Case Report: Cyclophosphamide in COVID-19 – when an absolute contraindication is an absolute necessity

Abstract

Background: Despite many studies on COVID-19, our knowledge of it remains incomplete. In some cases, treating SARS-CoV-2 infection concomitant with other diseases can be particularly challenging, as finding an appropriate treatment may involve some risks. Case presentation: A 34-year-old SARS-CoV-2 positive patient admitted due to fever, dyspnoea, haemoptysis and pneumonia, developed alveolar haemorrhage and acute kidney injury. Due to his severe state, abnormalities in laboratory tests and rapidly progressing loss of kidney function, kidney biopsy, as well as antibody panel were carried out, in which perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) were found with a high titer (>200; N: <1:20). The results of kidney biopsy, combined with clinical manifestation and laboratory findings prompted the diagnosis of rapidly progressing glomerulonephritis (RPGN) in the course of p-ANCA vasculitis. Initial treatment consisted of heamodialyses, remdesivir, plasmaphereses, intravenous immunoglobulins, antibiotics, corticosteroids and nadroparin. Once the haemorrhage had subsided, kidney function had been partially retrieved and heamodialyses had no longer been necessary, cyclophosphamide treatment was initiated, despite being contraindicated in COVID-19 according to its summary of product characteristics. Immunotherapy is still continued. The patient has already received a total of 2.4g of cyclophosphamide (4 cycles of 600mg each every three weeks). Pulmonary and radiological regression, as well as improvement of renal parameters have been achieved. Conclusions: We suspect that cyclophosphamide, the drug of choice in p-ANCA vasculitis, could be a potential factor providing regression of the radiological changes in the lungs and it could have prevented the patient from developing acute respiratory distress syndrome. COVID-19 diagnosis should not exclude searching for other diseases which can have a similar course. When treating a patient in a life-threatening condition, a departure from trying to find the perfect timing of cyclophosphamide delivery should be considered, as delaying it could cause potentially greater harm.

Atypical Immunologic Manifestations of COVID-19: a Case Report and Narrative Review

“…10 days later - fever, dyspnea, mild cough COVID +ve 10 days later Renal - impaired renal function (stage 3 renal failure), concerns of possible glomerulonephritis ANCA-associated vasculitis - +ve p-ANCA, ANA and rheumatoid factor Skin - painful necrotic ulcer-like lesions on both legs, with perilesional edema and erythema Pulse corticosteroids, monthly cyclophosphamide, vacuum assisted therapy and grafting for skin lesions - Bryant et al (2022) [ 18 ] 16/female Non-productive cough, wheezing, mild upper respiratory symptoms with anosmia, sinus pain, serosanguinous ear drainage, sensation of fullness in ears, hearing loss bilaterally (chronic bilateral serous otitis media), chest tightness, difficulty breathing, new onset myalgias, weight loss, intermittent conjunctivitis, sinus congestion, purulent nasal discharge, sinus headache, recurrent nosebleeds, bilateral arthralgias in knees, feet and elbows, intermittent rashes, sun sensitivity Yes Lungs - consolidations, multifocal pulmonary nodules, cavitation, central bronchiectasis AAV - +ve c-ANCA, proteinase 3 antibody, +ve ANA Albuterol, azithromycin, cefdinir, doxycycline, prednisone, tympanostomy tube placement, inhaled corticosteroids with long-acting beta agonists, rituximab, mycophenolate mofetil On follow-up, marked improvement in symptoms, but continued bilateral conductive hearing loss, which required hearing aids. Boltuc et al (2021) [ 19 ] 34/male Fever, dyspnea, hemoptysis, bilateral pneumonia, conjunctivitis, hypoxemia, transient arthralgia Yes Lungs - alveolar hemorrhage Renal - rapidly progressive glomerulonephritis Vasculitis - +ve p-ANCA Hemodialysis, remdesivir, plasmapheresis, immunoglobulins, clarithromycin, piperacillin with tazobactam, methylprednisolone, oral prednisone, nadroparin, cyclophosphamide Improved Valero et al (2022) [ 20 ] 62/female Purpuric lesions in upper limbs with a history of IgA vasculitis. No symptoms of COVID-19.…”