Treatment with interferon in early COVID-19

Simon Collins, HIV i-Base

Two studies have been recently published that report potential benefits from using interferon treatment in mild or early COVID-19.

A study by Zhou and colleagues reported the outcomes of 77 participants with moderate COVID-19 who were admitted to the Union Hospital in Shanghai between 16 January and 20 February 2020 and who were randomised to receive either nebulised IFN-α-2b (n=7), the antiviral umifenovir (UFV) (n=24) or dual treatment (n=46). [1]

Participants receiving IFN treatment had faster viral load clearance and reduced levels of inflammatory proteins IL-6 and C-reactive protein, regardless of age, sex and comorbidities.

Baseline characteristics that varied between groups included median age (IQR) 41 vs 40 vs 64 (p<0.001) the percentage of men 0%, 43% and 45% (p=0.076) and percentage with comorbidities 14%, 15% and 54% (p=0.002), in the IFN, dual and UFV arms respectively.

The dual therapy group was also treated approximately nine days later after symptoms, median 8, 17 and 8 days respectively, p=0.004.

None of the participants required oxygen supplementation, intubation or intensive care. Approximately 50% had fever 38°C that was managed by ibuprofen.

Mean days to viral clearance was approximately 21 vs 20 vs 28 days from the onset of symptoms for the IFN, dual and UFV arms respectively (p-0.002).

The dual therapy arms included 16/46 cases (34.8%) IFN was started after UFV and 24 cases where IFN was continued after UFV was stopped.

Although this was an exploratory, small, non-randomised, uncontrolled study with significant baseline differences between the groups the effects of IFN treatment on accelerated viral clearance and reductions in circulating IL-6 and CRP levels remained significant after adjusting for age, sex and comorbidities.

At least one publication has reported no benefit from using umifenovir (only available in China and Russia) against COVID-19. [2]

An open-label, randomised, phase 2 trial from Hung and colleagues using a triple combination regimen of interferon beta-1b, lopinavir/r and ribavirin reported better outcomes compared to a control arm using lopinavir/r alone. [3]

The triple therapy arm had significantly reduced time to negative throat PCR: 7 days (IQR: 5 to 11) vs 12 days (IQR: 8 to 15) [HR: 4.37 (95%CI: 1.86 to 10.24)], symptom alleviation: 0 of 4 days (IQR 3 to 8) vs 8 days (IQR: 7 to 9); [HR 3.92; 95%CI: 1.66 to 9.23], and duration of hospital stay (9.0 days (IQR: 7.0 to 13.0] vs 14.5 days (IQR: 9·3 to 16·0); HR 2.72 (95%CI: 1.2 to 6.13).

Although this is important for being a prospective study, participants were in early mild or moderate COVID-19 and there was no mortality in either group.

This report was first published on 26 May 2020.

References

Zhou Q et al. Interferon-α2b Treatment for COVID-19. Front. Immunol., DOI: 10.3389/fimmu.2020.01061. (15 May 2020). https://www.frontiersin.org/articles/10.3389/fimmu.2020.01061/full
Lian N et al. Umifenovir treatment is not associated with improved outcomes in patients with coronavirus disease 2019: a retrospective study. Clin Bicrociol and Inf. DOI: 10.1016/j.cmi.2020.04.026. (25 April 2020).
https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(20)30234-2/fulltext
Hung IF-N et al. Triple combination of interferon beta-1b, lopinavir–ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. Lancet. 2020; DOI: 10.1016/S0140-6736(20)31042-4. (8 May 2020).
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31042-4/fulltext

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