During the last two years, vaccines against the SARS-CoV-2 virus have been extensively used in Spain and the rest of Europe under a conditional marketing authorization granted by the European Medicines Agency. The lack of previous clinical experience with these therapeutic tools, especially regarding those based on a novel mRNA technology, makes the detection of adverse reactions a task of utmost importance in order to establish their risk–benefit ratio as precisely as possible.
Besides, according to the Spanish Pharmacovigilance System all healthcare professionals are obliged to report any suspected adverse reaction, giving priority to those related to drugs under additional surveillance. Regrettably, under-reporting of potential side effects is common and due to many reasons, of which the mere doubt about the causal relationship between drug and reaction is a leading factor.1 Even more problematic in the context of Covid-19 vaccines, the extraordinarily polarized social and media scenario has likely not encouraged the reporting of unexpected adverse events that might lower the high expectations placed on mass vaccination.
Here we present the case of a 48-year-old woman who, prior to vaccination with elasomeran (Spikevax®, Moderna), had not suffered from remarkable diseases, including Covid-19, and did not take any medication. Fifteen days after her first jab (June 2021) she noticed headache, sore throat and, 5 days later, left ear discomfort. One week later, she got a second vaccination with elasomeran. Thirteen days after this jab she developed otitis media and left ear hearing loss with moderate grade. Then, over the next three months, she was admitted two times to an ENT department for recurrent left facial paralysis, showing leukocytosis and a positive test (1/40) for c-PR3-ANCA. In view of these findings, in November 2021 she was referred to a rheumatology department and was diagnosed with possible granulomatosis with polyangiitis (GPA). One month later, a peribronchovascular nodule was detected in the upper lobe of the right lung (RUL), which increased its size for the next three months (Fig. 1A). Among the relevant laboratory findings over this period she tested negative two times to c-ANCA-PR3, and neutrophils, leukocytes and C-reactive protein were above the normal range, while lymphocytes were lower. In February 2022 she was admitted in a pneumology department for haemoptysis, where tested positive again (1/20) to c-PR3-ANCA and showed high levels of ferritin. In early March 2022 a bronchoscopy was performed, revealing significant bronchial destruction in the RUL. Samples collected during the procedure showed a moderate increase in CD3+ T lymphocytes with a high CD4/CD8 ratio (6.81). A Covid-19 booster jab was recommended and administered on 22 March 2022. Shortly after, a biopsy of the inferior nasal turbinate showed necrotizing epithelioid granuloma with vasculitis, also suggestive of GPA. Over time, a large range of drug treatments was prescribed in an attempt to control the different condition stages, including corticosteroids, antibiotics, painkillers, proton-pump inhibitors, alendronate, pregabalin, methotrexate or rituximab. Her first positive test result to SARS-CoV-2 infection was in October 2022, needing antibiotics for bacterial co-infection. Also in this month, the pulmonary nodule had decreased in size (Fig. 1B) and the renal function remained unaltered. On the other hand, hearing loss has not substantially improved and some breathing difficulty is currently under study.
New-onset autoimmune phenomena after COVID-19 vaccination have been reported increasingly,2 being molecular mimicry, the production of particular autoantibodies and the role of certain vaccine adjuvants some the potential substantial contributors to autoimmune phenomena.3 Also, it is possible that the enhanced immune response after booster vaccination and presence of HLA-DR+monocytes could be responsible for triggering the production of the observed MPO- and PR3-ANCA autoantibodies.4 A recent systematic review found 27 cases fulfilling the criteria for de novo ANCA-associated vasculitis reported in temporal association with SARS-CoV-2 vaccination, of which only four shared with our case PR3-ANCA involvement after vaccination with elasomeran.4 Thus, the present case is pioneering in highlighting a relevant example of mixed, gradually evolving, and long-lasting conditions potentially associated to vaccination.
The assessment of a causal link between vaccine and adverse events was made by following the WHO manual for causality assessment of an adverse event following immunization (AEFI).5 Although a temporal relationship and additional qualifying factors were deemed consistent with a side effect, the present case was classified as ‘indeterminate’ as the present evidence is it not yet conclusive, something usual for a new vaccine-linked event. To note, the age of GPA onset typically ranges between middle to older age, with some epidemiological studies reporting a cyclical occurrence. This would be consistent with an infectious trigger, whose role might have been played on this instance by the SARS-CoV-2 spike protein.
In conclusion, we suggest that this case should be taken into account as a safety signal deserving further and specific research. Healthcare professionals should remain vigilant and report any potential adverse reaction with Covid-19 vaccines to allow a truly comprehensive assessment of this intervention.
Patient consentInformed consent was obtained from the patient for publication of the case report and accompanying images.
Funding resourcesThis research has not received any specific grant from the public, commercial, or not-for-profit sectors.
Conflict of interestThe authors declare no conflict of interests.
To María José López Jiménez, Specialist in Respiratory Medicine at the Hospital San Pedro de Alcántara, Cáceres (Spain) for her precious assistance in the selection of the medical images.
