key: cord-0809019-l0ck1a41
authors: Horspool, A. M.; Russ, B. P.; Wolf, M. A.; Kang, J.; Blackwood, C. B.; Hall, J. M.; Wong, T. Y.; DeJong, M. A.; Bitzer, G.; Bevere, J. R.; Eggleston, R.; Stewart, A.; Costello, L.; Welch, S.; Kieffer, T.; Hodder, S.; Damron, F. H.
title: Serological survey of SARS-CoV-2 incidence conducted at a rural West Virginia hospital
date: 2021-08-18
journal: medRxiv : the preprint server for health sciences
DOI: 10.1101/2021.08.16.21262128
sha: 8cb99304083b5da11e33d44356c89cafe9239d11
doc_id: 809019
cord_uid: l0ck1a41

The SARS-CoV-2 pandemic has affected all types of global communities. Differences in urban and rural environments have led to varying levels of transmission within these subsets of the population. To fully understand the prevalence and impact of SARS-CoV-2 it is critical to survey both types of community. This study establishes the prevalence of SARS-CoV-2 in a rural community: Montgomery, West Virginia. Approximately 10% of participants exhibited serological or PCR-based results indicating exposure to SARS-CoV-2 within 6 months of the sampling date. Quantitative analysis of IgG levels against SARS-CoV-2 receptor binding domain (RBD) was used to stratify individuals based on antibody response to SARS-CoV-2. A significant negative correlation between date of exposure and degree of anti-SARS-CoV-2 RBD IgG (R2 = 0.9006) was discovered in addition to a correlation between neutralizing anti-SARS-CoV-2 antibodies (R2 = 0.8880) and days post exposure. Participants were confirmed to have normal immunogenic profiles by determining serum reactivity B. pertussis antigens commonly used in standardized vaccines. No significant associations were determined between anti-SARS-CoV-2 RBD IgG and age or biological sex. Reporting of viral-like illness symptoms was similar in SARS-CoV-2 exposed participants greater than 30 years old (100% reporting symptoms 30-60 years old, 75% reporting symptoms >60 years old) in contrast to participants under 30 years old (25% reporting symptoms). Overall, this analysis of a rural population provides important information about the SARS-CoV-2 pandemic in small rural communities. The study also underscores the fact that prior infection with SARS-CoV-2 results in antibody responses that wane over time which highlights the need for vaccine mediated protection in the absence of lasting protection.

Administration, 2021). Population densities in these areas are vastly different than major 54 urban centers, often having an average of 45 times fewer people per square mile than 55 major urban centers (Cohen, 2015) . The impact on these communities during infectious 56 disease outbreaks has been discussed for years. Specifically, rural communities have (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. obtained in addition to self-reported age, biological sex, ethnicity, race, medication list, 83 All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted August 18, 2021. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Pearson correlation analyses. To assess statistical differences between two groups, a 178 two-tailed Student t-tests was used, or a one-way ANOVA followed by Tukey's multiple 179 comparison test to assess differences between multiple groups. Statistical significance 180 was determined to be P < 0.05. (Table 1) . SARS-CoV-2 187 incidence was determined to be 10% (15/150 participants) (Table 1) (Table 1) . A similar commercial 194 qualitative SARS-CoV-2 IgG testing method (Abbott) identified 67% (10/15) exposed 195 individuals.

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(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. differences between SARS-CoV-2 exposed and non-exposed participants ( Figure 1A-B) .

Among those previously infected with SARS-CoV-2, neither age nor sex were associated whether the SARS-CoV-2 exposed participants from this study possessed abnormal 218 immunogenic profiles, we assessed antibody production to an additional pathogen most 219 people are vaccinated against: B. pertussis. Serum from SARS-CoV-2 exposed and a 220 All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted August 18, 2021. ; https://doi.org/10.1101/2021.08.16.21262128 doi: medRxiv preprint selection of non-exposed individuals were tested for IgG production against whole B. 221 pertussis and Pertussis toxin. The data indicate that there was no difference in anti-B. 222 pertussis (Figure 2A-B) or anti-Pertussis toxin ( Figure 2C -D) IgG levels between 223 individuals exposed or not exposed to SARS-CoV-2. These data suggest that there is a 224 similar immunogenic profile between each cohort and can assume this study was mostly 225 comprised of immunocompetent subjects. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted August 18, 2021. ; https://doi.org/10.1101/2021.08.16.21262128 doi: medRxiv preprint that were hospitalized had significantly higher levels of IgG and introduced bias un-related 244 to the demographic being evaluated. However, there was a noticeable difference in 245 reporting of viral-like symptoms between exposed individuals when compartmentalized 246 by age (Figures 4C-E) . Participants under 30 years old ( Figure 4C ) reported viral-like 247 symptoms at a lower frequency than individuals greater than 30 years old ( Figures 4D-248 E). (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted August 18, 2021. ; https://doi.org/10.1101/2021.08.16.21262128 doi: medRxiv preprint 2 antibody levels is a cause for concern for individuals that have convalesced from 267 infection and warrants further investigation. The comparable trend of declining nAbs in 268 participants is particularly alarming as this indicates that this decline may not be limited hospitalized for COVID-19 all of whom were over the age of 30 and two of whom were 289 All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Overall, this study provides a compact analysis of SARS-CoV-2 incidence 293 conducted at a rural West Virginia hospital. Total incidence taken at this community 294 hospital appears high relative to the national average at that time which may be due to (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted August 18, 2021. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted August 18, 2021. ; https://doi.org/10.1101/2021.08.16.21262128 doi: medRxiv preprint

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On Determining the Age Distribution of COVID-19 Pandemic

All rights reserved. No reuse allowed without permission.(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint this version posted August 18, 2021. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. SARS-CoV-2 exposure were determined for the participants of this study. Proportion of 441 patients exposed or not exposed to SARS-CoV-2 and the WVU VDC detection rates of 442 known exposed individuals. n = 150 participants. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. CoV-2 exposure 13 . C) Anti-SARS-CoV-2 RBD IgG levels of exposed participants were 465 plotted against the number of days after the participant tested positive for SARS-CoV-2. 466 Blue dots represent participants that were admitted to the hospital during infection. D) 467 Comparison of anti-RBD AUC values from a prior study and this study over time.

Statistical significance was assessed by a two-tailed Pearson correlation or a one-way 469 All rights reserved. No reuse allowed without permission.(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint this version posted August 18, 2021. ; https://doi.org/10.1101/2021.08.16.21262128 doi: medRxiv preprint ANOVA followed by a Tukey's multiple comparison test. **** = P < 0.0001, ns = not CoV-2 exposed, grey symbols = non-exposed, white symbols = negative control). B) Area 475 under the curve (AUC) analysis of B. pertussis ELISA curves of participants exposed or 476 not exposed to SARS-CoV-2. C) Titration of participant samples on Pertussis toxin ELISA 477 plates. Orange symbols = SARS-CoV-2 exposed, grey symbols = non-exposed , white 478 symbols = negative control). D) Area under the curve (AUC) analysis of Pertussis toxin 479 All rights reserved. No reuse allowed without permission.(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint this version posted August 18, 2021. ; https://doi.org/10.1101/2021.08.16.21262128 doi: medRxiv preprint ELISA curves of participants exposed or not exposed to SARS-CoV-2. Statistical 480 significance was assessed by a two-tailed student's t-test. ns = not significant. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. CoV-2 exposed participants C) <30 years old, D) 30-60 years old, and E) >60 years old. 

All rights reserved. No reuse allowed without permission.(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint this version posted August 18, 2021. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint this version posted August 18, 2021. ; https://doi.org/10.1101/2021.08.16.21262128 doi: medRxiv preprint