Retrospective observational study.
SETTING: A single tertiary-care center in Madrid.
PATIENTS: Treatment with a hospital-approved drug cocktail during hospitalization.
MEASUREMENTS AND MAIN RESULTS: Demographic, clinical, and laboratory data were compared between the patients with moderate and critical/fatal illness across both
infection waves. The median age of patients with critical/fatal
coronavirus disease 2019 was 67.5 years (interquartile range, 56.75-78.25 yr; 64.5% male) in the first wave and 59.0 years (interquartile range, 48.25-80.50 yr; 70.8% male) in the second wave.
Hypertension and
dyslipidemia were major comorbidities in both waves. Body mass index over 25 and presence of bilateral
pneumonia were common findings. Univariate logistic regression analyses revealed an association of a number of blood parameters with the subsequent illness progression and severity in both waves. However, some remarkable differences were detected between both waves that prevented an accurate extrapolation of prediction models from the first wave into the second wave.
Interleukin-6 and
d-dimer concentrations at the time of hospital admission were remarkably higher in patients who developed a critical/fatal condition only during the first wave (p < 0.001), although both parameters significantly increased with disease worsening in follow-up studies from both waves. Multivariate analyses from wave 1 rendered a predictive signature for critical/fatal illness upon hospital admission that comprised six blood
biomarkers: neutrophil-to-lymphocyte ratio (≥ 5; odds ratio, 2.684 [95% CI, 1.143-6.308]),
C-reactive protein (≥ 15.2 mg/dL; odds ratio, 2.412 [95% CI, 1.006-5.786]),
lactate dehydrogenase (≥ 411.96 U/L; odds ratio, 2.875 [95% CI, 1.229-6.726]),
interleukin-6 (≥ 78.8 pg/mL; odds ratio, 5.737 [95% CI, 2.432-13.535]),
urea (≥ 40 mg/dL; odds ratio, 1.701 [95% CI, 0.737-3.928]), and
d-dimer (≥ 713 ng/mL; odds ratio, 1.903 [95% CI, 0.832-4.356]). The predictive accuracy of the signature was 84% and the area under the receiver operating characteristic curve was 0.886. When the signature was validated with data from wave 2, the accuracy was 81% and the area under the receiver operating characteristic curve value was 0.874, albeit most
biomarkers lost their independent significance. Follow-up studies reassured the importance of monitoring the
biomarkers included in the signature, since dramatic increases in the levels of such
biomarkers occurred in critical/fatal patients over
disease progression.
CONCLUSIONS: Most parameters analyzed behaved similarly in the two waves of
coronavirus disease 2019. However, univariate logistic regression conducted in both waves revealed differences in some parameters associated with poor prognosis in wave 1 that were not found in wave 2, which may reflect a different disease stage of patients on arrival to hospital. The six-
biomarker predictive signature reported here constitutes a helpful tool to classify patient's prognosis on arrival to hospital.