Serum cytokine levels of COVID-19 patients after 7 days of treatment with Favipiravir or Kaletra

Abstract

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has infected 86,4 M patients and resulted in 1,86 M deaths worldwide. Severe COVID-19 patients have elevated blood levels of interleukin-6 (IL-6), IL-1β, tumor necrosis factor (TNF)α, IL-8 and interferon (IFN)γ.

Objective: To investigate the effect of antiviral treatment serum cytokines in severe COVID-19 patients.

Methods: Blood was obtained from 29 patients (aged 32-79 yr) with laboratory-confirmed COVID-19 upon admission and 7 days after antiviral (Favipiravir or Lopinavir/Ritonavir) treatment. Patients also received standard supportive treatment in this retrospective observational study. Chest computed tomography (CT) scans were evaluated to investigate lung manifestations of COVID-19. Serum was also obtained and cytokines levels were evaluated. 19 age- and gender-matched healthy controls were studied.

Results: Anti-viral therapy significantly reduced CT scan scores and the elevated serum levels of C-reactive protein (CRP) and lactate dehydrogenase (LDH). In contrast, serum levels of IL-6, IL-8 and IFNγ were elevated at baseline in COVID-19 subjects compared to healthy subjects with IL-6 (p = 0.006) and IL-8 (p = 0.011) levels being further elevated after antiviral therapy. IL-1β (p = 0.01) and TNFα (p = 0.069) levels were also enhanced after treatment but baseline levels were similar to those of healthy controls. These changes occurred irrespective of whether patients were admitted to the intensive care unit.

Conclusion: Antiviral treatments did not suppress the inflammatory phase of COVID-19 after 7 days treatment although CT, CRP and LDH suggest a decline in lung inflammation. There was limited evidence for a viral-mediated cytokine storm in these COVID-19 subjects.

Keywords: COVID-19; Cytokines storm; Flow cytometry; SARS-CoV-2.

Fig. 1

Serum levels of cytokines at baseline in healthy and COVID-19 patients and following 7 days of anti-viral therapy in COVID-19 subjects. Serum levels of IL-6 (A), IL-8 (B), IFN-γ (C), IL-1β (D) and TNFα (E) were measured in healthy subjects (n = 19) and COVID-19 patients (n = 29) before and after antiviral therapy. Results are presented as dot blots of individual values for each subject with the median (5–95% percentiles). *p < 0.05, **p < 0.01, ***p < 0.001 and **** p < 0.0001.

Fig. 2

Serum levels of cytokines in patients treated with Favipiravir or Kaletra. Serum levels of IL-6 (A), IL-8 (B), IFN-γ (C), IL-1β (D) and TNFα (E) were measured in non-ICU and ICU patients after 7 days of antiviral treatment. Results are presented as dot blots of individual values for each subject with the median (5–95% percentiles) also indicated. *p < 0.05; ns, not significant.