key: cord-0267819-wl4d97ge
authors: Tobolowsky, F. A.; Waltenburg, M.; Moritz, E. D.; Haile, M.; DaSilva, J. C.; Schuh, A. J.; Thornburg, N. J.; Westbrook, A.; McKay, S. L.; LaVoie, S. P.; Folster, J. M.; Harcourt, J. L.; Tamin, A.; Stumpf, M. M.; Mills, L.; Freeman, B.; Lester, S.; Beshearse, E.; Lecy, K. D.; Brown, L. G.; Fajardo, G.; Negley, J.; McDonald, L. C.; Kutty, P. K.; Brown, A. C.
title: Longitudinal serologic and viral testing post-SARS-CoV-2 infection and post-receipt of mRNA COVID-19 vaccine in a nursing home cohort--Georgia, October 2020-April 2021
date: 2022-01-01
journal: nan
DOI: 10.1101/2021.12.28.21268458
sha: 3804151e4646e5ba10a25896b6075743b658d2c2
doc_id: 267819
cord_uid: wl4d97ge

Importance: There are limited data describing SARS-CoV-2-specific immune responses and their durability following infection and vaccination in nursing home residents. Objective: To evaluate the quantitative titers and durability of binding antibodies detected after SARS-CoV-2 infection and subsequent COVID-19 vaccination. Design: A prospective longitudinal evaluation included nine visits over 150 days; visits included questionnaire administration, blood collection for serology, and paired anterior nasal specimen collection for testing by BinaxNOW COVID-19 Ag Card (BinaxNOW), reverse transcription polymerase chain reaction (RT-PCR), and viral culture. Setting: A nursing home during and after a SARS-CoV-2 outbreak. Participants: 11 consenting SARS-CoV-2-positive nursing home residents. Main Outcomes and Measures: SARS-CoV-2 testing (BinaxNOW, RT-PCR, viral culture); quantitative titers of binding SARS-CoV-2 antibodies post-infection and post-vaccination (beginning after the first dose of the primary series). Results: Of 10 participants with post-infection serology results, 9 (90%) had detectable Pan-Ig, IgG, and IgA antibodies and 8 (80%) had detectable IgM antibodies. At first antibody detection post-infection, two-thirds (6/9, 67%) of participants were RT-PCR-positive but none were culture positive. Ten participants received vaccination; all had detectable Pan-Ig, IgG, and IgA antibodies through their final observation [≤]90 days post-first dose. Post-vaccination geometric means of IgG titers were 10-200-fold higher than post-infection. Conclusions and Relevance: Nursing home residents in this cohort mounted robust immune responses to SARS-CoV-2 post-infection and post-vaccination. The augmented antibody responses post-vaccination are potential indicators of enhanced protection that vaccination may confer on previously infected nursing home residents.

COVID-19 outbreaks in nursing homes have caused significant morbidity and mortality, including 50 740,034 cases and 141,084 deaths in residents as of December 5, 2021 (1) . Although nursing home 51 residents are typically older with multiple comorbidities compared with the general population, 52 preliminary data show they frequently mount an immune response within 15 to 30 days of SARS-CoV-2 53 diagnosis (2, 3). However, the kinetics of SARS-CoV-2-specific binding antibody titers and isotypes that 54 persist beyond the early acute phase of infection are unknown. 55

Vaccination is a key strategy to prevent COVID-19 morbidity and mortality in nursing home 56

The facility began administering the primary series of mRNA COVID-19 vaccines during the 95 evaluation period (4); willing participants were vaccinated between January-February 2021. Timing of 96 vaccination was determined by the facility and timing of receipt of the first vaccine dose varied by 97 participant. CDC visits 6-9 occurred after facility vaccine clinics were initiated. In this evaluation, 98 participants were considered fully vaccinated two weeks after receiving the second dose of the mRNA 99 COVID-19 vaccine. 100

Electronic medical chart abstraction was performed to obtain supplemental information on 101 participants' past medical history, medications, laboratory test results, clinical outcomes, and vaccine 102 administration. Information from questionnaires and chart abstraction were entered into a Research 103

Electronic Data Capture (REDCap) database (15, 16). If visits occurred while a participant was 104 hospitalized, specimens and clinical data were not collected from that participant; however, that 105 participant could choose to continue in the evaluation upon return to the nursing home. 106

Reported COVID-19 symptom status was characterized as asymptomatic or symptomatic, and 107 participants' illnesses were further characterized as mild, moderate, or severe. A participant was 108 asymptomatic if he or she did not report any COVID-19 signs or symptoms in the 14 days before testing 109 positive or during the evaluation period. Mild illness included participants with asymptomatic COVID-19 110 infections and those who reported COVID-19 signs or symptoms without dyspnea or evidence of lower 111 respiratory tract involvement. Moderate illness included participants with signs of lower respiratory 112 disease by clinical assessment or imaging, and severe disease included participants with tachypnea (>30 113 breaths per minute), oxygen saturation <90% (or decrease from baseline over 3% for at least two 114 consecutive values), hospitalization, or death (17). An immunocompromised condition included the 115 following: recent or active malignancy, bone marrow transplant, solid organ transplant, primary or 116 secondary immune deficiency, or the use of oral or intravenous steroids or any immunosuppressant 117 drugs. 118 for use under a CC0 license. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available (which was not certified by peer review) 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 January 1, 2022. ; https://doi.org/10.1101/2021.12.28.21268458 doi: medRxiv preprint Details of specimen collection, BinaxNOW, RT-PCR, and viral culture methods have been 119 described previously (12). Viral culture was conducted on RT-PCR-positive specimens with a cycle 120 threshold (Ct) value <35. Serum specimens were tested for anti-SARS-CoV-2 antibodies using an 121 enzyme-linked immunosorbent assay targeting the extracellular domain of the SARS-CoV-2 spike protein 122 (18). This assay uses anti-pan-immunoglobulin (Ig) secondary antibodies that detect any SARS-CoV-2 123 immunoglobulin isotype, including IgG, IgM, and IgA. Seroconversion was defined as a signal to 124 threshold >1 at a serum dilution of 1:100 for any isotype; seroreversion occurred when a previously 125 seropositive participant became seronegative. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available (which was not certified by peer review) 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 January 1, 2022. ; https://doi.org/10.1101/2021.12.28.21268458 doi: medRxiv preprint

Research Protection Office and IRB review was not required. This work did not receive any non-CDC 142 funding support. 143

Demographic and clinical characteristics 145

Among 127 residents who participated in at least one CDC PPS, 47 (37%) antigen-positive 146 residents were identified; 31 (66%) antigen-positive residents were eligible for enrollment in this 147 longitudinal evaluation, of which 12 (39%) agreed to participate. Eight (67%) participants tested positive 148 by facility testing conducted prior to CDC PPS. One participant died before the second follow-up visit and 149 was excluded from analysis. The median age of the remaining 11 participants was 74 years (range: 37-150 90 years) and seven (64%) were male (Table 1) . Seven (64%) participants were White and four (36%) 151 were Black; no participants reported Hispanic ethnicity. The most common underlying conditions were 152 cardiovascular disease (11, 100%) and diabetes (6, 55%); 10 (91%) participants had ≥3 underlying 153 conditions (Table 1) This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available (which was not certified by peer review) 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 January 1, 2022. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available (which was not certified by peer review) 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 January 1, 2022. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available (which was not certified by peer review) 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 January 1, 2022. ; https://doi.org/10.1101/2021.12.28.21268458 doi: medRxiv preprint antibodies were consistently detected throughout the evaluation period in this nursing home cohort. 210

Furthermore, antibody responses in previously infected participants were augmented after vaccination 211 and were still present throughout the evaluation period. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available (which was not certified by peer review) 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 January 1, 2022. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available (which was not certified by peer review) 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 January 1, 2022. ; https://doi.org/10.1101/2021.12.28.21268458 doi: medRxiv preprint Our evaluation had several limitations. We had a small sample size, preventing statistical 256 comparisons and potentially limiting the generalizability of our findings. Participants enrolled in our 257 evaluation only received the Pfizer-BioNTech COVID-19 Vaccine; therefore, we were unable to describe 258 the impact of vaccination with other products. Some participants were unable to provide blood 259 specimens when requested and most visits occurred only monthly, so we likely missed the exact timing This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available (which was not certified by peer review) 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 January 1, 2022. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available (which was not certified by peer review) 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 January 1, 2022. ; https://doi.org/10.1101/2021.12.28.21268458 doi: medRxiv preprint for use under a CC0 license.

This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available (which was not certified by peer review) 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 January 1, 2022. ; https://doi.org/10.1101/2021.12.28.21268458 doi: medRxiv preprint * Participants were identified among the cohort of nursing home residents if they were medically stable, 295 had decision-making capacity, and provided informed consent after testing SARS-CoV-2-positive using 296 This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available (which was not certified by peer review) 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 January 1, 2022. ; https://doi.org/10.1101/2021.12.28.21268458 doi: medRxiv preprint Table 2 This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available (which was not certified by peer review) 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 January 1, 2022. ; https://doi.org/10.1101/2021.12.28.21268458 doi: medRxiv preprint calculations. Geometric means of IgM titers and ratios were not calculated during 61-90 days because 319 all post-vaccination titers were below the limit of detection. Participant G was not included in the post-320 infection analyses because they did not provide blood specimens during this time period. Participant C 321 was not included in the post-vaccination analyses due to vaccination refusal. This participant's titers 322 ranged from 2437-16977 for Pan-Ig, 4919-7045 for IgG, and 267-710 for IgA during the 90-150 days 323 post-infection; their IgM titers were below the limit of detection during this time period. 324 for use under a CC0 license. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available (which was not certified by peer review) 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 January 1, 2022. ; https://doi.org/10.1101/2021.12.28.21268458 doi: medRxiv preprint This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available (which was not certified by peer review) 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 January 1, 2022. ; https://doi.org/10.1101/2021.12.28.21268458 doi: medRxiv preprint This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available (which was not certified by peer review) 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 January 1, 2022. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available (which was not certified by peer review) 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 January 1, 2022. ; https://doi.org/10.1101/2021.12.28.21268458 doi: medRxiv preprint

COVID-19 nursing home data

SARS-CoV-2 antibody detection in skilled nursing facility 358 residents

Using Serologic Testing to Assess the Effectiveness of 360

Serial PCR Testing, and Cohorting of Positive SARS-CoV-2 Patients in a 361 Skilled Nursing Facility

Interim Clinical Considerations for Use of COVID-19 Vaccines Currently Approved or 364 Authorized in the United States

Short-term impact of nursing home SARS-CoV-2 vaccinations on 368 new infections, hospitalizations, and deaths

Vaccines and Related Biological Products Advisory 371 Committee Meeting

The Advisory Committee on Immunization 374

Practices' Interim Recommendation for Allocating Initial Supplies of COVID-19 Vaccine -United 375

COVID-19 Outbreak Associated with a SARS-CoV-2 R

Lineage Variant in a Skilled Nursing Facility After Vaccination Program -Kentucky

Effectiveness of Pfizer-BioNTech and Moderna Vaccines in 382 Preventing SARS-CoV-2 Infection Among Nursing Home Residents Before and During 383 Widespread Circulation of the SARS-CoV-2 B.1.617.2 (Delta) Variant -National Healthcare 384 Safety Network

Vaccine effectiveness of the BNT162b2 387 mRNA COVID-19 vaccine against RT-PCR confirmed SARS-CoV-2 infections, hospitalisations and 388 mortality in prioritised risk groups. medRxiv

Effectiveness of mRNA COVID-19 vaccines in preventing 391 SARS-CoV-2 infections and COVID-19 hospitalisations and deaths in elderly long-term care 392 facility residents

Antigen Testing During a Nursing Home Outbreak

Repeated Antigen Testing Among SARS-CoV-2-398

Positive Nursing Home Residents

In Vitro Diagnostics EUAs -Molecular Diagnostic Tests for 401 SARS-CoV-2. Updated 15

The REDCap consortium: Building an international 406 community of software platform partners

Research electronic data capture (REDCap)--a metadata-409 driven methodology and workflow process for providing translational research informatics 410 support

CoV-2 Infection in Healthcare Settings

Validation of a SARS-CoV-2 spike protein ELISA for use in 416 contact investigations and serosurveillance. bioRxiv

Association of SARS-CoV-2 Seropositive Antibody Test 424 With Risk of Future Infection

Shedding of infectious SARS-CoV-2 by hospitalized 427 COVID-19 patients in relation to serum antibody responses

Infectious Period of Severe Acute Respiratory Syndrome 430

Coronavirus 2 in 17 Nursing Home Residents-Arkansas

Clinical significance of the serum IgM and IgG to SARS-CoV-2 in 433 coronavirus disease-2019

Dynamic Changes of Antibodies to SARS-CoV-2 in COVID-19

Patients at Early Stage of Outbreak

IgG Seroconversion and Pathophysiology in Severe Acute 439 Respiratory Syndrome Coronavirus 2 Infection

The Utility of Specific Antibodies Against SARS-CoV-2 in Laboratory 442

Severe COVID-19 is associated with elevated serum IgA and 444 antiphospholipid IgA-antibodies

Immunological memory to SARS-CoV-2 assessed for up to 8 447 months after infection

Durability of SARS-CoV-2 IgG Antibody Among 450 Residents in a Long-Term Care Community

Durability of Responses after SARS-CoV-2 mRNA-1273

Antibody Responses after a Single Dose of SARS-455

CoV-2 mRNA Vaccine

Antibody response to first BNT162b2 dose in previously 458 SARS-CoV-2-infected individuals

Antibody Response to the BNT162b2 mRNA COVID-19

Vaccine in Subjects with Prior SARS-CoV-2 Infection

Correlates of protection against symptomatic and 464 asymptomatic SARS-CoV-2 infection

Human IgG and IgA responses to COVID-19 mRNA 467 vaccines

Antibody responses to SARS-CoV-2 mRNA 470 vaccines are detectable in saliva

Comprehensive assessment of humoral response 473 after Pfizer BNT162b2 mRNA Covid-19 vaccination: a three-case series

IgA dominates the early neutralizing antibody response to 476 SARS-CoV-2

Willingness of Long-Term Care Staff to Receive a COVID-19 479 Vaccine: A Single State Survey