Sex: F
Vaccine: COVID19, COVID19
Symptoms: Biopsy skin, COVID-19, Drug ineffective, Eosinophil count, Magnetic resonance imaging
Clinical narrative: Eosinophilic fasciitis following COVID-19; Eosinophilic fasciitis following COVID-19; The initial case was missing the following minimum criteria: [ICH-unspecified product]. Upon receipt of follow-up information on (18Jul2025), this case now contains all required information to be considered valid.  This is a literature report.  A 56-year-old female patient received BNT162b2, BNT162b2 omi ba.4-5 (BNT162B2, BNT162B2 OMI BA.4-5), as dose 3 (booster), single for covid-19 immunisation; COVID-19 vaccine (COVID-19 VACCINE), as dose 1, single and as dose 2, single for immunisation. The patient's relevant medical history included: "comprising gastroesophageal dysmotility" (unspecified if ongoing), notes: necessitating total parenteral nutrition; "intestinal dysmotility" (unspecified if ongoing), notes: necessitating total parenteral nutrition; "total parenteral nutrition" (ongoing), notes: no recent alterations in her total parenteral nutrition formulations; "rectal adenocarcinoma" (unspecified if ongoing); "primary hyperparathyroidism" (unspecified if ongoing); "osteoporosis" (unspecified if ongoing); "Melanoma" (unspecified if ongoing); "paresthesia" (unspecified if ongoing); "edema" (unspecified if ongoing); "progressive induration of the extremities with restricted motion" (unspecified if ongoing). The patient's concomitant medications were not reported. The following information was reported: DRUG INEFFECTIVE (medically significant), COVID-19 (medically significant), all with latency 3 weeks after the suspect product(s) administration, outcome "unknown" and all described as "Eosinophilic fasciitis following COVID-19"; EOSINOPHILIC FASCIITIS (medically significant), 2 months after the suspect product(s) administration, outcome "recovering", described as "Eosinophilic fasciitis following COVID-19". The patient underwent the following laboratory tests and procedures: Biopsy skin: moderate, mixed inflammatory infiltrate affecting, notes: affecting the fascia and skeletal muscle, with associated edema; Eosinophil count (0-0.36): 0.71 x10 3/mm3, notes: 10%; Magnetic resonance imaging: fascial enhancement without involvement of the, notes: subcutaneous fat or musculature; Physical examination: plaque formation and stiffness affecting the hips, notes: pelvic girdle, lower thoracic back, bilateral proximal thighs, distal legs, and forearms, with a positive "groove sign". Therapeutic measures were taken as a result of eosinophilic fasciitis. A woman, with a complex medical history comprising gastroesophageal and intestinal dysmotility necessitating total parenteral nutrition, rectal adenocarcinoma, primary hyperparathyroidism, osteoporosis, and melanoma, developed eosinophilia (10%, 0.71 [0.00 e 0.36 3 103/ _L]), paresthesia, edema, progressive induration of the extremities with restricted motion, and low-grade fever with progressive weight loss 2 months after contracting SARS-CoV-2. She reported no recent alterations in her total parenteral nutrition formulations. Physical examination showed plaque formation and stiffness affecting the hips, pelvic girdle, lower thoracic back, bilateral proximal thighs, distal legs, and forearms, with a positive "groove sign". A skin biopsy revealed a moderate, mixed inflammatory infiltrate affecting the fascia and skeletal muscle, with associated edema. Magnetic resonance imaging findings showed fascial enhancement without involvement of the subcutaneous fat or musculature. The patient was diagnosed with EF and received prednisone 10 mg per day with concurrent methotrexate at 10 mg per week. Six weeks later, dupilumab was introduced at a weekly subcutaneous dose of 300 mg, and prednisone and methotrexate doses were then tapered. The patient reported a significant reduction in edema and substantial improvement in range of motion. DISCUSSION: The etiology of EF is complex, with many factors potentially influencing its development. Although some triggers have been identified, the complete pathophysiologic landscape remains elusive. None of the 3 patients described in this case series had a history of preceding exercise, gadolinium exposure within 6 months of EF onset, comorbid Raynaud phenomenon, or symptoms compatible with lichen sclerosis. A noticeable pattern from our case series is the temporal correlation between onset of EF and COVID-19, spanning weeks to several months postinfection. Although this association could be coincidental, the incidence of such a rare disorder post-SARS-CoV-2 infection in 3 separate cases suggests a relationship worthy of further investigation. Moreover, there have been documented cases of EF emerging after administration of SARS-CoV-2 vaccination. Although it may be argued that these symptoms following SARS-CoV-2 vaccination or infection could potentially represent an exacerbation of preexisting conditions, there are cases where individuals without prior conditions have also developed EF. This offers a compelling clue regarding the potential association between EF and COVID-19. In the 3 cases outlined above, each patient exhibited mild COVID-19 symptoms and did not require hospitalization. Patient 3 received the Pfizer bivalent booster 3 weeks before COVID-19 and the onset of EF symptoms occurred 2 months after. For patient 3, pinpointing the clear trigger for EF would be complex, given the close interval between her SARS-CoV-2 vaccination and subsequent infection. The mechanisms by which SARS-CoV-2 might catalyze the onset of EF are multifarious, potentially encompassing direct viral-induced effects, immune dysregulation, and molecular mimicry. Direct effects of the virus could initiate local tissue damage and inflammation, instigating a cascade of immune responses that eventually manifest as fibrotic alterations, characteristic of EF. Furthermore, the severe systemic inflammatory response, commonly referred to as cytokine storm, that often accompanies COVID-19 could potentially disrupt the finely balanced immune regulation and tolerance mechanisms, leading to an autoimmune reaction. The principle of molecular mimicry posits an additional mechanism through which EF could be triggered. This principle describes a situation where the immune response, although targeting viral proteins, may inadvertently affect self-antigens in the fascia that share antigenic structures with these proteins, leading to an autoimmune reaction. Viruses, including SARS-CoV-2, are known to induce significant immune dysregulation, resulting in heightened inflammatory responses and imbalances in various immune cell regulations. This disruption could potentially compromise immune tolerance to self-antigens, setting the stage for the emergence of autoimmune conditions such as EF. Lastly, the concepts of bystander activation and epitope spreading, where a robust immune response to a viral infection inadvertently activates autoreactive immune cells or exposes previously concealed self-antigens, are plausible. Further research is necessary to solidify these hypotheses and elucidate the precise mechanisms underpinning the association between COVID-19 and EF. The mechanisms underlying the onset of EF often involve immune dysregulation, marked by eosinophilia. Intriguingly, in hospitalized patients with COVID-19, eosinopenia has emerged as a notable observation. Interpretations of its significance differ among studies, many of which are region-specific. Authors found a pronounced decrease in eosinophil counts among patients with severe COVID-19 symptoms, hinting that eosinopenia could be associated with increased disease severity. The underlying causes of eosinopenia are still debated and could be multifaceted. The possible triggers range from interruptions in the eosinophil life cycle, apoptosis triggered by type 1 interferon during the acute phase of the infection, eosinophil consumption due to their antiviral activities, to reflection of host immune exhaustion. Notably, the use of corticosteroids, one of the main drugs utilized in the treatment of severe COVID-19, could play a role in the development of eosinopenia. As patients approached discharge, eosinophil counts generally normalized, indicating that a rebound in these counts might correlate with a patient's clinical improvement. This resurgence in eosinophil activity during recovery prompts speculation regarding its potential role in predisposing individuals to conditions such as EF. Although the link between SARS-CoV-2 vaccination and EF has previously been described, to our knowledge, this case series is the first report of the potential association between COVID-19 and EF. A larger patient cohort and a more exhaustive molecular study are necessary to confirm a temporal relationship between EF and COVID-19.; Sender's Comments: Vaccine efficacy varies from person to person and is affected by many factors. The association between the event lack of effect/drug ineffective (CoVID-19) with the suspect product BNT162B2, BNT162B2 OMI BA.4-5 cannot be fully excluded.