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.