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.

Summary SARS CoV-2 S1 Protein in CD16+ Monocytes Post-Vaccination

Competing Interests: BP, EBF, EL, CB, and AP are employees of IncellDX. BP, RY, JB, EO, DJ, and MK are independent contractors of the CCTC.

This study did not receive any funding

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Ethics Statement: The independent Chronic COVID Treatment Center (CCTC) Ethics and IRB group reviewed and approved the study. All the patients/participants provided their written informed consent to participate in this study.

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Abbreviations: PASC, post-acute sequelae of COVID-19; POVIP, post-vaccination individuals with PASC-like symptoms; NCM, non-classical monocytes; IM, intermediate monocytes; CX3CL1, C-X3-C motif chemokine ligand 1; CX3CR1, C-X3-C motif chemokine receptor 1; IL, interleukin; RANTES, regulation on activation, healthy control T-expressed and secreted; CCR, chemokine receptor; IFN, interferon; TNF, tumor necrosis factor; MIP, macrophage inflammatory protein; PBMCs, peripheral blood mononuclear cells; VEGF, vascular endothelial growth factor; LH, long hauler or PASC.

All data produced in the present study are available upon reasonable request to the authors