ABSTRACT
Background. There remain important gaps in knowledge concerning the effects of SARS-CoV-2 infection or vaccination on the human blood proteome. Methods. The CCRP is a longitudinal surveillance study with information on SARS-CoV-2 infections, vaccinations and associated humoral immune responses in over 37,000 individuals. We selected a sample of blood spots cards (n=510) from serum antibody studies obtained between October 2020 and April 2021 for mass spectrometry proteomics analysis covering 540 unique plasma proteins. We analyzed the quantified protein differences based on dried blood samples obtained before and after infection or vaccination among previously non-infected individuals (immune naive) after adjustment for batch effects, age, sex, or prior diagnosis of cancer, cardiovascular or autoimmune disease, or diabetes. The majority of infected individuals were minimally symptomatic. Differentially expressed proteins were considered significant with an FDR adjusted p-value of < 0.05 and log2 fold change (L2FC) >0.2. Results. We found 11 and 12 proteins differentially expressed proteins in the naive/infected and naive/vaccinated people respectively, of which 10 were shared. Hepatocyte growth factor receptor (HGF) was upregulated (L2FC 0.24;p < 0.001) only in those who were infected while fibrillarin (L2FC -0.24;p< 0.001) and lambdacrystallin homolog (L2FC -0.29, p < 0.001) were downregulated only in the vaccinated samples (Fig 1). The remaining DE protein were associated with a wide array of functions including metabolic, cytostructural, extracellular matrix and DNA regulatory processes. Conclusion. We found changes in the proteome both from infection and vaccination. HGF, elevated in the infected, has been associated with endothelial inflammation, upregulation of pro-inflammatory cytokines to reduce lung fibrosis and is known to promote tissue repair. Fibrillarin, downregulated in the vaccinated, has been associated with higher rates of bacterial and viral clearance, inflammation reduction, and increased cell survival. These findings suggest detectable complex inflammation from mild to moderate infections. Further investigation is required to understand the mechanism of action and clinical implication of these findings.
ABSTRACT
Background. Well-regulated clinical trials have shown authorized COVID-19 vaccines to be immunogenic and highly efficacious. Information about antibody responses after vaccination in real-world settings is needed. Methods. We evaluated seroconversion rates in adults reporting ≥ 1 dose of an authorized COVID-19 vaccine in a U.S. multistate longitudinal cohort study, the COVID-19 Community Research Partnership. Participants were recruited through 12 participating healthcare systems and community outreach. Participants had periodic home-based serologic testing using either a SARSCoV-2 nucleocapsid and spike IgM/IgG lateral flow assay (63% of participants) or a SARS-CoV-2 spike IgG enzyme-linked immunosorbent assay (37% of participants). The timing and number of tests before and after vaccination varied based on participant time in study. Participants were included if they were seronegative on the last test before and had >1 test result after vaccination (some had previously been seropositive, but seroreverted). A weighted Cox regression model with right censoring was used to obtain adjusted hazard ratios for sex, age, race/ethnicity, and prior seropositivity. Time-to-event (seroconversion) was defined as time to first positive test > 4 days after vaccination;participants were censored at the date of their last available test result. Results. 13,459 participants were included and 11,722 seroconverted (Table). Median time in study was 272 days (range 31-395). Median follow-up time from vaccine to last available test was 56 days (range 1-147). Participants had a median of 3 tests (range 1-12) before and 2 tests (range 1-8) after vaccination. Based on the Kaplan-Meier method, median time to seroconversion after first COVID-19 vaccination was 35 days (interquartile range: 25-45). Likelihood of seroconversion decreased with older age (Table). Female participants, non-Hispanic Black participants, and participants who were previously seropositive were more likely to seroconvert (Table). Conclusion. All subgroups had high rates of seroconversion, with some small differences in likelihood of seroconversion between subgroups. These data demonstrate the excellent immunogenicity of COVID-19 vaccines in real-world settings in the US.
ABSTRACT
Background. Public health officials are concerned that adults may refuse to be vaccinated with an approved COVID-19 vaccine thereby limiting the community health benefit. Here, we studied the self-reported intent to be vaccinated of persons in North Carolina (NC) and then measured whether they did or did not get vaccinated. Methods. The Community COVID-19 Research Partnership (CCRP) is a large prospective study exploring COVID-19 epidemiology and sequelae in participants of several mid-Atlantic and Southern States. All participants complete an online daily survey where they are asked questions about COVID-like symptoms, infections, and their vaccination status. In addition to the daily survey, in December 2020, we implemented a short online cross-sectional survey questioning NC participants on whether they intended to be vaccinated. After completing the cross-sectional survey, we used daily survey data through 15 May 2021 to see if participants reported receiving vaccine. Unvaccinated participants who did not complete the daily survey 30 days or more prior to 15 May 2021 were excluded. Results. 18,874 participants completed the cross-sectional survey and reported vaccination status. Of these participants, 90% were white, 68% were female, 26% were healthcare workers, and 2% self-reported COVID-19 diagnosis The median age was 54 years (IQR: 41 - 65). 79%, 13%, 9%, and 2% answered yes, unsure, no, and prefer not to answer, respectively, about intention to be vaccinated (Table). 99% of the participants who intended to receive the COVID-19 vaccine reporting being vaccinated. Those who were unsure or intended not to get vaccinated had vaccination rates of 80% and 53%, respectively. 78% of the participants who preferred not to answer were vaccinated. Conclusion. More than three-quarters of NC participants intended to get vaccinated and by mid-May 2021, the vast majority had received at least one dose. Similarly, those who were unsure or preferred not to say were mostly vaccinated. Even among those who reported they would not get vaccine in January, more than half had received vaccine by May. The nature of our sample makes it difficult to generalize results to the population of NC;nevertheless, further investigation as to the causes of the shift in attitudes is warranted.