ProfG has written about the the effect of continous B cell depletion and the the influence of B cell depletion.
However, this posts asked if continous B cell depletion can put you at risk of catching SARS-CoV-2 virus. Although B cells are important in fighting off bacteria, there is a small increased risk of catching some viral infections (Hauser et al. 2019). CD20 is expressed by the B cells that will form new B cell responses to new infections(Immunology 101). In MS we know that the response to vaccination is blunted with ocrelizumab and rituximab (Stokmaier et al. 2018; Kim et al. 2013). So maybe it could increase risk of COVID infection.
Of all the MS DMT, we have heard the most about rituximab. Much of this has been from the International Women in MS meetings and congrats to them for keeping this initiative going. This could be simply due to B clldepletion deemed as a useful treatment
Looking a the Biology we have made the case that B cells and antibody may not be absolutely necessary based on:
- Genetic B cell deficient people can recover from COVID Infection (Soresino et al. 2020; )
- In animals models B cells are a minor population in COVID-19 Lesions (Boa et al. 2020a)
- In animal models the virus can be cleared before a notable antibody response is produced (Boa et al. 2020a, Boa et al. 2020b).
- Humans can recover before a significant anti-viral response develops (Thevarajan et al. 2020)
- Humans can recover in the apparent absence of anti-COVID19 antibody responses (Wang et al. 2020; Wu et al. 202)
- B cells are a minor population in the covid lesion in humans (Christine et al. 2020)
- Humans with depleted with B cells can recover and that is not just anti-CD20 B cell depleting drugs (Somarni et al. 2020)
- Importantly people with MS provide most news for this statistic (Novi et al. 2020; Louapre et al. 2020 Montero-Escribano et al. 2020; Somarni et al. 2020).
Although there have been COVID-19-related deaths in people taking CD20 antibodies, there have been deaths in people not taking anything and based on infromation presented at the iWiMS meetings older people and people with co-mordibities like hyper tension; diabetes and other cardiovascular issues are at risk as reported in the General Population (Xhu et al. 2020) and todate the vast majorit of people treated have recovered (Novi et al. 2020; Louapre et al. 2020 Montero-Escribano et al. 2020; Somarni et al. 2020). This is also the case in this new report involving 50 people taking anti-CD20. So thats good news in my book.
Blocking B cells from generating antiboides could be good news as:
- High levels of antibodies can be associated with more severe disease (Liu et al. 2019; Zhoa et al. 2020).
- Anti-viral antibodies may be destructive as evidenced by activated complement (Hole-producing molecules) and complement inhibitors may have value (Mastaglio et al. 2020; Magro et al. 2020)
- Antibodies can cause cells like neutrophils and macrophages to act get activated to destroy virus but if exaggerated could destroy tissues (Barnes et al. 2020; Magro et al. 2020).
- Antibodies can induce antibody inducted macophagee enhancement, where by antibodies bind to virus and take it to macrophages via the Fc receptor (Iwaski & Yang 2020) and help cause the
However, there is also evidence that B cells are of value in COVID-19
- Theorectically B cells can activate T cells for immunity (Immunology 101. Jelic et al. 2019)
- SARS-CoV2 antibodies can be detected within a few days of symptom on set and some can neutralize the virus (Guo et al. 2020; Xiang et al. 2020; van der Heide et al. 2020;Okba et al. 2020; de Assis et al. 2020)
- SARS-CoV2 antibodies can clear the virus in humans (Zeng et al. 2020)
- SARS-C0V2 antibodies can facilititate recovery in some people (Rajendran et al. 2020; van der Heide et al. 2020 )
- SARS-CoV2 may limit re-infection (Boa et al. 2020b)
- Genetically impaired B cells may associate with more severe disease (Quinti et al. 2020) .
- Rituximab use may be associated with a higher risk of catching COVID-19
B-cell depleting therapies may affect susceptibility to acute respiratory illness among patients with Multiple Sclerosis during the early COVID-19 epidemic in Iran,Farinaz Safavi, Bardia Nourbakhsh, Amir Reza AzimiPublication stage: Multiplesclerosis and related disorder In Press Journal Pre-Proof.
- 4.8% of MS patients fulfilled defined criteria for COVID-19-suspect group. (There was no viral testing)
- Two patients required hospitalization; no intubation or ICU admission was reported
- Patients on B-cell depleting agents had three times higher risk of being in COVID-19 group
In a cross-sectional survey, data were collected by sending a questionnaire to 2000 patients with a demyelinating disease through an online portal system. Collected data included the current MS DMT and patient-reported disability level, history of recent sick contact, recent fever, respiratory symptoms, diagnosis with COVID-19 and the disposition after the diagnosis. We defined a COVID-19-suspect group as patients having fever and cough or fever and shortness of breath, or a presumptive diagnosis based on suggestive chest computed tomography. We calculated the proportion of COVID-19-suspect patients and compared their demographics, clinical characteristics, and DMT categories with the rest of survey-responders, using univariable and multivariable models.
Out of 712 patients, 34 (4.8%) fulfilled our criteria for being in the COVID-19-suspect group. Only two patients required hospitalization. No patient required intensive care. In a multivariable model, disease duration (p-value=0.017), DMT category (p-value=0.030) and history of sick contact (p-values<0.001) were associated with the risk of being in the COVID-19-suspect group. Patients on B-cell depleting antibodies had 3.6 times higher risk of being in the COVID-19-suspect group as compared to patients on none-lymphocyte-depleting and non-cell trafficking inhibitor DMTs (95%CI: 1.45, 8.68, p-value=0.005).
The course of infection in MS patients suspected of having COVID-19 was mild to moderate, and all patients had a full recovery. B-cell depleting antibodies may increase the susceptibility to contracting COVID-19.
There are many explanations of why this view may not be right, but as we know…SH1 sticks. First you have to determine how blocking CD20- cells could make a problem. In this sample there was 21/285 people taking rituimab with suspected COVID-19, but 0/12 taking ocrelizumab.
However, last night Professor Jan Hillert from Rituxiland…Oops I mean Sweden, gave International women in multiple sclerosis a taster of the data of COVID-19 infection and their view was associated with more infection. Now does this blow my ideas into touch. Not really because again even if there was more infection, one the whole people were recovering from the infection.
If you want to hear ProfB’s presentation and those of Prof Hillert, plus French and US updates watch youtube from the IWiMS. As you can see there was a cock-up at the start. ProfB thought he would pre-record a video to keep too time, but it was done live.
Anyone can make suggestions after the event, but we have put our necks out tomake some suggestions. However, we will eat humble pie when we are proved wrong.