Pegylated interferon alpha-2b: A good bet for treating COVID-19?

Pegylated interferon alpha-2b (PEG IFN) appears to be beneficial in the treatment of patients with moderate COVID-19 infection, with the results of a phase III trial showing that its use has facilitated clinical status improvement, early viral clearance, and weaning off oxygen.

Significantly more of the patients who were given a single dose of PEG IFN (1-µg/kg subcutaneous injection, single dose) along with standard of care (SOC) achieved a 2-point improvement on the 7-point World Health Organization (WHO) ordinal scale for clinical improvement on day 8, as compared with those who received SOC only (80.36 percent vs 68.18 percent; p=0.0379). [Int J Infect Dis 2021;doi:10.1016/j.ijid.2021.08.044]

“Type I interferons such as IFN alpha-2b are produced as a first response to most viral infections by the affected cells. In contrast to other respiratory viruses, a COVID-19 viral infection does not seem to produce a strong early type I interferon response,” the investigators explained. [Cell 2020;181:1036-1045]

“[T]herefore, intervention with PEG IFN may have filled this gap in the early response to COVID-19 infection, leading to a reduction in viral load, followed by a clinical improvement on the WHO ordinal scale, as well as the time to resolution of clinical signs and symptoms,” they added.

Of the 250 COVID-19 patients (70.8 percent male) with moderate signs and symptoms, 120 (mean age 49.6 years) had been randomized to receive PEG IFN plus SOC and the remaining 130 (mean age 50.1 years) to treatment with SOC alone.

While the number of patients who achieved clinical improvement based on a 2-point improvement on the WHO ordinal scale was greater with PEG IFN plus SOC group vs SOC only at day 8, there was no longer any difference observed at day 11 (91.60 percent vs 92.56 percent, respectively; p=0.781) and at day 15 (94.12 percent vs 95.93 percent; p=0.515).

Viral clearance, defined as negative RT-PCR, rates were 91.15 percent at day 7, 97.44 percent at day 11, and 98.31 percent at day 14 among patients who received PEG IFN plus SOC. The corresponding rates among those who received SOC only were 78.90 percent, 96.58 percent, and 98.35 percent. There was a statistically significant between-group difference observed at day 7, in favour of PEG IFN, indicating that the drug helped clear the viral load early (p<0.05). This benefit correlated very well with drug’s effect on clinical status at day 8 (p=0.01).

In terms of oxygen support, a total 131 patients overall required supplemental oxygen: 64 (61.54 percent) patients in PEG IFN plus SOC group and 67 in the SOC group alone. The use of PEG IFN led to early weaning (median, 56.00 vs 84.00 hours; p<0.05).

Why patients given PEG IFN showed a significantly reduced requirement for supplemental oxygen as well as early resolution of signs and symptoms, the investigators pointed out that “PEG IFN-mediated early reduction in viral load may have helped the lungs in performing their function better, likely due to a reduced level of lung infection, although this was not directly studied in this clinical trial.”

Finally, there was a time-dependent decrease in the biomarkers C-reactive protein, interleukin-6, D-dimer, and ferritin in both the treatment groups. There also were no clinically significant changes in lab parameters, and the safety profiles were similar.

As suggested in the lack of statistically difference in clinical status at day 11, the majority of patients with moderate COVID-19 eventually become virus-free, according to the investigators. “Therefore, the benefit of PEG IFN therapy is in the early cure of moderate patients and thereby minimizing the risk of their getting severe disease.” 

Taken together and despite the presence of study limitations, the results of the current trial indicate that PEG IFN provides a viable treatment option during the current pandemic situation and can limit the spread of virus in the community, the investigators said.