Anti-COVID-19 Vaccination in Patients with Autoimmune-Autoinflammatory Disorders and Primary/Secondary Immunodeficiencies: The Position of the Task Force on Behalf of the Italian Immunological Societies

The Coronavirus disease 2019 (COVID-19) pandemic has represented an unprecedented challenge for humankind from health, economic, and social viewpoints. In February 2020, Italy was the first western country to be deeply hit by the pandemic and suffered the highest case/fatality rate among western countries. Brand new anti-COVID-19 vaccines have been developed and made available in <1-year from the viral sequence publication. Patients with compromised immune systems, such as autoimmune-autoinflammatory disorders (AIAIDs), primary (PIDs) and secondary (SIDs) immunodeficiencies, have received careful attention for a long time regarding their capacity to safely respond to traditional vaccines. The Italian Immunological Societies, therefore, have promptly faced the issues of safety, immunogenicity, and efficacy/effectiveness of the innovative COVID-19 vaccines, as well as priority to vaccine access, in patients with AIADs, PIDs, and SIDs, by organizing an ad-hoc Task Force. Patients with AIADs, PIDs, and SIDs: (1) Do not present contraindications to COVID-19 vaccines if a mRNA vaccine is used and administered in a stabilized disease phase without active infection. (2) Should usually not discontinue immunosuppressive therapy, which may be modulated depending on the patient’s clinical condition. (3) When eligible, should have a priority access to vaccination. In fact, immunizing these patients may have relevant social/health consequences, since these patients, if infected, may develop chronic infection, which prolongs viral spread and facilitates the emergence of viral variants.

[1]  C. von Kalle,et al.  Safety, reactogenicity, and immunogenicity of homologous and heterologous prime-boost immunisation with ChAdOx1 nCoV-19 and BNT162b2: a prospective cohort study , 2021, The Lancet Respiratory Medicine.

[2]  R. Myers,et al.  Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant , 2021, The New England journal of medicine.

[3]  U. Stervbo,et al.  Correspondence on ‘SARS-CoV-2 vaccination in rituximab-treated patients: evidence for impaired humoral but inducible cellular immune response’ , 2021, Annals of the Rheumatic Diseases.

[4]  J. Klingström,et al.  Heterologous ChAdOx1 nCoV-19 and mRNA-1273 Vaccination , 2021, The New England journal of medicine.

[5]  A. Yılmaz,et al.  Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): interim results of a double-blind, randomised, placebo-controlled, phase 3 trial in Turkey , 2021, The Lancet.

[6]  P. Kalra,et al.  Safety and Efficacy of NVX-CoV2373 Covid-19 Vaccine , 2021, The New England journal of medicine.

[7]  L. Cooper,et al.  Myocarditis Following Immunization With mRNA COVID-19 Vaccines in Members of the US Military. , 2021, JAMA cardiology.

[8]  S. Zaffina,et al.  SARS-CoV-2 Vaccine Induced Atypical Immune Responses in Antibody Defects: Everybody Does their Best , 2021, Journal of Clinical Immunology.

[9]  G. Burmester,et al.  Successful BNT162b2 booster vaccinations in a patient with rheumatoid arthritis and initially negative antibody response , 2021, Annals of the Rheumatic Diseases.

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

[11]  H. Ulmer,et al.  The Safety and Immunogenicity of the mRNA-BNT162b2 SARS-CoV-2 Vaccine in Hemodialysis Patients , 2021, Frontiers in Immunology.

[12]  Andrew T. Kroger,et al.  American College of Rheumatology Guidance for COVID‐19 Vaccination in Patients With Rheumatic and Musculoskeletal Diseases: Version 2 , 2021, Arthritis & rheumatology.

[13]  C. Rice,et al.  Naturally enhanced neutralizing breadth against SARS-CoV-2 one year after infection , 2021, Nature.

[14]  G. Debnath,et al.  Antibody Responses to SARS-CoV-2 mRNA Vaccines Are Detectable in Saliva , 2021, Pathogens & immunity.

[15]  K. Pradhan,et al.  Seroconversion rates following COVID-19 vaccination among patients with cancer , 2021, Cancer Cell.

[16]  Andrew L. Phillips,et al.  Prevention and Attenuation of COVID-19 by BNT162b2 and mRNA-1273 Vaccines , 2021, medRxiv.

[17]  G. Shefer,et al.  Immunogenicity and safety of the BNT162b2 mRNA COVID-19 vaccine in adult patients with autoimmune inflammatory rheumatic diseases and in the general population: a multicentre study , 2021, Annals of the Rheumatic Diseases.

[18]  A. Sheikh,et al.  SARS-CoV-2 Delta VOC in Scotland: demographics, risk of hospital admission, and vaccine effectiveness , 2021, The Lancet.

[19]  N. Freund,et al.  Immunogenicity of Pfizer-BioNTech COVID-19 vaccine in patients with inborn errors of immunity , 2021, Journal of Allergy and Clinical Immunology.

[20]  F. Kirchhoff,et al.  Heterologous ChAdOx1 nCoV-19 and BNT162b2 prime-boost vaccination elicits potent neutralizing antibody responses and T cell reactivity , 2021, medRxiv.

[21]  Changgui Li,et al.  Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy children and adolescents: a double-blind, randomised, controlled, phase 1/2 clinical trial , 2021, The Lancet Infectious Diseases.

[22]  A. Gaggioli,et al.  Detection of antibodies against SARS-CoV-2 both in plasma pools for fractionation and in commercial intravenous immunoglobulins produced from plasma collected in Italy during the pandemic. , 2021, Blood transfusion = Trasfusione del sangue.

[23]  P. Dormitzer,et al.  Safety, Immunogenicity, and Efficacy of the BNT162b2 Covid-19 Vaccine in Adolescents , 2021, The New England journal of medicine.

[24]  M. Neurath,et al.  Methotrexate hampers immunogenicity to BNT162b2 mRNA COVID-19 vaccine in immune-mediated inflammatory disease , 2021, Annals of the Rheumatic Diseases.

[25]  D. Segev,et al.  High antibody response to two-dose SARS-CoV-2 messenger RNA vaccination in patients with rheumatic and musculoskeletal diseases , 2021, Annals of the Rheumatic Diseases.

[26]  A. Joshi,et al.  Seroconversion after coronavirus disease 2019 vaccination in patients with immune deficiency , 2021, Annals of Allergy, Asthma & Immunology.

[27]  E. Callaway Mix-and-match COVID vaccines trigger potent immune response , 2021, Nature.

[28]  G. Aurigemma,et al.  Myocarditis following COVID-19 vaccination , 2021, Radiology Case Reports.

[29]  P. Kalra,et al.  Efficacy of the NVX-CoV2373 Covid-19 Vaccine Against the B.1.1.7 Variant , 2021, medRxiv.

[30]  G. Alter,et al.  Immunogenicity of COVID-19 mRNA Vaccines in Pregnant and Lactating Women. , 2021, JAMA.

[31]  M. Snape,et al.  Heterologous prime-boost COVID-19 vaccination: initial reactogenicity data , 2021, The Lancet.

[32]  D. Jannat-Khah,et al.  Rituximab, but not other antirheumatic therapies, is associated with impaired serological response to SARS- CoV-2 vaccination in patients with rheumatic diseases , 2021, Annals of the Rheumatic Diseases.

[33]  L. Piemonti,et al.  Neutralizing antibody responses to SARS-CoV-2 in symptomatic COVID-19 is persistent and critical for survival , 2021, Nature Communications.

[34]  H. Haslacher,et al.  SARS-CoV-2 vaccination in rituximab-treated patients: evidence for impaired humoral but inducible cellular immune response , 2021, Annals of the Rheumatic Diseases.

[35]  C. Berking,et al.  SARS-CoV-2 vaccination responses in untreated, conventionally treated and anticytokine-treated patients with immune-mediated inflammatory diseases , 2021, Annals of the Rheumatic Diseases.

[36]  L. Abu-Raddad,et al.  Effectiveness of the BNT162b2 Covid-19 Vaccine against the B.1.1.7 and B.1.351 Variants , 2021, The New England journal of medicine.

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

[38]  L. Cosmi,et al.  First-dose mRNA vaccination is sufficient to reactivate immunological memory to SARS-CoV-2 in recovered COVID-19 subjects. , 2021, The Journal of clinical investigation.

[39]  J. Szer,et al.  COVID‐19 vaccination in haematology patients: an Australian and New Zealand consensus position statement , 2021, Internal medicine journal.

[40]  E. Woo,et al.  US Case Reports of Cerebral Venous Sinus Thrombosis With Thrombocytopenia After Ad26.COV2.S Vaccination, March 2 to April 21, 2021. , 2021, JAMA.

[41]  M. Malim,et al.  Safety and immunogenicity of one versus two doses of the COVID-19 vaccine BNT162b2 for patients with cancer: interim analysis of a prospective observational study , 2021, The Lancet Oncology.

[42]  H. Fennema,et al.  Safety and Efficacy of Single-Dose Ad26.COV2.S Vaccine against Covid-19 , 2021, The New England journal of medicine.

[43]  C. Olson,et al.  Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons , 2021, The New England journal of medicine.

[44]  D. Goldblatt,et al.  Pathologic Antibodies to Platelet Factor 4 after ChAdOx1 nCoV-19 Vaccination , 2021, The New England journal of medicine.

[45]  E. Clementi,et al.  How to Manage COVID-19 Vaccination in Immune-Mediated Inflammatory Diseases: An Expert Opinion by IMIDs Study Group , 2021, Frontiers in Immunology.

[46]  M. Suchard,et al.  Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil , 2021, Science.

[47]  D. Rimar,et al.  Herpes zoster following BNT162b2 mRNA Covid-19 vaccination in patients with autoimmune inflammatory rheumatic diseases: a case series , 2021, Rheumatology.

[48]  I. Youngster,et al.  SARS-CoV-2-Specific Antibodies in Breast Milk After COVID-19 Vaccination of Breastfeeding Women. , 2021, JAMA.

[49]  Gregory F. Wu,et al.  Glucocorticoids and B Cell Depleting Agents Substantially Impair Immunogenicity of mRNA Vaccines to SARS-CoV-2 , 2021, medRxiv.

[50]  C. Conrad,et al.  Impaired Humoral and Cellular Immunity after SARS-CoV2 BNT162b2 (Tozinameran) Prime-Boost Vaccination in Kidney Transplant Recipients , 2021, medRxiv.

[51]  J. Blankson,et al.  SARS-CoV-2 mRNA vaccines induce broad CD4+ T cell responses that recognize SARS-CoV-2 variants and HCoV-NL63. , 2021, The Journal of clinical investigation.

[52]  D. Stuart,et al.  Antibody evasion by the P.1 strain of SARS-CoV-2 , 2021, Cell.

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

[54]  E. Lee,et al.  COVID-19 Vaccination in Patients with Autoimmune Inflammatory Rheumatic Diseases: Clinical Guidance of the Korean College of Rheumatology , 2021, Journal of Korean medical science.

[55]  P. Hoff,et al.  Immunogenicity and safety of anti-SARS-CoV-2 mRNA vaccines in patients with chronic inflammatory conditions and immunosuppressive therapy in a monocentric cohort , 2021, Annals of the Rheumatic Diseases.

[56]  D. Segev,et al.  Safety of the first dose of mRNA SARS-CoV-2 vaccines in patients with rheumatic and musculoskeletal diseases , 2021, Annals of the Rheumatic Diseases.

[57]  R. Rubin COVID-19 Vaccines vs Variants-Determining How Much Immunity Is Enough. , 2021, JAMA.

[58]  N. Sullivan,et al.  Serum Neutralizing Activity Elicited by mRNA-1273 Vaccine , 2021, The New England journal of medicine.

[59]  S. Madhi,et al.  ChAdOx1 nCoV-19 (AZD1222) Covid-19 vaccine efficacy against the B.1.351 variant , 2021, The New England Journal of Medicine.

[60]  William T. Harvey,et al.  Author Correction: Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies , 2021, Nature.

[61]  Ahmed Abdul Azim,et al.  Immunogenicity of the Ad26.COV2.S Vaccine for COVID-19. , 2021, JAMA.

[62]  K. Ella,et al.  Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: interim results from a double-blind, randomised, multicentre, phase 2 trial, and 3-month follow-up of a double-blind, randomised phase 1 trial , 2021, The Lancet Infectious Diseases.

[63]  P. Dormitzer,et al.  Neutralizing Activity of BNT162b2-Elicited Serum , 2021, The New England journal of medicine.

[64]  Carl A. B. Pearson,et al.  Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England , 2021, Science.

[65]  K. Agarwal,et al.  Immunogenicity and protective efficacy of inactivated SARS-CoV-2 vaccine candidate, BBV152 in rhesus macaques , 2021, Nature Communications.

[66]  Eun-Ju Lee,et al.  Thrombocytopenia following Pfizer and Moderna SARS‐CoV‐2 vaccination , 2021, American journal of hematology.

[67]  J. Bijlsma EULAR December 2020 viewpoints on SARS-CoV-2 vaccination in patients with RMDs , 2021, Annals of the Rheumatic Diseases.

[68]  Naomi R. Waterlow,et al.  Increased mortality in community-tested cases of SARS-CoV-2 lineage B.1.1.7 , 2021, Nature.

[69]  V. Gushchin,et al.  Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia , 2021, The Lancet.

[70]  P. McKay,et al.  Heterologous vaccination regimens with self-amplifying RNA and adenoviral COVID vaccines induce robust immune responses in mice , 2021, Nature Communications.

[71]  I. Quinti,et al.  Clinical management of patients with primary immunodeficiencies during the COVID-19 pandemic , 2021, Expert review of clinical immunology.

[72]  I. Donatelli,et al.  Immunogenicity of Viral Vaccines in the Italian Military , 2021, Biomedicines.

[73]  Jialu Zhang,et al.  Heterologous prime-boost: breaking the protective immune response bottleneck of COVID-19 vaccine candidates , 2021, Emerging microbes & infections.

[74]  J. Mascola,et al.  Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine , 2020, The New England journal of medicine.

[75]  E. Phillips,et al.  Maintaining Safety with SARS-CoV-2 Vaccines , 2020, The New England journal of medicine.

[76]  Smita Y. Patel,et al.  COVID-19 in patients with primary and secondary immunodeficiency: The United Kingdom experience , 2020, Journal of Allergy and Clinical Immunology.

[77]  P. Dormitzer,et al.  Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine , 2020, The New England journal of medicine.

[78]  Nguyen H. Tran,et al.  Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK , 2020, Lancet.

[79]  C. Rice,et al.  Enhanced SARS-CoV-2 neutralization by dimeric IgA , 2020, Science Translational Medicine.

[80]  A. Druyan,et al.  The risk for severe COVID 19 in patients with autoimmune and/or inflammatory diseases: First wave lessons , 2020, Dermatologic therapy.

[81]  Nguyen H. Tran,et al.  Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial. , 2020, Lancet.

[82]  K. Chu,et al.  Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18–59 years: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial , 2020, The Lancet Infectious Diseases.

[83]  Gaurav D. Gaiha,et al.  Persistence and Evolution of SARS-CoV-2 in an Immunocompromised Host , 2020, The New England journal of medicine.

[84]  D. Micic,et al.  Prevalence and clinical outcomes of COVID-19 in patients with autoimmune diseases: a systematic review and meta-analysis , 2020, Annals of the Rheumatic Diseases.

[85]  B. Lambrecht,et al.  Coronavirus disease 2019 in patients with inborn errors of immunity: An international study , 2020, Journal of Allergy and Clinical Immunology.

[86]  J. Tregoning,et al.  Vaccines for COVID‐19 , 2020, Clinical and experimental immunology.

[87]  A. Gintsburg,et al.  Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia , 2020, The Lancet.

[88]  V. Shinde,et al.  Phase 1–2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine , 2020, The New England journal of medicine.

[89]  N. Patel,et al.  NVX-CoV2373 vaccine protects cynomolgus macaque upper and lower airways against SARS-CoV-2 challenge , 2020, bioRxiv.

[90]  V. Munster,et al.  ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques , 2020, Nature.

[91]  Rebecca J. Loomis,et al.  Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates , 2020, The New England journal of medicine.

[92]  Matthew S. Miller,et al.  Cross-sectional evaluation of humoral responses against SARS-CoV-2 Spike , 2020, bioRxiv.

[93]  Y. Hu,et al.  Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial , 2020, The Lancet.

[94]  R. Gajardo,et al.  Currently available intravenous immunoglobulin contains antibodies reacting against severe acute respiratory syndrome coronavirus 2 antigens , 2020, Immunotherapy.

[95]  V. Lougaris,et al.  A possible role for B cells in COVID-19? Lesson from patients with agammaglobulinemia , 2020, Journal of Allergy and Clinical Immunology.

[96]  S. Antinori,et al.  COVID-19, cytokines and immunosuppression: what can we learn from severe acute respiratory syndrome? , 2020, Clinical and experimental rheumatology.

[97]  John Hodgson,et al.  The pandemic pipeline , 2020, Nature Biotechnology.

[98]  M. Dougados,et al.  Efficacy, immunogenicity and safety of vaccination in adult patients with autoimmune inflammatory rheumatic diseases: a systematic literature review for the 2019 update of EULAR recommendations , 2019, RMD Open.

[99]  M. Dougados,et al.  2019 update of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases , 2019, Annals of the rheumatic diseases.

[100]  A. Winkelmann,et al.  Vaccination in Multiple Sclerosis: Friend or Foe? , 2019, Front. Immunol..

[101]  Stig Egil Bojesen,et al.  Lymphopenia and risk of infection and infection-related death in 98,344 individuals from a prospective Danish population-based study , 2018, PLoS medicine.

[102]  G. Valesini,et al.  Anti-polysaccharide and anti-diphtheria protective antibodies after 13-valent pneumococcal conjugate vaccination in rheumatoid arthritis patients under immunosuppressive therapy. , 2018, Clinical immunology.

[103]  H. Herfarth,et al.  Vaccinations in Adult Patients with Inflammatory Bowel Diseases in the West , 2018, Inflammatory Intestinal Diseases.

[104]  V. Gallo,et al.  Vaccination in immunocompromised host: Recommendations of Italian Primary Immunodeficiency Network Centers (IPINET). , 2018, Vaccine.

[105]  A. Guffroy,et al.  [Systemic lupus erythematosus and lymphopenia: Clinical and pathophysiological features]. , 2017, La Revue de medecine interne.

[106]  S. Bühler,et al.  Safety of live vaccinations on immunosuppressive therapy in patients with immune-mediated inflammatory diseases, solid organ transplantation or after bone-marrow transplantation - A systematic review of randomized trials, observational studies and case reports. , 2017, Vaccine.

[107]  A. Bertoletti,et al.  Memory T cell responses targeting the SARS coronavirus persist up to 11 years post-infection , 2016, Vaccine.

[108]  A. Bolhassani,et al.  Prime-boost vaccine strategy against viral infections: Mechanisms and benefits. , 2016, Vaccine.

[109]  L. Carli,et al.  Leukopenia, lymphopenia, and neutropenia in systemic lupus erythematosus: Prevalence and clinical impact--A systematic literature review. , 2015, Seminars in arthritis and rheumatism.

[110]  M. Eibl,et al.  Vaccination in patients with primary immune deficiency, secondary immune deficiency and autoimmunity with immune regulatory abnormalities. , 2015, Immunotherapy.

[111]  M. Cattaruzza,et al.  Infection risk in Rheumatoid Arthritis and Spondyloarthropathy patients under treatment with DMARDs, Corticosteroids and TNF-α antagonists , 2014, Journal of Translational Medicine.

[112]  A. Bousvaros,et al.  2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. , 2014, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[113]  E. Mendelson,et al.  The cellular immune response to influenza vaccination is preserved in rheumatoid arthritis patients treated with rituximab. , 2011, Vaccine.

[114]  S. Salemi,et al.  Are Anti-Infectious Vaccinations Safe and Effective in Patients with Autoimmunity? , 2010, International reviews of immunology.

[115]  R. Koup,et al.  Persistent memory CD4+ and CD8+ T-cell responses in recovered severe acute respiratory syndrome (SARS) patients to SARS coronavirus M antigen. , 2007, The Journal of general virology.

[116]  Marrow Transplantation Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients , 2000, Biology of Blood and Marrow Transplantation.

[117]  R. Meidan,et al.  LB0003 IMMUNOGENICITY AND SAFETY OF THE BNT162b2 mRNA COVID-19 VACCINE IN ADULT PATIENTS WITH AUTOIMMUNE INFLAMMATORY RHEUMATIC DISEASES AND GENERAL POPULATION: A MULTICENTER STUDY , 2021, Annals of the Rheumatic Diseases.

[118]  L. Leibovici,et al.  Influenza vaccines in immunosuppressed adults with cancer. , 2018, The Cochrane database of systematic reviews.

[119]  M. A. Meledeo,et al.  Recent advances in use of fresh frozen plasma, cryoprecipitate, immunoglobulins, and clotting factors for transfusion support in patients with hematologic disease , 2020, Seminars in Hematology.