Humoral protection to SARS-CoV2 declines faster in patients on TNF alpha blocking therapies

Abstract

BackgroundThe persistence of the SARS-CoV2 pandemic, partly due to the appearance of highly infectious variants, has made booster vaccinations necessary for vulnerable groups. Questions remain as to which cohorts require SARS-CoV2 boosters. However, there is a critical lack of data on the dynamics of vaccine responses in patients with chronic inflammatory diseases (CID) undergoing immunosuppressive/disease modifying anti-rheumatic (DMARD) treatment. Here, we present the first data regarding the decline of the vaccine-induced humoral immune responses in patients with CID.Methods23 patients with CID were monitored clinically and for anti-spike IgG and IgA levels, neutralization efficacy and antigen-specific CD4+ T cell responses over the first 6 months after SARS-CoV2 vaccination. 24 healthy individuals were included as controls.ResultsWhile anti-spike IgG-levels declined in CID patients and healthy controls, patients receiving anti-TNF treatment showed significantly greater declines at 6 months post second vaccination in IgG and especially neutralizing antibodies. IgA levels were generally lower in CID patients, particularly during anti-TNF therapy. No differences in SARS-CoV2 spike-specific CD4+ T-cell frequencies were detected.ConclusionAlthough the long-term efficacy of SARS-CoV2 vaccination in CID patients undergoing disease-modifying therapy is still not known, the pronounced declines in humoral responses towards SARS-CoV2 6 months after mRNA vaccination in the context of TNF blockade should be considered when formulating booster regimens. These patients should be considered for early booster vaccinations.

Accelerated waning of immunity to SARS-CoV-2 mRNA vaccines in patients with immune mediated inflammatory diseases

“…Our data are consistent with recent data suggesting reduced vaccine efficacy against Omicron infection in immunocompromised patients (14). The observed waning of antibody responses to mRNA vaccines in anti-TNF patients are in agreement with a recent small study from Geissen et al (13) who showed decreased responses and waning immunity with anti-TNF agents in 23 IMID patients at 6 months post dose 2, and also confirmed with a larger cohort in a recent pre-print (19). We also observed that IMID patients overall showed more substantial waning of both antibody and T cell responses compared to healthy controls.…”

“…Although many IMID patients mount adequate serological responses to vaccination after two doses of an mRNA vaccine, a proportion of IMID patients show reduced responses compared to healthy controls (7)(8)(9)(10)(11)(12)(13)(14), as confirmed in recent meta-analyses (15,16). In particular, patients receiving glucocorticoids, methotrexate, mycophenolate, anti-TNF and B-cell depleting therapy may have attenuated serological responses to COVID-19 vaccines (7,11,13,15,17,18).…”

“…In particular, patients receiving glucocorticoids, methotrexate, mycophenolate, anti-TNF and B-cell depleting therapy may have attenuated serological responses to COVID-19 vaccines (7, 11, 13, 15, 17, 18). A small study of 23 IMID patients showed that patients on anti-TNF therapy have greater waning of humoral immunity compared to healthy controls (13), as confirmed in a larger study still in preprint (19).…”

“…Although many IMID patients mount adequate serological responses to vaccination after two doses of an mRNA vaccine, a proportion of IMID patients show reduced responses compared to healthy controls (7)(8)(9)(10)(11)(12)(13)(14), as confirmed in recent meta-analyses (15,16). In particular, patients receiving glucocorticoids, methotrexate, mycophenolate, anti-TNF and B-cell depleting therapy may have attenuated serological responses to COVID-19 vaccines (7,11,13,15,17,18). A small study of 23 IMID patients showed that patients on anti-TNF therapy have greater waning of humoral immunity compared to healthy controls (13), as confirmed in a larger study still in preprint (19).…”

Desenvolvimento de vacinas contra a COVID-19: uma revisão de literatura / Development of vaccines against COVID-19: a literature review

“…Efeitos adversos foram equivalentes em ambos os grupos e não há relatos de efeitos graves ou de piora no quadro clínico. 5 Em estudo mais recente dos efeitos da vacina em pessoas que foram expostas ao vírus e apresentaram sintomas para COVID-19, foi concluído que apenas uma dose já é suficiente para garantir os níveis ideais de anticorpos. Após a primeira dose, os voluntários que nunca entraram em contato com SARS-CoV-2 possuíram respostas imunológicas inferiores aos outros participantes.…”