Material and Methods
Patients and data: This study was conducted in a tertiary
center with diagnosis of COVID-19 patients. Study population consisted
of patients with positive polymerase chain reaction and computer
tomography findings compatible with COVID-19 as well as critical illness
requiring high flow nasal oxygen supplement, or its equivalent defined
according to National Institute of Health (NIH) COVID-19 disease
severity scale (5). Clinical and laboratory features of patients were
obtained from their medical cards and hospital software system and
evaluated by retrospectively. All laboratory results were recorded at
patients’ admission and inflammatory parameters such as C-reactive
protein (CRP), ferritin, d-dimer, lactate dehydrogenase (LDH) also on
the highest levels and last day of hospitalization. Hyperinflammatory
state of the patients were evaluated and scored according to COVID-19
hyperinflammatory syndrome score (cHIS score) (6).
Treatment protocol and outcome: All patients received
background glucocorticoid treatment with methylprednisolone 80 mg/day
intravenously or equivalent concomitant anticoagulant prophylaxis with
enoxaparin 0.4 mg/day subcutaneously. Anakinra was initiated in patients
who did not respond to two days of corticosteroid treatment or
concomitantly in high risky patients with 400 mg/day intravenously in
two divided dose and gradually increased to 1600 mg/day if necessary.
The dose adjustment was performed by daily for each patient according to
current clinical and laboratory findings by the same rheumatologist
(MB). In combination group, baricitinib was started in 8 mg/day in two
divided dose (4 mg/day in chronic renal failure) in addition to steroid
and anakinra in patients with unresponsive to anakinra 1600 mg/day at
least three days, thereafter dose reduction was performed according to
clinical and laboratory results of the patients. Drug tapering was
performed in anakinra doses initially when clinical and laboratory
response achieved thereafter treatment was stopped when the patients
were oxygen free and/or had normal inflammatory parameters such as CRP
and ferritin. Treatment failure was defined as no reduction in oxygen
support and/or inflammatory parameters as well as need for intensive
care unit (ICU) admission and/or invasive mechanical ventilation and/or
development of mortality. Age, gender, disease severity (NIH score 4,
critically ill patients) and inflammatory burden according to cHIS score
matched patients who receiving steroid and anakinra defined as control
group. Steroid and anakinra treatment protocol were similar between two
groups. Individual patient consent and ethical committee approval were
obtained for this study (date/number: 24.02.2022, 2022/04-09).
Statistical analysis : In our study, 21.0 version (IBM, Armonk,
NY, USA) of the SPSS (Statistical Package for the Social Sciences)
program was used for statistical analysis of data. Descriptive
statistics, discrete and continuous numerical variables were expressed
as mean, ± standard deviation or median and interquartile range (IQR).
Categorical variables were expressed as number of cases and (%). Cross
table statistics were used to compare categorical variables (Chi-Square,
Fisher exact test). Normally distributed parametric data were compared
with Student’s t-test and Paired t-test; non-parametric data that did
not meet normal distribution were compared with Mann Whitney U and
Kruskal Wallis tests. Multiple intergroup comparisons were made by Post
Hoc Tukey analysis. Kaplan-Meier and log-rank methods were used for
survival analysis. Multivariable analysis was performed by using
logistic regression. Correlation analysis was performed with Pearson or
Spearman method according to normality distribution. p<0.05
value was considered statistically significant.