A complex COVID-19 case with rheumatoid arthritis treated with tocilizumab

Abstract

Recurrences of COVID-19 were observed in a patient with long-term usage of hydroxychloroquine, leflunomide, and glucocorticoids due to her 30-year history of rheumatoid arthritis (RA). Tocilizumab was applied and intended to target both COVID-19 and RA. However, disease of this patient aggravated after usage of tocilizumab. After the discussion of a multiple disciplinary team (MDT) including rheumatologists, antimicrobial treatments were applied to target the potential opportunistic infections (Pneumocystis jirovecii and Aspergillus fumigatus), which were authenticated several days later via high throughput sequencing. As an important cytokine in immune responses, IL-6 can be a double-edged sword: interference in the IL-6-IL-6 receptor signaling may save patients from cytokine release storm (CRS), but can also weaken the anti-infectious immunity, particularly in rheumatic patients, who may have received a long-term treatment with immunosuppressive/modulatory agents. Thus, we suggest careful considerations before and close monitoring in the administration of tocilizumab in rheumatic patients with COVID-19. Besides tocilizumab, several disease-modifying antirheumatic drugs (DMARDs) can also be applied in the treatment of COVID-19. Therefore, we also reviewed and discussed the application of these DMARDs in COVID-19 condition. Keywords Coronavirus disease 2019. Rheumatoid arthritis. Secondary opportunistic infection. Tocilizumab Coronavirus disease 2019 (COVID-19) has progressed to a worldwide pandemic situation, and millions of people are suffering from this lethal disease. Many cytokines involved in the pathogenesis of rheumatic diseases (particularly rheumatoid arthritis, RA), such as IL-6, were elevated in COVID-19 [1-3]. Persistent and dramatic elevation of serum IL-6 level was associated with higher mortality in COVID-19 patients [4]. It seems that administration of tocilizumab can be a perfect solution to treat COVID-19 and RA at the same time. However, every coin has two sides. Application of tocilizumab may bring unsuspected effects. Here, we first reported the complex treatment process of a COVID-19 patient with RA history and illustrated the importance of recognizing the feasibility of tocilizumab application in the therapeutic process. Case presentation The case we reported here was a 72-year-old female with a history of RA for nearly 30 years. She had taken leflunomide (LEF, 20 mg po qd) for 10 years and hydroxychloroquine (HCQ, 0.2 g po bid) for 1 year. Based on the clinical characteristics and therapeutic processes, this report was divided into two parts.

Impact of COVID-19 pandemic on rheumatoid arthritis from a Multi-Centre patient-reported questionnaire survey: influence of gender, rural–urban gap and north–south gradient

“…Moreover, the doubts raised about the likely side effects lead to the urgent situation arising from patients’ fear of taking antimalarials during these COVID-19 times [ 19 ]. Recurrence of COVID-19 was reported with long-term use of HCQ, leflunomide, and steroids and was paradoxically aggravated after use of tocilizumab [ 20 ]. Data for other drugs are conflicting or incomplete and the rationale for their use is based on the immune system runaway and the secretion of pro-inflammatory cytokines in severe forms of the disease [ 21 ].…”

“…Even though several national authorities have defined patients under immunosuppressive therapy as at risk for severe COVID-19, it is currently unknown whether immunosuppressive and/or immunomodulating agents, such as biologics, affect the rate and the outcome of COVID-19 infections in RDs patients [ 22 ]. Thus, a call for careful consideration and close monitoring in the administration of biologics in RDs patients with COVID-19 is warranted [ 20 ].…”

Invasive Pulmonary Aspergillosis in Patients with SARS-CoV-2 Infection: A Systematic Review of the Literature

“…In one case, the question of secondary hemophagocytic lymphohistiocytosis (HLH) was raised due to elevated ferritin level (2442 ng/mL), decreased platelet count (83 × 10 9 /L) and hypofibrinogenemia (1.9 g/L). However, a diagnosis of HLH was not confirmed as these laboratory abnormalities may reflect the underlying pro-inflammatory state associated with COVID-19 [ 33 ]. Elevated ferritin level was reported in other studies as well (range: 465–2442 ng/mL) [ 34 , 35 , 36 , 37 , 38 , 39 ].…”

“…Exceptions included (i) one patient who was a renal transplant recipient on maintenance immunosuppressive therapy (mycophenolate mofetil 1 g twice daily and prednisone 20 mg daily) [ 39 ], (ii) one patient who had a remote history of lung transplant on maintenance immunosuppressive therapy with tacrolimus and prednisone (unspecified doses) [ 40 ], (iii) one patient who was on chronic steroids for pemphigus foliaceus [ 9 ], (iv) one patient who had history of multiple myeloma and was on steroids [ 41 ], (v) one patient with history of rheumatoid arthritis on long-term leflunomide [ 33 ], (vi) one patient with a history of chronic myelomonocytic leukemia [ 40 ] and (vii) one patient with a history of unspecified hematologic malignancy [ 42 ]. For the last two patients, it was not specified in the studies whether their disease was active or in remission, and whether they were neutropenic at baseline or not.…”

Pneumocystis jirovecii y SARS-CoV-2; COVID-19

“…Adicionalmente, se manifiesta que las neumonías por COVID-19 y P. jirovecii, comparten características clínicas como infiltrados multifocales bilaterales e hipoxemia profunda. Por otro lado, la coinfección con P. jirovecii, puede no ser detectada en pacientes con infección grave por SARS-CoV-2 y la condición puede revestir mayor gravedad si estos presentan condición de inmunodeficiencia previa a la infección por SARS-CoV-2 (11,12,13,14).…”