Plasma gp96 is a Novel Predictive Biomarker for Severe COVID-19.

Early and effective identification of severe coronavirus disease 2019 (COVID-19) may allow us to improve the outcomes of associated severe acute respiratory illness with fever and respiratory symptoms. This study analyzed plasma concentrations of heat shock protein gp96 in nonsevere (including mild and typical) and severe (including severe and critical) patients with COVID-19 to evaluate its potential as a predictive and prognostic biomarker for disease severity. Plasma gp96 levels that were positively correlated with interleukin-6 (IL-6) levels were significantly elevated in COVID-19 patients admitted to the hospital but not in non-COVID-19 patients with less severe respiratory impairment. Meanwhile, significantly higher gp96 levels were observed in severe than nonsevere patients. Moreover, the continuous decline of plasma gp96 levels predicted disease remission and recovery, whereas its persistently high levels indicated poor prognosis in COVID-19 patients during hospitalization. Finally, monocytes were identified as the major IL-6 producers under exogenous gp96 stimulation. Our results demonstrate that plasma gp96 may be a useful predictive and prognostic biomarker for disease severity and outcome of COVID-19. IMPORTANCE Early and effective identification of severe COVID-19 may allow us to improve the outcomes of associated severe acute respiratory illness with fever and respiratory symptoms. Some heat shock proteins (Hsps) are released during oxidative stress, cytotoxic injury, and viral infection and behave as danger-associated molecular patterns (DAMPs). This study analyzed plasma concentrations of Hsp gp96 in nonsevere and severe patients with COVID-19. Significantly higher plasma gp96 levels were observed in severe than those in nonsevere patients, and its persistently high levels indicated poor prognosis in COVID-19 patients. The results demonstrate that plasma gp96 may be a useful predictive and prognostic biomarker for disease severity and outcome of COVID-19.

Clinical Characteristics and Immune Responses of 137 Deceased Patients With COVID-19: A Retrospective Study.

Objective: This study aimed to evaluate the factors associated with death in patients with coronavirus disease 2019 by clarifying the clinical characteristics and immune responses. Methods: The clinical characteristics and laboratory findings, including cytokine and lymphocyte subsets, were obtained from the electronic medical records of patients in Wuhan Tongji Hospital. Results: This study included 836 patients with confirmed COVID-19. In total, 699 (83.6%) were cured and discharged, and 137 (16.4%) died. Our analysis revealed that age ≥ 65 years, male sex, malignancy, chronic obstructive pulmonary disease, dyspnea, dizziness, respiratory rate > 20 bpm, heart rate > 100 bpm, systolic blood pressure < 90 mmHg, neutrophils > 6.3×109/L, lymphopenia, thrombocytopenia, D-dimer ≥ 0.5 mg/L, lactate dehydrogenase > 250 U/L, aspartate aminotransferase > 40 U/L, total bilirubin > 26 µmol/L, albumin < 35 g/L, blood urea nitrogen > 9.5 mmol/L, estimated glomerular filtration rate < 90 ml/min/1.73, elevated cardiac troponin I, N-terminal pro-brain natriuretic peptide ≥ 900 pg/ml, C-reactive protein ≥ 25 mg/L, procalcitonin ≥ 0.05 ng/ml and ferritin > 400 µg/L were associated with death in patients with COVID-19. The multivariate logistic regression analysis revealed that an estimated glomerular filtration rate < 90 ml/min/1.73, elevated cardiac troponin I, C-reactive protein ≥ 25 mg/L and procalcitonin ≥ 0.05 ng/ml were predictive of mortality. Regarding immune responses, IL-2R, IL-6, IL-8, IL-10, and TNFα were remarkably higher in the deceased group at admission, and the levels of IL-2R, IL-6, IL-8, IL-10, and TNFα in the deceased group showed a rapid increase; the dynamics of these cytokines were highly consistent with disease deterioration. Lymphocyte subset analysis revealed that the deceased patients showed significant decreases in lymphocyte counts, especially helper T cells, suppressor T cells and NK cells. Conclusions: This study identified that an estimated glomerular filtration rate < 90 ml/min/1.73, elevated cardiac troponin I, C-reactive protein ≥ 25 mg/L and procalcitonin ≥ 0.05 ng/ml were predictors of mortality in COVID-19 patients. Elevated cytokine levels and a continued increasing trend, including in IL-2R, IL-6, IL-8, IL-10 and TNFα, and a decrease in lymphocyte subsets, especially helper T cells, suppressor T cells and NK cells, were associated with a poor prognosis.