Table 2.

Spearman rank correlation coefficients (rs) of peripheral neutrophil-based markers with clinical measures of severity in acute COVID-19 patients (n = 36)

	Clinical Measures
	Causal Variable-A t1-SOFA		Outcome-A t2-SOFA		Causal Variable-B t1-SF		Outcome-B t2-SF		Outcome-C ICUFD
Potential Mediator	rs [95% C.I.]	PB value	rs [95% C.I.]	PB value	rs [95% C.I.]	PB value	rs [95% C.I.]	PB value	rs [95% C.I.]	PB value
t1 #DEspR + [NET + Ns]	0.71 [0.48, 0.84]	1 × 10–5	0.62 [0.35, 0.79]	7 × 10–4	-0.63 [-0.80, -0.38]	2 × 10–4	-0.65 [-0.81, -0.40]	1 × 10–4	-0.63 [-0.80, -0.37]	3 × 10–4
t1%DEspR + [NET + Ns]	0.29 [-0.06,0.57]	0.630	0.27 [-0.07,0.56]	0.756	-0.50 [-0.72,-0.20]	0.014	-0.29 [-0.57,0.05]	0.602	-0.35 [-0.62,-0.02]	0.245
t1 #DEspR(-) [NET + Ns]	0.51 [0.21, 0.72]	0.007	0.47 [0.16, 0.70]	0.027	-0.51 [-0.72, -0.20]	0.014	-0.56 [-0.75, -0.27]	0.003	-0.45 [-0.69, -0.14]	0.042
t1 #DEspR + [NET(-)Ns]	0.60 [0.33,0.78]	8 × 10–4	0.52 [0.22,0.73]	0.009	-0.44 [-0.68,-0.12]	0.049	-0.53 [-0.74,-0.23]	0.006	-0.53 [-0.74,-0.24]	0.007
t1 #DEspR + total Ns	0.67 [0.43,0.82]	6 × 10–5	0.59 [0.31,0.77]	0.001	-0.55 [-0.75,-0.26]	0.007	-0.60 [-0.78,-0.33]	7 × 10–4	-0.58 [-0.77,-0.31]	0.001
t1 NLR	0.74 [0.53,0.86]	2 × 10–6	0.51 [0.21,0.72]	0.011	-0.51 [-0.72,-0.20]	0.014	-0.50 [-0.72,-0.19]	0.014	-0.57 [-0.76,-0.29]	0.002
t1 ANC	0.71 [0.50,0.85]	7 × 10–6	0.61 [0.35,0.79]	7 × 10–4	-0.55 [-0.75,-0.26]	0.007	-0.69 [-0.83,-0.46]	2 × 10–5	-0.51 [-0.72,-0.21]	0.014

Clinical Measures: ICUFD, ICU-free days by day 28 [28—ICUx days] with death scored as [-1] and > ICU-28 days scored as [0]; rs, Spearman correlation coefficient, rho; SF, SaO2/FiO2 ratio; SOFA-score, non-neurologic Sequential Organ Failure Assessment score; t1, earlier study timepoint on day of informed consent; t2, later study timepoint on day of discharge or death

Neutrophil-based Markers: #, 10³ (K)/μL per microliter whole blood; ANC, absolute neutrophil count K/μL in whole blood; Ns, neutrophils; NET + Ns, NET-forming neutrophils; NLR, neutrophil to lymphocyte ratio; DEspR + [NET + Ns], DEspR + CD11b + NET-forming neutrophils; DEspR(-)[NET + Ns], DEspR-negative CD11b positive/negative [NET + Ns]; DEspR + [NET(-)Ns], DEspR + CD11b + neutrophils with circularity index > 0.8

Statistical analysis: Spearman Rank Order Correlation (GraphPad PRISM9.4). Correlation Coefficient rho (r_s), r_s > 0.46 for n = 36 attains power > 0.8, alpha 0.05. P^B, p value with Bonferroni correction for the 7 hypotheses tested. 95% C.I., 95% Confidence Interval

In bold: max correlation coefficients in column

Variables for Causal Pathway Hypotheses: Exposure, the predictor or causal variable; Mediator, potential intermediate variable, and Outcome, the outcome variable