Yesterday we heard that if you have not made an anti-vaccine response after two jabs, then there is a big chance that you wont after three. This work in MS confirms what we have seen in other conditions using anti-CD20. This has implications of people treated with anti-CD20 which depletes memory B cells and the cells that will make new vaccine responses, as it means that you will not have protection to prevent infection from occuring. You then have to hope your memory T cells possibly supplemented with an anti-viral will do the trip to protect you from severe infection
How long does immunity last for….You woud think a couple of months. The simple answer is it lasts for life, but the magnitude of responses will vary and this in part dependson how much you see the targets of the immune response. See it alot and the immunity may hang around and see it not alot and it will disappear but bring back the target and off it will go again but it may take a few days.
Gurevich M, Zilkha-Falb R, Sonis P, Magalashvili D, Menascu S, Flechter S, Dolev M, Mandel M, Achiron A. SARS-COV-2 Memory B and T Cells Profile in Mild COVID-19 Convalescents subjects. Int J Infect Dis. 2021:S1201-9712(21)01203-0.
Objectives: . Antiviral adaptive immunity involves memory B-(MBC) and T-cells (MTC), however their dynamics in SARS-CoV-2 convalescents warrant further investigation.
Methods: . In the cross-sectional and longitudinal study, we evaluated blood-derived MBC- and MTC-responses in 68 anti-spike IgG-positive mild-COVID-19 convalescents at visit 1 between 1-7 months (median 4.1 months) after disease onset. SARS-CoV-2 anti-spike IgG was performed by ELISA, MBC by SARS-COV-2 specific receptor binding domain (RBD) Elispot and Interferon gamma (IFNg), interleukin 2 (IL2) and IFNg+IL2 secreting MTC by IFNg and IL2 SARS-CoV-2 FluoroSpot. For 24 patients sampled at first visit, the IgG, MBC and MTC analysis were also performed 3 months later at second visit.
Results: . Seventy two percent were both MBC- and MTC-positive, 18 % – MBC-positive and MTC-negative, and 10% – MTC-positive and MBC-negative. The peak of MBC-response level was detected at 3 months after COVID-19 onset and persisted up to 7 months post infection. A significant MTC-levels were detected one month after onset in response to S1, S2_N and SNMO peptide pools. The frequency and magnitude of MTC response to SNMO (Spike, nucleocapsid, membrane and open reading frame)was higher than to S1 and S2_N. Longitudinal analysis demonstrated that even when specific humoral immunity declined, the cellular immunity persisted.
Conclusion: . Our findings demonstrate durability of adaptive cellular immunity at least for 7-months after SARS-CoV-2 infection that suggest long-lasting protection
However one imagines some of the memory may get affected by MS treatments, if that a mechanism of how they stop MS. There are two classess of drugs that inhibit antibody responses from generating. These are the anti-CD20s and the sphingosine-1-phosphate receptor modulators, notably fingolimod. When you look in the people in UK, this lack of antibody response seems to associated with an increased risk of COVID-19-related infection.
Garjani A, Patel S, Bharkhada D, Rashid W, Coles A, Law GR, Evangelou N. Impact of mass vaccination on SARS-CoV-2 infections among multiple sclerosis patients taking immunomodulatory disease-modifying therapies in England. Mult Scler Relat Disord. 2021 Dec 5;57:103458. doi: 10.1016/j.msard.2021.103458.
- Risk of SARS-CoV-2 infection in pwMS on ocrelizumab compared to the general population is increased despite mass vaccination.
- Risk of SARS-CoV-2 infection in pwMS on fingolimod compared to the general population is increased despite mass vaccination.
- The risk remains the same as the general population for pwMS on other MS therapies after mass vaccination.
Background: Contradicting assumptions have been made about the effectiveness of SARS-CoV-2 vaccines in patients with multiple sclerosis (MS) receiving immunomodulatory disease-modifying therapies (DMTs) based on the quantification of humoral and cellular immune responses. This study aimed to understand changes in the risk of SARS-CoV-2 infection among the total population of patients receiving MS DMTs in England following mass vaccination.
Methods: This is a retrospective analysis of national data collected prospectively and longitudinally. National Health Service (NHS) England and NHS Improvement (NHSE/I) hold prescribing data on all commissioned MS DMTs in England. United Kingdom Health Security Agency (UKHSA) has been collecting data on all registered SARS-CoV-2 test results, including polymerase chain reaction and rapid antigen tests. All patients receiving MS DMTs were identified using NHSE/I datasets. All patients receiving MS DMTs with SARS-CoV-2 infection (i.e., positive test) from March 2020 to August 2021 were identified by merging NHSE/I and UKHSA datasets. Similar data for the general population were captured using publicly available datasets of the United Kingdom government. The incidence rate ratios (IRR) of SARS-CoV-2 infection among patients receiving MS DMTs compared to the general population during the pre-vaccination (November 2020 to January 2021) and post-vaccination (June to August 2021) periods were calculated.
Results: A mean (standard deviation) of 41,208 (4,301) patients received an MS DMT in England during each month from March 2020 to August 2021. The IRR (95% confidence interval) of infection in patients taking ocrelizumab versus the general population increased from 1.13 (0.97-1.31) during the pre-vaccination period to 1.79 (1.57-2.03) during the post-vaccination period. For patients on fingolimod, it increased from 0.87 (0.73-1.02) to 1.40 (1.20-1.63) during the same periods. There were no significant changes for patients on other MS DMTs.
Conclusion: SARS-CoV-2 vaccines offer less protection against infection to patients taking ocrelizumab or fingolimod, who have an impaired immune response to vaccines, than the general population. These findings will have implications for vaccination policies.
If you can’t get the paper from the link above get the preprint here
If you get COVID-19 and don’t make antibodies you should be eligible for one of the antibodies that neutralise infection. These work against the Wuhan and to some extent the delta strain but there are some that may not be that good for omicron
Cameroni et al. Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift. BioRXiv https://doi.org/10.1101/2021.12.12.472269
Preprint. COI some of the authours work for VIR who work with Glaxo Smith Klein. So if you are based in UK and catch COVID sotrovimab may be useful
Importantly the effects of sotrovimab and relative lack of effect with the REGen_CoV cocktail is confirmed in this unreviewed preprint and many others.
SARS-CoV-2 Omicron variant escapes neutralization by vaccinated and convalescent sera and therapeutic monoclonal antibodiesIkemura, N., Hoshino, A., Higuchi, Y., Taminishi, S., Inaba, T., Matoba, S MEdRXiv 2021 .10.1101/2021.12.13.21267761
These preprints also show the effects of the different vaccines on their capacity to neutralise omicron. The adenoviral versions were less active than the RNA vaccines
Analysis: A meta-analysis of Early Results to predict Vaccine efficacy against OmicronKhoury, D. S., Steain, M., Triccas, J., Sigal, A., Davenport, M. P., Cromer, D. MEDRXIV 10.1101/2021.12.13.21267748
In the studies to date, the estimated fold-drop in neutralisation titre against Omicron ranges from 2- to over 20-fold depending on the study and serum tested. Collating data results in a combined estimate of the fold drop in neutralisation titre against Omicron of 9.7 (95%CI 5.5-17.1). We use our previously established model to predict that six months after primary immunisation with an mRNA vaccine, efficacy for Omicron is estimated to have waned to around 40% against symptomatic and 80% against severe disease. A booster dose with an existing mRNA vaccine (even though it targets the ancestral spike) has the potential to raise efficacy to 86.2% (95% CI: 75.4-92.9) (symptomatic) and 98.2% (95% CI 90.9-99.7) (severe) against Omicron.
This suggests that a booster as it may help give protection as supported by numerous preprints surfacing recently
mRNA booster immunization elicits potent neutralizing serum activity against the SARS-CoV-2 Omicron variantGruell, H., Vanshylla, K., Tober-Lau, P., Hillus, D., Schommers, P., Lehmann, C., Kurth, F., Sander, L. E., Klein, F.MedRXiv 10.1101/2021.12.14.21267769
mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variantGarcia-Beltran, W. F., St Denis, K. J., Hoelzemer, A., Lam, E. C., Nitido, A. D., Sheehan, M. L., Berrios, C., Ofoman, O., Chang, C. C., Hauser, B. M., Feldman, J., Gregory, D. J., Poznansky, M. C., Schmidt, A. G., Iafrate, A. J., Naranbhai, V., Balazs, A. B.10.1101/2021.12.14.21267755
SARS-CoV-2 Omicron: reduction of potent humoral responses and resistance to clinical immunotherapeutics relative to viral variants of concernAggarwal, A., Ospina Stella, A., Walker, G., Akerman, A., Milogiannakis, V., Hoppe, A. C., Mathivanan, V., Fichter, C., McAllery, S., Amatayakul-Chantler, S., Roth, N., Coppola, G., Munier, M. L., Darley, D. R., Khoury, D. S., Foster, C. S. P., Lu, Y., Schofield, P., Jackson, J., Henry, J., Mazigi, O., Jaeck, H.-M., Langles, D., Cromer, D., Davenport, M. P., Christ, D., Matthews, G., Rawlinson, W., Kelleher, A. D., Turville, S. G.10.1101/2021.12.14.21267772 — Posted: 2021-12-15
And finally…A couple of weeks ago we suggested that omicron had so many unknown mutations that it could have come from animal where the virus was mutating and adapting to the animal before jumping back to humans. Whilst we pointed a finger at deer, it seems it could have been the meeces. Do you buy this idea?
Evidence for a mouse origin of the SARS-CoV-2 Omicron variantWei, C., Shan, K.-J., Wang, W., Zhang, S., Huan, Q., Qian, W.10.1101/2021.12.14.472632 — Posted: 2021-12-15
COI No relevant.
Disclaimer: This is not clinical advice and the views are those of the author and do not represent the views of any institution