Diagnosis and prognosis stratification model for asymptomatic
and presymptomatic patients
To ascertain the differences between severe and non-severe COVID-19
patients who were asymptomatic at the time of admission, data of the 63
indicators listed in Table S2 and Table S3 were retrieved and
systematically compared. We found systematic differences in laboratory
indicators between severe and non-severe COVID-19 patients who were
asymptomatic on admission (Fig. S1 and Table S3). To optimize precise
risk-stratification management and improve the prognosis of patients, we
constructed a two-step risk-stratification model with the data obtained
from 39 asymptomatic, 34 presymptomatic, and 1,751 symptomatic COVID-19
patients. The initial diagnostic model developed with the top 10
laboratory indicators could accurately classify asymptomatic and
presymptomatic patients (area under the curve [AUC]=0.89, 5-fold
cross-validation 95% confidence interval [CI] 0.81–0.98; Fig. 4A),
and the degrees of contribution of the relevant 10 indicators are shown
in Fig. 4B. It is noteworthy that the top five indicators (brain
natriuretic peptide (BNP), IgG, IgM, glucose (GLU), and DD) might have
similar stratification efficiencies (AUC=0.86, 5-fold cross-validation
95% CI, 0.73–1.00, Fig. S2A).
To stratify the non-severe and severe presymptomatic patients, we
included the non-severe and severe symptomatic patients in a training
dataset, and the constructed model with the top 10 laboratory indicators
was then used to predict the severity of disease in presymptomatic
patients with an AUC of 0.82 (Fig. 4C). The degrees of contribution of
the 10 indicators included in this model are shown in Fig. 4D. The top
five indicators were BNP, IgG, IgM, procalcitonin (PCT), and
albumin/globulin ratio (A/G ratio), which could accurately predict
illness severity (AUC=0.75, Fig. S2B), and their degrees of contribution
were 26%, 16%, 11%, 7%, and 4%, respectively (Fig. 4D). Severe
presymptomatic patients had significantly higher levels of BNP, PCT,
magnesium, etc. than non-severe presymptomatic patients (Fig. 4E) .
Moreover, we obtained the validation data of 27 presymptomatic patients
(non-severe, n=25; severe, n=2) from another study center (the First
People’s Hospital, Jiangxia District, Wuhan, China) and found that the
levels of N-Terminal-proBNP (NT-proBNP), PCT, magnesium, etc., were high
in severely ill COVID-19 patients (Fig. 4F). These results suggest that
the application of laboratory indicators to stratify asymptomatic and
presymptomatic COVID-19 patients is feasible, and such a
risk-stratification model could be used to screen non-severe and severe
presymptomatic patients on admission. The package-based stratification
calculator was provided online
(https://github.com/liangyuan-njmu/SeverePredictModel) for clinicians to
assess whether presymptomatic patients will show disease progression.