Persistence of S1 Spike Protein in CD16+ Monocytes up to 245 Days in SARS-CoV-2 Negative Post COVID-19 Vaccination Individuals with Post-Acute Sequalae of COVID-19 (PASC)-Like Symptoms

There have been concerning reports about people experiencing new onset persistent complications (greater than 30 days) following approved SARS-CoV-2 vaccines (BNT162b2 (Pfizer), mRNA-1273 (Moderna), Janssen (Johnson and Johnson), and ChAdOx1 nCoV-19 (AstraZeneca)). We sought to determine the immunologic abnormalities in these patients and to investigate whether the potential etiology was similar to Post-Acute Sequalae of COVID (PASC), or long COVID. We studied 50 individuals who received one of the approved COVID-19 vaccines and who experienced new onset PASC-like symptoms along with 45 individuals post-vaccination without symptoms as controls. We performed multiplex cytokine/chemokine profiling with machine learning as well as SARS-CoV-2 S1 protein detection on CD16+ monocyte subsets using flow cytometry and mass spectrometry. We determined that post-vaccination individuals with PASC- like symptoms had similar symptoms to PASC patients. When analyzing their immune profile, Post-vaccination individuals had statistically significant elevations of sCD40L (p<0.001), CCL5 (p=0.017), IL-6 (p=0.043), and IL-8 (p=0.022). Machine learning characterized these individuals as PASC using previously developed algorithms. Of the S1 positive post-vaccination patients, we demonstrated by liquid chromatography/ mass spectrometry that these CD16+ cells from post-vaccination patients from all 4 vaccine manufacturers contained S1, S1 mutant and S2 peptide sequences. Post-COVID vaccination individuals with PASC-like symptoms exhibit markers of platelet activation and pro-inflammatory cytokine production, which may be driven by the persistence of SARS-CoV-2 S1 proteins in intermediate and non-classical monocytes. The data from this study also cannot make any inferences on epidemiology and prevalence for persistent post-COVID vaccine symptoms. Thus, further studies and research need to be done to understand the risk factors, likelihood and prevalence of these symptoms. SummarySARS CoV-2 S1 Protein in CD16+ Monocytes Post-Vaccination