Evaluation of Immune Response and Disease Status in Systemic Lupus Erythematosus Patients Following SARS–CoV‐2 Vaccination

Abstract

Objective To evaluate seroreactivity and disease flares after COVID‐19 vaccination in a multi‐ethnic/racial cohort of patients with systemic lupus erythematosus (SLE). Methods 90 SLE patients and 20 healthy controls receiving a complete COVID‐19 vaccine regimen were included. IgG seroreactivity to the SARS‐CoV‐2 spike receptor‐binding domain (RBD) and SARS‐CoV‐2 microneutralization were used to evaluate B cell responses; IFN‐γ production to assess T cell responses was measured by ELISpot. Disease activity was measured by the hybrid SLE disease activity index (SLEDAI) and flares were assigned by the SELENA/SLEDAI flare index. Results Overall, fully vaccinated SLE patients produced significantly lower IgG antibodies against SARS‐CoV‐2 spike RBD than controls. Twenty‐six SLE patients (28.8%) generated an IgG response below that of the lowest control (<100 units/ml). In logistic regression analyses, the use of any immunosuppressant or prednisone and a normal anti‐dsDNA level prior to vaccination associated with decreased vaccine responses. IgG seroreactivity to the SARS‐CoV‐2 Spike RBD strongly correlated with the SARS‐CoV‐2 microneutralization titers and antigen‐specific IFN‐γ production determined by ELISpot. In a subset of patients with poor antibody responses, IFN‐γ production was likewise diminished. Pre‐/post‐vaccination SLEDAI scores were similar. Only 11.4% of patients had a post‐vaccination flare; 1.3% were severe. Conclusion In a multi‐ethnic/racial study of SLE patients 29% had a low response to the COVID‐19 vaccine which was associated with being on immunosuppression. Reassuringly, disease flares were rare. While minimal protective levels remain unknown, these data suggest protocol development is needed to assess efficacy of booster vaccination.

Immunological and clinical efficacy of COVID-19 vaccines in immunocompromised populations: a systematic review

“…The vast majority of included studies evaluated vaccines developed by Pfizer (BNT162b2) or Moderna (mRNA-1273). Thirteen studies included patients who received the vaccine developed by Janssen (Ad26.COV2.S) [ [25] , [26] , [27] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] ], nine included patients vaccinated with the AstraZeneca vaccine (ChAdOx1) [ [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] ], three included patients receiving the CoronaVac vaccine (Sinovac Biotech) [ [50] , [51] , [52] ], and one randomized controlled trial evaluated the vaccine developed by Novavax (NVX-CoV2373) vaccine [ 53 ]. One study included patients receiving the BBV152-Covaxin (Bharat Biotech) vaccine [ 44 ] and one included patients receiving the BBIBP-CorV (Sinopharm) vaccine [ 54 ].…”

“…Most studies assessed anti-SARS-CoV-2 immunity through an immunoassay to detect antibodies targeted at the spike protein, including some targeting specifically the receptor-binding domain (RBD) of the spike protein. Thirty studies reported neutralization assay results in addition to anti-SARS-CoV-2 antibody assays [ 34 , 37 , 41 , 48 , 51 , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] , [69] , [70] , [71] , [72] , [73] , [74] , [75] , [76] , [77] , [78] , [79] ]. Thirty-one studies provided data on cellular immunity [ 17 , 21 , 22 , 34 , 37 , 41 , 45 , 46 , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , 72 , [74] , [75] , [76] , [77] , [79] , [80] , [81] , [82] , [83] , [84] ].…”

“…Thirty-one studies reported immunogenicity in 4680 patients with inflammatory immune-mediated diseases ( Table S6 ) [ 27 , 28 , 32 , 36 , 37 , 39 , [45] , [46] , [47] , 50 , 51 , 54 , 55 , 82 , [161] , [162] , [163] , [164] , [165] , [166] , [167] , [168] , [169] , [170] , [171] , [172] , [173] , [174] , [175] , [176] , [177] , [178] ]. Main represented groups included rheumatoid arthritis ( n = 665), inflammatory bowel diseases ( n = 476) and multiple sclerosis ( n = 231).…”

“…Main represented groups included rheumatoid arthritis ( n = 665), inflammatory bowel diseases ( n = 476) and multiple sclerosis ( n = 231). Twenty of those studies had a control group [ 32 , 37 , [45] , [46] , [47] , 50 , 51 , 55 , [161] , [162] , [163] , [164] , 166 , 167 , 169 , 171 , 172 , 174 , 177 , 178 ] ( n = 1609), among which 16 participants failed to mount a post-vaccine antibody response [ 47 , 50 , 51 , 55 , 163 , 164 ].…”

“…found high rates (respectively 47% and 50%) in patients with multiple sclerosis (MS) [ 164 , 168 ]. Six studies tested participants' sera with neutralization assays [ 32 , 37 , 51 , 163 , 172 , 174 ], one tested neutralization on a SARS-CoV-2 spike protein bearing the N501Y mutation (present in the alpha variant) [ 32 ]. Two studies provided non-response rates which were either the same as with anti-S IgG assay (0%, 0/26 [ 172 ]) or higher (44%, 375/859 vs. 29%, 245/859 with the anti-S assay [ 51 ]).…”