key: cord-0305556-38e20fpa authors: Mathema, B.; Chen, L.; Chow, K. F.; Zhao, Y.; Zody, M. C.; Mediavilla, J. R.; Cunningham, M. H.; Composto, K.; Lee, A.; Oschwald, D. M.; Germer, S.; Fennessey, S.; Patel, K.; Wilson, D.; Cassell, A.; Pascual, L.; Ip, A.; Corvelo, A.; Dar, S.; Kramer, Y.; Maniatis, T.; Perlin, D. S.; Kreiswirth, B. N. title: Post-vaccination SARS-COV-2 among healthcare workers in New Jersey: a genomic epidemiological study date: 2021-07-05 journal: nan DOI: 10.1101/2021.06.30.21259761 sha: 5c07b2acc704ba4dcd5c984c28ac719bb53fe071 doc_id: 305556 cord_uid: 38e20fpa Emergence of SARS-CoV-2 with high transmission and immune evasion potential, the so-called Variants of Concern (VOC), is a major concern. We describe the early genomic epidemiology of SARS-CoV-2 recovered from vaccinated healthcare professionals (HCP). Our post-vaccination COVID-19 symptoms-based surveillance program among HCPs in a 17-hospital network, identified all vaccinated HCP who tested positive for COVID-19 after routine screening or after self-reporting. From 01/01/2021 to 04/30/2021, 23,687 HCP received either mRNA-1273 or BNT162b2 mRNA vaccine. All available post-vaccination SARS-CoV-2 samples and a random collection from non-vaccinated patients during the similar timeframe were subjected to VOC screening and whole genome sequencing (WGS). 62% (23,697/37,500) of HCPs received at least one vaccine dose, with 95% (22,458) fully vaccinated. We detected 138 (0.58%, 138/23,697) COVID-19 cases, 105 among partially vaccinated and 33 (0.15%, 33/22,458) among fully vaccinated. Five partially vaccinated required hospitalization, four with supplemental oxygen. VOC screening from 16 fully vaccinated HCPs identified 6 (38%) harboring N501Y and 1 (6%) with E484K polymorphisms; concurrent non-vaccinated samples was 37% (523/1404) and 20% (284/1394), respectively. There was an upward trend from January to April for E484K/Q (3% to 26%) and N501Y (1% to 49%). WGS analysis from vaccinated and non-vaccinated individuals indicated highly congruent phylogenies. We did not detect an increased frequency of any RBD/NTD polymorphism between groups (P>0.05). Our results support robust protection by vaccination, particularly among recipients of both doses. Despite VOCs accounting for over 40% of SARS-CoV-2 from fully vaccinated individuals, the genomic diversity appears to proportionally represent those among non-vaccinated populations. 3 IMPORTANCE 52 A number of highly effective vaccines have been developed and deployed to combat the 53 COVID-19 pandemic. The emergence and epidemiological dominance of SARS-CoV-2 mutants, 54 with high transmission potential and immune evasion properties, the so-called Variants of 55 Concern (VOC), continues to be a major concern. Whether these VOCs alter the efficacy of the 56 administered vaccines is of great concern, and a critical question to study. We describe the 57 initial genomic epidemiology of SARS-CoV-2 recovered from vaccinated healthcare . CC-BY-NC-ND 4.0 International license It is made available under a 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 July 5, 2021. ; https://doi.org /10.1101 /10. /2021 Since the beginning of the pandemic in 2020, SARS-CoV-2 has infected and spread within an 72 immunologically naïve global population (1, 2). With the application of convalescent plasma and 73 therapeutic antibody treatment, along with highly effective vaccines, the virus is now starting to 74 experience the immune pressure that will ultimately shape its evolutionary trajectory ( (Delta) (9) emerged in India and has spread globally. The mapping of specific mutations in the 84 spike protein has revealed strong evidence of convergent evolution, and particularly the E484K 85 polymorphism, which is able to evade certain monoclonal therapy and it is less responsive to 86 neutralizing antibodies from recovered patients. This mutant shows reduced response to 87 convalescent plasma and reported reinfections and it has been identified in discrete lineages in 88 different geographic locations and associated with variant clones with increased incidence (4). The impact of these antibody escape mutants harboring VOCs on driving community incidence 90 and whether they alter the efficacy of the administered vaccines is of great concern. 91 In this report, we describe the initial genomic epidemiology of SARS-CoV-2 recovered from 92 vaccinated healthcare professionals (HCPs) within a large healthcare network in New Jersey. We specifically probe whether specific SARS-CoV-2 variants skew viral diversity indicative of 94 vaccine-induced selection; and compare against a random collection of SARS-CoV-2 recovered 95 from non-vaccinated individuals during the same time period. Although we find steep increases 96 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 5, 2021. ; https://doi.org /10.1101 /10. /2021 Of those that were symptomatic, five individuals requiring hospitalization received only one dose 118 and had recorded BMI of >25 (4 individuals with BMI >30) and four of these patients required . CC-BY-NC-ND 4.0 International license It is made available under a 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 July 5, 2021. ; https://doi.org /10.1101 /10. /2021 6 123 To further characterize the SARS-CoV-2 genotypes recovered from the post-vaccinated 126 individuals, we examined the spread of key mutations underlying VOCs (i.e., B.1.1.7) in New 127 Jersey using a high-throughput molecular beacon assay designed to screen for polymorphisms 128 N501Y/T and E484K/Q in the RBD region (10) . Among 138 HCPs, 83 swabs were available for 129 rapid screening providing 76 genotypic results (60 from partial and 16 from fully vaccinated). There were 3 and 6 viral samples with E484K and N501Y polymorphisms respectively ( Figure 131 1). Among 16 fully vaccinated HCPs, we found 1 (6.3%) and 6 (38%) samples with E484K and 132 N501Y mutations, respectively. To contextualize the prevalence of E484K and N501Y mutations among the non-vaccinated 142 genotypes or genetic characteristics. To understand the population structure of SARS-CoV-2 post-vaccination, we first analyzed 144 WGS data for 68 available SARS-CoV-2 isolates from 83 symptomatic COVID-19 cases 145 included in this study. WGS failed for 15 samples due to high Ct values, suggestive of low viral 146 burden. We specifically probed whether specific variants or mutations were overrepresented 147 among SARS-CoV-2 recovered from vaccinated individuals. The 68 genomes were divided into 148 . CC-BY-NC-ND 4.0 International license It is made available under a 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 July 5, 2021. evasion -L452R, T478K, E484K and S494P -were found in 3, 1, 3 and 2 genomes, 152 respectively. We did not detect any genomes with more than two of the four polymorphisms. The N501Y mutation was found in 4% (3/68) of the genomes, and all belonged to the VOC 154 B.1.1.7 lineage. We recorded 3 viral samples harboring the E484K mutation, two belonged to 155 the B.1.526 lineage first identified in New York (11, 12) and one from the R.1 lineage. Importantly, among the 9 individuals fully vaccinated (i.e., To compare viral diversity from vaccinated and non-vaccinated individuals, we randomly . CC-BY-NC-ND 4.0 International license It is made available under a 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 July 5, 2021. ; https://doi.org /10.1101 /10. /2021 Rapid expansion and contraction of SARS-CoV-2 populations coupled with increasing anti-CoV-175 2 immunity dynamics have contributed to pandemic phases accompanied by emergent genomic 176 signatures (1, 13). Extensive polymorphisms in the spike protein have been documented, 177 including N501Y and E484K mutations that are particularly concerning (14). In this report, we 178 present early genomic analysis of SARS-CoV-2 from an ongoing post-vaccination COVID-19 179 surveillance program among healthcare workers in New Jersey. We detected SARS-CoV-2 in 33 (0.15%) HCPs who were fully vaccinated, none of whom 181 required hospitalization. All symptomatic cases were noted among partially vaccinated HCPs 182 and were self-limiting with only 5 requiring hospitalization. Although our passive surveillance 183 system was intended to capture the HCP vaccinated population who self-reported symptoms or 184 who were exposed to a COVID-19 positive case, and not able to report true prevalence of CC-BY-NC-ND 4.0 International license It is made available under a 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 July 5, 2021. ; https://doi.org /10.1101 /10. /2021 neutralization in vitro (2, 3, 6, 14) . Whether the rollout of vaccination would offer selective 199 advantage to VOCs is a critical question to determine. . CC-BY-NC-ND 4.0 International license It is made available under a 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 July 5, 2021. There is mounting evidence that currently available vaccines, including those used in our CC-BY-NC-ND 4.0 International license It is made available under a 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 July 5, 2021. ; https://doi.org /10.1101 /10. /2021 after reporting out sick. Non-team members who were vaccinated at our mass-vaccination site 249 or by physician report (and were thus in the HMH EMR) and subsequently tested positive for CC-BY-NC-ND 4.0 International license It is made available under a 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 July 5, 2021. ; https://doi.org /10.1101 /10. /2021 trimmed from the 3' end of the remaining reads, using Cutadapt v2. 10 (34) . Processed reads 275 pairs were then merged using NGmerge v0.2 (36) , allowing for dovetailed alignments. The 276 resulting single end reads were mapped against the SARS-CoV-2 genome reference using 277 and the resulting alignments filtered using the following criteria: 1) CC-BY-NC-ND 4.0 International license It is made available under a 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 July 5, 2021. ; https://doi.org /10.1101 /10. /2021 13 N501Y mutations, as previously described (10) . In brief, 50 µl aliquots of SARS-CoV-2 swab 301 specimens were treated by proteinase K and heated at 95°C for 5 min. 5ul of heat inactivated 302 sample was used as template for the asymmetric RT-PCR testing on a Mic Real Time PCR 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 July 5, 2021. ; https://doi.org /10.1101 /10. /2021 CC-BY-NC-ND 4.0 International license It is made available under a 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 July 5, 2021. ; https://doi.org /10.1101 /10. /2021 . CC-BY-NC-ND 4.0 International license It is made available under a 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 July 5, 2021. ; https://doi.org /10.1101 /10. /2021 . CC-BY-NC-ND 4.0 International license It is made available under a 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 July 5, 2021. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 5, 2021. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 5, 2021. ; https://doi.org /10.1101/2021.06.30.21259761 doi: medRxiv preprint L18F T20N,I T22I L24S P26S A27S T29I V36F V47I L54F W64L A67T H69V70-H69Y D80G S94F T95I S98F D111N N121D V130L D138Y G142D V143-Y144-Y144D,S W152L,C M153I E154K,G S155R F157S R190S,W D198G D215Y A222V L241-L242-A243-R246K D253G S255F S256L,A,P W258F V289I T323I R346K A348S E406Q K417T L452R T470K T478K,I E484K,Q S494P N501Y,T A novel diagnostic test to 390 screen SARS-CoV-2 variants containing E484K and N501Y mutations A Novel SARS-CoV-2 Variant of Concern, B.1.526 Rapid Emergence and Epidemiologic 398 Characteristics of the SARS-CoV-2 B.1.526 Variant Concerns about SARS-CoV-2 401 evolution should not hold back efforts to expand vaccination Antibody resistance of SARS-CoV-2 variants B.1.351 406 and B.1.1.7 COVID-19 vaccine impact on rates of 410 SARS-CoV-2 cases and post vaccination strain sequences among healthcare workers at 411 an urban academic medical center: a prospective cohort study Early Evidence of the Effect of 414 SARS-CoV-2 Vaccine at One Medical Center SARS-CoV-2 Infection after Vaccination in Health Care Workers Postvaccination SARS-CoV-2 Infections Among Skilled 420 COVID-19 vaccine coverage in 425 health-care workers in England and effectiveness of BNT162b2 mRNA vaccine against 426 infection (SIREN): a prospective, multicentre, cohort study COVID-19 Outbreak Associated with a 429 SARS-CoV-2 R.1 Lineage Variant in a Skilled Nursing Facility After Vaccination 430 United States Evolution and epidemic spread of SARS-466 CoV-2 in Brazil Variants of concern are overrepresented among post-vaccination 471 breakthrough infections of SARS-CoV-2 in Washington State CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 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The copyright holder for this preprint this version posted July 5, 2021. CC-BY-NC-ND 4.0 International license It is made available under a 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 July 5, 2021. ; https://doi.org /10.1101 /10. /2021 17 neutralization of B.1.617 and other SARS-CoV-2 variants. Nature doi: 10.1038/s41586-387 021-03693-y. 388 . CC-BY-NC-ND 4.0 International license It is made available under a 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 July 5, 2021. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)The copyright holder for this preprint this version posted July 5, 2021.