449. Elevated Lactate Dehydrogenase in Convalescent Severe COVID-19 Patients Reflects Delayed Clinical Recovery and Activated Th(1) and Th(17) Responses

BACKGROUND: Elevated lactate dehydrogenase (LD) levels during acute phase of COVID-19 is known to reflect multiple organ injuries and clinical severity. However, clinical implication and origin of elevated LD after convalescence have not been elucidated. METHODS: We prospectively enrolled non-vaccinated severe COVID-19 patients with an oxygen demand greater than FiO(2) 0.4 and followed them up to one year after discharge. Laboratory values and modified Medical Research Council (mMRC) dyspnea scale were collected at each outpatient visit. To investigate the potential association between elevated LD levels and CD4(+)T cell activities, fluorescence-activated cell sorting (FACS) and intracellular cytokine staining (ICS) of INF-γ, TNF-α, IL-4, and IL-17A were conducted. RESULTS: A total of 74 patients were included, of which 46 (62%) were male, the median age was 59 years (IQR 52–69), and peak FiO(2) during hospitalization was 0.65 (IQR 0.50–0.80). At discharge, median absolute lymphocyte count (ALC) was 1.29 x10(3)/μL (IQR 0.93–1.75), median C-reactive protein (CRP) was 0.23 mg/dL (IQR 0.06–0.52), and median LD was 334 IU/L (IQR 276–450). After discharge, ALC increased (R(2) = 0.1434, P < 0.001) and LD decreased (R(2) = 0.0838, P < 0.001) overtime, but CRP level did not show time-dependent changes (Figure 1A-C). Increased LD (R(2) = 0.160, P < 0.001) and CRP (R(2) = 0.028, P = 0.024) levels were significantly associated with higher grade of mMRC scales, while ALC was not associated with mMRC scale (Fig 1D-F). To investigate the potential association between elevated LD level and CD4(+)T cell activation, serial 38 PBMC specimens from 10 patients were further investigated. CD4(+)T cells were identified using FACS gating and then stained for intracellular cytokines. The proportion of TNF-α(+)CD4(+)T cells (R(2) = 0.547, P < 0.001; Fig 2A) and IL-17A(+)CD4(+)T cells (R(2) = 0.419, P = 0.009; Fig 2B) after spike protein stimulation were positively correlated with LD levels, while the proportion of Treg did not. [Figure: see text] [Figure: see text] CONCLUSION: Elevated LD in convalescent severe COVID-19 patients reflects delayed clinical recovery and activated Th(1) and Th(17) responses DISCLOSURES: All Authors: No reported disclosures