Post-vaccination SARS-COV-2 among healthcare workers in New Jersey: a genomic epidemiological study (preprint)

ABSTRACT 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. IMPORTANCE A number of highly effective vaccines have been developed and deployed to combat the COVID-19 pandemic. The emergence and epidemiological dominance of SARS-CoV-2 mutants, with high transmission potential and immune evasion properties, the so-called Variants of Concern (VOC), continues to be a major concern. Whether these VOCs alter the efficacy of the administered vaccines is of great concern, and a critical question to study. We describe the initial genomic epidemiology of SARS-CoV-2 recovered from vaccinated healthcare professionals and probe specifically for VOC enrichment. Our findings support the high-level of protection provided by full vaccination despite a steep increase in the prevalence of polymorphisms associated with increased transmission potential (N501Y) and immune evasion (E484K) in the non-vaccinated population. Thus, we do not find evidence of VOC enrichment among vaccinated groups. Overall, the genomic diversity of SARS-CoV-2 recovered post-vaccination appears to proportionally represent the observed viral diversity within the community.

Emergence of multiple SARS-CoV-2 antibody escape variants in an immunocompromised host undergoing convalescent plasma treatment (preprint)

SARS-CoV-2 Variants of Concerns (VOC), e.g., B.1.351 (20H/501Y.V2) and P1 (20J/501Y.V3), harboring N-terminal domain (NTD) or the receptor-binding domain (RBD) (e.g., E484K) mutations, exhibit reduced in vitro susceptibility to convalescent serum, commercial antibody cocktails, and vaccine neutralization, and have been associated with reinfection. The accumulation of these mutations could be the consequence of intra-host viral evolution due to prolonged infection in immunocompromised hosts. In this study, we document the microevolution of SARS-CoV-2 recovered from sequential tracheal aspirates from an immunosuppressed patient on tacrolimus, steroids and convalescent plasma therapy, and identify the emergence of multiple NTD and RBD mutations associated with reduced antibody neutralization as early as three weeks after infection. SARS-CoV-2 genomes from the first swab (Day 0) and three tracheal aspirates (Day 7, 21 and 27) were compared at the sequence level. We identified five different S protein mutations at the NTD or RBD regions from the second tracheal aspirate sample (21 Day). The S:Q493R substitution and S:243-244LA deletion had ~70% frequency, while ORF1a:A138T, S:141-144LGVY deletion, S:E484K and S:Q493K substitutions demonstrated ~30%, ~30%, ~20% and ~10% mutation frequency, respectively. However, the third tracheal aspirate sample collected one week later (Day 27) was predominated by the haplotype of ORF1a:A138T, S:141-144LGVY deletion and S:E484K (> 95% mutation frequency). Notably, S protein deletions (141-144LGVY and 243-244LA deletions in NTD region) and substitutions (Q493K/R and E484K in the RBD region) previously showed reduced susceptibly to monoclonal antibody or convalescent plasma. The observation supports the hypothesis that VOCs can independently arise and that immunocompromised patients on convalescent plasma therapy are potential breeding grounds for immune-escape mutants.