I have been looking at the immune response and how it is used to deal with the virus and how it may be involved in the adverse effects.
Today we look at the B cells. Whilst I have made the case that in at least some people that the virus is dealt with before the antibody response kicks in. However, the antibody response is important as it can cause some protection and this is shown by taking peoples blood and injecting this into other people. This is the “Outbreak” (Film with Dustbin Hoffman) bleeding the Monkey to save the World Approach.
People who recover from COVID make and antibody response to the virus that provides immunity from re-infection. In China they bleed people who recovered and injected this into severely ill people and this seemed to do go, implying that the antibody response is beneficial. Therefore you dont want to deplete your B cell response, but most MS treatments deplete your B cells. I have argued this is why they work. However to make a new immune response yo want to spare your immature and mature/naive B cells to recover, this occurs quickly with alemtuzumab withina few months and abit longer with cladribine. Ocrelizumab keeps B cells low and so it is more difficult to make an anti-vaccine response. With alemtuzumab they come back quickly. Whilst the data below says that the B cell or an anti-viral B cells responsel is beneficial, it has also been suggested that anti-COVID antibody responses can be associated with a more severe disease. This does not surprise me because if any viral proteins are left on the cell surface after infection and it could be a target for antibody induced damage. When people with COVID-19 have been bled there is IgG1 and IgG3 response and we know that IgG1 and particularly IgG3 is very good at punching holes in their target by a process called complement fixation, so it could be damaging. This has been seen in other lower respiratory diseases, where sometimes the anti-viral response is damaging. Now in this study it was seen to beneficial, it may not always be. There is little IgG4 anti-COVID being made, so one images companies are making thes antibodies as fast as we can say COVID19 as these do not cause complement fixation. There is a trial doing the same in France and this should have finished. Hopefully we will get real life experience of what happens in people on ocrelizumab who are COVID infected to see where the good-bad balance lies.
UPDATE IN RESPONSE TO COMMENTS: Now so you know. CD20 is not expressed on the antibody making B cells and so once you make an antibody response then the plasma cells are not going to be initially touched by ocrelizumab, rituximab, ofatumumab, etc, etc,. Likewise despite being on ocrelizumab and depleting all your B cells in the blood, only about 2% of your B cells are in the blood. You still have B cells in your lymph nodes and this is were antibodies will be formed. Now it is true that ocrelizumab treatment will inhibit your capacity to make vaccine responses, it is the case that you still can make vaccine responses. The data is on NCT02545868. It seems like putting this easily findable in the public domain in approrpriate.
Deployment of convalescent plasma for the prevention and treatment of COVID-19. Bloch EM, Shoham S, Casadevall A, Sachais BS, Shaz B, Winters JL, van Buskirk C, Grossman BJ, Joyner M, Henderson JP, Pekosz A, Lau B, Wesolowski A, Katz L, Shan H, Auwaerter PG, Thomas D, Sullivan DJ, Paneth N, Gehrie E, Spitalnik S, Hod E, Pollack L, Nicholson WT, Pirofski LA, Bailey JA, Tobian AA.J Clin Invest. 2020 Apr 7. pii: 138745. doi: 10.1172/JCI138745. [Epub ahead of print]
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease (COVID-19), has spurred a global health crisis. To date, there are no proven options for prophylaxis for those who have been exposed to SARS-CoV-2, nor therapy for those who develop COVID-19. Immune (i.e. “convalescent”) plasma refers to plasma that is collected from individuals, following resolution of infection and development of antibodies. Passive antibody administration through transfusion of convalescent plasma may offer the only short-term strategy to confer immediate immunity to susceptible individuals. There are numerous examples, where convalescent plasma has been used successfully as post-exposure prophylaxis and/or treatment of infectious diseases, including other outbreaks of coronaviruses (e.g., SARS-1, Middle East Respiratory Syndrome [MERS]). Convalescent plasma has also been used in the COVID-19 pandemic; limited data from China suggest clinical benefit, including radiological resolution, reduction in viral loads and improved survival. Globally, blood centers have robust infrastructure to undertake collections and construct inventories of convalescent plasma to meet the growing demand. Nonetheless, there are nuanced challenges, both regulatory and logistical, spanning donor eligibility, donor recruitment, collections and transfusion itself. Data from rigorously controlled clinical trials of convalescent plasma are also few, underscoring the need to evaluate its use objectively for a range of indications (e.g., prevention vs treatment) and patient populations (e.g., age, comorbid disease). We provide an overview of convalescent plasma, from evidence of benefit, regulatory considerations, logistical work flow and proposed clinical trials, as scale up is brought underway to mobilize this critical resource. .
Duan K et al. Effectiveness of convalescent plasma therapy in severe COVID-19 patients.PNAS first published April 6, 020 https://doi.org/10.1073/pnas.2004168117
COVID-19 is currently a big threat to global health. However, no specific anti-viral agents are available for its treatment. In this work, we explore the feasibility of convalescent plasma (CP) transfusion to rescue severe patients. The results from 10 severe adult cases showed that one dose (200 mL) of CP was well tolerated and could significantly increase or maintain the neutralizing antibodies at a high level, leading to disappearance of viremia in 7 d. Meanwhile, clinical symptoms and paraclinical criteria rapidly improved within 3 d. Radiological examination showed varying degrees of absorption of lung lesions within 7 d. These results indicate that CP can serve as a promising rescue option for severe COVID-19, while the randomized trial is warranted.
Currently, there are no approved specific antiviral agents for novel coronavirus disease 2019 (COVID-19). In this study, 10 severe patients confirmed by real-time viral RNA test were enrolled prospectively. One dose of 200 mL of convalescent plasma (CP) derived from recently recovered donors with the neutralizing antibody titers above 1:640 was transfused to the patients as an addition to maximal supportive care and antiviral agents. The primary endpoint was the safety of CP transfusion. The second endpoints were the improvement of clinical symptoms and laboratory parameters within 3 d after CP transfusion. The median time from onset of illness to CP transfusion was 16.5 d. After CP transfusion, the level of neutralizing antibody increased rapidly up to 1:640 in five cases, while that of the other four cases maintained at a high level (1:640). The clinical symptoms were significantly improved along with increase of oxyhemoglobin saturation within 3 d. Several parameters tended to improve as compared to pretransfusion, including increased lymphocyte counts (0.65 × 109/L vs. 0.76 × 109/L) and decreased C-reactive protein (55.98 mg/L vs. 18.13 mg/L). Radiological examinations showed varying degrees of absorption of lung lesions within 7 d. The viral load was undetectable after transfusion in seven patients who had previous viremia. No severe adverse effects were observed. This study showed CP therapy was well tolerated and could potentially improve the clinical outcomes through neutralizing viremia in severe COVID-19 cases. The optimal dose and time point, as well as the clinical benefit of CP therapy, needs further investigation in larger well-controlled trials.
Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. Shen C, Wang Z, Zhao F, Yang Y, Li J, Yuan J, Wang F, Li D, Yang M, Xing L, Wei J, Xiao H, Yang Y, Qu J, Qing L, Chen L, Xu Z, Peng L, Li Y, Zheng H, Chen F, Huang K, Jiang Y, Liu D, Zhang Z, Liu Y, Liu L.JAMA. 2020 Mar 27. doi: 10.1001/jama.2020.4783. [Epub ahead of print]
All 5 patients (age range, 36-65 years; 2 women) were receiving mechanical ventilation at the time of treatment and all had received antiviral agents and methylprednisolone. Following plasma transfusion, body temperature normalized within 3 days in 4 of 5 patients, the SOFA score decreased, and Pao2/Fio2 increased within 12 days (range, 172-276 before and 284-366 after). Viral loads also decreased and became negative within 12 days after the transfusion, and SARS-CoV-2-specific ELISA and neutralizing antibody titers increased following the transfusion (range, 40-60 before and 80-320 on day 7). ARDS resolved in 4 patients at 12 days after transfusion, and 3 patients were weaned from mechanical ventilation within 2 weeks of treatment. Of the 5 patients, 3 have been discharged from the hospital (length of stay: 53, 51, and 55 days), and 2 are in stable condition at 37 days after transfusion.