Serologic Response to Coronavirus Disease 2019 (COVID-19) Vaccination in Patients With Immune-Mediated Inflammatory Diseases: A Systematic Review and Meta-analysis

Abstract

Background and aims Patients with immune-mediated inflammatory diseases (IMIDs) have an increased risk of COVID-19, primarily attributed to the use of immunosuppressive drugs such as glucocorticoids, which may attenuate the response to vaccines. This meta-analysis aims to assess the serologic response to COVID-19 vaccination in patients with IMIDs. Methods Electronic databases were searched on August 1, 2021 for observational studies. Data including reference population, medications, vaccination, and proportion of patients achieving a serologic response were extracted. Results Twenty-five observational studies (5360 patients) were included for analyses. A majority of the studies used mRNA vaccines (BNT162b2, mRNA-1273) with a small number of studies including other types of vaccines (AZD1222, Coronavac, BBV152, Ad26.COV2.S). Serologic response after a single (6 studies) and two doses (17 studies) of mRNA vaccine were 73.2% (95% confidence interval [CI] 65.7-79.5) and 83.4% (95%CI 76.8-88.4), respectively. On meta-regression, anti-CD20 therapy was associated with lower response rates ( P <0.001) and anti-TNF therapy also showed a trend toward lower response rates ( P = 0.058). Patients with IMIDs were less likely to achieve a serologic response compared to controls after two doses of mRNA vaccine (6 studies; odds ratio 0.086, 95% CI 0.036-0.206, P < .001). There were not enough studies to assess response to the adenoviral or inactivated vaccines. Conclusions Our meta-analysis demonstrated that patients with IMIDs have a reduced response to mRNA COVID-19 vaccines. These results suggest that IMID patients receiving mRNA vaccines should complete the vaccine series without delay and support the strategy of providing a 3rd dose of the vaccine.

Meta-analysis of immunologic response after COVID-19 mRNA vaccination in solid organ transplant recipients

“…Therefore, the clinical effectiveness might remain sub-optimal compared to healthy population. The seroconversion after 2 doses was 40.1%, much lower than the rates reported in other vulnerable population, such as patients with immune-mediated inflammatory diseases (73.2%) [8] , cancer patients (51%) [9] , and patients with end-stage kidney disease (86%) [10] . Thus, SOTRs should receive the complete vaccination regimen without delay.…”

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

“…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, 7–13 as confirmed in recent meta-analyses. 14,15 In particular, patients receiving glucocorticoids, methotrexate, anti-TNF and B-cell depleting therapy may have attenuated serological responses to COVID-19 vaccines. 7,11,13,14,16 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.…”

“…14,15 In particular, patients receiving glucocorticoids, methotrexate, anti-TNF and B-cell depleting therapy may have attenuated serological responses to COVID-19 vaccines. 7,11,13,14,16 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. 17…”

Antibody decay, T cell immunity and breakthrough infections following two SARS-CoV-2 vaccine doses in infliximab- and vedolizumab-treated patients

“…Drugs targeting tumor necrosis factor (TNF), such as infliximab, are the most frequently prescribed biological therapies used in the treatment of immune-mediated inflammatory disorders (IMIDs). Observational studies indicate that most patients with inflammatory bowel disease (IBD), an archetypal IMID, mount serological responses following SARS-CoV-2 vaccines, although most were underpowered to discern the impact of specific drugs, including immunomodulators (azathioprine, mercaptopurine, and methotrexate) and/or biologic therapies 5–8 . We reported that antibody responses following SARS-CoV-2 infection 9,10 or a single-dose of either the BNT162b2 or ChAdOx1 nCoV-19 SARS-CoV-2 vaccines were impaired in anti-TNF treated patients when compared to vedolizumab treated patients 11 .…”