Clinical and Genomic Characterization of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) Infections in mRNA Vaccinated Health Care Personnel in New York City

Abstract

Background

Vaccine-induced clinical protection against severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) variants is an evolving target. There are limited genomic level data on SARS CoV-2 breakthrough infections and vaccine effectiveness (VE) since the global spread of the B.1.617.2 (Delta) variant.

Methods

In a retrospective study from 1 November 2020 to 31 August 2021, divided as pre-Delta and Delta-dominant periods, laboratory-confirmed SARS CoV-2 infections among healthcare personnel (HCP) at a large tertiary cancer center in New York City were examined to compare the weekly infection rate-ratio in vaccinated, partially vaccinated, and unvaccinated HCP. We describe the clinical and genomic epidemiologic features of post-vaccine infections to assess for selection of variants of concern (VOC)/variants of interest (VOI) in the early post-vaccine period and impact of B.1.617.2 (Delta) variant domination on VE.

Results

Among 13658 HCP in our cohort, 12379 received at least 1 dose of a messenger RNA (mRNA) vaccine. In the pre-Delta period overall VE was 94.5%. Whole genome sequencing (WGS) of 369 isolates in the pre-Delta period did not reveal a clade bias for VOC/VOI specific to post-vaccine infections. VE in the Delta dominant phase was 75.6%. No hospitalizations occurred among vaccinated HCP in the entire study period, compared to 17 hospitalizations and 1 death among unvaccinated HCP.

Conclusions

Findings show high VE among HCP in New York City in the pre-Delta phase, with moderate decline in VE post-Delta emergence. SARS CoV-2 clades were similarly distributed among vaccinated and unvaccinated infected HCP without apparent clustering during the pre-Delta period of diverse clade circulation. Strong vaccine protection against hospitalization was maintained through the entire study period.

study of >13000 healthcare personnel (HCP) showed that messenger RNA (mRNA) vaccine effectiveness (VE) against coronavirus disease 2019 (COVID-19) was 94% through initial 5 months of follow-up, with moderate VE reduction to 75% during subsequent Delta-dominant period. No hospitalizations occurred among vaccinated HCP throughout the study period.

The currently Food and Drug Administration (FDA)-approved coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccines BNT162b2 (Pfizer-BioNtech) and FDA-authorized mRNA-1273 (Moderna) have demonstrated clinical efficacy >94% in preventing symptomatic COVID-19 in Phase III clinical trials [1, 2]. The extraordinary effectiveness of the mRNA vaccines was sustained in the initial post-authorization real-world experience among US healthcare personnel (HCP), a population prioritized to receive the vaccine. The reported vaccine effectiveness remained close to 90% for both symptomatic and asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) infections across studies [3–8]. Still, the dynamic landscape of the COVID-19 pandemic poses substantial future uncertainty on the durability of the immune response and vaccine effectiveness against SARS CoV-2 variants which are more transmissible and possibly influence disease severity [9–14]. The emergence of the Delta variant (B.617.2) in July 2021 in the United States challenged these earlier VE estimates of SARS-CoV-2 infection as an increasing number of vaccine breakthrough infections were reported [15, 16].

In 2021, as the pandemic evolved in the United States, the circulating proportion of the variants of interest (VOI) and variants of concern (VOC) remained geographically variable. In spring 2021, the B.1.1.7 (Alpha) VOC became the dominant strain in the United States. At the same time, the regional prevalence of B.1.526 (Iota), VOI harboring the immune evading E484K and L452R spike protein mutation, was high during the second surge in New York City [17]. Since July 2021, Delta emerged as the predominant variant and reached 98% of circulating strains in New York City by early August [18]. Delta dominance coincided with relaxation of many COVID restrictions in the same region [19]. With this successive upsurge of multiple variants with immune escape mutations and some with higher transmissibility, constant genomic surveillance of vaccine breakthrough infections from geographically diverse cases is imperative. This information is critical to inform future public health strategies in the post-vaccine phase of the COVID-19 pandemic.

The present study reports the weekly rates of SARS CoV-2 infection in vaccinated and unvaccinated HCP at a large tertiary care center in New York City through 8 months of follow-up after the initial COVID-19 vaccine rollout. We compare VE during 2 distinct time periods: (1) pre-Delta (29 January to 30 June, 2021) characterized by co-circulation of multiple VOC/VOI and (2) Delta-dominant (1 July to 31 August 2021). In the pre-Delta period, we characterize the epidemiologic, clinical, and genomic characteristics of infections diagnosed following the first and second dose of the mRNA vaccine with a focus on identifying SARS CoV-2 virus lineages among post-vaccine infections.

METHODS

Memorial Sloan Kettering Cancer Center (MSKCC), a 514-bed tertiary cancer center in New York City that employs 21110 individuals. Data on HCP who received at least 1 COVID-19 RNA test or antibody test reported to our institutional database was collected for analysis. A subset of 13658 HCP who had at least 1 polymerase chain reaction (PCR) test during the study period between 1 November 2020, and 1 September 2021 and no positive tests prior to 1 November 2020 were eligible for the study inclusion. Phase 1a vaccination began on 16 December 2020 per Centers for Disease Control and Prevention (CDC) guidance and emergency use authorization (EUA) of the first mRNA vaccine against COVID-19. The MSKCC vaccine rollout coincided with a second surge of COVID-19 cases in New York City beginning in December 2020. Exclusion criteria for mRNA vaccine effectiveness analyses are outlined in Supplementary Figure 1.

Employee Testing Policy

Since 11 March 2020, all employees have had access to voluntary symptomatic and surveillance COVID-19 PCR testing through a self-scheduling platform and accessible testing sites. Surveillance testing was mandated for unvaccinated staff caring for high-risk groups (eg, Bone Marrow Transplant unit HCP) and was recommended biweekly for other HCP with patient contact prior to full vaccination. HCP external test results were systematically reported to the occupational health service through electronic submission and clinician follow up. Clinical characteristics of HCP with post-vaccination infections were obtained from the occupational health database.

Laboratory Methods

SARS-CoV-2 RNA test

The viral RNA was detected in nasopharyngeal swabs (NPS) or saliva samples as previously described [20, 21]. Briefly, real-time reverse transcription-polymerase chain reaction (RT-PCR) testing for SARS-CoV2 RNA was performed using 2 commercial assays, the TaqPath™ COVID-19 Combo Kit (Thermo Fisher Scientific, Waltham, Massachusetts USA) targeting the N, S and ORF genes or the cobas® SARS-CoV-2 test (Roche Molecular Diagnostics, Indianapolis, Indiana USA) targeting the ORF1 a/b and E gene. Samples were reported as positive per manufacturers’ instructions. The cycle threshold (Ct) value, a semi-quantitative estimate of the viral SARS-CoV-2 RNA load, was retrieved for all gene targets from each instrument record.

SARS-CoV-2 whole genome sequencing

Whole genome sequencing (WGS) was performed on available samples with a Ct value <30. For all vaccinated HCP, WGS was performed for all positive samples, including those with Ct values >30. Total viral nucleic acids were extracted from 200 µL of NPS or saliva samples on the KingFisher Flex Magnetic Particle Processor using the MagMAX™ Viral/Pathogen Nucleic Acid Isolation Kit (Thermo Fisher Scientific, Waltham, Massachusetts USA). Amplicon sequencing was performed following the Artic protocol with version 3 primers (Integrated DNA Technologies [IDT], Coralville, Iowa USA). Following cDNA synthesis and multiplexed PCR, libraries were prepared for the 2 amplicons pools using the Nextera XT DNA kit followed by sequencing on an Illumina Miseq platform (Illumina, San Diego, California USA) as paired end (2×150 base pair read). The Pangolin software (https://github.com/cov-lineages/pangolin) was used to assign lineages for each consensus sequence using the Pango nomenclature for all sequences passing sequencing quality check. Phylogeny reconstruction and clade frequencies were computed and statistically analyzed as described in the Supplementary Methods.

Data availability

All sequences were uploaded to GISAID (Global initiative on sharing all influenza data).

Statistical Analysis

To analyze vaccine effectiveness, we compared estimates of test positivity rates among vaccinated individuals versus unvaccinated in both the pre-Delta and Delta-dominant phases of the pandemic. To calculate these rates while accounting for the changing background community infection rate of COVID-19, a risk set was defined each day (from 1 November 2020 to 31 August 2021) consisting of everyone who had no positive tests at any time prior to that day, omitting those who may have had multiple positive tests. Each day, rates were calculated by dividing the total number of positive tests that day by the number of individuals in each vaccination state on that day. An individual’s vaccination state was defined in multiple ways to estimate effectiveness of various “partially” vaccinated states (first dose + 7 days, at date of second dose, second dose + 7 days) and a “full” vaccine course (second dose + at least 14 days). “Full” vaccination status and “breakthrough infections” were defined using CDC criteria as detection of SARS-CoV-2 RNA in a respiratory or saliva specimen collected from an HCP ≥14 days (about 2 weeks) after receipt of second dose of the mRNA vaccine.

To adjust for changing background community infection rates and to visualize changing vaccine effectiveness over the course of the pandemic, daily calculated positivity rates and rate ratios were smoothed using an adaptive moving window. Rate ratios are driven by the number of positives split between vaccine groups and a small total can make estimations unstable, therefore the window was adjusted from a minimum of 7 days up to 20 days if the total number of positives in the window was fewer than 20 to stabilize rates calculated on low incidence weeks. These rates were aggregated (daily rate × 7) to estimate and visualize weekly rates.

To calculate overall effectiveness before and during the Delta-dominant phase, we categorized individuals in 3 groups: unvaccinated (no vaccine doses, or 1 dose + ≤ 6 days), partially vaccinated (first dose + ≥ 7 days), or fully vaccinated (second dose + ≥ 14 days). We then calculated the rate ratio of total number of positive tests in each vaccination state over the number of person-days in each state for the specified time period (pre-Delta VE period: 29 January 2021 to 30 June 2021, and Delta-dominant phase: 1 July 2021 to 1 September 2021). The 95% confidence intervals (CIs) were calculated for rate ratios using 1000 bootstrap iterations and the percentile method was used to approximate confidence bounds. “Effectiveness” (percent relative effect) was calculated as 1 minus this rate ratio (RR).

The MSKCC Institutional Review Board granted a HIPAA (Health Insurance Portability and Accountability) approval to conduct the study.

RESULTS

Of 13658, evaluable participants in the cohort 12379 received at least 1 dose of the mRNA vaccine, and 12046 received both doses by the end of the study period. Most (n=9379) of the vaccinated individuals received the BNT162b2 vaccine (75.7%), which was the primary vaccine allocated to the study institution. The timing of administered vaccine doses is shown in Supplementary Figure 2. The median follow-up time for the cohort calculated from 1 November 2020 to the last recorded test for each individual was 4.5 months. Overall, 1450 SARS CoV-2 infections were diagnosed in HCP during the study period (1052 in unvaccinated and 398 after 1 or more doses).

Vaccine Effectiveness in Partially and Fully Vaccinated HCP

Laboratory-confirmed SARS CoV-2 infection during the study period occurred in 398 (3.2%) of vaccinated individuals. A comparison of the weekly rate ratio of positive tests among vaccinated versus unvaccinated HCP relative to the time elapsed since the first vaccine dose is shown in Figure 1. The infection rate ratio (ratio of number positives/ person-days in each vaccine status class) for fully vaccinated/ unvaccinated individuals was 0.055 (95% CI, .042–.071) in the pre-Delta period, and 0.24 (95% CI, .19–.32) in the Delta dominant period Similarly, The infection rate ratio (ratio of number positives/person-days in each vaccine status class) for partially vaccinated/ unvaccinated was 0.34 (95 % CI, .28–.41) and 0.38 (95% CI, 082.–.83) in the 2 time periods (Figure 2). These findings translate to an overall vaccine effectiveness (1 – RR) of 94.5% (92.9%–95.8%) for fully vaccinated HCP for pre-Delta period and 75.6% (68.2%–81.0%) for Delta-dominant period. From 1 July to 31 August 2021 there were 184 infections among vaccinated HCP including 178 vaccine BT infections.

Figure 1.

Weekly positivity rates and rate ratios for HCP at designated time points following initial vaccine dose. Bar graphs show weekly positivity rate for HCP who received at least one dose of mRNA vaccine compared to unvaccinated HCP. Line graphs compare rate ratios of HCP undergoing vaccination with unvaccinated HCP with bootstrap confidence intervals (gray). HCP are categorized as vaccinated by key time points in vaccination schedule as designated in each panel: 1 week after administration of first dose (A), at time of dose 2 (B), 1 week after dose 2 (C), and 2 weeks after dose 2 (D). Abbreviations: HCP, healthcare personnel; mRNA, messenger RNA.

Figure 2.

Weekly positivity rates and rate ratios comparing fully vaccinated with unvaccinated HCP and partially vaccinated with unvaccinated HCP. The bar graph shows weekly positivity rates for HCP in each vaccine status category (fully vaccinated: ≥14 days from dose 2; partially vaccinated: >1 day from dose 1 to <14 days from dose 1 and unvaccinated) with raw number of weekly positives, and number of HCP in each vaccination group depicted below. Rate ratios (solid vs dashed lines) are displayed with bootstrap confidence intervals (gray). Bootstrap CIs are truncated at RR = 7.

Clinical Characteristics of Post-Vaccine Infections

Figure 3 shows the timing of 398 post-vaccine infections, including 242 infections diagnosed after the second vaccine dose. The median time from vaccine to positive test was 9 days (range: 1–83 days) after dose 1 and 56 days (range: 1–100 days) after dose 2. The demographic and clinical characteristics of the post-vaccine infections are shown in Table 1. The cases were predominantly identified in female HCP, who accounted for 65% of the study institution’s workforce. A higher proportion of cases detected after the second dose were asymptomatic compared to the first dose only. The probable source of infection was household exposure in the pre-Delta period, whereas community exposures were increasingly identified in the Delta-dominant phase. All infections were mild, and none required hospitalization among vaccine recipients. Importantly, 17 COVID-19 related hospitalizations and 1 death occurred during the entire study period and all among unvaccinated HCP.

Figure 3.

Post-vaccination positives tests for SARS-CoV-2 PCR. Swimmer plot shows days from initial vaccine dose to laboratory confirmed SARS-CoV-2 infection by PCR test (+) and includes 139 cases after the first dose and 259 after second dose, including 242 breakthrough infections ≥ 14 days from dose 2. Abbreviations: PCR, polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Table 1.

Clinical Characteristics of Post-Vaccine Infections in HCP After Receiving COVID-19 mRNA Vaccine Series

	Pre-Delta Period		Delta Period
No. (%)	After Dose 1	After Dose 2	After Dose 1	After Dose 2
	134 (63)	80 (37)	5 (3)	179 (97)
Age, y
Median (range)	35 (22–69)	37 (22–65)	30 (26–59)	33 (21–63)
20–29	42 (31)	20 (25)	2 (40)	64 (36)
30–39	41 (31)	24 (30)	2 (40)	66 (37)
40–49	28 (21)	16 (20)	0	31 (17)
50–59	15 (11)	14 (18)	1 (20)	14 (8)
>60	8 (6)	6 (7)	0	4 (2)
Sex
Female	91 (68)	60 (75)	3 (60)	127 (71)
Male	43 (32)	20 (25)	2 (40)	52 (29)
Vaccine type
BNT162b2 (Pfizer-BioNtech)	108 (81)	73 (91)	4 (80)	142 (79)
mRNA-1273 (Moderna)	26 (19)	7 (9)	1 (20)	37 (21)
Type of exposure
Household exposure	47 (35)	39 (49)	1 (20)	44 (25)
Community exposure	16 (12)	10 (13)	1 (20)	45 (25)
Unknown exposure	60 (45)	27 (34)	2 (40)	53 (30)
Travel exposure	4 (3)	2 (2)	0	29 (16)
Workplace exposure	6 (4)	0	1 (20)	8 (4)
Data unavailable	1 (1)	2 (2)
Job requiring direct patient care
Yes	58 (43)	36 (45)	3 (60)	89 (50)
No	76 (57)	44 (55)	2 (40)	90 (50)
Median days from vaccine dose 2 to positive test (range)	9 (1–83)	56 (1–100)	7 (4–223)	185 (8–235)
<7 days	43 (32)	6 (7)	2 (40)	0
7–13 days	54 (40)	10 (13)	1 (20)	1 (1)
≥14 days	37 (28)	64 (80)	2 (40)	178 (99)
Median days from vaccine dose to symptom onset (range)	7 (0–82)a	59 (0–97)	7 (2–216)	184 (17–231)
<7 days	54 (40)	8 (10)	2 (40)	0
7–13 days	43 (32)	2 (2)	1 (20)	0
≥14 days	21 (13)	53 (66)	2 (40)	164 (92)
Symptomsb
Asymptomatic	16 (12)	16 (20)	0	15 (8)
Headache	69 (51)	44 (55)	5 (100)	81 (45)
Fatigue	76 (57)	36 (45)	1 (20)	99 (55)
Body aches	62 (46)	22 (28)	2 (40)	66 (37)
Fever (including subjective)	49 (37)	15 (19)	2 (40)	58 (32)
Loss of smell/taste	43 (32)	22 (28)	3 (60)	51 (28)
Chills	54 (40)	16 (20)	1 (20)	48 (27)
Sore throat	45 (34)	17 (21)	2 (40)	79 (44)
Rhinorrhea, nasal congestion, sneezing	68 (51)	42 (53)	2 (40)	93 (52)
GI symptoms (nausea, vomiting, diarrhea or abdominal pain)	23 (17)	14 (18)	1 (20)	30 (17)
Cough	83 (62)	25 (31)	5 (100)	95 (53)
Shortness of breath	25 (19)	6 (8)	1 (20)	17 (9)
Hospitalizations/death	0	0	0	0

Abbreviations: COVID-19, coronavirus disease 2019; GI, gastrointestinal; HCP, healthcare personnel; mRNA, messenger RNA.

One healthcare worker (HCW) reported mild symptoms 4 days before vaccination.

Symptoms at the time of diagnosis.

Genomic Characterization of Cases in Vaccinated HCP in Pre-Delta Period

Sequencing analysis with variant lineage assignation was restricted to the pre-Delta period and included 259/969 (27%) of unvaccinated cases and more than 50% (110/214) of cases in vaccinated individuals. The presence of spike-gene immune escape mutations was evenly distributed among partially and fully vaccinated cases (Supplementary Table 1). The clade distribution of 259 viral genomes from unvaccinated HCP with infection and those who developed illnesses after the first (n=71) and second dose (n=39 are shown against the background of clade frequencies in New York during the pre-Delta period (Figure 4). We compare the observed case numbers in specific VOI/VOC with numbers expected under the assumption of random infections from circulating clades. We find a statistical overrepresentation of variant Alpha in the observed cases, but it is not significantly different before and after vaccination. We find no bias with respect to the number of mutations in the receptor binding domain (RBD) of the spike protein (Supplementary Figure 3). Together, our analysis does not reveal specific clustering of post-vaccine cases within a particular VOI/VOC class either after the first or the second dose in the pre-Delta period.

Figure 4.

SARS-CoV-2 genetic clade distribution by vaccination status compared to regionally circulating variants in pre-Delta period. A, Tree of New York state sequences with MSKCC HCW cases marked (open circles: unvaccinated, half-filled: single dose, filled: 2 doses), colored by the major genetic clades. B–D, Left: Cases on the background of time-dependent clade frequencies. Right: Count histograms comparing the number of MSKCC cases vs. the expected numbers according to New York clade frequency background. Case numbers depend on the temporal distribution of observed cases. Clade labels are detailed in Supplementary Table 2. Abbreviations: HCW, healthcare worker; MSKCC, Memorial Sloan Kettering Cancer Center; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

DISCUSSION

The present study results demonstrate durable clinical protection from the COVID-19 mRNA vaccines with a moderate reduction in VE against infections due to Delta variant. BT infections were limited 64/214 (30%) in the pre-Delta period but increased 178/184 (97%) in the latter part of the study period as cases of Delta variant expanded and co-incident with the relaxation of public health mitigation strategies and increased overall number of vaccinated HCPs. BT infections across both periods manifested mildly, with no hospitalization or deaths. Whole-genome sequencing of a majority of vaccinated HCP strains, did not show a disproportionate selection of VOC or VOI among fully or partially vaccinated individuals during the pre-Delta period [22].

An assessment of vaccine effectiveness outside of clinical trial settings can be subject to many wide-ranging parameters that can influence effectiveness, including the evaluated population, geographic region, community transmission rates, circulating strains, and pre-existing immunity. The current study was conducted in the backdrop of a second New York City surge marked initially by the rapid expansion of the B.1.1.7 (Alpha) variant and the regional emergence of 2 B.1.526 (Iota) lineages, which were followed by a third wave of infections characterized by national and regional Delta domination. Overall, we detected SARS CoV-2 breakthrough infection in 2% of fully vaccinated vaccinees and with no severe illnesses or hospitalizations identified among all vaccinated HCP. Most infections resulted from a recognized community or household exposure, emphasizing the proximity of infected HCP to the source and potentially high inoculum exposure.

Most importantly, in the pre-Delta period the viral lineages identified from 110 sequenced infections in vaccinated HCP did not differ from those detected among unvaccinated HCP in the corresponding period. The findings provide reassurance on vaccine effectiveness against the B.1.1.7 (Alpha) and B.1.526 (Iota) variants. A report that evaluated a small number (n=32) of breakthrough infections from New York City in the pre-Delta period found that 25% of the infections were attributed to B.1.526 (Iota variant, E484K +) and 22% to the B.1.1.7 (Alpha) variant, the predominant circulating strains in New York City [22]. Interestingly, previously seropositive individuals had slightly higher infection rates with the B.1.526 (Iota, variant E484 K+) variant compared to other sequenced strains. This finding was non-significant, and it is unclear if the seropositive individuals were vaccinated before infection with the B.1.526 (Iota) strain. The early experience from Israel with 396 post-vaccine infection describes a disproportionate occurrence of B.1.1.7 (Alpha) infections in partially vaccinated and B. 1.351 infections in fully vaccinated individuals [23]. Similarly, a study from Qatar during its second SARS-CoV-2 surge in early 2021 driven by a rise in B.1.1.7 (Alpha) and B.1.351 (Beta) shows lower vaccine effectiveness against B.1.351 variant than had been reported in clinical trials (75%, 95% CI, 70.5–78.9), but protection against severe or critical illness was maintained for fully vaccinated persons [24].

The latter study period’s abrupt and moderate decline in VE is probably multifactorial and attributed to the combined effects of higher exposure to the Delta variant [16], its immune evasion properties, and an overall decrease in vaccine-induced humoral immunity over time [25, 26]. In our study, although the VE against infection declined 20%, the protection against hospitalization was preserved. Both these findings are consistent with emerging reports among U.S. HCP [27, 28] where the VE in Delta dominant phase is estimated to be around 66%. Additionally, BT infections among HCP in our study were overwhelmingly attributed to community and household exposures rather than workplace transmissions where universal adherence to PPE mitigated the risk even with the observed decline in VE.

There are several limitations to our study. First, testing was not standardized across the vaccinated and unvaccinated employees and influenced by health-seeking behavior. Vaccinated individuals were more likely to have had at least one test during our study period (67% of vaccinated employees vs 38% of unvaccinated employees) and therefore disproportionately appear in our analysis cohort. Additionally, vaccinated employees, especially those in direct patient-facing roles, underwent a greater number of tests per person (vaccinated: median 3 tests, interquartile range [IQR] 2–6 vs unvaccinated: median 3 tests, IQR 1–5). Second, variability in estimations of positivity rates were subject to changing community infection rates of COVID-19 over the study period affecting rates of employee testing, along with a drop in testing frequency among already vaccinated individuals. Finally, although vaccine shortage in the early phase precluded HCP vaccination outside of the study institution, mis-categorization of unvaccinated study participants due to the absence of records is possible. To minimize this limitation, we actively sought records of outside COVID-19 vaccination an included those that could be verified in the analysis. We do not think this limits our study findings. Majority of vaccine recipients in our cohort received BNT162b2 and we could not directly examine the vaccine-specific BT risk posed by the Delta variant [29].

Regarding WGS, local genomic epidemiology in New York City reveals that although B.1.526 (Iota) emerged in February 2021, strains harboring the E 484K mutation expanded in the early part of April 2021 and were completely replaced by B.617.2 (Delta) by July 2021 (Supplementary Figure 4). Due to the short follow-up period after emergence of Delta, our study findings should be considered preliminary. Finally, our data on the mild nature of post-vaccine infections and variant distribution are derived from a young and healthy population of HCP and cannot be generalized to other populations in whom vaccines may be less effective.

In summary, our study shows high vaccine effectiveness rates against multiple VOC/ VOI’s circulating in the New York region in the early part of 2021 with a moderate decline in VE since July 2021, when the Delta variant dominated. Despite the reduction in VE, the COVID-19 mRNA vaccines-maintained protection against severe disease. Our findings should encourage further vaccine uptake and inform the booster strategy for US HCP. Finally, concerted efforts for genomic surveillance of SARS CoV-2 infections after immunization are essential to stay ahead of current and future variants that may threaten vaccine protection.

Supplementary Data

Supplementary materials are available at Clinical Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.

Notes

Financial support. This work was supported by the Memorial Sloan Kettering Cancer Center core grant (grant number P30 CA008748), the Burroughs Wellcome Fund Investigator in the Pathogenesis of Infectious Diseases Award (T. M. H.), the Jack and Dorothy Byrne Family Fund (T. M. H., N. E. B., M. K.), Pew Biomedical Scholar (M. Ł.), CRIPT (Center for Research on Influenza Pathogenesis and Transmission) (M. Ł.), National Institute of Allergy and Infectious Diseases (NIAID) Center of Excellence for Influenza Research and Response (M. Ł.), Deutsche Forschungsgemeinschaft (D. R., M. L.), Department of Medicine, Memorial Sloan Kettering Cancer Center, and Weill Cornell Medicine.

Potential conflicts of interest. K. W. declares stock ownership in Moderna, Pfizer, and Johnson & Johnson. B. G. has received support from Pershing Square Foundation for this work. B. G. has received consulting fees from Darwin Health, Merck, PMV Pharma and Rome Therapeutics as well as honoraria from Merck, Bristol Meyers Squibb, and Chugai Pharmaceuticals outside the scope of this work. S. F. has received payment or honoraria from Amgen, GSK, Daiichi, Astra Zeneca, G1, Coherus, Regeneron outside the scope of this work. T. M. H. has served on the Scientific Advisory Board of Boerhinger Ingelheim. N. E. B. reports grants from GenMark Dx (Clinical Trial Research Grant), personal fees from Roche Diagnostics (Scientific Advisory board), outside the submitted work.

All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.