After rejection from the Lancet doi:SSRN ID3631244, this COVID paper Disease modifying therapies and Covid-19 severity in Multiple Sclerosis.Sormani et al.Ann Neurol. 2021. doi: 10.1002/ana.26028. arrives in the Anals of Neurology.
This is about 7 months later, when I guess people don’t really care much any more.. The media may pick it up, but there is now data from the global registires that has been circulated and the orginal gave the punchline many months ago, so the original story is “old hat”.
The original paper was non-peer reviewed, but did the message really change? (See below). This study suggests worsing of disease associated with CD20 (mainly orcelizumab) yet this study COVID-19 in ocrelizumab-treated people with multiple sclerosis.Hughes R, et al.Mult Scler Relat Disord. 2020 Dec 30;49:102725 suggests use of ocrelizumab induces mild to moderate disease if you develop COVID-19. Where is the Swedish rituximab data that has something to add to this subject?
So perhaps a good reason to have all preprints in one searchable site rather than publishing on many difficult to search journal-specific sites. So another good idea going down the pan .SSRN is an Elsevier pre print site where the Info originally surfaced, which was open access but it is now a sign-up site, so they can send you adverts. When does it become a pay to deposit site?
The orininal non-peer reviewed iteration said
Findings (Jan to May): Of 784 PwMS with suspected (n=593) or confirmed (n=191) .13 (1·66%) died: We found an excess of patients treated with Ocrelizumab OR=1·84,95%CI=1·31-2·56,p<0·001) and a reduction of patients treated with Interferon (OR=0·47,95%CI=0·33-0·67, p<0·001) as compared to the frequency of use of these DMTs in the Italian MS population. The therapy with an anti-CD20 agent (Ocrelizumab or Rituximab) was significantly associated (OR=2·59,95%CI=1·43-4·67, p=0·002) with an increased risk of severe Covid-19 course. Recent use (<1 month) of methylprednisolone was also associated with a worse outcome (OR=6·0,95%CI=2·2-16·5, p=0·007).
The new paper (Jan to Sepetmeber 2020) says
Results (Jan to September): Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) Covid-19, 13 (1.54%) died: 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had a radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, EDSS, disease duration, BMI, comorbidities and recent methylprednisolone use, the therapy with an anti-CD20 agent (Ocrelizumab or Rituximab) was significantly associated (OR = 2.37,95%CI = 1.18-4.74,p = 0.015) with an increased risk of severe Covid-19. Recent use (<1 month) of methylprednisolone was also associated with a worse outcome (OR = 5.24,95%CI = 2.20-12.53, p = 0.001). Results were confirmed by the PS-weighted and by all the sensitivity analyses.
In this study 89/94 CD20 takers were taking ocrelizumab
The new study concluded
Interpretation: This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, some specific elements of risk emerged. These will need to be considered while the Covid-19 pandemic is persisting.
There is a warning of increased COVID-19 risks with ant-CD20 therapy. The preprint gave the rapid insight but if you ignore this and only use the peer-reviewed litterature as your source than in a fast moving world your papers are hopelessly out of date by the time they are published such as this paper which suggests that the the main worry is alemtuzumab and cladribine which has not really materialized.
Multiple Sclerosis During the COVID-19 Pandemic.Naik S, Jha N, Naik S, Lippmann S.Prim Care Companion CNS Disord. 2021 Jan 21;23(1):20com02820.