Extensive progressive heterotopic ossification post-Covid-19 in a man

Abstract

Heterotopic ossification (HO) is the formation of extraskeletal bone in muscle and soft tissues and could be genetic or non-genetic. The classic presentation of non-genetic HO is in young adults with a clear history of local trauma, surgery or prolonged immobilization after spinal cord and traumatic brain injuries. Genetic HO has a significant clinical severity compared to non-genetic causes and includes fibrodysplasia ossificans progressiva (FOP). FOP is an extremely rare genetic skeletal disorder characterized by congenital malformations of the great toes and progressive heterotopic ossification that forms qualitatively normal bone in characteristic extraskeletal sites affecting skeletal muscles, fascia, tendons, and ligaments. Previously, it has been reported an association between SARS-CoV-2 infection (COVID-19) and HO or FOP exacerbation with unclear etiopathogenesis. The possible mechanisms could be prolonged immobilization and systemic inflammation. Here, we describe the case of a 55-year-old apparently healthy man who suffered from a severe SARS-CoV-2 infection after that he experienced an extensive and progressive heterotopic ossification around the shoulders, the elbows, the hip, the knees, and the ankles. Because of the clinical severity, the painful soft-tissue swelling, the progressive HO, and the bilateral congenital hallux valgus deformity, a late-onset atypical FOP was suspected. Nevertheless, no variant of clinical significance has been identified in the coding regions and splicing sites in the ACVR1 gene and no deletions and/or duplications have been identified in exonic regions.

SARS-CoV-2-specific humoral and cellular immune responses to BNT162b2 vaccine in Fibrodysplasia ossificans progressiva patients

“…Therefore, patients with FOP are anticipated to be at high risk of adverse outcomes related to COVID-19. In addition, COVID-19 alone may serve as a possible disease-flare trigger, as recently described (11,12). Thus, disease prevention should be paramount for patients with FOP.…”

“…It is worth mentioning that a viral infection itself, including but not limited to SARS-CoV-2, may lead to disease flare-ups (34). The risk of FOP flare-ups and HO in COVID-19 has been described in two case reports (11,12). In addition, a small registry-based trial of the International FOP Association (IFOPA) Registry reported that two out of ten patients with confirmed SARS-CoV-2 infection experienced disease flare-ups.…”

A follow-up report on the published paper Social and clinical impact of COVID-19 on patients with fibrodysplasia ossificans progressiva

“…Thus, our findings that the COVID-19 vaccination can be tolerated in patients with FOP should not be extended to other intramuscularly administered vaccinations. In addition, there has been at least two case reports of patients with FOP or suspected FOP having post-COVID-19 exacerbation of flare up and HO formation activity [ 6 , 7 ]. There are reported cases of higher prevalence of HO in patients with ARDS due to prolonged immobilization [ 8 ].…”

“…Our observations on a small cohort suggest that patients with FOP have similar risks as the general population to COVID-19 infection, and that patients with FOP may be able to tolerate COVID-19 vaccination when treated following a consensus protocol to mitigate flare risk [ 1 ]. Because other vaccinations and viral infections are known [ 4 – 7 ] to be associated with HO formation in patients with FOP, this information should be used to guide individual discussions about risks and benefits for vaccination within the FOP community.…”

Heterotopic Ossification of Bilateral Hips Post–COVID-19 and Prolonged Immobilization

“…HO seems to be more prevalent in patients with coronavirus disease 2019 (COVID-19)-induced immobilization possibly due to local myositis, deranged calcium metabolism, and systemic inflammatory condition 2 . While many COVID-19-related HO cases are reported, none describe surgery [2][3][4][5][6][7][8][9] . Surgical resection is recommended only for severe joint limitation severely interfering with quality of life (QoL) and autonomy 1 .…”