Validation of Predictors of Disease Severity and Outcomes in COVID-19 Patients: A Descriptive and Retrospective Study

Abstract

Background: The severity and outcome of COVID-19 cases has been associated with the percentage of circulating lymphocytes (LYM%), levels of C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT), lactic acid (LA), and viral load (ORF1ab Ct). However, the predictive power of each of these indicators in disease classification and prognosis remains largely unclear.

Methods: We retrospectively collected information on the above parameters in 142 patients with COVID-19, stratifying them by survival or disease severity.

Findings: CRP, PCT, IL-6, LYM%, and ORF1ab Ct were significantly altered between survivors and non-survivors. LYM%, CRP, and IL-6 were the most sensitive and reliable factors in distinguishing between survivors and non-survivors. These indicators were significantly different between critically ill and severe/moderate patients. Only LYM% levels were significantly different between severe and moderate types. Among all the investigated indicators, LYM% was the most sensitive and reliable in discriminating between critically ill, severe, and moderate types and between survivors and non-survivors.

Conclusions: CRP, PCT, IL-6, LYM%, and ORF1ab Ct, but not LA, could predict prognosis and guide classification of COVID-19 patients. LYM% was the most sensitive and reliable predictor for disease typing and prognosis. We recommend that LYM% be further investigated in the management of COVID-19.

Funding: This study was supported in part by awards from the National Natural Science Foundation of China, the Foundation and Frontier Research Project of Chongqing, and the Chongqing Youth Top Talent Project.

Keywords: C-reactive protein; COVID-19; SARS-CoV-2; disease classification; interlukin-6; lymphocytes; lymphopenia; procalcitonin; prognosis; viral load.

Graphical abstract

Figure 1

Validation of Indicators for the Prognosis of COVID-19 Patients (A–D) Levels of CRP (A), PCT (B), IL-6 (C), and LYM% (D) in the peripheral blood of survivors (n = 117) or non-survivors (n = 15) with COVID-19 from admission to discharge. (E) LA levels in the blood of survivors (n = 23) or non-survivors (n = 15) with COVID-19. (F) ORF1ab Ct values in viral tests with qRT-PCR in survivors (n = 55) or non-survivors (n = 15) with COVID-19. (G) Time windows of indicators for predicting prognosis. The initial day with difference (IDD) indicates the first day when the indicator levels were significantly different between two groups. The duration with difference (DD) indicates the time frame when the indicator levels were significantly different between two groups. Comparing two groups, the time points when the values of three consecutive measurements were significantly different were counted as days of DD. The endpoint of observation was 36 days after disease onset. The dotted arrow indicates the IDD. Data show means ± SEM. ∗∗∗p < 0.001; a mixed model with repeated measure. CRP, C-reactive protein; PCT, procalcitonin; LYM%, lymphocyte percentage; LA, lactic acid; ns, not significant.

Figure 2

CRP Discriminates between Critically Ill and Severe/Moderate COVID-19 Patients (A) Blood CRP levels in critically ill (n = 25), severe (n = 21), and moderate (n = 96) patients with COVID-19 from admission to discharge. (B) Time windows of CRP for disease classification between critically ill, severe, and moderate types. The dotted arrow indicates the IDD. Data show means ± SEM. ∗∗∗p < 0.001; a mixed model with repeated measure. ns, not significant.

Figure 3

PCT Discriminates between Critically Ill and Severe/Moderate COVID-19 Patients (A) Blood PCT levels in critically ill (n = 25), severe (n = 21), and moderate (n = 96) patients with COVID-19 from admission to discharge. (B) Time windows of PCT for disease classification between those three types. The IDD is marked by the dotted lines. Data show means ± SEM. ∗p < 0.05, ∗∗p < 0.01, and ∗∗∗p < 0.001; a mixed model with repeated measure. ns, not significant.

Figure 4

IL-6 Discriminates between Critically Ill and Severe/Moderate COVID-19 Patients (A) Blood IL-6 levels in critically ill (n = 25), severe (n = 21), and moderate (n = 96) patients with COVID-19 from admission to discharge. (B) Time windows of IL-6 for disease classification between those three types. The IDD is marked by the dotted lines. Data show means ± SEM. ∗∗p < 0.01 and ∗∗∗p < 0.001; a mixed model with repeated measure. ns, not significant.

Figure 5

LYM% Distinguishes between Critically Ill, Severe, and Moderate COVID-19 Patients (A) Blood LYM% in critically ill (n = 25), severe (n = 21), and moderate (n = 96) patients with COVID-19 from admission to discharge. (B) Time windows of LYM% for disease classification between those three types. The IDD is marked by the dotted lines. Data show means ± SEM. ∗∗∗p < 0.001; a mixed model with repeated measure.

Figure 6

LA Cannot Distinguish between Critically Ill and Severe COVID-19 Patients (A) Blood LA in critically ill (n = 25) and severe (n = 21) patients with COVID-19 from admission to discharge. (B) Time windows of LA for disease classification between critically ill, severe, and moderate. Data show means ± SEM. A mixed model with repeated measure. ns, not significant; ND, not detected.

Figure 7

ORF1ab Ct Values Distinguish between Critically Ill and Moderate COVID-19 Patients (A) ORF1ab Ct values in viral tests with qRT-PCR in critically ill (n = 25), severe (n = 15), and moderate (n = 40) patients with COVID-19 from admission to discharge. (B) Time windows of ORF1ab Ct values for disease classification between those three types. The IDD is marked by the dotted lines. Data show means ± SEM. ∗∗p < 0.01; a mixed model with repeated measure. ns, not significant.