Inactivated vaccines may not provide adequate protection in immunosuppressed patients with rheumatic diseases

Shenoy, Padmanabha; Ahmed, Sakir; Paul, Aby; Cherian, Somy; Vijayan, Anuroopa; Babu, Sageer As; Sukumaran, Aswathy

doi:10.1136/annrheumdis-2021-221496

Cited by 11 publications

(13 citation statements)

References 7 publications

(4 reference statements)

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“…In contrast, two German cohorts reported lower rates of sero negativity (6% and 0%) post-BNT162b2 vaccine3 6 however their sample sizes were smaller. One of the determinants of antibody response was the type of vaccine used, with poorer responses in those who received the inactivated BBV152 vaccine consistent with results previously reported in healthy controls as well as AIRD patients 14 20 21. The number of our patients on RTX might be proportionately smaller and hence it might not reach a statistical significance due to a type 2 error.…”

Section: Discussionsupporting

confidence: 80%

“…This might be a type II error due to limited numbers (48) in this subgroup analysis. A good correlation between neutralising antibodies and anti-RBD has been reported previously 14 15. Though neutralisation assays may provide some additional data about susceptibility, it remains to be seen what the practical benefit of such data is.…”

Section: Discussionsupporting

confidence: 52%

“…We have previously shown that antibody titres have a good correlation with neutralisation assays in patients with AIRD. 14 We have also explored the effects of past symptomatic COVID-19 on postvaccination humoral response. 15 Our previous work has not included assays for cellmediated immunity.…”

Section: Epidemiologymentioning

confidence: 99%

“…Their antibody titres against the SARS-CoV-2 Spike protein were measured at 4–6 weeks after the second dose of COVID-19 vaccination. We have previously shown that antibody titres have a good correlation with neutralisation assays in patients with AIRD 14. We have also explored the effects of past symptomatic COVID-19 on postvaccination humoral response 15.…”

Section: Introductionmentioning

confidence: 99%

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Postvaccination antibody titres predict protection against COVID-19 in patients with autoimmune diseases: survival analysis in a prospective cohort

et al. 2022

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IntroductionTo assess the incidence and risk factors for breakthrough COVID-19 infection in a vaccinated cohort of patients with autoimmune rheumatic diseases (AIRDs) and determine whether antibodies to receptor binding domain of spike protein (anti-RBD) serve as a reliable predictor of susceptibility to such infections.MethodsPatients with AIRDs who had completed two doses of SARS-CoV2 vaccines were included and anti-RBD antibodies were determined 4–6 weeks post the second vaccine dose and stratified into good responders (GR) (>212 IU), inadequate responders (IR) (0.8–212 IU) and non-responders (NR) (<0.8 IU). Patients who had completed a minimum of 8 weeks interval after the second dose of vaccine were followed up every 2 months to identify breakthrough infections. All sero converted patients who had contact with COVID-19 were also analysed for neutralising antibodies.ResultsWe studied 630 patients of AIRDs (mean age 55.2 (±11.6) years, male to female ratio of 1:5.2). The majority of patients had received AZD1222 (495, 78.6%) while the remaining received the BBV152 vaccine. The mean antibody titre was 854.1 (±951.9), and 380 (60.3%) were GR, 143 (22.7%) IR and 107 (16.9%) NR.Breakthrough infections occurred in 47 patients (7.4%) at a mean follow-up of 147.3 (±53.7) days and were proportionately highest in the NR group (19; 17.75%), followed by the IR group (13; 9.09%) and least in the GR group (15; 3.95%). On log-rank analysis, antibody response (p<0.00001), vaccine(p=0.003) and mycophenolate mofetil (p=0.007) were significant predictors of breakthrough infections. On multivariate Cox regression, only NR were significantly associated with breakthrough infections (HR: 3.6, 95% CI 1.58 to 8.0, p=0.002). In sero converted patients with contact with COVID-19, neutralisation levels were different between those who developed and did not develop an infection.ConclusionBreakthrough infections occurred in 7.4% of patients and were associated with seronegativity following vaccination. This provides a basis for exploring postvaccination antibody titres as a biomarker in patients with AIRD.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionsupporting

confidence: 52%

Section: Epidemiologymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Postvaccination antibody titres predict protection against COVID-19 in patients with autoimmune diseases: survival analysis in a prospective cohort

et al. 2022

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“…In the last two groups, patients were queried about any past symptoms suggestive of COVID-19, and they were excluded from the vaccine-only groups if they reported any such symptoms. To avoid confounding due to different vaccines, 8 we included only patients who had received the ChAdOx1 vaccine.…”

mentioning

confidence: 99%

Hybrid immunity versus vaccine-induced immunity against SARS-CoV-2 in patients with autoimmune rheumatic diseases

Shenoy¹,

Ahmed

Paul³

et al. 2022

The Lancet Rheumatology

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Effects of the second dose of COVID-19 vaccines in patients with autoimmune rheumatic diseases with hybrid immunity

et al. 2022

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Patients with autoimmune rheumatic diseases with a previous infection by the SARS-CoV-2 virus have exaggerated responses to a single dose of COVID-19 vaccination as compared to fully vaccinated infection naive patients. The second dose is currently recommended at an extended gap after the infection, but the information available regarding response to the second dose in this subgroup is limited. Patients with AIRDs previously infected with COVID-19, who have received at least one dose of AZD1222/ChAdOx1 (n = 200) were included and stratified based on vaccine doses (V), and infection (I) into I + V, I + V + V, V + I, V + V + I. Anti-RBD (receptor binding domain) antibodies were compared across the four groups. In 49 patients of the I + V + V group (AZD12222), paired sera were compared for antibody levels and neutralization after each vaccine dose. Thirty patients with hybrid immunity after BBV152 and 25 with complete vaccination without infection were included as controls. The highest anti-RBD antibody levels were observed in the V + V + I group (18,219 ± 7702 IU/ml) with statistically similar titers in the I + V + V (10,392 ± 8514 IU/ml) and the I + V (8801 ± 8122 IU/ml). This was confirmed in the 49 paired samples that paradoxically showed a lowering of antibody titers after the second dose [9626 (IQR: 4575-18,785)-5781 (2484-11,906); p < 0.001]. Neutralization of the Delta variant was unaffected but Omicron neutralization was significantly reduced after the second dose [45.7 (5.3-86.53)-35% (7.3-70.9); p = 0.028]. Ancillary analyses showed that only the hybrid immune sera could neutralize the Omicron variant and AZD1222 hybrids performed better than BBV152 hybrids. The second dose of AZD1222 did not boost antibody titers in patients with RD who had COVID-19 previously. In the analysis of paired sera, the second dose led to a statistically significant reduction in antibody titers and also reduced neutralization of the Omicron variant.

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Inactivated vaccines may not provide adequate protection in immunosuppressed patients with rheumatic diseases

Cited by 11 publications

References 7 publications

Postvaccination antibody titres predict protection against COVID-19 in patients with autoimmune diseases: survival analysis in a prospective cohort

Postvaccination antibody titres predict protection against COVID-19 in patients with autoimmune diseases: survival analysis in a prospective cohort

Hybrid immunity versus vaccine-induced immunity against SARS-CoV-2 in patients with autoimmune rheumatic diseases

Effects of the second dose of COVID-19 vaccines in patients with autoimmune rheumatic diseases with hybrid immunity

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