COVID Thursday Lunch

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Benchmark of what we can hope when you get vaccinated…UK non-MS experience

Impact of vaccination on SARS-CoV-2 cases in the community: a population-based study using the UK COVID-19 Infection SurveyPritchard, E., Matthews, P., Stoesser, N., Eyre, D., Gethings, O., Vitha, K.-D., Jones, J., House, T., VanSteenhouse, H., Bell, I., Bell, J., Newton, J., Farrar, J., Diamond, I., Rourke, E., Studley, R., Crook, D. W., peto, t. E., Walker, A. S., Pouwels, K. B., Coronavirus Infection Survey team10.1101/2021.04.22.21255913 — Posted: 2021-04-23

Objectives To assess the effectiveness of COVID-19 vaccination in preventing SARS-CoV-2 infection in the community.

Setting The UK population-representative longitudinal COVID-19 Infection Survey.

Participants 373,402 participants aged ≥16 years contributing 1,610,562 RT-PCR results from nose and throat swabs between 1 December 2020 and 3 April 2021.

Main outcome measures New RT-PCR-positive episodes for SARS-CoV-2 overall, by self-reported symptoms, by cycle threshold (Ct) value (<30 versus ≥30), and by gene positivity (compatible with the B.1.1.7 variant versus not).

Results Odds of new SARS-CoV-2 infection were reduced 65% (95% CI 60 to 70%; P<0.001) in those ≥21 days since first vaccination with no second dose versus unvaccinated individuals without evidence of prior infection (RT-PCR or antibody). In those vaccinated, the largest reduction in odds was seen post second dose (70%, 95% CI 62 to 77%; P<0.001).There was no evidence that these benefits varied between Oxford-AstraZeneca and Pfizer-BioNTech vaccines (P>0.9).There was no evidence of a difference in odds of new SARS-CoV-2 infection for individuals having received two vaccine doses and with evidence of prior infection but not vaccinated (P=0.89). Vaccination had a greater impact on reducing SARS-CoV-2 infections with evidence of high viral shedding Ct<30 (88% reduction after two doses; 95% CI 80 to 93%; P<0.001) and with self-reported symptoms (90% reduction after two doses; 95% CI 82 to 94%; P<0.001); effects were similar for different gene positivity patterns.

Conclusion Vaccination with a single dose of Oxford-AstraZeneca or Pfizer-BioNTech vaccines, or two doses of Pfizer-BioNTech, significantly reduced new SARS-CoV-2 infections in this large community surveillance study. Greater reductions in symptomatic infections and/or infections with a higher viral burden are reflected in reduced rates of hospitalisations/deaths, but highlight the potential for limited ongoing transmission from asymptomatic infections in vaccinated individuals.

Impact of Vaccine on Antibody responses in the non-MS population

The impact of SARS-CoV-2 vaccines on antibody responses in the general population in the United KingdomWei, J., Stoesser, N., Matthews, P. C., Studley, R., Bell, I., Bell, J. I., Newton, J. N., Farrar, J., Diamond, I., Rourke, E., Howarth, A., Marsden, B. D., Hoosdally, S., Jones, E. Y., Stuart, D. I., Crook, D. W., Peto, T. E., Pouwels, K. B., Eyre, D. W., Walker, A. S., COVID-19 Infection Survey team10.1101/2021.04.22.21255911 — Posted: 2021-04-23

Real-world data on antibody response post-vaccination in the general population are limited. 45,965 adults in the UK’s national COVID-19 Infection Survey receiving Pfizer-BioNTech or Oxford-AstraZeneca vaccines had 111,360 anti-spike IgG measurements. Without prior infection, seroconversion rates and quantitative antibody levels post single dose were lower in older individuals, especially >60y. Two doses achieved high responses across all ages, particularly increasing seroconversion in older people, to similar levels to those achieved after prior infection followed by a single dose. Antibody levels rose more slowly and to lower levels with Oxford-AstraZeneca vs Pfizer-BioNTech, but waned following a single Pfizer-BioNTech dose. Latent class models identified four responder phenotypes: older people, males, and those having long-term health conditions were more commonly ‘low responders’. Where supplies are limited, vaccines should be prioritised for those not previously infected, and second doses to individuals >60y.

There is nothing new in these conclusions but this is certainly done on a large scale

Rapid induction of antigen-specific CD4+ T cells guides coordinated humoral and cellular immune responses to SARS-CoV-2 mRNA vaccinationPainter, M. M., Mathew, D., Goel, R. R., Apostolidis, S. A., Pattekar, A., Kuthuru, O., Baxter, A. E., Herati, R. S., Oldridge, D. A., Gouma, S., Hicks, P., Dysinger, S., Lundgreen, K. A., Kuri-Cervantes, L., Adamski, S., Hicks, A., Korte, S., Giles, J. R., Weirick, M. E., McAllister, C. M., Dougherty, J., Long, S., D’Andrea, K., Hamilton, J. T., Betts, M. R., Bates, P., Hensley, S. E., Grifoni, A., Weiskopf, D., Sette, A., Greenplate, A. R., Wherry, E. J.10.1101/2021.04.21.440862 — Posted: 2021-04-22

The SARS-CoV-2 mRNA vaccines have shown remarkable clinical efficacy, but questions remain about the nature and kinetics of T cell priming. We performed longitudinal antigen-specific T cell analyses in healthy individuals following mRNA vaccination. Vaccination induced rapid near-maximal antigen-specific CD4+ T cell responses in all subjects after the first vaccine dose. CD8+ T cell responses developed gradually after the first and second dose and were variable. Vaccine-induced T cells had central memory characteristics and included both Tfh and Th1 subsets, similar to natural infection. Th1 and Tfh responses following the first dose predicted post-boost CD8+ T cell and neutralizing antibody levels, respectively. Integrated analysis of 26 antigen-specific T cell and humoral responses revealed coordinated features of the immune response to vaccination. Lastly, whereas booster vaccination improved CD4+ and CD8+ T cell responses in SARS-CoV-2 naïve subjects, the second vaccine dose had little effect on T cell responses in SARS-CoV-2 recovered individuals. Thus, longitudinal analysis revealed robust T cell responses to mRNA vaccination and highlighted early induction of antigen-specific CD4+ T cells.

You get T cell responses after vaccination response

And lastly Fancy a Swim…You can get in the pool

Inactivation of SARS-CoV-2 in chlorinated swimming pool waterBrown, J. C., Blackwell, A., Moshe, M., Barclay, W. S.10.1101/2021.04.19.440446 — Posted: 2021-04-20

SARS-CoV-2 transmission remains a global problem which exerts a significant direct cost to public health. Additionally, other aspects of physical and mental health can be affected by limited access to social and exercise venues as a result of lockdowns in the community or personal reluctance due to safety concerns. Swimming pools have reopened in the UK as of April 12th, but the effect of swimming pool water on inactivation of SARS-CoV-2 has not yet been directly demonstrated. Here we demonstrate that water which adheres to UK swimming pool guidelines is sufficient to reduce SARS-CoV-2 infectious titre by at least 3 orders of magnitude.

Cerebral venous sinus thrombosis (CVST) is not significantly linked to COVID-19 vaccines or non-COVID vaccines in a large multi-state US health systemColin Pawlowski, John Rincón-Hekking, Samir Awasthi, Viral Pandey, Patrick Lenehan, AJ Venkatakrishnan, Sairam Bade, John C. O’Horo, Abinash Virk, Melanie D. Swift, Amy W. Williams, Gregory J. Gores, Andrew D. Badley, John Halamka, Venky SoundararajanmedRxiv 2021.04.20.21255806; doi: https://doi.org/10.1101/2021.04.20.21255806

Cerebral venous sinus thrombosis (CVST) has been reported in a small number of individuals who have received the mRNA vaccines or the adenoviral vector vaccines for COVID-19 in the US and Europe. Continued pharmacovigilance is integral to mitigating the risk of rare adverse events that clinical trials are underpowered to detect, however, these anecdotal reports have led to the pause or withdrawal of some vaccines in many jurisdictions and exacerbated vaccine hesitancy at a critical moment in the fight against the COVID-19 pandemic. We investigated the frequencies of CVST seen among individuals who received FDA-authorized COVID-19 vaccines from Pfizer-BioNTech (n = 94,818 doses), Moderna (n = 36,350 doses) and Johnson & Johnson – J&J (n = 1,745 doses), and among individuals receiving one of 10 FDA-approved non-COVID-19 vaccines (n = 771,805 doses). Comparing the incidence rates of CVST in 30-day time windows before and after vaccination, we found no statistically significant differences for the COVID-19 vaccines or any other vaccines studied in this population. In total, we observed 3 cases of CVST within the 30 days following Pfizer-BioNTech vaccination (2 females, 1 male; Ages (years): [79, 80, 84]), including one individual with a prior history of thrombosis and another individual with recent trauma in the past 30 days. We did not observe any cases of CVST among the patients receiving Moderna or J&J vaccines in this study population. We further found the baseline CVST incidence in the study population between 2017 and 2021 to be 45 to 98 per million patient years. Overall, this real-world evidence-based study highlights that CVST is rare and is not significantly associated with COVID-19 vaccination. In addition, there is a need for a concerted international effort to monitor EHR data across diverse patient populations and to investigate the underlying biological mechanisms leading to these rare clotting events.

This re-iterates ProfGs post https://multiple-sclerosis-research.org/2021/04/covid-19-vaccine-thrombosis-update/

Mattia Manica, Serena Pancheri, Piero Poletti, Giulia Giovanazzi, Giorgio Guzzetta, Filippo Trentini, Valentina Marziano, Marco Ajelli, Maria Grazia Zuccali, Pier Paolo Benetollo, Stefano Merler, Antonio Ferro The risk of symptomatic reinfection during the second COVID-19 wave in individuals previously exposed to SARS-CoV-2. doi: https://doi.org/10.1101/2021.04.14.21255502

In this cohort study, we analyzed surveillance records of COVID-19 cases identified between June 2020 and January 2021 in five Italian municipalities, where 77.7% of the entire population was screened for IgG antibodies in May 2020. We compared the risk of observing symptomatic infections in two mutually exclusive groups defined by the initial serological response( We they previously infected and had a detectable antibody response or not). We estimated that the cumulative incidence of identified symptomatic infections in the IgG negative and positive cohorts was 2.67% (95%CI: 2.12%-3.37%) and 0.14% (95%CI: 0.04%-0.58%), respectively. The adjusted odd ratio of developing symptomatic infection in individuals previously exposed to SARS-CoV-2 was estimated at 0.054 (95%CI: 0.009-0.169). (Small chance of re-infection if you have been infected previously = immunity in action) Quantifying protective immunity against COVID-19 disease elicited by natural infection with SARS-CoV-2 is essential to inform strategies for controlling the pandemic in the forthcoming months.

Therefore antibodies and hence vaccinations that produce such antibodies are protective

Immunogenicity and Safety of the BNT162b2 mRNA COVID-19 Vaccine in People Living with HIV-1. Levey et al SSRN http://dx.doi.org/10.2139/ssrn.3829650

When the Green boook first surfaced is suggested that because adenovirus had been used in Ebola studies where some individuals were HIV positive, that the vaccines would be OK in immunosuppressed people. However in the ebola studies very few people in the studies were HIV positive and there was no suggestion that such people had AIDS. Treatments for the HIV virus have improved substantially. This report demonstrates that people infected with HIV can give an anti-vaccine response that 98% (n=139/141) after the second vaccine however cell counts were about 500-700. Many agents do not deplete CD4 cells by this amount.

Disclaimer: (a) This information is from a Preprint and has not recived external peer review. Make of it the information as you see fit. (b) Please note that the opinions expressed here are those of the author and do not reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust or Queen Mary Univeristy of London.

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MouseDoctor

7 comments

  • Thus, longitudinal analysis revealed robust T cell responses to mRNA vaccination and highlighted early induction of antigen-specific CD4+ T cells.

    So does that give another hint that OCR treated persons with no antobody (b-cell) response can hope for „base immunity“ through t-cell response and therefore a low(er) probability of severe covid?

    I have no antibody response but will do now
    an ELISPOT t-cell test to find out whether tjere was a reaction or not.

    Furthermore do you think the pfizer and rocje/atea oral covid treatment pills (if successful in phase3) would work with OCR?
    Thank you!

    • I suspect most people on ocrelizumab will make a CD4 T cell response, which is good news and supports the idea that there is some protection. So come back and let us know hw your T cells are doing. I am sure the manufacturers are doing these very experiments as I write. When that data surfaces in MS, which I suspect will happen then I have a question.

      We do back to the T cell dominated Neuro and then ask them how does ocrelizumab work?

      A large number of them believe it works because ocrelizuab depletes the CD20 population that controls MS (i.e. 1-2% of the CD4 population). However say it blocks B cells that activate T cells. So now the question why would ocrelizumab not stop T cells to help fight COVID-19 whilst it blocks T cells to stop MS. I think the efficacy of anti CD19 antibodies blow out the suggestion that anti-CD20 work by killing CD20+ T cells. There are very very few T cells tha express CD19.

      The pfizer pill is a SARS-CoV2-3CL protease inhibitor there should be no reason why it wouldnt work if you are B cell depleted. Maybe Pfizer have the midas touch but there have been hundreds of agents said to kill the virus and none have really gone anywhere yet but lets hope

      • Thank you very much – gonna respond here when results are available – blood will be taken in 10 days and it seems they need roughly a week to become results.

      • and what do you think would this kind of vaccine a better working approach for OCR or does it remain the same problem with out b-cells?:

        The company, Valneva SE, has a vaccine that could be more
        variant-proof, giving it an edge over other shots in what may be
        an annual campaign against a disease that’s already killed more
        than 3 million people. The first participant in its phase three
        trials will be dosed this week. If successful, that could lead
        to an approved shot in the fall.
        Valneva’s shot is the only candidate in clinical trials in
        Europe that uses a tried-and-true vaccine technology involving
        an inactivated version of the whole virus it’s targeting.
        Inactivated vaccines — a century-old approach adopted for flu
        and polio — take a sample of the disease that has been killed
        and use it to stimulate an immune response without creating
        infection.

        • If the trials are only just starting they are behind the cure there are already an number of inactivated viruses approved outside of europe e.g. sinovac
          Nucleopcapside is a useful target for T cells

      • The theory would be that B cells act as antigen presenting cells in MS presenting an MS specific protein (EBV?) to T cells. Anti-cd20 depletes this specific subpopulation of cd20 positive B cells and so T cells dont get activated. For Sars-cov-2 vaccines, dendritic cells and macrophages act as the antigen presenting cells and activate sars-cov-2 T cells and so you might get T cells after vaccination, hopefully.

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