key: cord-0336791-scf1kbxk
authors: Iliaki, E.; Lan, F.-Y.; Christophi, C. A.; Guidotti, G.; Jobrack, A. D.; Buley, J.; Nathan, N.; Osgood, R.; Bruno-Murtha, L. A.; Kales, S. N.
title: COVID-19 Vaccine Efficacy in a Diverse Urban Healthcare Worker Population
date: 2021-09-06
journal: nan
DOI: 10.1101/2021.09.02.21263038
sha: e341d087a60e37f60bbb1351ca8d6a399cc5a759
doc_id: 336791
cord_uid: scf1kbxk

Objective: To investigate COVID-19 vaccine efficacy (VE) among healthcare workers (HCWs) in an ethnically diverse community healthcare system, during its initial immunization campaign. Methods: HCWs of the system were retrospectively included from the beginning of a COVID-19 vaccination program (December 16, 2020) until March 31, 2021. Those with a prior COVID-19 infection before December 15 were excluded. The Occupational Health department of the system ran a COVID-19 screening and testing referral program for workers, consistently throughout the study period. A master database had been established and updated comprising of the demographics, COVID-19 PCR assays, and vaccinations of each HCW. Andersen-Gill extension of the Cox models were built to estimate the VE of fully/partially vaccinated person-days at risk. Results: Among the 4317 eligible HCWs, 3249 (75%) received any vaccination during the study period. Vaccinated HCWs were older, less likely to be Black/African American, Hispanic/Latino or identify as two or more races, and more likely to be medical providers. After adjusting for age, sex, race, and the statewide background incidence at the time of vaccination, we observed a VE of 80.2% (95% CI: 57.5-90.8%) for [greater double equals]14 days after the first dose of Pfizer/Moderna, and 95.5% (95% CI: 88.2-98.3%) among those fully vaccinated (i.e. [greater double equals]14 days after the second dose of Pfizer/Moderna or the single dose of J&J/Janssen). Conclusion: COVID-19 vaccine effectiveness in the real world is promising, and these data in concert with culturally appropriate may decrease vaccine hesitancy.

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The copyright holder for this this version posted September 6, 2021. ; https://doi.org/10.1101/2021.09.02.21263038 doi: medRxiv preprint dose of Pfizer/Moderna, and 95.5% (95% CI: 88.2-98.3%) among those fully vaccinated (i.e.

≧14 days after the second dose of Pfizer/Moderna or the single dose of J&J/Janssen).

Conclusion: COVID-19 vaccine effectiveness in the real world is promising, and these data in concert with culturally appropriate may decrease vaccine hesitancy.

. CC-BY-ND 4.0 International license It is made available under a perpetuity.

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

The copyright holder for this this version posted September 6, 2021. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

Healthcare workers (HCWs) have been essential workers in the fight against the SARS-CoV-2 (the virus causing COVID-19) pandemic. 1 Due to close contact with patients and coworkers, healthcare workers have been at risk for COVID-19, and some have suffered from serious illness. [2] [3] [4] [5] [6] Apart from workplace exposures, other sociodemographic risk factors for COVID-19 infection include race/ethnicity and incidence in the community of the employee's residence. 5, 7 Although universal masking and other personal protective equipment (PPE) offer some protection, 8,9 COVID-19 vaccines show the most promise for preventing SARS-CoV-2 among HCWs. 10 Vaccine efficacy (VE) in the clinical trials was approximately 95% for fully immunized persons with both the Pfizer-BioNTech and Moderna mRNA vaccines 11,12 and 66% for the J&J/Janssen vaccine. 13 Real world data on vaccine effectiveness in the US have emerged from healthcare populations in large academic hospital systems showing encouraging results, including a study by the CDC team in 8 US locations enrolled in a longitudinal program, 14 and a 90% vaccine effectiveness in the Mayo Clinic system amongst others. [15] [16] [17] However, specific data on vaccine effectiveness from urban hospital settings with diverse employee populations are lacking, and most studies have not controlled for . CC-BY-ND 4.0 International license It is made available under a perpetuity.

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

The copyright holder for this this version posted September 6, 2021. ; https://doi.org/10.1101/2021.09.02.21263038 doi: medRxiv preprint demographics including race and background community COVID-19 incidence, which have been demonstrated to be COVID-19 risk factors among HCWs. Our demographically diverse workforce is representative of its surrounding community, and many of our employees reside in communities that were disproportionately affected by COVID-19. 18 Therefore, we analyzed employee records at our socio-demographically diverse community healthcare system for COVID-19 vaccination and molecular-testing-confirmed cases. Our analyses accounted for prior COVID-19 infection and controlled for age, sex, race and background rate of COVID-19 in the state during the study period.

The active serving (as of March 31, 2021) HCWs of a public, community-based healthcare organization in the Greater Boston area of Massachusetts, USA older than 18 years of age were studied retrospectively. As described previously, 19 the occupational health service of the organization implemented a staff "COVID-19 hotline" system on March 9, 2020 for HCW-COVID-19-related concerns; electronically documented clinical information;

and coordinated testing, result communication and return to work. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint In addition, the Occupational Health department coordinated periodic asymptomatic voluntary screening testing for those employees working with high risk-populations, including geriatrics, inpatient psychiatry, and those visiting congregate care settings.

Mandatory weekly screenings of employees visiting/working in long-term care facilities and home healthcare settings began on July 2, 2020 and included 107 employees.

Masking was obligatory since March 26, 2020, and patient-facing staff wore eye protection in addition to appropriate medical masking, as well as gowns for contact with known COVID-19 positive patients. Common spaces and break rooms were adjusted to accommodate for social distancing. Public mask mandates were in effect in all of Massachusetts during the present study period. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted September 6, 2021. ; https://doi.org/10.1101/2021.09.02.21263038 doi: medRxiv preprint additional town hall was presented on February 28, 2021 by a multi-racial and multi-ethnic panel to further promote vaccine information. A warning about the risk of vaccine induced thrombotic thrombocytopenia from the J&J/Janssen was communicated to our employees on April 13, 2021. Moreover, several additional focus-group discussions in different languages were held to further increase vaccine uptake.

Occupational health vaccine administration records were matched against a human resources roster of active employees of the healthcare organization to create a unified database including demographics, vaccination details, and SARS-CoV2 infection history.

We obtained PCR cycle threshold (CT) values on all positive samples run on the Hologic Panther Fusion system utilizing the Aptima SARS-CoV-2 PCR assay from immunized HCWs, and the samples were sent to the Commonwealth of Massachusetts laboratory for whole genome sequencing to potentially identify variants of concern after approval by the State epidemiologist. Employees with breakthrough infections had follow up by our Occupational health medical staff via telephonic interviews following the same protocol that we use for COVID-19 infected employees which includes recording dates of . CC-BY-ND 4.0 International license It is made available under a perpetuity.

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The copyright holder for this this version posted September 6, 2021. ; https://doi.org/10.1101/2021.09.02.21263038 doi: medRxiv preprint symptoms, potential exposures, types and severity of symptoms, employee risk factors, vaccine dates and type as well as contact investigation when indicated.

HCWs with a documented history of COVID-19 infection prior to December 15, 2020 were excluded from the main analyses. First, we compared the characteristics between the HCWs having received any vaccination by March 31, 2021 versus those that did not, using the chi-square test of independence for categorical variables, or the t-test for continuous variables, after checking for normality of the distribution. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted September 6, 2021. ; https://doi.org/10.1101/2021.09.02.21263038 doi: medRxiv preprint vaccinated" -person-days over 14 days after the 2 nd dose; or person-days over 14 days after the single dose (for those receiving J&J/Janssen).

For each category, we counted the number of COVID-19 infections and calculated the crude incidence rate per 10,000 person-days. Kaplan-Meier curves were used to visualize person-days of infection-free survival across the exposure categories. Since a HCW could contribute to person-days in multiple categories, we built an Andersen-Gill extension of the Cox proportional hazards models to account for correlated data, 14 and further adjusted for potential confounders including age, sex, race, and the Massachusetts statewide 7-day average of new cases 20 on the date of the first vaccine dose. The VE was calculated as 100% × (1−hazard ratio), and 95% confidence intervals (95% CIs) were presented along with the point estimates. Statistical analyses were performed using the SAS software version 9.4 (SAS Inc, Cary, NC, USA) and the R software (version 3.6.3). All P values presented are two-tailed and a P <.05 was considered statistically significant.

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is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint Figure 1 ). During the study period, the statewide 7-day averaged incidence rate fell from 3,257 cases per day on the date of start to the to 1,563 at the end of the study.

Using the Andersen-Gill extension of the Cox proportional hazards model (adjusted for age, sex, race, and the Massachusetts statewide 7-day average of new cases), we observed an is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint Figure 1 ).

During the study period, there were six breakthrough infections among fully vaccinated personnel. None of these employees required hospitalization and symptoms were mild for five and moderate for one. All but one were due to household exposure to family members.

One had an immunocompromising condition. Two of the six had a CT value above 30. The state lab was not able to isolate any viral material for one of the six, raising suspicion of a false positive. None of the other five samples sent for genomic sequencing revealed any variants of concern.

Our study suggests a very high, pre-Delta variant vaccine effectiveness in the HCW population of a university-affiliated urban healthcare system, with an estimated adjusted VE is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted September 6, 2021. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted September 6, 2021. ; https://doi.org/10.1101/2021.09.02.21263038 doi: medRxiv preprint It is worth noting that we observed that in the two weeks after the first vaccination the adjusted VE is very small (28%), likely reflecting the time period needed to build immune response. Although VE in our data set increases 14 days after the first dose to 80.2%, which is mirrored in the findings of other US HCW studies, 14, 17, 22 it is important to highlight that the second vaccine dose seems essential to increase the strength and likely the durability of the immune response. This is supported by data on the new delta variant from the UK that clearly show that there is a reduction in VE of 15-20% after a receipt of only a single vaccine dose. 33 Our study was conducted in an ethnically diverse population (non-white employees represented 44% of our employee population), where vaccination uptake for employees identifying as Black/African American was only 54%, which is much lower than white non-Hispanic employees (83%). This large difference in vaccine hesitancy/acceptance is a serious issue that merits further study and intervention. Out of the five studies in healthcare workers in the US within similar study period, 21 only 3 report adequate data on employee race. 14, 17, 34 HEROES-RECOVER is a network of longitudinal cohorts in eight locations (Phoenix, Tucson, and other areas in Arizona; Miami, Florida; Duluth, Minnesota; Portland, Oregon;

Temple, Texas; and Salt Lake City, Utah) that includes healthcare personnel, first-responders, and other essential frontline workers. They report a higher vaccine acceptance on employees is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted September 6, 2021. ; https://doi.org/10.1101/2021.09.02.21263038 doi: medRxiv preprint identifying as non-White for race than ours (68%) but only a small proportion of participants (14%) were non-white, 14 On the other hand, our vaccine acceptance within the healthcare system was more than double that of citizens identifying as Black in the Commonwealth of MA-only 22% had received at least one COVID-19 vaccination as of March 30, 2021. 35 The reasons for differential racial vaccine hesitancy/acceptance rates are most likely socioeconomic. 36 This is consistent with our finding that clinical providers with generally higher socioeconomic status had higher vaccination rates (89%) when compared to non-provider HCWs (73%). These data support greater education and outreach efforts be focused on non-white and nonprovider groups.

We had few breakthrough infections during the study period (albeit is was conducted prior to the arrival of delta in Massachusetts), with the majority (five out of six) cases being . CC-BY-ND 4.0 International license It is made available under a perpetuity.

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The copyright holder for this this version posted September 6, 2021. ; https://doi.org/10.1101/2021.09.02.21263038 doi: medRxiv preprint very mild and none resulting in hospitalizations or death. No variants of concern were discovered amongst the samples that were genotyped.

Our study has several strengths including that other than age and gender-we adjusted for race/ethnicity and 7-day incidence in MA at the time of vaccination to account for the dropping background rate of COVID-19 during the study period. Our population is multiethnic and 44% non-white which provides a great lens into communities with such makeup and allows us to draw better conclusions about such populations which are often under-represented in vaccine trials. It is worth noting that of the five studies in healthcare populations in the US, adequate race/ethnicity data are reported only in three. To study and address this phenomenon better it is imperative that data on race and ethnicity is gathered.

Limitations include the fact that this was not a randomised clinical trial and may be subject to biases and confounders that could skew the results. For example, vaccinated individuals may take more precautions due to being more health-conscious, but conversely may take fewer precautions due to perceived vaccination-induced protection. Thus, we do not expect any significant influence on our results. The infection rates decreased during the study period and may have potentiated the vaccine effectiveness, although we controlled for the 7day MA infection rate. Since we do not conduct regular surveillance of the entire HCW is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted September 6, 2021. ; https://doi.org/10.1101/2021.09.02.21263038 doi: medRxiv preprint population, there may have been additional asymptomatic breakthrough infections.

Nonetheless, no asymptomatic cases were detected for the subset of HCW participating in surveillance testing, and there were no clusters of employee infections connected to non fully vaccinated individuals since the vaccination program started until the end of the study. This points to the fact that even if there was forward transmission, this was largely asymptomatic and non-consequential.

Vaccination of HCWs is safest and effective and real-world protection during the study period among an ethnically diverse population was very similar (about 95%) to that achieved in clinical trials. We did observe a disparity with lower vaccine acceptance among non-white employees and those who are not medical providers. Efforts to develop culturally appropriate educational outreach to involve persons of different ethnicities and different healthcare roles should be explored to decrease vaccine hesitancy. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted September 6, 2021. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted September 6, 2021. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted September 6, 2021. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted September 6, 2021. ; https://doi.org/10.1101/2021.09.02.21263038 doi: medRxiv preprint

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It is made available under a perpetuity.is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprintThe copyright holder for this this version posted September 6, 2021. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprintThe copyright holder for this this version posted September 6, 2021. ; https://doi.org/10.1101/2021.09.02.21263038 doi: medRxiv preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprintThe copyright holder for this this version posted September 6, 2021. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprintThe copyright holder for this this version posted September 6, 2021. ; https://doi.org/10.1101/2021.09.02.21263038 doi: medRxiv preprint Vaccine effectiveness (95% CI) derived from the Andersen-Gill extension of the Cox proportional hazards model a Adjust for age, sex, race, and the Massachusetts statewide 7-day average of new cases at the date for the first vaccine dose. Those with the race of "American Indian or Alaska Native", "Hawaiian or Pacific Islander", or "Two or More" were pooled into one level "other race". is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprintThe copyright holder for this this version posted September 6, 2021. ; https://doi.org/10.1101/2021.09.02.21263038 doi: medRxiv preprint