Predictive indicators of severe COVID-19 independent of comorbidities and advanced age: a nested case-control study

Abstract

To determine what exacerbate severity of the COVID-19 among patients without comorbidities and advanced age and investigate potential clinical indicators for early surveillance, we adopted a nested case-control study, design in which severe cases (case group, n = 67) and moderate cases (control group, n = 67) of patients diagnosed with COVID-19 without comorbidities, with ages ranging from 18 to 50 years who admitted to Wuhan Tongji Hospital were matched based on age, sex and BMI. Demographic and clinical characteristics, and risk factors associated with severe symptoms were analysed. Percutaneous oxygen saturation (SpO2), lymphocyte counts, C-reactive protein (CRP) and IL-10 were found closely associated with severe COVID-19. The adjusted multivariable logistic regression analyses revealed that the independent risk factors associated with severe COVID-19 were CRP (OR 2.037, 95% CI 1.078-3.847, P = 0.028), SpO2 (OR 1.639, 95% CI 0.943-2.850, P = 0.080) and lymphocyte (OR 1.530, 95% CI 0.850-2.723, P = 0.148), whereas the changes exhibited by indicators influenced incidence of disease severity. Males exhibited higher levels of indicators associated with inflammation, myocardial injury and kidney injury than the females. This study reveals that increased CRP levels and decreased SpO2 and lymphocyte counts could serve as potential indicators of severe COVID-19, independent of comorbidities, advanced age and sex. Males could at higher risk of developing severe symptoms of COVID-19 than females.

Keywords: C-reactive protein; Coronavirus disease 2019; nested case−control study; peripheral oxygen saturation; severe acute respiratory syndrome coronavirus 2.

Fig. 1.

A flow diagram representing recruitment of patients with COVID-19 for the study. *Other diseases included surgical histories, hepatitis, gout, anaemia, thyroid diseases, breast diseases, tuberculosis and obesity. COVID-19, Coronavirus disease 2019.

Fig. 2.

Percentages of patients with severe COVID-19 at different concentrations of (a) CRP, (b) SpO₂ and (c) lymphocyte. In this study, approximately 98.51% (132/134), 94.03% (126/134) and 100% (134/134) of patients with COVID-19 had examinations for CRP, SpO₂ and lymphocyte counts, respectively. A high proportion of patients with severe COVID-19 exhibited high CRP concentrations, low SpO₂ concentrations and low lymphocyte counts. With reference to CRP, 10 mg/l is the 99th percentile upper reference limit (99^th % URL), 50 mg/l indicates 5 × 99^th % URL of CRP, while for SpO₂, 95% is the 99th percentile upper reference limit (99^th% URL), and for lymphocyte counts, 0.8 × 10⁹/l is the 99th percentile upper reference limit (99^th% URL). COVID-19, corona virus disease 2019; CRP, C-reactive protein; SpO₂, peripheral oxygen saturation.