Hybrid Immunity Provides the Best COVID-19 Humoral Response in Immunocompromised Patients with or without SARS-CoV-2 Infection History

Immunization against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has significantly limited the spread of coronavirus disease 2019 (COVID-19) and reduced the associated complications, especially mortality. To prolong immunity, an immune booster was implemented. We evaluated the role of SARS-CoV-2 infection history in the vaccination schedules of kidney and liver transplant recipients and patients with chronic kidney disease (CKD). To this end, we retrospectively analyzed the data of 78 solid organ transplantation (SOT) recipients and 40 patients with immunoglobulin A (IgA) nephropathy as representatives of the CKD group. Patients received two or three doses of the BNT162b2 vaccine. At the follow-up, antibody (Ab) titer, graft function, COVID-19 history, and patients’ clinical condition were assessed. Ab level was higher after two doses in patients with a COVID-19 history over three doses in patients with no COVID-19 history. Compared to three doses, subjects who were administered two doses had a longer median time to infection. Positive antibodies, in response to the third dose, were not observed in up to 8.4% of SOT patients. The results show that the vaccination schedule should take into account the vaccine response rate and COVID-19 history. So-called hybrid immunity appears to be most efficient at providing humoral responses against SARS-CoV-2 infection in immunocompromised patients.

[1]  G. Kang,et al.  Vaccines and therapeutics for immunocompromised patients with COVID-19 , 2023, eClinicalMedicine.

[2]  D. Montefiori,et al.  Safety, immunogenicity and antibody persistence of a bivalent Beta-containing booster vaccine against COVID-19: a phase 2/3 trial , 2022, Nature Medicine.

[3]  Gheyath K Nasrallah,et al.  Protective Effect of Previous SARS-CoV-2 Infection against Omicron BA.4 and BA.5 Subvariants , 2022, The New England journal of medicine.

[4]  A. Tsalouchos,et al.  Assessing T-Cell Immunity in Kidney Transplant Recipients with Absent Antibody Production after a 3rd Dose of the mRNA-1273 Vaccine , 2022, International journal of molecular sciences.

[5]  D. Montefiori,et al.  A Bivalent Omicron-Containing Booster Vaccine against Covid-19 , 2022, The New England journal of medicine.

[6]  J. Izopet,et al.  Humoral and Cellular Responses to a Delayed Fourth SARS-CoV-2 mRNA-Based Vaccine in Weak Responders to 3 Doses Kidney Transplant Recipients , 2022, Vaccines.

[7]  R. Balicer,et al.  BNT162b2 vaccine effectiveness in chronic kidney disease patients—an observational study , 2022, Clinical kidney journal.

[8]  D. Barouch,et al.  Neutralization Escape by SARS-CoV-2 Omicron Subvariants BA.2.12.1, BA.4, and BA.5 , 2022, The New England journal of medicine.

[9]  Gheyath K Nasrallah,et al.  Effects of Previous Infection and Vaccination on Symptomatic Omicron Infections , 2022, The New England journal of medicine.

[10]  Y. Soon,et al.  Efficacy of covid-19 vaccines in immunocompromised patients: systematic review and meta-analysis , 2022, BMJ.

[11]  A. Charlett,et al.  Protection against SARS-CoV-2 after Covid-19 Vaccination and Previous Infection , 2022, The New England journal of medicine.

[12]  E. Herzel,et al.  The Incidence of SARS-CoV-2 Reinfection in Persons With Naturally Acquired Immunity With and Without Subsequent Receipt of a Single Dose of BNT162b2 Vaccine , 2022, Annals of Internal Medicine.

[13]  D. Segev,et al.  SARS-CoV-2 antibody testing for transplant recipients: A tool to personalize protection versus COVID-19 , 2022, American Journal of Transplantation.

[14]  S. Zeger,et al.  Duration of effectiveness of vaccines against SARS-CoV-2 infection and COVID-19 disease: results of a systematic review and meta-regression , 2022, The Lancet.

[15]  P. Moss The T cell immune response against SARS-CoV-2 , 2022, Nature Immunology.

[16]  J. Izopet,et al.  Anti-SARS-CoV-2 spike protein and neutralizing antibodies at 1 and 3 months after three doses of SARS-CoV-2 vaccine in a large cohort of solid organ transplant patients , 2022, American Journal of Transplantation.

[17]  G. Screaton,et al.  Heterologous versus homologous COVID-19 booster vaccination in previous recipients of two doses of CoronaVac COVID-19 vaccine in Brazil (RHH-001): a phase 4, non-inferiority, single blind, randomised study , 2022, The Lancet.

[18]  S. Bernardini,et al.  Evaluation of serological anti-SARS-CoV-2 chemiluminescent immunoassays correlated to live virus neutralization test, for the detection of anti-RBD antibodies as a relevant alternative in COVID-19 large-scale neutralizing activity monitoring , 2021, Clinical Immunology.

[19]  K. Mucha,et al.  Unexpectedly High Efficacy of SARS-CoV-2 BNT162b2 Vaccine in Liver versus Kidney Transplant Recipients—Is It Related to Immunosuppression Only? , 2021, Vaccines.

[20]  Scott M Elliott,et al.  Safety and immunogenicity of seven COVID-19 vaccines as a third dose (booster) following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK (COV-BOOST): a blinded, multicentre, randomised, controlled, phase 2 trial , 2021, The Lancet.

[21]  J. Izopet,et al.  Assessment of 4 Doses of SARS-CoV-2 Messenger RNA–Based Vaccine in Recipients of a Solid Organ Transplant , 2021, JAMA network open.

[22]  S. Bernardini,et al.  Serological anti-SARS-CoV-2 neutralizing antibodies association to live virus neutralizing test titers in COVID-19 paucisymptomatic/symptomatic patients and vaccinated subjects , 2021, International Immunopharmacology.

[23]  M. Hernán,et al.  Effectiveness of a third dose of the BNT162b2 mRNA COVID-19 vaccine for preventing severe outcomes in Israel: an observational study , 2021, The Lancet.

[24]  A. Mangia,et al.  Harmonization of six quantitative SARS-CoV-2 serological assays using sera of vaccinated subjects , 2021, Clinica Chimica Acta.

[25]  G. Tomlinson,et al.  Randomized Trial of a Third Dose of mRNA-1273 Vaccine in Transplant Recipients , 2021, The New England journal of medicine.

[26]  V. Kulasingam,et al.  Humoral and cellular immune response and safety of two-dose SARS-CoV-2 mRNA-1273 vaccine in solid organ transplant recipients , 2021, American Journal of Transplantation.

[27]  G. Shurin,et al.  Differential Antibody Response to mRNA COVID-19 Vaccines in Healthy Subjects , 2021, Microbiology spectrum.

[28]  K. Lu,et al.  The Efficacy of COVID-19 Vaccines in Chronic Kidney Disease and Kidney Transplantation Patients: A Narrative Review , 2021, Vaccines.

[29]  J. Izopet,et al.  Efficiency of a boost with a third dose of anti-SARS-CoV-2 messenger RNA-based vaccines in solid organ transplant recipients , 2021, American Journal of Transplantation.

[30]  S. Fafi-Kremer,et al.  Antibody Response After a Third Dose of the mRNA-1273 SARS-CoV-2 Vaccine in Kidney Transplant Recipients With Minimal Serologic Response to 2 Doses. , 2021, JAMA.

[31]  D. Segev,et al.  SARS-CoV-2 Messenger RNA Vaccine Immunogenicity in Solid Organ Transplant Recipients With Prior COVID-19 , 2021, Transplantation.

[32]  J. Izopet,et al.  Three Doses of an mRNA Covid-19 Vaccine in Solid-Organ Transplant Recipients , 2021, The New England journal of medicine.

[33]  F. Jouret,et al.  Serological response to mRNA SARS-CoV-2 BNT162b2 vaccine in kidney transplant recipients depends on prior exposure to SARS-CoV-2 , 2021, American Journal of Transplantation.

[34]  William T. Harvey,et al.  SARS-CoV-2 variants, spike mutations and immune escape , 2021, Nature Reviews Microbiology.

[35]  D. Segev,et al.  Antibody Response to 2-Dose SARS-CoV-2 mRNA Vaccine Series in Solid Organ Transplant Recipients. , 2021, JAMA.

[36]  S. Adamopoulos,et al.  Immunogenicity of SARS-CoV-2 BNT162b2 vaccine in solid organ transplant recipients , 2021, American Journal of Transplantation.

[37]  L. Stamatatos,et al.  mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection , 2021, Science.

[38]  D. Segev,et al.  Immunogenicity of a Single Dose of SARS-CoV-2 Messenger RNA Vaccine in Solid Organ Transplant Recipients. , 2021, JAMA.

[39]  P. Rodari,et al.  Antibody Response to the BNT162b2 mRNA COVID-19 Vaccine in Subjects with Prior SARS-CoV-2 Infection , 2021, Viruses.

[40]  M. Camacho-Rivera,et al.  Preventive behaviors and mental-health related symptoms among immunocompromised adults during the COVID-19 pandemic: an analysis of the COVID Impact Survey. , 2021, AIDS research and human retroviruses.

[41]  David C. Yeo,et al.  Brief clinical evaluation of six high-throughput SARS-CoV-2 IgG antibody assays , 2020, Journal of Clinical Virology.

[42]  Nicola Clementi,et al.  Poor correlation between antibody titers and neutralizing activity in sera from SARS-CoV-2 infected subjects , 2020, medRxiv.