Table 3. Associations between serum NFL and outcomes in patients with COVID-19.
For descriptive summaries of NFL concentration and for ease of presentation, LOS was categorized using the sample median, whereas mRS at discharge was categorized using a predefined cutoff of interest. Associations of intubation, ICU admission, LOS, and mRS at discharge (all as independent variables) with NFL concentration (as the dependent variable) were evaluated using linear regression models (for the continuous mean NFL per patient, minimum NFL per patient, and maximum NFL per patient variables) and logistic regression models (for the binary occurrence of an NFL value >25th percentile and occurrence of an NFL value >75th percentile variables). Regression coefficients are interpreted as the change in the mean NFL outcome measure (on the natural logarithmic scale) corresponding to the presence of the given characteristic (intubation and ICU admission), to each doubling of LOS, and to each 1-unit increase in mRS at discharge. CI, confidence interval; CKD, chronic kidney disease. P values <0.0025 were considered as statistically significant after applying a Bonferroni correction for multiple testing.
Association
examined |
Median (minimum, maximum) NFL
or no. (%) for the given group |
Association
measure |
Unadjusted analysis |
Adjusting for age, sex, BMI,
and CKD |
|||
Estimate (95% CI) | P value | Estimate (95% CI) | P value | ||||
Association between intubation and |
No intubation (N = 112) |
Intubation (N = 30) |
|||||
Mean NFL per patient |
19.7 (3.4, 972.7) |
107.4 (15.9, 1538.4) |
Regression coefficient |
1.61 (1.16, 2.06) | <0.001 | 1.66 (1.24, 2.07) | <0.001 |
Minimum NFL per patient |
16.6 (2.2, 585.6) |
50.3 (3.1, 1538.4) |
Regression coefficient |
1.25 (0.78, 1.72) | <0.001 | 1.31 (0.87, 1.75) | <0.001 |
Maximum NFL per patient |
22.2 (3.4, 1359.7) |
111.5 (15.9, 2131.0) |
Regression coefficient |
1.75 (1.27, 2.24) | <0.001 | 1.79 (1.35, 2.24) | <0.001 |
NFL value >25th percentile |
74 (66.1%) |
30 (100.0%) |
Odds ratio | N/A* | <0.001 | N/A* | N/A* |
NFL value >75th percentile |
15 (13.4%) |
19 (63.3%) |
Odds ratio | 11.17 (4.45, 28.03) | <0.001 | 10.64 (3.80, 29.80) | <0.001 |
Association between ICU admission and |
No ICU admission (N = 88) |
ICU admission (N = 54) |
|||||
Mean NFL per patient |
18.7 (3.4, 972.7) |
52.2 (4.8, 1538.4) |
Regression coefficient |
1.10 (0.69, 1.50) | <0.001 | 1.13 (0.76, 1.49) | <0.001 |
Minimum NFL per patient |
15.8 (2.2, 585.6) |
33.2 (3.1, 1538.4) |
Regression coefficient |
0.82 (0.41, 1.23) | <0.001 | 0.86 (0.48, 1.24) | <0.001 |
Maximum NFL per patient |
20.4 (3.4, 1359.7) |
64.5 (7.9, 2131.0) |
Regression coefficient |
1.23 (0.80, 1.66) | <0.001 | 1.26 (0.87, 1.65) | <0.001 |
NFL value >25th percentile* |
55 (62.5%) |
49 (90.7%) |
Odds ratio | 5.88 (2.13, 16.25) | <0.001 | 9.84 (3.00, 32.29) | <0.001 |
NFL value >75th percentile |
10 (11.4%) |
24 (44.4%) |
Odds ratio | 6.24 (2.67, 14.59) | <0.001 | 8.00 (3.08, 20.75) | <0.001 |
Association between LOS and |
LOS ≤ 9 days (N = 79) |
LOS > 9 days (N = 63) |
|||||
Mean NFL per patient |
15.9 (3.4, 972.7) |
47.8 (4.8, 1538.4) |
Regression coefficient |
0.81 (0.60, 1.01) | <0.001 | 0.74 (0.55, 0.93) | <0.001 |
Minimum NFL per patient |
13.9 (2.2, 585.6) |
33.4 (3.1, 1538.4) |
Regression coefficient |
0.66 (0.44, 0.87) | <0.001 | 0.60 (0.40, 0.80) | <0.001 |
Maximum NFL per patient |
18.6 (3.4, 1359.7) |
66.4 (7.9, 2131.0) |
Regression coefficient |
0.89 (0.67, 1.10) | <0.001 | 0.82 (0.62, 1.02) | <0.001 |
NFL value >25th percentile* |
45 (57.0%) |
59 (93.7%) |
Odds ratio | 5.34 (2.53, 11.24) | <0.001 | 4.90 (2.27, 10.62) | <0.001 |
NFL value >75th percentile |
8 (10.1%) |
26 (41.3%) |
Odds ratio | 3.17 (1.91, 5.24) | <0.001 | 3.24 (1.92, 5.47) | <0.001 |
Association between mRS at discharge and |
mRS at discharge ≤3 (N = 109) |
mRS at discharge >3 (N = 33) |
|||||
Mean NFL per patient |
19.5 (3.4, 405.3) |
91.9 (17.9, 1538.4) |
Regression coefficient |
0.56 (0.46, 0.67) | <0.001 | 0.54 (0.42, 0.66) | <0.001 |
Minimum NFL per patient |
14.7 (2.2, 304.9) |
47.8 (3.1, 1538.4) |
Regression coefficient |
0.49 (0.38, 0.61) | <0.001 | 0.45 (0.33, 0.58) | <0.001 |
Maximum NFL per patient |
21.4 (3.4, 779.0) |
105.0 (18.1, 2131.0) |
Regression coefficient |
0.60 (0.48, 0.71) | <0.001 | 0.58 (0.46, 0.71) | <0.001 |
NFL value >25th percentile* |
71 (65.1%) |
33 (100.0%) |
Odds ratio | 3.67 (2.17, 6.22) | <0.001 | 3.00 (1.71, 5.29) | <0.001 |
NFL value >75th percentile |
16 (14.7%) |
18 (54.5%) |
Odds ratio | 2.27 (1.66, 3.11) | <0.001 | 3.04 (2.02, 4.58) | <0.001 |
*When evaluating the association between intubation and NFL value >25th percentile, logistic regression was not possible owing to the occurrence of a zero cell count. Therefore, the P value in unadjusted analysis results from Fisher’s exact test, and multivariable analysis was not performed.