Interferons (IFNs) are proteins that interfere with viral replication and accelerate viral clearance. However, with COVID-19, the production and function of type I interferons are markedly reduced. Therefore, type I interferon deficiency is a sign of severe COVID-19. In addition, worsening patients’ clinical symptoms occur after a decrease in the level of IFN-I in plasma. Therefore, IFN-I deficiency may help identify patients at risk for severe COVID-19.

IFN-alpha is a type I interferon used to treat viral diseases, including hepatitis B and C infections. IFN-alpha accelerated lung recovery in hospitalized SARS patients during the 2003 SARS-CoV outbreak in Canada and China. Laboratory studies have shown that SARS-CoV-2 is more sensitive to type I interferons than SARS-CoV.

Research on type I interferons for the treatment and prevention of COVID-19:

  • Systematic review and meta-analysis of clinical trials: early administration of IFN-beta in combination with antiviral drugs reduced mortality by 3 times and reduced the duration of hospitalization of patients with COVID-19 by 1.4 times.
  • Interferon-alpha nasal drops, combined with standard prevention methods, protected healthcare workers from contracting the coronavirus. Among the study, participants are doctors from the red zone.

COVID-19 Treat With Interferon-Alpha

Iranian scientists systematically reviewed the treatment results with IFN-alpha in patients with COVID-19.

The review included five studies involving 541 patients. The average age of patients is over 41 years. The control group of patients received standard antiviral treatment (lopinavir/ritonavir/arbidol), and the intervention group received antiviral therapy in combination with IFN-alpha.

In most studies, 5 µg/mL (12 million IU/mL) IFN-alpha was administered twice daily for two consecutive weeks or until discharge. After that, IFN-alpha was administered subcutaneously or by aerosol inhalation.

Scientists evaluated:

  • virus clearance rate;
  • duration of hospitalization;
  • time from symptom onset to initiation of interferon-alpha treatment;
  • markers of inflammation;
  • the timing of the disappearance of symptoms, including fever;
  • adverse reactions;
  • number of blood cells;
  • the severity of the disease.

All studies included patients with mild to severe COVID-19. The time from the onset of symptoms to the start of treatment is 5 to 10 days.

Most patients had a fever on admission. The number of leukocytes and lymphocytes in the intervention group was reduced. By the end of the study, most of the patients in the intervention group were fever-free. The fever went away within 4 days. The time from symptom onset to two repeated negative PCR tests was 13 days in patients treated with IFN-alpha.

Interferon-Alpha Outcomes for COVID-19

  • With early treatment with IFN-alpha, viral clearance was 5.13 days faster than in the control group: 27.3 versus 32.43 days.
  • Time to negative PCR test results were shorter in the IFN-alpha group.
  • Mean hospital stay (16±9.7 versus 23±10.5 days) was shorter in the IFN alfa-2b combination group than in the control group. In the IFN-alpha early treatment group, the duration of hospital stay decreased from 25±8.5 days to 10±2 days.

In most of the included studies, there was no significant difference in side effects between the intervention and control groups.

Conclusions

The risk of SARS-CoV-2 transmission is very high during the virus replication stage. In addition, prolonged shedding of the virus is directly related to mortality or disease severity. Therefore, reducing the duration of virus shedding is the most effective strategy to fight a pandemic. IFN-alpha reduced the time of hospitalization and accelerated the clearance of the virus. No significant adverse drug or IFN-alpha reactions were reported in the studies.

The leading cause of severe illness and death in COVID-19 is uncontrolled inflammation with high levels of inflammatory markers, including C-reactive protein (CRP) and IL-6. IFN-alpha shortened the duration of virus shedding and reduced CRP and IL-6 levels. In addition, inhalations of IFN-alpha-2b accelerated the clearance of the virus from the respiratory tract and could accelerate the resolution of the systemic inflammatory process.

In the Chinese study, researchers compared the efficacy of ribavirin (RBV) + IFN-alpha, lopinavir/ritonavir (LPV/r) + IFN-alpha, and RBV + LPV/r + IFN-alpha in patients with mild to moderate COVID-19. The researchers concluded that the antiviral efficacy of the three antiviral regimens mentioned above was not significantly different in mild to moderate COVID-19.

Some patients may have autoantibodies to type I IFN, which complicates the course of COVID-19. IFN-alpha treatment is less effective in such cases and should be replaced with IFN-beta therapy.

With coronavirus, the interferon response is delayed. In the early stages of infection, SARS-CoV-2 suppresses IFN-I signaling, but in severe COVID-19, the IFN-I response and the expression of interferon-stimulated genes are enhanced. The most effective is the early administration of IFN-alpha. Combining IFN-alpha with two or more antiviral drugs in the first days after infection can enhance the body’s antiviral response and speed up recovery.

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Reference

Interferon-alpha position in combating with COVID-19: A systematic review

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