Castleman disease patients report mild COVID-19 symptoms and mount a humoral response to SARS-CoV-2 vaccination

Abstract

The coronavirus disease of 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in increased morbidity and mortality in patients with impaired immunity, hematologic malignancies, and immunosuppressive regimens. COVID-19 can cause a cytokine storm with some patients benefiting from blockade of the pro-inflammatory cytokine, interleukin 6 (IL6). As Castleman disease (CD) is an atypical lymphoproliferative disorder that can involve a cytokine storm and often requires immunosuppressive therapies, including IL6 inhibition, we sought to evaluate outcomes following COVID-19 and SARS-CoV-2 vaccination in CD patients. We administered a survey in April 2021 to characterize experiences with COVID-19 and SARS-CoV-2 vaccination among 300 CD patients enrolled in ACCELERATE, a natural history registry of CD patients. Among 128 respondents, the prevalence of SARS-CoV-2 infection (16/95, 17%), severe disease (1/16, 6%), vaccination rates (112/128, 88%), and vaccine adverse effects after dose one (62/112, 55%) were comparable to the general U.S. population. While there were two cases of CD flares occurring shortly after SARS-CoV-2 infection (N=1) and vaccination (N=1), over 100 patients in this study that were infected and/or vaccinated did not experience CD flares. The median anti-spike titer six months after the second dose among CD patients was comparable to individuals with other immune-related diseases and healthy populations. Data from this small cohort suggest that, despite being on immunosuppressive therapies, CD patients do not appear to be at increased risk of poor COVID-19 outcomes and can mount a humoral response to SARS-CoV-2 vaccination. This study was registered on clinicaltrials.gov (#NCT02817997).

Graphical abstract

Figure 1.

Study selection CONSORT diagram. CAS, certification and access subcommittee.

Figure 2.

Possible temporal association observed between COVID-19 diagnosis and CD progression. (A) Timeline of events from natural history of CD, COVID-19 diagnosis, and subsequent CD flare. Upon initial presentation of CD symptoms, the patient was on corticosteroids and underwent an excisional biopsy diagnostic of CD (regimen 1). For the next regimen, corticosteroids were tapered, and the patient received siltuximab (regimen 2). As a result of the CD flare and subsequent hospitalization, siltuximab was discontinued and the patient went on to receive cyclophosphamide, thalidomide, lenalidomide, and corticosteroids. Figure created using BioRender.com. (B) Any CD-specific symptoms assessed and positive up to 1 year before and after COVID-19 diagnosis. (C) CD-specific laboratory markers measured up to 1 year before and after COVID-19 diagnosis. Time (t) = 0 days is denoted by the vertical dotted line and represents the date of COVID-19 diagnosis. Data points preceding t = 0 highlights laboratory markers before COVID-19 diagnosis (gray shaded region) whereas data points after t = 0 highlights laboratory markers after COVID-19 diagnosis (blue shaded region). For comparison, at TAFRO syndrome diagnosis, creatinine peaked at 3.4 mg/dL and C-reactive protein (CRP) at 8 mg/dL, both normalized with siltuximab. CS, corticosteroids; eGFR, estimated glomerular filtration rate; LN, lymph node.

Figure 3.

Possible temporal association observed between SARS-CoV-2 vaccination and CD progression. (A) Timeline of events from start of CD symptoms, administration of SARS-CoV-2 vaccination (first dose), and subsequent hospitalization from CD progression. Upon initial presentation of CD symptoms, the patient was on corticosteroids (regimen 1) and had 2 excisional biopsies of the enlarged LN with the latter biopsy being diagnostic of CD. The patient continued to receive corticosteroids and was also placed on tocilizumab (regimen 2). The patient was then switched to siltuximab and dexamethasone (regimen 3) for the next regimen preceding the SARS-CoV-2 vaccine. Figure created using BioRender.com. (B) Any CD-specific symptoms identified before and after SARS-CoV-2 vaccination. (C) CD-specific laboratory markers measured before and after SARS-CoV-2 vaccine. Time (t) = 0 days is denoted by the vertical dotted line and represents the date of the first SARS-CoV-2 vaccine. Data points preceding t = 0 highlights laboratory markers measured before SARS-CoV-2 vaccine (gray shaded region) whereas data points after t = 0 highlights laboratory markers measured after SARS-CoV-2 vaccine (blue shaded region). CS, corticosteroids; eGFR, estimated glomerular filtration rate; LN, lymph node.