Abstract
Background
Belief that vaccination is not needed for individuals with prior infection contributes to coronavirus disease 2019 (COVID-19) vaccine hesitancy. Among individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) before vaccines became available, we determined whether vaccinated individuals had reduced odds of reinfection.
Methods
We conducted a case-control study among adult New York City residents who tested positive for SARS-CoV-2 infection in 2020 and had not died or tested positive again >90 days after an initial positive test as of 1 July 2021. Case patients with reinfection during July 2021–November 2021 and controls with no reinfection were matched (1:3) on age, sex, timing of initial positive test in 2020, and neighborhood poverty level. Matched odds ratios (mORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression.
Results
Of 349 827 eligible adults, 2583 were reinfected during July 2021–November 2021. Of 2401 with complete matching criteria data, 1102 (45.9%) were known to be symptomatic for COVID-19-like illness, and 96 (4.0%) were hospitalized. Unvaccinated individuals, compared with individuals fully vaccinated within the prior 90 days, had elevated odds of reinfection (mOR, 3.21; 95% CI, 2.70 to 3.82), of symptomatic reinfection (mOR, 2.97; 95% CI, 2.31 to 3.83), and of reinfection with hospitalization (mOR, 2.09; 95% CI, .91 to 4.79).
Conclusions
Vaccination reduced odds of reinfections when the Delta variant predominated. Further studies should assess risk of severe outcomes among reinfected persons as new variants emerge, infection- and vaccine-induced immunity wanes, and booster doses are administered.
Keywords: SARS-CoV-2, COVID-19, Delta variant, reinfection, vaccination
Among New York City adults with severe acute respiratory syndrome coronavirus 2 infection diagnosed in 2020, unvaccinated individuals, compared with individuals fully vaccinated in the past 90 days, had 3.21 times the odds of reinfection and 2.09 times the odds of hospitalization when the Delta variant predominated.
Graphical Abstract
Graphical Abstract.
The first cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) were detected in New York City (NYC) in February 2020 [1, 2]. NYC quickly became a pandemic epicenter, with daily case counts exceeding 6000 [2]. By 31 December 2020, 398 969 individuals had tested positive for SARS-CoV-2 infection among approximately 7.1 million adult NYC residents [2], and an unknown number of infected persons were never tested due to inability to access care and limited initial testing availability [2, 3].
On 14 December 2020, a NYC healthcare worker received the first COVID-19 vaccine dose administered under phase 1 of New York State’s Vaccine Distribution Plan [4]. Subsequently, eligibility and availability in NYC expanded for the 3 COVID-19 vaccines authorized or approved in the United States, that is, BNT162b2 from Pfizer-BioNTech, mRNA-1273 from Moderna, and Ad26.COV2 from Janssen (Johnson & Johnson). All 3 vaccines are highly effective at preventing SARS-CoV-2 infection and severe outcomes, including hospitalization and death, and serious adverse events after vaccination are rare [5–11].
Increasing vaccination rates became the core strategy to enable NYC’s reopening, including mandates for healthcare workers [12] and city employees [13] and the “Key to NYC” program that required vaccination proof for indoor activities, such as dining and entertainment [14]. Despite strong evidence of COVID-19 vaccine safety and effectiveness and vaccination mandates, 15% of NYC adults were unvaccinated as of 19 October 2021 [2]. A national survey conducted in June 2020 before any COVID-19 vaccine was available found that 12% of respondents who anticipated rejecting vaccination cited the belief that they were already immune from prior infection [15]. According to the NYC Health Opinion Poll in June 2021 of NYC adults who were unvaccinated and did not intend to or were unsure if they would get vaccinated in the future, one-quarter reported that they did not think they needed a COVID-19 vaccine because of immunity from prior infection (Sarah Dumas, NYC Department of Health and Mental Hygiene [DOHMH], unpublished data, 2021) (Estimates were potentially unreliable [relative standard error >30% or 95% confidence interval half-width >10] and should be interpreted with caution). Half were concerned that COVID-19 vaccines might not protect people against new variants (ibid.).
Delta (B.1.617.2 and AY lineages) was classified as a variant of concern by the World Health Organization in May 2021 [16]. Given its high transmissibility, Delta constituted approximately one-third of sequenced cases among NYC residents as of mid-June 2021, half of sequenced cases as of early July, and nearly all cases (97%) by late July through November, after which Omicron emerged [2]. Modest reductions in COVID-19 vaccine effectiveness (VE) against symptomatic disease with the Delta variant compared with the Alpha variant have been noted [9, 17, 18].
Cavanaugh et al conducted a case-control study of the association between vaccination and SARS-CoV-2 reinfection in Kentucky during May 2021–June 2021 among persons who tested positive for SARS-CoV-2 infection in 2020. Kentucky residents who were unvaccinated had 2.34 times the odds of reinfection compared with those who were fully vaccinated, supporting recommendations for COVID-19 vaccination for those with prior SARS-CoV-2 infection [19]. In Health and Human Services Region 4, which includes Kentucky, Delta constituted a minority of sequenced cases through June 2021 [20]. This study was conducted before Delta predominance, potentially limiting its generalizability. VE against reinfection in an urban population while Delta was the dominant variant is unknown.
We aimed to assess VE against reinfection among NYC adult residents who tested positive for SARS-CoV-2 infection in 2020. We assessed the effectiveness of full and partial COVID-19 vaccination, overall and by vaccine manufacturer, against the outcomes of reinfection, symptomatic reinfection, and reinfection with hospitalization during July 2021–November 2021 when the Delta variant predominated.
METHODS
Study Population and Data Source
The study population consisted of NYC residents who tested positive for SARS-CoV-2 by a molecular or antigen test in 2020 and did not have evidence of reinfection, defined as a positive SARS-CoV-2 molecular or antigen test result >90 days after the initial positive test, before 1 July 2021. We excluded residents of selected congregate settings (ie, nursing homes, adult care facilities, and jails/prisons), individuals aged <18 years as of their initial positive test in 2020, and individuals who died before 1 July 2021.
Demographic, laboratory, hospitalization, and mortality data were collected as part of routine public health surveillance and vital statistics monitoring by DOHMH, as previously described [1]. Symptom status was ascertained by routine interview, for example, for contact tracing. Data were extracted from the DOHMH COVID-19 surveillance database on 30 January 2022.
Cases and Controls
To assess VE against reinfection, we defined case patients as individuals who tested positive for SARS-CoV-2 reinfection during 1 July 2021–30 November 2021. In a subset analysis, we restricted to case patients with symptomatic reinfection to reduce bias from differential ascertainment of asymptomatic infections among populations with frequent testing (eg, as an occupational requirement), which could vary by vaccination status. Symptomatic reinfections were defined as case patients who met the clinical criteria for COVID-19–like illness, per the US Centers for Disease Control and Prevention and Council of State and Territorial Epidemiologists case definition [21]. Controls were selected from the study population as having had no documented reinfection through 30 November 2021.
To assess protection by vaccination against reinfection resulting in severe illness, we further defined case patients as individuals who tested positive for SARS-CoV-2 reinfection during July 2021–November 2021 and who met criteria for COVID-19 hospitalization. COVID-19 hospitalization was defined as a hospitalization within ±14 days of a positive SARS-CoV-2 test or at time of COVID-19 death (which was defined as death within ±30 days of a positive SARS-CoV-2 test or where COVID-19 was listed as a cause of death on the death certificate). Controls for this analysis were selected from the study population as having had either no reinfection through November 2021 or a reinfection during July 2021–November 2021 but no hospitalization or death. We did not separately assess protection by vaccination against reinfection resulting in death because only 9 individuals from the study population who tested positive for SARS-CoV-2 reinfection during July 2021–November 2021 died.
Three controls were matched to each case patient on sex, age within ±3 years, specimen collection date in 2020 of initial positive SARS-CoV-2 test within ±1 week (to control for temporal trends and waning infection-induced immunity), and neighborhood poverty level. Neighborhood poverty (based on census tract of residence as of initial laboratory report in 2020) was defined as the percent of residents with incomes below the federal poverty level, per the American Community Survey 2015–2019 [22]. The controls that matched most closely on age and specimen collection date in 2020 were selected.
Exposure
By matching with the DOHMH Citywide Immunization Registry [23], case patients were assigned a vaccination status based on their reinfection date, defined as the specimen collection date of the first positive test indicating reinfection, and controls were assigned a vaccination status based on the reinfection date of their matched case patient. Individuals were considered fully vaccinated if they received 2 doses of a COVID-19 mRNA vaccine (Pfizer-BioNTech or Moderna) or 1 dose of a viral vector vaccine (Janssen) ≥14 days before the reinfection date. Time between full vaccination and reinfection was categorized as within 0–90 days, 91–180 days, or >180 days. Partially vaccinated individuals received 1 dose of an mRNA vaccine ≥14 days before the reinfection date, and unvaccinated individuals did not receive any vaccine doses ≥14 days before the reinfection date.
Analyses
Matched odds ratios (mORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression to estimate the odds of reinfection, of symptomatic reinfection, and of reinfection with hospitalization by vaccination status, with persons fully vaccinated regardless of timing and within the past 90 days as referents. Odds of reinfection by vaccine manufacturer were also estimated. In addition, VE against reinfection was calculated as 100% × (1 − mOR), with unvaccinated persons as the referent [24]. Case patients with identical matching criteria and their matched controls were pooled to retain more data and increase precision. We assessed potential selection and confounding bias by using a case-control weighted target maximum likelihood estimation method (CCW-TMLE) (Supplementary Material). Statistical analyses were performed using SAS Enterprise Guide, version 7.1 (SAS Institute). This work was deemed public health surveillance that is nonresearch by the DOHMH Institutional Review Board.
RESULTS
Of 432 375 NYC residents who tested positive for SARS-CoV-2 infection in 2020, 349 827 (80.9%) were eligible for analysis of COVID-19 vaccination status and reinfection (Figure 1). Of these, 2583 (0.7%) were reinfected during July 2021–November 2021. These 2583 individuals represented 1.6% of the 157 024 NYC adults who did not reside in congregate settings and tested positive for SARS-CoV-2 infection during this period. Of the 2583 individuals, 2401 (93.0%) had complete data on matching criteria and were included in the analysis; of these, 1102 (45.9%) were symptomatic for COVID-19–like illness. Of the remaining 1299, 445 (34.3%) identified as asymptomatic, 734 (56.5%) had missing symptom information, and 120 (9.2%) had symptoms that did not meet clinical criteria for COVID-19–like illness. Ninety-six (4.0%) case patients were hospitalized; of these, 10 (10.4%) presented to the emergency department (ED) with COVID-19–like illness within ±14 days of specimen collection, suggesting the hospitalization was for COVID-19; 45 (46.9%) presented to the ED without COVID-19–like illness, suggesting SARS-CoV-2 infection was incidental to hospitalization; and 41 (42.7%) were not known to have presented to the ED, indicating unknown reason for hospitalization. Case-patients and matched controls were similar on sex, age, timing of initial positive test in 2020, and neighborhood poverty level (Table 1). Reinfections were most common among females, case patients aged 25–34 years, and case patients who first tested positive for SARS-CoV-2 infection in April 2020 or December 2020. Reinfections and symptomatic reinfections were most common among residents of neighborhoods with low and medium poverty levels, while hospitalized case patients with reinfection most commonly resided in medium and high poverty neighborhoods (Table 1).
Figure 1.
Eligibility for analysis of COVID-19 vaccination status and SARS-CoV-2 reinfection during July 2021–November 2021 among New York City residents with first SARS-CoV-2 infection in 2020. Abbreviations: COVID-19, coronavirus disease 2019; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
Table 1.
Characteristics of Case Patients With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Reinfection During July 2021–November 2021 and Matched Controls Without Reinfection Among New York City Adults With First SARS-CoV-2 Infection in 2020
| Characteristic | Reinfection vs No Reinfection | Symptomatic Reinfection vs No Reinfection | Reinfection With Hospitalization vs No Reinfectiona | |||
|---|---|---|---|---|---|---|
| Cases, N (%) | Controls, N (%) | Cases, N (%) | Controls, N (%) | Cases, N (%) | Controls, N (%) | |
| Total | 2401 | 7203 | 1102 | 3306 | 96 | 288 |
| Sex | ||||||
| ȃFemale | 1327 (55.3) | 3981 (55.3) | 625 (56.7) | 1875 (56.7) | 50 (52.1) | 150 (52.1) |
| Age group, yb | ||||||
| ȃ18–24 | 309 (12.9) | 922 (12.8) | 152 (13.8) | 454 (13.7) | 5 (5.2) | 16 (5.6) |
| ȃ25–34 | 829 (34.5) | 2490 (34.6) | 398 (36.1) | 1196 (36.2) | 18 (18.8) | 52 (18.1) |
| ȃ35–44 | 490 (20.4) | 1467 (20.4) | 230 (20.9) | 687 (20.8) | 14 (14.6) | 43 (14.9) |
| ȃ45–54 | 314 (13.1) | 947 (13.1) | 142 (12.9) | 429 (13.0) | 11 (11.5) | 33 (11.5) |
| ȃ55–64 | 267 (11.1) | 809 (11.2) | 112 (10.2) | 342 (10.3) | 16 (16.7) | 48 (16.7) |
| ȃ65–74 | 140 (5.8) | 413 (5.7) | 48 (4.4) | 136 (4.1) | 21 (21.9) | 63 (21.9) |
| ȃ75+ | 52 (2.2) | 155 (2.2) | 20 (1.8) | 62 (1.9) | 11 (11.5) | 33 (11.5) |
| Census tract–based poverty levelb | ||||||
| ȃLow | 773 (32.2) | 2319 (32.2) | 373 (33.8) | 1119 (33.8) | 16 (16.7) | 48 (16.7) |
| ȃMedium | 748 (31.2) | 2244 (31.2) | 348 (31.6) | 1044 (31.6) | 38 (39.6) | 114 (39.6) |
| ȃHigh | 450 (18.7) | 1350 (18.7) | 203 (18.4) | 609 (18.4) | 25 (26.0) | 75 (26.0) |
| ȃVery high | 430 (17.9) | 1290 (17.9) | 178 (16.2) | 534 (16.2) | 17 (17.7) | 51 (17.7) |
| Month of initial positive SARS-CoV-2 test (2020) | ||||||
| ȃMarch | 394 (16.4) | 1184 (16.4) | 171 (15.5) | 513 (15.5) | 16 (16.7) | 48 (16.7) |
| ȃApril | 487 (20.3) | 1460 (20.3) | 212 (19.2) | 637 (19.3) | 21 (21.9) | 63 (21.9) |
| ȃMay | 127 (5.3) | 381 (5.3) | 57 (5.2) | 170 (5.1) | 5 (5.2) | 15 (5.2) |
| ȃJune | 45 (1.9) | 135 (1.9) | 16 (1.5) | 48 (1.5) | 2 (2.1) | 6 (2.1) |
| ȃJuly | 81 (3.4) | 239 (3.3) | 42 (3.8) | 126 (3.8) | 2 (2.1) | 6 (2.1) |
| ȃAugust | 43 (1.8) | 130 (1.8) | 26 (2.4) | 77 (2.3) | 2 (2.1) | 6 (2.1) |
| ȃSeptember | 89 (3.7) | 268 (3.7) | 33 (3.0) | 102 (3.1) | 2 (2.1) | 6 (2.1) |
| ȃOctober | 116 (4.8) | 346 (4.8) | 55 (5.0) | 162 (4.9) | 5 (5.2) | 15 (5.2) |
| ȃNovember | 366 (15.2) | 1101 (15.3) | 168 (15.2) | 505 (15.3) | 11 (11.5) | 33 (11.5) |
| ȃDecember | 653 (27.2) | 1959 (27.2) | 322 (29.2) | 966 (29.2) | 30 (31.3) | 90 (31.3) |
| Vaccination statusc | ||||||
| ȃNot vaccinatedd | 1436 (59.8) | 2940 (40.8) | 632 (57.4) | 1385 (41.9) | 40 (41.7) | 111 (38.5) |
| ȃPartially vaccinated | 83 (3.5) | 368 (5.1) | 29 (2.6) | 163 (4.9) | 9 (9.4) | 8 (2.8) |
| ȃFully vaccinated | 882 (36.7) | 3895 (54.1) | 441 (40.0) | 1758 (53.2) | 47 (49.0) | 169 (58.7) |
| Vaccine manufacturere | ||||||
| ȃNot vaccinated | 1436 (61.9) | 2940 (43.0) | 632 (58.9) | 1385 (44.1) | 40 (46.0) | 111 (39.6) |
| ȃFully vaccinated with Pfizer | 490 (21.1) | 2236 (32.7) | 244 (22.7) | 1024 (32.6) | 27 (31.0) | 87 (31.1) |
| ȃFully vaccinated with Moderna | 311 (13.4) | 1307 (19.1) | 153 (14.3) | 566 (18.0) | 16 (18.4) | 73 (26.1) |
| ȃFully vaccinated with Janssen | 81 (3.5) | 352 (5.1) | 44 (4.1) | 168 (5.3) | 4 (4.6) | 9 (3.2) |
| Days from fully vaccinatede to reference datef | ||||||
| ȃ0–90 | 186 (21.1) | 1153 (29.6) | 86 (19.5) | 533 (30.3) | 11 (23.4) | 56 (33.1) |
| ȃ91–180 | 430 (48.8) | 1916 (49.2) | 217 (49.2) | 862 (49.0) | 24 (51.1) | 82 (48.5) |
| ȃ>180 | 266 (30.2) | 826 (21.2) | 138 (31.3) | 363 (20.6) | 12 (25.5) | 31 (18.3) |
| Month tested positive for SARS-CoV-2 reinfection (2021) | ||||||
| ȃJuly | 304 (12.7) | – | 155 (14.1) | – | 20 (20.8) | – |
| ȃAugust | 686 (28.6) | – | 325 (29.5) | – | 36 (37.5) | – |
| ȃSeptember | 582 (24.2) | – | 251 (22.8) | – | 16 (16.7) | – |
| ȃOctober | 425 (17.7) | – | 186 (16.9) | – | 14 (14.6) | – |
| ȃNovember | 404 (16.8) | – | 185 (16.8) | – | 10 (10.4) | – |
| Severity of initial infection | ||||||
| ȃHospitalized | 186 (7.7) | 690 (9.6) | 70 (6.4) | 286 (8.7) | 41 (42.7) | 43 (14.9) |
Abbreviation: SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
For this case definition, matched controls were selected from the study population as having had either no reinfection through 30 November 2021 or a reinfection during July 2021–November 2021 but no hospitalization or death. Four selected controls had a nonhospitalized reinfection.
Age and census tract of residence as of initial positive SARS-CoV-2 test in 2020. Low poverty level defined as <10% of residents below the federal poverty level, medium as 10% to <20%, high as 20% to <30%, and very high as ≥30%.
Individuals were considered fully vaccinated if they received 2 doses of a coronavirus disease 2019 mRNA vaccine (Pfizer-BioNTech or Moderna) or 1 dose of a viral vector vaccine (Janssen) ≥14 days before the reinfection date. Partially vaccinated individuals received 1 dose of an mRNA vaccine ≥14 days before the reinfection date, and unvaccinated individuals did not receive any vaccine doses ≥14 days before the reinfection date.
Some individuals classified as unvaccinated received 1 dose of vaccine <14 days before the reinfection date: 42 case patients with reinfection and 127 controls, 15 case patients with symptomatic reinfection and 54 controls, and 1 case patient with reinfection with hospitalization and 5 controls. Some individuals classified as partially vaccinated received a second dose of an mRNA vaccine <14 days before the reinfection date: 23 case patients with reinfection and 99 controls, 6 case patients with symptomatic reinfection and 48 controls, and 1 case patient with reinfection with hospitalization and 2 controls.
Partially vaccinated persons excluded.
For case patients, the reference date was the specimen collection date of the first positive test indicating SARS-CoV-2 reinfection in 2021. For controls, the reference date was the reinfection date of their matched case patient.
NYC adult residents who initially tested positive for SARS-CoV-2 infection in 2020 and remained unvaccinated had elevated odds of reinfection (mOR, 2.32; 95% CI, 2.09 to 2.57) and of symptomatic reinfection (mOR, 1.92; 95% CI, 1.66 to 2.23) during July 2021–November 2021 compared with those who were fully vaccinated (Table 2). Unvaccinated individuals also had higher, but not statistically significantly higher, odds of reinfection with hospitalization (mOR, 1.39; 95% CI, .82 to 2.36). In other words, with unvaccinated persons as the referent, VE for full vaccination against reinfection was 57% (95% CI, 52% to 61%), against symptomatic reinfection VE was 48% (95% CI, 40% to 55%), and against reinfection with hospitalization VE was 28% (95% CI, –22% to 58%). Findings were robust to reanalysis using CCW-TMLE, suggesting negligible selection and confounding bias (Supplementary Material).
Table 2.
Associations of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Reinfection During July 2021–November 2021 With Coronavirus Disease 2019 Vaccination Status and Vaccine Manufacturer Among New York City Adults With First SARS-CoV-2 Infection in 2020
| Vaccination Status | Reinfection vs No Reinfection | Symptomatic Reinfection vs No Reinfection | Reinfection With Hospitalization vs No Reinfectiona | |||
|---|---|---|---|---|---|---|
| mOR (95% CI) | P Value | mOR (95% CI) | P Value | mOR (95% CI) | P Value | |
| Fully vaccinated as referent | ||||||
| ȃNot vaccinated | 2.32 (2.09–2.57) | <.0001 | 1.92 (1.66–2.23) | <.0001 | 1.39 (.82–2.36) | .22 |
| ȃPartially vaccinated | 1.04 (.80–1.33) | .79 | 0.71 (.47–1.08) | .11 | 4.30 (1.53–12.15) | .006 |
| Fully vaccinated within 90 days as referent | ||||||
| ȃNot vaccinated | 3.21 (2.70–3.82) | <.0001 | 2.97 (2.31–3.83) | <.0001 | 2.09 (.91–4.79) | .08 |
| ȃPartially vaccinated | 1.45 (1.08–1.93) | .01 | 1.12 (.70–1.77) | .64 | 6.33 (1.91–21.00) | .003 |
| ȃFully vaccinated 91–180 days prior | 1.38 (1.14–1.68) | .0009 | 2.50 (1.81–3.46) | .002 | 1.68 (.68–4.10) | .26 |
| ȃFully vaccinated >180 days prior | 2.02 (1.61–2.52) | <.0001 | 2.97 (2.31–3.83) | <.0001 | 2.46 (.76–7.94) | .13 |
| Not vaccinated as referent | ||||||
| ȃPartially vaccinated | 0.45 (.35–.57) | <.0001 | 0.37 (.25–.56) | <.0001 | 3.10 (1.11–8.64) | .03 |
| ȃFully vaccinated | 0.43 (.39–.48) | <.0001 | 0.52 (.45–.60) | <.0001 | 0.72 (.42–1.22) | .22 |
| ȃFully vaccinated within 90 days | 0.31 (.26–.37) | <.0001 | 0.34 (.26–.43) | <.0001 | 0.48 (.21–1.10) | .08 |
| ȃFully vaccinated 91–180 days prior | 0.43 (.38–.49) | <.0001 | 0.52 (.44–.63) | <.0001 | 0.80 (.44–1.47) | .48 |
| ȃFully vaccinated >180 days prior | 0.63 (.53–.74) | <.0001 | 0.84 (.66–1.07) | .16 | 1.18 (.45–3.05) | .75 |
| Vaccine manufacturer, not vaccinated as referent | ||||||
| ȃFully vaccinated with Pfizer | 0.42 (.37–.48) | <.0001 | 0.50 (.42–.60) | <.0001 | 0.82 (.45–1.49) | .51 |
| ȃFully vaccinated with Moderna | 0.46 (.39–.53) | <.0001 | 0.57 (.46–.70) | <.0001 | 0.58 (.28–1.17) | .13 |
| ȃVaccinated with Janssen | 0.44 (.34–.57) | <.0001 | 0.55 (.39–.78) | .0008 | 1.09 (.32–3.73) | .89 |
Abbreviations: CI, confidence interval; mOR, matched odds ratio.
For this case definition, matched controls were selected from the study population as having had either no reinfection through 30 November 2021 or a reinfection during July 2021–November 2021 but no hospitalization or death. Four selected controls had a nonhospitalized reinfection.
Restricting the referent to individuals who were recently fully vaccinated (within 90 days of the reference date) increased the magnitude of these effects, as those who were unvaccinated had higher odds of reinfection (mOR, 3.21; 95% CI, 2.70 to 3.82), of symptomatic reinfection (mOR, 2.97; 95% CI, 2.31 to 3.83), and of reinfection with hospitalization (mOR, 2.09; 95% CI, .91 to 4.79; P = .08; Table 2). With unvaccinated persons as the referent, the strongest protective effect was observed for those fully vaccinated within the prior 90 days (mOR, 0.31; 95% CI, .26 to .37). Protective effects weakened for those fully vaccinated 91–180 days prior (mOR, 0.43; 95% CI, .38 to .49) and >180 days prior (mOR, 0.63; 95% CI, .53 to .74). Similar waning trends were observed for symptomatic reinfection and reinfection with hospitalization (Table 2).
Few partially vaccinated persons were included in the analysis (Table 1). Compared with NYC residents who tested positive for SARS-CoV-2 infection in 2020 and were fully vaccinated, those who were partially vaccinated had 1.04 (95% CI, .80 to 1.33) times the odds of reinfection, that is, VE for partial vaccination against reinfection was 55% (95% CI, 43% to 65%; Table 2).
With unvaccinated persons as the referent, persons fully vaccinated with vaccines from any manufacturer had reduced odds of reinfection (mOR point estimates similar by manufacturer, range: 0.42–0.46, ie, VE ≈ 56%), as well as of symptomatic reinfection (mOR point estimates, range: 0.50–0.57, ie, VE range, 43%–50%; Table 2).
DISCUSSION
Among adult NYC residents who previously tested positive for SARS-CoV-2 infection in 2020, unvaccinated individuals, compared with those who were fully vaccinated, had 2.32 (95% CI, 2.09 to 2.57) times the odds of reinfection during a period when the Delta variant predominated (July 2021–November 2021). This finding is consistent with that of Cavanaugh et al, who found that among Kentucky residents who tested positive for SARS-CoV-2 infection in 2020, unvaccinated individuals had 2.34 (95% CI, 1.58 to 3.47) times the odds of reinfection during a period before Delta variant predominance (May 2021–June 2021) compared with those who were fully vaccinated [19]. We additionally found that unvaccinated individuals had significantly greater odds of symptomatic reinfection and higher, but not statistically significantly higher, odds of reinfection with hospitalization, particularly compared with individuals recently fully vaccinated. The consistency of the mORs between Kentucky before Delta variant predominance and NYC during Delta variant predominance, as well as evidence of protection against symptomatic reinfection in NYC, supports existing recommendations to vaccinate persons with a prior COVID-19 diagnosis [25]. As previously noted, there were few observations among individuals who were previously infected and were partially vaccinated, limiting our conclusions for this population.
Individuals in this population who were fully vaccinated with any of the 3 vaccines authorized or approved for full or emergency use in the United States were similarly protected against SARS-CoV-2 reinfection. These vaccines are known to be protective against SARS-CoV-2 infection, including against the Delta variant [5, 9]. However, literature on risk of reinfections is limited. Our finding of 28% (95% CI, –22% to 58%) effectiveness of full vaccination against reinfection with hospitalization among previously infected individuals was lower than VE against infection with hospitalization among individuals without a previous infection. This difference in estimates could be attributable to different study populations, in that the benefit of vaccination would be expected to be greater for individuals without prior immunity than for previously infected individuals. Also, some patients who met COVID-19 hospitalization criteria were likely admitted for a reason unrelated to COVID-19 (eg, surgery, labor and delivery, or mental health). This misclassification likely biased estimates of the protective association between vaccination and reinfection with hospitalization toward the null. Full VE against all 3 reinfection outcomes waned with increasing time since vaccination, supporting existing recommendations for booster doses.
There are at least 4 limitations to this study. First, persons who were infected with SARS-CoV-2 in 2020 but who were not tested (eg, due to limited testing availability) could not be included. Thus, our analysis of 2401 first reinfections during July 2021–November 2021 among those initially infected in 2020 is an undercount, reducing sample size and precision of estimates. Because symptom status was missing for half of reinfected individuals, the number of symptomatic reinfections was also an undercount.
Further, our study population was likely biased toward those with more severe illnesses from initial infection (ie, those who were hospitalized and thus eligible to access testing during the first wave of infections). If this selection bias resulted in a population with stronger infection-induced immunity [26], then our VE estimates against reinfection would be conservative and biased toward the null, relative to estimates based on an unobservable study population of all persons infected with SARS-CoV-2 in 2020. Second, some NYC residents were more likely to be repeatedly tested (eg, as an occupational requirement, particularly if unvaccinated), increasing the probability of ascertaining mild initial infections and/or reinfections. Further, if vaccinated persons were less likely to be tested, then given disproportionate ascertainment of reinfections among unvaccinated persons, VE could be overestimated. However, by assessing VE for symptomatic reinfection and for reinfection with hospitalization, we reduced this potential ascertainment bias from discretionary testing for nonclinical reasons.
Third, persons vaccinated outside of New York State and by federal entities were likely misclassified as unvaccinated; however, we expect any such misclassification was nondifferential by outcome status. Further, NYC residents who tested positive for SARS-CoV-2 infection in 2020 and then moved out of jurisdiction and were reinfected could have been misclassified as controls; however, we expect any such misclassification was nondifferential by vaccination status. In addition, some persons with persistent positivity from their first infection in 2020 [27] could have been misclassified as reinfected, although this is unlikely given the minimum 6-month interval between the date of first positive test in 2020 and the study period beginning 1 July 2021 for first possible date of reinfection.
Finally, while we found that vaccines from all 3 manufacturers significantly reduced the odds of reinfection, differences in the timing of vaccine availability in the context of potentially waning infection-induced and vaccine-induced immunity and differences in the health status of recipients made direct comparisons between vaccines difficult. In particular, the Janssen vaccine did not become available until early March 2021 and was prioritized for more vulnerable groups in NYC, such as homebound seniors and the homeless population, given the operational benefit of requiring only 1 dose [28]. Similarly, our finding that VE against reinfection waned with increasing time since vaccination was limited by an inability to adjust for patient characteristics (eg, immunocompromised status) associated with initial vaccination eligibility and timing [29].
In summary, our findings support current vaccine recommendations for people with prior SARS-CoV-2 infection. These results counter the belief that COVID-19 vaccines are unnecessary because of immunity from prior infection or that vaccines developed prior to Delta variant emergence may not have been effective against reinfections while Delta predominated. Among adult NYC residents with documented infection in 2020, a small percentage (0.7%) were reinfected during a 5-month period when Delta predominated. However, unvaccinated individuals had elevated odds of SARS-CoV-2 reinfection and of reinfection with hospitalization compared with those who were fully vaccinated. Vaccines from all 3 manufacturers were similarly and significantly effective against reinfections. Further studies should continue to assess risk of severe outcomes among reinfected persons, particularly as new variants (eg, Omicron) emerge, immunity conferred by prior infection and/or vaccination potentially wanes, and more persons receive booster doses.
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
Acknowledgments. The authors thank all New York City Department of Health and Mental Hygiene (DOHMH) staff serving in the Surveillance and Epidemiology Section and Vaccine Operations Center of the Incident Command System, including Jennifer Baumgartner, Katelynn Devinney, Daniel Bertolino, and Dr Alexandra Ternier for contributions to data management; Dr Corinne Thompson for constructive manuscript review; and Matthew Montesano for contributions to data communication. This article was preprinted at https://www.medrxiv.org/content/10.1101/2021.12.09.21267203v1.
Disclaimer. The findings and conclusions presented here are those of the authors and do not necessarily represent the official position of the DOHMH or the Centers for Disease Control and Prevention (CDC).
Financial support. The authors received no specific funding for this work beyond their usual salaries. Salary support from CDC included A.L.R by NU50CK000517-01-09, S.K.G. by NU90TP922035-03-03, and L.F. by 4021-04Z
Supplementary Material
Contributor Information
Alison Levin-Rector, Bureau of Communicable Disease, New York City Department of Health and Mental Hygiene, Long Island City, New York, USA.
Lauren Firestein, Bureau of Communicable Disease, New York City Department of Health and Mental Hygiene, Long Island City, New York, USA.
Emily McGibbon, Bureau of Communicable Disease, New York City Department of Health and Mental Hygiene, Long Island City, New York, USA.
Jessica Sell, Bureau of Communicable Disease, New York City Department of Health and Mental Hygiene, Long Island City, New York, USA.
Sungwoo Lim, Bureau of Epidemiology Services, New York City Department of Health and Mental Hygiene, Long Island City, New York, USA.
Ellen H Lee, Bureau of Communicable Disease, New York City Department of Health and Mental Hygiene, Long Island City, New York, USA.
Don Weiss, Bureau of Communicable Disease, New York City Department of Health and Mental Hygiene, Long Island City, New York, USA.
Anita Geevarughese, Bureau of Public Health Training and Information Dissemination, New York City Department of Health and Mental Hygiene, Long Island City, New York, USA.
Jane R Zucker, Bureau of Immunization, New York City Department of Health and Mental Hygiene, Long Island City, New York, USA; Immunization Services Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Sharon K Greene, Bureau of Communicable Disease, New York City Department of Health and Mental Hygiene, Long Island City, New York, USA.
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