Benefit vs risk for COVID-19 vaccination in patients with systemic lupus erythematosus

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger ribonucleic acid (mRNA) vaccine significantly decreases the risk of infection and COVID-19 clinical events in the general population. However, there is ambiguity surrounding the risk-benefit balance of SARS-CoV-2 mRNA vaccines in patients with SLE.

Kikuchi et al.¹ recently published an article in Immunological Medicine, assessing the effects of SARS-CoV-2 mRNA vaccination, including disease flare rates, neutralizing antibody titers, adverse reactions, and associated factors, in patients with SLE. Here, we summarize their findings.

Methods¹

• The study enrolled uninfected patients with SLE who received two doses of vaccines (BNT162b2 or mRNA-1273) and historically unvaccinated patients, matched by age and SLE Disease Activity Index (SLEDAI).
• Following the second vaccination adverse reactions, and disease flares were evaluated via clinical assessment, and serum samples were collected to measure neutralizing antibodies.

Key findings¹

• The study involved 90 uninfected vaccine-administered patients and 90 unvaccinated control patients.

Seroconversions and adverse reactions

• Within 3 days of the second dose, 88.9% of patients experienced adverse reactions, with 73.6% having local reactions (72.2% with local pain), and 79.2% experiencing systemic reactions.
• Neutralizing antibodies were measured at a mean of 27.6 days post-second dose, where 21.1% of patients tested negative.
• Predictors of non-seroconversion:
  • as per univariate analysis were age, longer disease duration, anemia with hemoglobin ≤11 mg/dL, hydroxychloroquine use, mycophenolate mofetil use, and a lower percentage of fever as an adverse reaction; and
  • as per multivariate logistic regression analysis were anemia and mycophenolate mofetil use.

Disease activity and flares of SLE

• The SLEDAI increased modestly but significantly after the second dose of vaccination (p = 0.016).
• After ≥8 days post-second dose, 14.4% of patients experienced flares, with 4.4% experiencing severe flares (nephritis in three cases and vasculitis in one). On average, the flares occurred 35 days after the second dose of the vaccine.
• Predictors of flares:
  • as per univariate analysis were high titers of SLEDAI, anti-dsDNA antibodies, rash, and azathioprine use before the first dose of the vaccine; and
  • as per multivariate logistic regression analysis were high levels of SLEDAI and anti-dsDNA antibodies.
• Flares were not associated with hydroxychloroquine use, neutralizing antibody titers, vaccine type, and adverse reactions or flares in the year before the first dose of vaccine.

Comparison of vaccine-administered patients vs historical unvaccinated controls

• The vaccine-administered patients experienced significantly higher flare incidence and slightly increased SLEDAI, compared with unvaccinated controls (Figure 1).

dsDNA, double-stranded deoxyribonucleic acid; SLEDAI, SLE Disease Activity Index.
*Data from Kikuchi, et al.^1
†Error bars represent the interquartile range; change (∆) was calculated by subtracting the baseline visit from the subsequent visit.
Statistical significance was set at p < 0.05.

Key learnings

The study shows a favorable risk-benefit balance for SARS-CoV-2 mRNA vaccine administration in patients with SLE and supports the vaccination recommendation by the European League against Rheumatism. Careful follow-up is required in cases of residual disease activity, particularly in critical organs; further research is required to study effect of other vaccines.