Saturday COVID Lunch

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CD20-depleting antibodies and catching COVID-19 is reported to be bad news however

In this study there were 9/258 people who got COVID and the conclusion was that “rituximab seems not to be safe enough during the pandemic”. This is a opinion. This could be countered other opinions, by the data from the Global Data Sharing approach where hundreds of CD20-treated people developed COVID-19 and the vast, vast majority recovered.

Esmaeili S, Abbasi MH, Abolmaali M, Mojtahed M, Alavi SNR, Soleimani S, Mokhtari M, Hatam J, Khotbehsara ST, Motamed MR, Joghataei MT, Mirzaasgari Z, Moghaddasi M. Rituximab and risk of COVID-19 infection and its severity in patients with MS and NMOSD. BMC Neurol. 2021; 21:183.

Background: Choosing a safe disease modifying therapy during the COVID-19 pandemic is challenging. This case series study was conducted to determine the incidence rate and the course of Covid-19 infection in MS/NMOSD patients treated with rituximab.

Methods: In this study, we designed a web-based questionnaire. Baseline information such as patient- reported walking disability, total number of rituximab infusions received, delayed injections, occurrence of any relapse, and the use of corticosteroids during the pandemic were collected. Also, information regarding the Covid-19 pandemic such as adherence to self-isolation, any recent exposure to an infected individual and the presence of suggestive symptoms were collected. In case of positive test results, patients were grouped into 2 categories; mild to moderate and seriously ill and outcomes were evaluated as favorable (improved/ discharged) and unfavorable (expired).

Results: Two hundred fifty-eight patients with Multiple Sclerosis were enrolled in this study, 9 of the subjects (3.4%) were confirmed positive for Covid-19, five of which required hospitalizations (55.5%), two patients required ICU admission (22.2%) and 2 two patients died (22.2%). None of these patients ever mentioned using corticosteroids during the pandemic. In comparison to MS patients who were not receiving disease modifying therapy (DMT), our study indicated a higher incidence of Covid-19 infection, higher ratio of serious illness and a higher fatality ratio.

Conclusions: Rituximab seems not to be safe enough during the pandemic.

Risk of COVID-19 in MS

Barzegar M, Mirmosayyeb O, Gajarzadeh M, Afshari-Safavi A, Nehzat N, Vaheb S, Shaygannejad V, Maghzi AH. COVID-19 Among Patients With Multiple Sclerosis: A Systematic Review. Neurol Neuroimmunol Neuroinflamm. 2021 May 20;8(4):e1001.

Objective: We systematically reviewed the literature on COVID-19 in patients with multiple sclerosis (MS).

Methods: We searched PubMed, Scopus, EMBASE, CINAHL, Web of Science, Google Scholar, and World Health Organization database from December 1, 2019, to December 18, 2020. Three conference abstract databases were also searched. We included any types of studies that reported characteristics of patients with MS with COVID-19.

Results: From an initial 2,679 publications and 3,138 conference abstracts, 87 studies (67 published articles and 20 abstracts) consisting of 4,310 patients with suspected/confirmed COVID-19 with MS met the inclusion criteria. The female/male ratio was 2.53:1, the mean (SD) age was 44.91 (4.31) years, the mean disease duration was 12.46 (2.27), the mean Expanded Disability Status Scale score was 2.54 (0.81), the relapsing/progressive ratio was 4.75:1, and 32.9% of patients had at least 1 comorbidity. The most common symptoms were fever (68.8%), followed by cough (63.9%), fatigue/asthenia (51.2%), and shortness of breath (39.5%). In total, 837 of 4,043 patients with MS with suspected/confirmed COVID-19 (20.7%) required hospitalization, and 130 of 4,310 (3.0%) died of COVID-19. Among suspected/confirmed patients, the highest hospitalization and mortality rates were in patients with no disease-modifying therapies (42.9% and 8.4%), followed by B cell-depleting agents (29.2% and 2.5%).

Conclusion: Our study suggested that MS did not significantly increase the mortality rate from COVID-19. These data should be interpreted with caution as patients with MS are more likely female and younger compared with the general population where age and male sex seem to be risk factors for worse disease outcome.

So maybe anti-CD20 is a risk factor for COVID19

Etemadifar M, Sigari AA, Sedaghat N, Salari M, Nouri H. Acute relapse and poor immunization following COVID-19 vaccination in a rituximab-treated multiple sclerosis patient. Hum Vaccin Immunother. 2021 May 20:1-3. doi: 10.1080/21645515.2021.1928463

Brain lesions (white bits) Etamadfir et al. 2021

With the progress of COVID-19 vaccination programs worldwide, some new adverse events associated with the available vaccines may unfold, especially in subpopulations, representatives of whom were not included in phase I, II, and III clinical trials of these vaccines, such as patients with autoimmune diseases, including multiple sclerosis (MS). A 34-year-old woman presented with severe right hemiplegia and ataxia. She was diagnosed with relapsing-remitting MS (RRMS) 13 years ago and treated with rituximab (an anti-CD20 monoclonal antibody) during the last 15 months. She had received her first dose of adenovirus-vectored COVID-19 vaccine Gam-COVID-Vac (Sputnik V) three months after her last infusion of rituximab and three days before experiencing her latest MS relapse episode, preceded by mild symptoms (fatigue, myalgia, generalized weakness, etc.). Magnetic resonance imaging revealed several new periventricular, juxtacortical, brainstem, and cerebellar peduncle lesions. She received corticosteroid therapy for five consecutive days, and her neurological deficits slightly improved. Twenty-one days after receiving the first dose of the vaccine, her anti-SARS-CoV-2 antibodies were below the lower detection limit. However, a decision was made to adhere to the vaccination schedule and not risk the patient’s safety against an unfortunate COVID-19 contraction, and thus, she was advised to receive the second Gam-COVID-Vac dose after discontinuation of oral steroid taper. The safety of adenovirus-based vaccines in patients with autoimmune diseases requires further investigation. Meanwhile, clinicians should raise awareness among their patients regarding the potentially limited efficacy of COVID-19 vaccination in those treated with anti-CD20 treatments. After careful, individualized risk-benefit assessments, planning a delay/pause in such treatments to create a time window for patients to receive the vaccine and develop anti-SARS-CoV-2 immunity may be recommended.

Was the relapse due to the vaccine or was it going to happen anyway especially as it occurred 3 days after vaccine. I don’t know on another issue and the anti-vaccine response having see alot of the antibody responses after the first dose of vaccine, I would say ensure you get the second jab because the antibody response to the first cycle may be abit rubbish even if you dont have a DMT, compared to what happens after the second cycle. Mine was rubbish. But the question we are waiting for what happened after the second vaccine dose. It would be known by now.

Maybe a way to reduce the risk of relative vaccine failure

We sort of know that people on ocrelizumab are not going to make a good vaccine-related ocrelizumab whilst on active treatment and one wonders if the way to to deal with this is to give people an antibody response. It is being shown that anti-COVID-19 antibodies produced from the makers of anti-CD20 can reduce the the risk of hospitalisation from infection. It makes me think that this could protect people with cancer and MS.

REGEN-COV Antibody Cocktail Clinical Outcomes Study in Covid-19 OutpatientsWeinreich, D et al. MedRXiv 10.1101/2021.05.19.21257469 — Posted: 2021-05-21

Background: REGEN-COV antibody cocktail (casirivimab with imdevimab) rapidly reduced viral load and decreased medically-attended visits in the phase 1/2 portion of this trial; REGEN-COV, retains activity in vitro against emerging SARS-CoV-2 variants of concern. Methods: The phase 3 portion of this adaptive, randomized, master protocol, included 4,057 Covid-19 outpatients with one or more risk factors for severe disease.

Conclusions: Treatment with REGEN-COV was well-tolerated and significantly reduced Covid-19-related hospitalization or all-cause death, rapidly resolved symptoms, and reduced viral load. (NCT04425629.)

No some good news for MS as a covid-19 trial shows benefit…so it should work in MS?

Metforin is reported to rejuveniate macrophages and oligodendrocytes by making them useful. We have suggested that macropahges are key to surviving covid-19. So if this is true then metforin should protect against COVID-19. So what happens? Yet you guessed it, So Cambridge and the rest seem to be on the right track. So if they can get the trials right it should be good news….Watch this space

Metformin Is Associated with Favorable Outcomes in Patients with COVID-19 and Type 2 Diabetes MellitusMa, Z., Patel, N., Vemparala, P., Krishnamurthy, M.10.1101/2021.05.20.21257490 — Posted: 2021-05-21

Aim: We aim to address whether metformin use offers a low mortality on patients with COVID-19 and pre-existing type 2 diabetes mellitus (T2DM). Materials and Methods: A cohort of 1356 hospitalized patients with COVID-19 and pre-existing T2DM was analyzed

. Conclusions: Our results provide supporting evidence that metformin may confer increased survival in patients with COVID-19 and T2DM treated with Metformin prior to hospitalization

Disclaimer: Please note that the opinions expressed here are those of author and do not necessarily reflect the position of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust.

About the author

MouseDoctor

14 comments

  • I must say i feel discouraged by the continuous supply of new data indicating that anti-CD20 treated patienta are not faring well. I know you’re not a clinician, mousedoc, but I can’t help but wonder – just how bad do you think the association with anti-CD20 and covid is? And to prof G if he sees this comment – how careful do you tell your patients on these therapies to be during the pandemic? Does age matter? Should these patients socially isolate, or just take regular precautions? I’m really curious.

    • I don’t think anyone really knows. The big question is how important are T-cells…

      I can tell you what I do: I wear FFP2 mask in indoor spaces where others are around (office, shops, public transport, official mandate is for any type of mask with varying compliance). I limit time in office as far as feasible but have not really completely refused to go there since last summer.

      I make an exception for my MS clinic where I wear surgical masks (as mandated and enforced) mainly because O2 tends to drop a bit during infusions because of shallow breathing anyhow and because physiotherapy with FFP2 is too much. It helps that the clinic is physically separate from infectious diseases dep. on another campus.

    • “I must say i feel discouraged by the continuous supply of new data indicating that anti-CD20 treated patienta are not faring well”. If this relates to the antibody response after vaccine…..I am sorry to say this is just the tip of the iceberg so far….Should I stop posting on this?….we have to publish our data, Cardiff their data, Cambridge their data, rituxiland, Italian, American, Frence, German, Israel mark2….etc, etc, etc, etc, you will get a paper or three from every country and condition (arthritis, cancer lup etc etc) using anti-CD20 then there will be a Roche Paper and Novartis papers looking on the bright side….as they will show a T cell response.

      However, in relation to CD20 and COVID-19 the increased risks are present but are low. Other risk factors include disability and then there aeei, age, co-morbidities are all additional risk factors which are the risk factors of the general population. I am not a neuro and dont give advice but I have succificient risk factors to have a bad time following COVID-19. I try to use common sense and remain cautious, like you.

      • Thanks for sharing MD. Will keep reading maybe eventually there will be some good news for people on anti cd 20… meantime are hearing some are self treating my getting a third dose of a non mRNA vaccine and that worked for some – thoughts on this? It feels like we should do something rather than continue to live with the crappy choice of isolate or risk serious illness. The more mask mandates are removed the higher the real risk of getting out there too – so greater urgency to find a solution…

      • Thank you for the response.
        I absolutely don’t want you to stop posting on the associations between DMTs, covid and the covid vaccine. By ”discouraged” I don’t mean that I don’t want to hear it – quite the contrary. It’s very important for me, and I think most patients on potent DMTs will agree. But of course it’s sad to be on an anti-CD20 and then see more and more data suggesting it’s associated with bad outcomes in terms of both infection and vaccine-response. However we also need to know this – so as to perhaps bring it up to our neurologists attention and figure out possible solutions or life-style adaptations.

          • My guess would be people who don’t have complete CD20 depletion at the time of vaccination, or people who are responding abnormally to CD20 treatments are the ones that get a antibody vaccine response. Perhaps patients who are on ritux/ocr and still develop antibodies following vaccination also have more MS activity than those who don’t? Just a laymans speculations …

          • Good speculation but I think the cells making vaccine response and MS are differnt and have different repopulation characteristics

      • I count on t-cell theory as it seems to be the „more important“ immune reaction when it comes to disease no?
        and the vaccines make pretty good t-cell
        responses (higher measures than convalescent persons) and should be therefore limiting the severe covid?
        for sure we have higher infection risks as no or low antibodies are there but so it will be for most people after some month anyway…
        i think we keep the masking for now and distancing but most of our friends now are getting jabbed so there should be some herdprotection as well…
        we have booked holidays on an island (1.5h duration flight with ffp3 mask) – will hit the beach for 14 days (i guess no risk down there) and my jabbed husband will take care of food and in the small
        boutique hotel we get room service – we gonna exercise self tests every 24h and when positive we gonna get back home…i think it is important to have some more normal days! would the mouse agree on that?

  • Just something I don’t understand on covid vaccines and anti CD-20

    If your not on anti a CD- 20 and have a vaccine, then move onto a anti CD-20.

    Does the vaccine have less efficacy if you’ve had the vaccine before the anti CD-20 therapy or is it still good response?

      • Haha no, I’m looking to move onto it. I’ve had 1 jab. But didn’t know if the anti cd 20 would take away the efficacy of the jab.

  • Here is the Regeneron press release concerning the prophylaxis use of its monoclonal antibody cocktail.

    https://investor.regeneron.com/news-releases/news-release-details/phase-3-prevention-trial-showed-81-reduced-risk-symptomatic-sars

    I’m not sure what the delay is with respect to getting this an FDA EUA or EMA approval. Given the poor antibody response to the various vaccines by those taking Ocrelizumab this should be an option. Thank you mousedoc for posting on this issue and referencing the potential use of monoclonal antibody cocktail. We need more visibility to such a solution. People wMS and others that are immune suppressed must not be left behind.

  • Ocrevus (O) was to be a great DMT. I got on the O Train too. Who would have thought a “damn pandemic”, on the backs of people with immune dysfunction? But it HAS happened. Some people will be better able to handle the jeopardy than others, both physically and emotionally (psychologically). My MS doc stopped new treatments of people on O because of the long term risk that covid presents, i.e. the “long haulers”, if you get a “good” case. You may not die, that’s pretty certain, but you’re still at risk for acquiring long term deficits. So you are more at risk of the infection, and consequently more at risk for developing long haul effects, than others not on the B-Cell depleting DMT’s. You are already in this boat of long term risk (from MS) and reality has put more icebergs in the ocean. So what do you do? If you’re OK with jeopardy, do nothing, the risk is not huge. But it really is too bad that you can’t just stop the O, make new plans, and move on swiftly. (Rest assured, Roche would not want that, the O Train is not scheduled to make stops, and passengers jumping off is not good for the reputation of the train).

    I am back going to crowded auctions and interacting cheerfully with vaxxed people and others I suppose, at my local antique market where I sell. I feel pretty happy and confident about my whole current status. I myself couldn’t do that if I were still on O.

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