Inactivated COVID-19 Vaccine Induces a Low Humoral Immune Response in a Subset of Dermatological Patients Receiving Immunosuppressants

Abstract

Inactivated Sinovac-CoronaVac vaccine (Sinovac Life Sciences, Beijing) for coronavirus disease 2019 (COVID-19) has been used in many countries. However, its immunogenicity profile in immunosuppressed dermatological patients is lacking. This prospective observational case-control study compared the humoral immune response between adult dermatological patients receiving systemic immunosuppressive therapies (n = 14) and those who did not (n = 18); excluding patients with HIV infection, cancer, non-dermatological autoimmune conditions, previous COVID-19 infection, and positive anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG prior to vaccination. The subjects were advised to withhold methotrexate for 1 week after each vaccine dose while continuing other therapies unadjusted. Anti-SARS-CoV-2 IgG antibody, surrogate neutralizing antibody (sNAb), and seroconversion rates (calculated from the percentages of participants in the group with positive sNAb) were used to assess immunogenicity. We found that participants using azathioprine, cyclosporin, mycophenolate mofetil, or prednisolone ≥ 10 mg/day had a lower level of serum anti-SARS-CoV-2 IgG antibody and sNAb than those received methotrexate ≤ 10 mg/week, prednisolone < 10 mg/day, or biologics (i.e., secukinumab, ixekizumab, omalizumab). Patients who received methotrexate ≤ 10 mg/week, prednisolone < 10 mg/day or the biologics had a similar immunogenicity profile to those without immunosuppressive therapies. Despite the lack of statistical significance, a reduction of humoral immune response was observed among the study participants who used ≥2 immunosuppressants or pemphigus patients. Our findings suggest that a subset of patients with immune-mediated skin conditions respond poorly to the vaccine despite having low-level immunosuppression. These patients could benefit from vaccines that trigger a greater level of immunogenicity or booster doses.

The Impact of Immune-Modifying Treatments for Skin Diseases on the Immune Response to COVID-19 Vaccines: a Narrative Review

“…Of 6 individuals who did not have detectable antibodies, 4 were receiving JAKi monotherapy or combination therapy, 1 methotrexate/prednisolone co-therapy and 1 methotrexate/prednisolone co-therapy. Neutralising A neutralising humoral response was detected in 13/16 (81%) individuals on standard systemic therapy, 17/18 (94%) on cytokine targeted biologic therapy, 4/5 (80%) on abatacept, and 8/12 (67%) on JAKi therapy Ruddy et al [ 37 ] Rheumatological disease (n = 404) including RA, ankylosing spondylitis, PsA, reactive arthritis, SLE, Sjogren’s syndrome, myositis, systemic sclerosis and vasculitis No controls Median age: 44 years Gender: 385 (96%) female Ethnicity: 367 (91%) White Standard systemic Azathioprine, ciclosporin, dimethyl fumarate, hydroxychloroquine, leflunomide, methotrexate, mycophenolate mofetil, sirolimus, sulfasalazine and tacrolimus Targeted Abatacept, anakinra, belimumab, guselkumab, IL-6i, IL-17i, JAKi, rituximab, TNFi and ustekinumab BNT162b2 (198/404, 49%) mRNA-1273 (204/404, 51%) N/A Humoral Seroconversion 378/404 (94%) of individuals with rheumatological disease seroconverted at a median of 29 days after 2nd dose A greater proportion of those receiving TNFi had detectable antibodies (100%), vs those receiving mycophenolate (73%, p < 0.001), rituximab (26%, p < 0.001) or glucocorticoids (82%, p < 0.001) or those with a diagnosis of myositis (79%, p = 0.01) Lower median antibody titres in individuals receiving mycophenolate mofetil (8 U/mL) and rituximab (< 0.4 U/mL) vs individuals receiving glucocorticoid monotherapy (> 250 U/mL) Seree-aphinan et al [ 38 ] Cases: Individuals with pemphigus, psoriasis and chronic spontaneous urticaria who are receiving immune-modifying therapy ( n = 14) Controls: individuals (with acne, melasma, androgenetic alopecia, seborrheic keratosis) who are not receiving immune-modifying therapy ( n = 18) Mean age: Controls – 45 years Cases – 44 years Gender: Controls – 11 (61%) female Cases – 10 (71%) female Ethnicity: Not included Standard systemic Azathioprine, ciclosporin, methotrexate, mycophenolate mofetil and prednisone Targeted Ixekizumab, omalizumab and secukinumab CoronaVac (Sinovac) N/A Humoral Seroconversion No individuals (0/6, 0%) taking azathioprine, ciclosporin, mycophenolate mofetil, or moderate-to-high dose corticosteroids seroconverted 4 weeks post-second vaccine. 7/8 (87.5%) individuals on low dose methotrexate, low d...…”

“…In ten studies where neutralisation was investigated [ 23 , 25 – 27 , 29 , 34 •, 36 , 38 , 40 , 41 ], the majority of individuals receiving immune-modifying therapy developed a neutralising response after the second vaccine dose (range 63–100%, with the exception of those receiving rituximab); however, neutralisation titres were lower compared to healthy controls in 3 studies [ 27 , 29 , 38 ]. Our own study (individuals with psoriasis, n = 67; healthy controls, n = 15) showed that all study participants had detectable neutralising antibodies against wild-type, Alpha and Delta SARS-CoV-2 variants following the second vaccine dose, and there were higher neutralising antibody titres after the second dose compared to the first [ 34 •].…”

Exacerbation of Autoimmune Bullous Diseases After Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination: Is There Any Association?

“…It has been shown that immunosuppressive drugs reduce the efficacy of SARS-CoV2 vaccines ( 31 ). Patients with immune-mediated skin conditions treated with immunosuppressants had low levels of serum anti-SARS-CoV-2 IgG antibodies, according to a recent study ( 32 ). The higher doses of corticosteroids in patients with active disease would attenuate the response to the vaccine.…”

Subacute Cutaneous Lupus Erythematosus-Like Eruption Induced by Durvalumab: A Case Report and Literature Review

“…16 Lastly, focusing on mechanism of action, anti-PD-1 or PD-L1 may modulate humoral immunity which enhances pre-existing autoantibodies and unmask latent auto-immunity. [17][18][19] Therefore, anti-PD-L1 might be involved with immune-related adverse events, not only by increasing the activity of the immune system against antigens in both cancers and healthy tissue, but also by increasing levels of pre-existing autoantibodies. These mechanisms may explain the positive autoantibodies in our case.…”