Mild Course of COVID‐19 and Spontaneous Virus Clearance in a Patient With Depleted Peripheral Blood B Cells Due to Rituximab Treatment

Fallet, Bénédict; Kyburz, Diego; Walker, Ulrich A.

doi:10.1002/art.41380

Cited by 35 publications

(36 citation statements)

References 5 publications

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“…Therefore, it is perhaps not surprising that there is currently more information about the influence of CD20 depletion and COVID‐19 disease outcome than for other high‐efficacy DMT in MS [49,44] (Table 1). This is consistent with, albeit limited, information in people with rheumatic diseases [66,68] indicating that people generally recover, while the few reported deaths may be linked to co‐morbidities [44]. The suggestion that rituximab treatment may increase risk of infection should be considered in the context of possible sampling biases, although this could be supported by data reported in social media from Sweden [40,54] (Table 1).…”

Section: Introductionsupporting

confidence: 81%

COVID-19 vaccine-readiness for anti-CD20-depleting therapy in autoimmune diseases

Baker

Roberts

Pryce

et al. 2020

Clinical and Experimental Immunology

171

201

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Based on the known and emerging biology of autoimmune diseases and COVID‐19, it was hypothesised that whilst B‐cell depletion should not necessarily expose people to severe SARS‐CoV‐2‐related issues, it may inhibit or blunt the protective immunity following infection and vaccination. This is supported clinically, as the majority of SARS‐CoV‐2 infected, CD20‐depleted people with autoimmunity, have recovered. However, in CD‐20 treated people until naïve B‐cells repopulate, based on B‐cell repopulation‐kinetics and vaccination responses, from published rituximab, and unpublished ocrelizumab (NCT00676715, NCT02545868) trial data shown here suggests that it may be possible to undertake dose‐interruption to maintain inflammatory disease control, whilst allowing effective vaccination against SARS‐CoV‐29, if and when an effective vaccine is available.

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Section: Introductionsupporting

confidence: 81%

COVID-19 vaccine-readiness for anti-CD20-depleting therapy in autoimmune diseases

Baker

Roberts

Pryce

et al. 2020

Clinical and Experimental Immunology

171

201

View full text Add to dashboard Cite

show abstract

“…These 10 patients were from various case reports and case series. Of these 10 patients, 8 had bilateral pneumonia requiring hospitalization and supplementary oxygen and three died [9,[15][16][17][18][19][20]. All these reports suggest a possible association between rituximab treatment for RMDs and poor prognoses for SARS-CoV-2 infected patients, but no study to date has analyzed the risk of SARS-CoV-2 infection and prognosis of such patients.…”

Section: Discussionmentioning

confidence: 99%

High rates of severe disease and death due to SARS-CoV-2 infection in rheumatic disease patients treated with rituximab: a descriptive study

et al. 2020

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The objective of this study is to describe the characteristics and outcomes of rheumatic and musculoskeletal disease (RMD) patients who were treated with rituximab and had suspected or confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this descriptive study, RMD patients who were treated with rituximab in the last 12 months at the Rheumatology Department of our hospital were screened for SARS-CoV-2 infection via telephone interview and a comprehensive review of clinical health records (01/02/2020-26/05/2020). Those with probable or confirmed SARS-CoV-2 infection were included. In total, 76 patients were screened. Of these, 13 (17.1%) had suspected or confirmed SARS-CoV-2 infection. With regard to these 13 patients, the median age at coronavirus disease (COVID-19) diagnosis was 68 years (range 28-76 years) and 8 (61.5%) were female. Five patients had rheumatoid arthritis, three had systemic vasculitis, two had Sjögren syndrome, and two had systemic lupus erythematosus. Additionally, seven patients (53.8%) had pulmonary involvement secondary to RMD. Eight patients (61.5%) developed severe disease leading to hospitalization, and seven developed bilateral pneumonia and respiratory insufficiency. Of the eight hospitalized patients, five (62.5%) fulfilled the acute respiratory distress syndrome criteria and three developed a critical disease and died. Our cohort had a high rate of severe disease requiring hospitalization (61.5%), with bilateral pneumonia and hyperinflammation leading to a high mortality rate (23.1%). Treatment with rituximab should be considered a possible risk factor for unfavorable outcomes in COVID-19 patients with RMD. However, further study is required to confirm this association.

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“…Moreover, SYK, which is essential for B cell development, was identified as the most significant upstream regulator that was downregulated in B cells within the severe group 48 , 49 . Although recovery from SARS-CoV-2 infection is not fully dependent on B cell function and antibody production 50 , these immune cells likely still have an important role in controlling the severity of disease, and a dysfunctional humoral response may result in higher viral titers and delayed viral clearance that could contribute to the development of ARDS during SARS-CoV-2 infection.…”

Section: Discussionmentioning

confidence: 99%

Cell type-specific immune dysregulation in severely ill COVID-19 patients

Yao

Bora

Parimon

et al. 2020

Preprint

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Coronavirus disease 2019 (COVID-19) has quickly become the most serious pandemic since the 1918 flu pandemic. In extreme situations, patients develop a dysregulated inflammatory lung injury called acute respiratory distress syndrome (ARDS) that causes progressive respiratory failure requiring mechanical ventilatory support. Recent studies have demonstrated immunologic dysfunction in severely ill COVID-19 patients. To further delineate the dysregulated immune response driving more severe clinical course from SARS-CoV-2 infection, we used single-cell RNA sequencing (scRNAseq) to analyze the transcriptome of peripheral blood mononuclear cells (PBMC) from hospitalized COVID-19 patients having mild disease (n = 5), developing ARDS (n = 6), and recovering from ARDS (n = 6). Our data demonstrated an overwhelming inflammatory response with select immunodeficiencies within various immune populations in ARDS patients. Specifically, their monocytes had defects in antigen presentation and deficiencies in interferon responsiveness that contrasted the higher interferon signals in lymphocytes. Furthermore, cytotoxic activity was suppressed in both NK and CD8 lymphocytes whereas B cell activation was deficient, which is consistent with the delayed viral clearance in severely ill COVID-19 patients. Finally, we identified altered signaling pathways in the severe group that suggests immunosenescence and immunometabolic changes could be contributing to the dysfunctional immune response. Our study demonstrates that COVID-19 patients with ARDS have an immunologically distinct response when compared to those with a more innocuous disease course and show a state of immune imbalance in which deficiencies in both the innate and adaptive immune response may be contributing to a more severe disease course in COVID-19.

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Mild Course of COVID‐19 and Spontaneous Virus Clearance in a Patient With Depleted Peripheral Blood B Cells Due to Rituximab Treatment

Cited by 35 publications

References 5 publications

COVID-19 vaccine-readiness for anti-CD20-depleting therapy in autoimmune diseases

COVID-19 vaccine-readiness for anti-CD20-depleting therapy in autoimmune diseases

High rates of severe disease and death due to SARS-CoV-2 infection in rheumatic disease patients treated with rituximab: a descriptive study

Cell type-specific immune dysregulation in severely ill COVID-19 patients

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