Immune Regulatory Markers in Post-Acute Sequelae of COVID-19: A Clinical Case Report 2253140

Abstract Introduction The interplay between apoptotic versus non-apoptotic programmed cell death (PCD) mechanisms may have a significant role in post-acute sequelae of COVID-19 (PASC). The objective of the current study is to investigate PCD markers in serum and plasma samples derived from PASC patient cases in comparison with unaffected controls. Methods The study protocol was approved by the Hackensack Meridian Health (HMH) Biorepository Research Integrity Committee and is an IRB-exempt study for deidentified samples. Serum and plasma samples derived from PASC cases and unaffected controls (N = 15) were analyzed by Enzyme-Linked ImmunoSorbent Assays (ELISAs) for PCD markers and antiviral immune-responsive cytokines. One-way analysis of variance (ANOVA) combined with Tukey’s multiple comparisons statistical analyses of the data was performed. Statistical significance level set at p < 0.05 and data presented as mean-fold increase in PASC cases compared to controls. Results Preliminary ELISA results indicated no significant differences in serum or plasma levels of caspase-3, serum cleaved caspase-3 and serum caspase-1 between PASC cases and unaffected controls (p > 0.05). However, plasma levels of cleaved caspase-3 and caspase-1 were significantly higher in PASC cases versus unaffected controls (2.5-fold, *p=0.02 and 4-fold, ****p< 0.0001, respectively). SQSTM1/p62 showed significantly higher levels in serum and plasma from PASC cases compared to controls (90-fold, **p=0.006 and 60-fold, *p=0.03, respectively). Serum and plasma antiviral immune responsive cytokines IL-1-beta (over 10-fold, ****p< 0.0001), IFN-gamma (over 5-fold, ****p< 0.0001) and TNF-alpha (over 10-fold, **p< 0.01) were significantly elevated in PASC cases compared to controls. Conclusion Significant elevation of non-apoptotic PCD markers in serum and/or plasma samples derived from PASC cases compared to unaffected controls might indicate the diagnostic utility of non-apoptotic PCD markers in PASC cases. Funding Source New Jersey Health Foundation Topic Categories Translational and Interventional Immunology (TI)