Discussion
Effective interventions for treating patients with SARS-CoV-2 infection are still urgently needed. While benefit of Kaletra and interferon alpha-2b was suggested by preclinical studies, the present study showed that neither interferon alfa-2b nor Kaletra plus interferon alfa-2b added to standard care were not associated with the duration of oxygen-support requirement and virus clearance time compared with standard care alone. The question of whether interferon alfa-2b or Kaletra plus interferon alpha-2b treatment could have clinical benefit in COVID-19 is an critical crucial one that requires further study.
Prior research from Y. Arabi el showed that Kaletra/interferon therapy were not associated with clinical improvement or CoV RNA clearance, which are consistent with our study13, 17, 18. Besides, the Society of Critical Care Medicine provides recommendation against of use Kaletra in critically ill COVID-19 patients19. However, previous studies also showed Kaletra and interferon alfa-2b have benefits in clinical improvement for patients with SARS-CoV and MERS-CoV infection10-12, 20. The reasons for the similar treatment with different results of clinical outcome and viral RNA clearance are uncertain. The nonrandomized design, differences of baseline characteristics, and small sample sizes might be the related to the inconsistency. Additionally, owing to the nonstandard initiation of therapy, such research are prone to two biases: indication bias and immortal time bias.
To assess safety profile of interferon alfa-2b and Kaletra plus interferon alfa-2b, the incidence of nausea, diarrhea, rash and levels of WBC count, neutrophil count, hemoglobin, platelet count, alanine aminotransferase, bilirubin, and creatinine kinase were compared and no differences were observed among the 3 groups over the hospitalization stay. Of note, we found that the incidence of increased creatine kinase were higher in patients treated with interferon alfa-2b or Kaletra plus interferon alfa-2b than in standard care group. This change may be related to interferon alpha-2b therapy, which is in accordance with the previous reports21, 22. Otherwise, recent research from Yanchao Pan et al consider that the increased creatine kinase is correlate with virus23 . Further studies might confirm or exclude the cause of creatinine kinase through in vitro or animal trails.
The retrospective, non-randomized nature is the limitations of this study. Inevitably, selection and unmeasured confounding bias couldn’t be excluded completely. Further interventions should be evaluated ideally in randomized, controlled clinical trials. Otherwise, such methods are generally accepted to not always be practical in the emerging context. The small number of control group is another limitation of this study. Thus, further research should enlarge the sample size to make the results more accurate.
In patients with confirmed SARS-CoV-2 infection, no benefit was observed with interferon alfa-2b and Kaletra plus interferon alfa-2b treatment beyond standard care. Further trials in appropriately randomized design may contribute to validate the effective role and safety profile of the test drugs.