Association of Cytomegalovirus Serostatus With Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Responsiveness in Nursing Home Residents and Healthcare Workers

Michael L Freeman; Oladayo A Oyebanji; Daniela Moisi; Michael Payne; Maegan L Sheehan; Alejandro B Balazs; Jürgen Bosch; Christopher L King; Stefan Gravenstein; Michael M Lederman; David H Canaday

doi:10.1093/ofid/ofad063

Association of Cytomegalovirus Serostatus With Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Responsiveness in Nursing Home Residents and Healthcare Workers

Open Forum Infect Dis. 2023 Feb 4;10(2):ofad063. doi: 10.1093/ofid/ofad063. eCollection 2023 Feb.

Authors

Affiliations

¹ Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
² Center for Global Health and Diseases, Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
³ Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, USA.
⁴ Department of Health Services, Policy, and Practice, Brown University School of Public Health, Providence, Rhode Island, USA.
⁵ Center on Innovation in Long-Term Services and Supports, Providence Veterans Administration Medical Center, Providence, Rhode Island, USA.
⁶ Division of Geriatrics and Palliative Medicine, Alpert Medical School of Brown University, Providence, Rhode Island, USA.
⁷ Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Geriatric Research Education and Clinical Center, Cleveland, Ohio, USA.

Abstract

Background: Latent cytomegalovirus (CMV) infection is immunomodulatory and could affect mRNA vaccine responsiveness. We sought to determine the association of CMV serostatus and prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with antibody (Ab) titers after primary and booster BNT162b2 mRNA vaccinations in healthcare workers (HCWs) and nursing home (NH) residents.

Methods: Nursing home residents (N = 143) and HCWs (N = 107) were vaccinated and serological responses monitored by serum neutralization activity against Wuhan and Omicron (BA.1) strain spike proteins, and by bead-multiplex immunoglobulin G immunoassay to Wuhan spike protein and its receptor-binding domain (RBD). Cytomegalovirus serology and levels of inflammatory biomarkers were also measured.

Results: Severe acute respiratory syndrome coronavirus 2-naive CMV seropositive (CMV⁺) HCWs had significantly reduced Wuhan-neutralizing Ab (P = .013), anti-spike (P = .017), and anti-RBD (P = .011) responses 2 weeks after primary vaccination series compared with responses among CMV seronegative (CMV^-) HCWs, adjusting for age, sex, and race. Among NH residents without prior SARS-CoV-2 infection, Wuhan-neutralizing Ab titers were similar 2 weeks after primary series but were reduced 6 months later (P = .012) between CMV⁺ and CMV^- subjects. Wuhan-neutralizing Ab titers from CMV⁺ NH residents who had prior SARS-CoV-2 infection consistently trended lower than titers from SARS-CoV-2 experienced CMV^- donors. These impaired Ab responses in CMV⁺ versus CMV^- individuals were not observed after booster vaccination or with prior SARS-CoV-2 infection.

Conclusions: Latent CMV infection adversely affects vaccine-induced responsiveness to SARS-CoV-2 spike protein, a neoantigen not previously encountered, in both HCWs and NH residents. Multiple antigenic challenges may be required for optimal mRNA vaccine immunogenicity in CMV⁺ adults.

Keywords: COVID-19; SARS-CoV-2; antibodies; cytomegalovirus; vaccination.