Post-COVID-19 exacerbation of fibrodysplasia ossificans progressiva with multiple flare-ups and extensive heterotopic ossification in a 45-year-old female patient

Rheumatol Int. 2021 Aug;41(8):1495-1501. doi: 10.1007/s00296-021-04911-6. Epub 2021 Jun 10.


Fibrodyplasia ossificans progressiva (FOP) is a rare hereditary disease, which has a variable course characterized by occasional flare-ups of heterotopic ossification (HO) in soft tissues that are followed by swelling, stiffness, pain and warmth. Here, we report for the first time a case of a 45-year-old female patient with known FOP recovering from COVID-19 with disease progression potentially linked with the viral illness. In December 2020 the patient contracted a mild form of COVID-19 infection without need for hospital admission. Since January 2021, the patient felt unwell, with occasional abdominal pain which progressively intensified. In March 2021 she presented with new onset of HO, complaining of pain, swelling and thickening sensation in the lower abdomen and left part of the neck. Computerized tomography (CT) and cytokine analysis were performed. CT scan revealed new heterotopic bone formation in multiple soft tissue areas of the neck indicating clear radiological progression. Radiotherapy, which has proven to be an efficient tool to control HO in this patient, was not able to halt HO formation after COVID-19 infection. Cytokine analysis of a plasma sample obtained during a flare-up after COVID-19 infection showed a significantly elevated pro-inflammatory cytokines compared to a flare-up panel prior to infection. Of the 23 analyzed levels of cytokines, a staggering number of 21 were above normal levels. This case is the first confirmation of uncontrolled post-COVID-19 effects in a FOP patient, which manifested with flare-ups followed by progressive HO, possibly caused by a thus far, never described form of post-COVID syndrome.

Keywords: COVID-19; Cytokines; Heterotopic ossification; Myositis ossificans.

Publication types

  • Case Reports
  • Review

MeSH terms

  • COVID-19 / blood
  • COVID-19 / diagnosis
  • COVID-19 / immunology*
  • COVID-19 / virology
  • Cytokines / blood*
  • Female
  • Host-Pathogen Interactions
  • Humans
  • Inflammation Mediators / blood*
  • Middle Aged
  • Myositis Ossificans / diagnosis
  • Myositis Ossificans / immunology*
  • Myositis Ossificans / virology
  • Ossification, Heterotopic / diagnosis
  • Ossification, Heterotopic / immunology*
  • Ossification, Heterotopic / virology
  • SARS-CoV-2 / immunology*
  • SARS-CoV-2 / pathogenicity
  • Symptom Flare Up


  • Cytokines
  • Inflammation Mediators