Cytokine Storms After COVID-19 Vaccination

Severe post-vaccinal complications could be driven by an overactive immune response.

In a new case series, recently published in Cureus, three rheumatic disease patients with low disease activity needed hospitalization and new biological treatments, and one patient died after her 4th dose of SARS-CoV-2 mRNA vaccine.

Cytokine analysis showed elevated levels of IL-1β, IL-6, IL-17, and TNF-α, indicating a cytokine storm, possibly triggered by IL-6 amplification (IL-6 Amp). This mechanism involves excessive IL-6 production through a feedback loop activated by simultaneous stimulation of NF-κB and STAT3 pathways

Case 1: Acute Exacerbation of Interstitial Pneumonia in an 80-Year-Old Woman

An 80-year-old woman with a history of rheumatoid arthritis (RA) had been in remission for five years thanks to a regimen including subcutaneous tocilizumab (TCZ-SC) and tacrolimus. However, after receiving the Pfizer-BioNTech vaccine, she developed severe dyspnea requiring oxygen. Her CT scan revealed new reticular shadows and ground-glass opacities, and her blood tests showed a significant increase in inflammatory markers and rheumatoid factor.

The diagnosis was acute exacerbation of interstitial pneumonia triggered by RA with vasculitis. High-dose methylprednisolone followed by prednisolone, along with continued RA treatment, led to initial improvement. Unfortunately, her RA symptoms flared up again after reducing the steroid dosage, leading to another adjustment in her medication. Cytokine levels measured 17 months post-vaccination revealed elevated IL-1β, IL-6, IL-17A, and TNF-α, indicating a persistent inflammatory response exacerbated by the vaccine.

Case 2: Rheumatoid Pleural Effusion in a 78-Year-Old Man

A 78-year-old man with RA had maintained low disease activity with Iguratimod. Following his third Moderna vaccination, he developed systemic arthralgia and significant pleural effusion, suggesting a relapse of RA. Blood tests and imaging confirmed elevated inflammatory markers and the presence of rheumatoid pleural effusion.

Infectious and malignant causes were ruled out, and the condition was attributed to RA exacerbated by the vaccination. Treatment with abatacept led to a reduction in symptoms. Cytokine measurements post-vaccination showed elevated levels of IL-1β, IL-6, IL-17A, and TNF-α, confirming a vaccine-induced cytokine storm.

Case 3: Diffuse Alveolar Damage in a 75-Year-Old Woman

A 75-year-old woman with RA managed with methotrexate experienced severe respiratory symptoms after her third and fourth Moderna vaccinations. She developed diffuse ground-glass opacities on her chest CT and elevated inflammatory markers, indicative of a diffuse alveolar damage (DAD) pattern. Despite intensive immunosuppressive therapy, her condition deteriorated, culminating in a fatal outcome due to aspiration during SARS-CoV-2 testing.

Cytokine analysis revealed high levels of IL-6 and other cytokines, underscoring the severe immune response triggered by the vaccine. Despite aggressive treatment, the cytokine storm led to a cascade of complications that ultimately proved fatal.

A retrospective study by Ma et al. involved 4627 autoimmune rheumatic disease patients, including 1943 with RA. 18% of autoimmune inflammatory rheumatic disease patients flared after SARS-CoV-2 mRNA vaccination, with 14% requiring hospitalization or significant medication adjustments vaccination, with some requiring hospitalization or increased medication. 


Iwamura N, Eguchi K, Takatani A, Tsutsumi K, Koga T, Araki T, Aramaki T, Terada K, Ueki Y. A Case Series of Rheumatoid Arthritis Flare Including Extra-articular Manifestations Following SARS-CoV-2 mRNA Vaccination: A Comprehensive Cytokine Assay. Cureus. 2024 Apr 22;16(4):e58740. doi: 10.7759/cureus.58740. PMCID: PMC11110478.

Ma M, Santosa A, Fong W, Chew LC, Low AH, Law A, Poh YJ, Yeo SI, Leung YY, Ng VW, Koh JZ, Tay SH, Mak A, Teng GG, Xu C, Tang JG, Kong KO, Angkodjojo S, Goh WR, Chuah TY, Roslan NE, Arkachaisri T, Teh KL, Sriranganathan M, Tan TC, Phang KF, Yap QV, Chan YH, Cheung PP, Lahiri M. Post-mRNA vaccine flares in autoimmune inflammatory rheumatic diseases: Results from the COronavirus National Vaccine registry for ImmuNe diseases SINGapore (CONVIN-SING). J Autoimmun. 2023 Jan;134:102959. doi: 10.1016/j.jaut.2022.102959. Epub 2022 Nov 29. PMID: 36473406; PMCID: PMC9705203.


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