Analysis After PS Matching
After 1:1 PS matching, 88 patients in SoC and 88 patients in Anakinra
group were matched and included into the analysis. Baseline clinical and
laboratory features of the patients were described in table 1. After
adjustment of potential confounders age, gender, presence of
comorbidities (DM, HT, CHD, CRF, chronic lung disease, and malignancy),
disease severity, vaccination history, mcHIS scores were not different
between two groups (table 1). Only baseline d-dimer and peak levels of
LDH were higher in Anakinra arm compared to SoC (p=0.05 and
p<0.001). Severe infection (28.4% vs 16%, p=0.05; OR:3.9),
development of any thromboembolic event (15.9% vs 3.4%, p=0.005;
OR:7.9), PTE (12.5% vs 3.4%, p=0.026; OR:5), MI (6.8% vs 0, p=0.013;
OR:6.2) were higher in SoC arm compared to Anakinra. ICU requirement and
mortality did not differ between two arms (p=0.2 and p=0.4,
respectively).
Patients experienced any thromboembolic event had more frequent CHD
(p=0.04; OR:4.1), critical illness (p<0.001; OR:12.5), lower
hemoglobin and baseline ferritin levels (p=0.03 and p=0.04,
respectively), higher mcHIS scores (p=0.001), higher peak levels of CRP
(p<0.001), d-dimer (p<0.001), LDH (p=0.038).
Furthermore, severe infection (41% vs 20.3%, p=0.05; OR:3.9) and
mortality (64.7% vs 27.7%, p=0.002; OR:9.8) were higher in patients
had any thromboembolic event than those had not (table 2). Similarly PTE
was higher in patients had critical illness (p=0.002; OR:9.5), lower
hemoglobin and ferritin levels (p=0.02 and p=0.04, respectively), higher
mcHIS score (p=0.002), peak levels of CRP (p<0.001), d-dimer
(p<0.001), pneumothorax (p=0.03; OR:4.8), MI
(p<0.001; OR:15), and mortality (p=0.03; OR:4.7) (table 3).
PTE development was associated with peak levels of d-dimer levels
(p=0.02, OR:1.08, 95% CI: 1.01-1.15) in multivariate analysis.
Development of MI was higher in patients had history of CHD and
malignancy (p=0.007; OR:7.3 and p=0.02; OR:5.5, respectively), critical
illness (p=0.02; OR:5.4), higher mcHIS scores (p=0.02), peak levels of
CRP (p=0.043), d-dimer (p=0.03), LDH (p=0.004) (table 4). MI was also
higher in SoC (P=0.016; OR:6.2) and patients had mortality
(p<0.001; OR:13.7) in univariate analysis. MI development was
associated with the history of CHD (p=0.038, OR:6.9, 95% CI:1.1-42.3)
and PTE (p=0.008, OR:11.5, 95% CI:1.9-69.5) in multivariate analysis.
In survival analysis, development of any thromboembolic event, PTE, and
MI were higher in SoC compared to Anakinra (Log-Rank; p=0.003 [figure
1], p=0.003 [supplementary figure 4], and p=0.007 [supplementary
figure 5], respectively). Survival rate was also lower in patients
with SoC arm than Anakinra in patients who had any thromboembolic event
as well as MI (Log-Rank; p=0.03 [figure 2] and p<0.001
[figure 3], respectively). Survival rate of patients with and
without PTE did not differ in patients with COVID-19 (supplementary
figure 6).
ROC analysis revealed a cut-off value of d-dimer for the development of
any thromboembolic event 16.75 (Area under curve [AUC]: 0.804,
p<0.001 [95% CI: 0.710-0.898]) with 61.9% sensitivity
and 84.8% specificity (likelihood ratio [LR]:4), for the
development of PTE 14.97 (AUC: 0.867, p<0.001 [95% CI:
0.774-0.960]) with 86.7% sensitivity and 83.5% specificity (LR:5.3),
for the development of MI 5.83 (AUC: 0.736, p<0.016 [95%
CI: 0.585-0.887]) with 66.7% sensitivity and 66.7% specificity
(LR:2) (Supplementary figure 7,8, and 9, respectively). Cut-off value of
mcHIS score for the development of any thromboembolic event 3.5 (AUC:
0.726, p=0.001 [95% CI: 0.632-0.821]) with 71.4% sensitivity and
63.2% specificity (LR:1.94), for the development of PTE 3.5 (AUC:
0.740, p=0.002 [95% CI: 0.624-0.855]) with 73.3% sensitivity and
62.4% specificity (LR:1.95), for the development of MI 3.5 (AUC: 0.750,
p=0.01 [95% CI: 0.630-0.870]) with 77.8% sensitivity and 61.7%
specificity (LR:2) (Supplementary figure 10,11, and 12, respectively).
Cut-off value of peak levels of CRP for the development of any
thromboembolic event 171.2 mg/L (AUC: 0.780, p<0.001 [95%
CI: 0.684-0.875]) with 76.5% sensitivity and 72.3% specificity
(LR:2.8), for the development of PTE 201 mg/L (AUC: 0.800,
p<0.001 [95% CI: 0.694-0.905]) with 71.4% sensitivity
and 78.4% specificity (LR:3.3), for the development of MI 145.3 mg/L
(AUC: 0.743, p=0.043 [95% CI: 0.629-0.857]) with 100% sensitivity
and 54.7% specificity (LR:2.2) (Supplementary figure 13,14, and 15,
respectively). Other results of ROC analysis were shown in table 5 and
supplementary figure 16 and 17).