resulted negative for SARS-CoV-2 at day 14 or before, discharged in the absence of symptoms, were selected for…”

“…Early studies with combination treatments of a type I IFN and IFN- revealed synergistic inhibition of SARS-CoV replication In vitro [21,22]. Recently a phase II randomized clinical trial demonstrated the potent anti-SARS-CoV-2 activity of combination of IFN-2b and IFN- in mild to moderate patients positive to SARS-CoV-2 by RT-PCR  [32].…”