chuka_lis (chuka_lis) wrote,

Вакцинирование иммунокомпромиссных

Статья от шведов, по тому что там наблюдалось с антителами и побочками после прививок у 4 групп иммунокомпромиссных пациентов (449 человек) по сравнению с контролем (90).
Иммунный ответ был (ожидаемо) хуже у больных, к 35 дню (14 дней после 2 дозы) он сформировался  у двух третей больных (в среднем). Хуже всего обстояло дело у тех, у кого была пересадка органа или лейкемия  (у тех иммунитет выработался примерно у половины). Конечно, скорее всего, это было связано с иммуносупрессивной терапией.
Титры среди больных были существенно ниже, чем у контроля. Разброс титров- большой.
В группе иммунокомпромиссных у 4% были серьезные побочки на прививку, 1 смерть. Некоторые изза побочек не смогли получить 2 дозу.
В контроле, были более частные местные и общие реакции на прививку, а тяжелых- не было. Примерно как и в других  испытаниях на безопасность.
Так же, серопозитивность группы больных была 4.6% на начало исследования. Авторы считают, что это отражает (примерно) общую ситуацию в Стокгольме на то время.
И во время исследования случилось несколько пробоев (у неполностью и полностью привитых) иммунокомпромиссных пациентов (но не у контроля).
Тк в основном, иммунокомпромиссные ответили слабым иммунитетом на прививку, и не все притом- авторы склоняются к мысли, что таким людям мало 2х доз вакцины, нужна бустерная.

This study reports the results of a prospective clinical trial evaluating the safety and humoral immune responses followingtwo doses of COVID-19 mRNA BNT162b2 vaccination in five selected groups ofimmunocompromised patientsand healthy controls. The patient groups included were selected to represent different types of primaryimmunosuppression conditions as well as different secondary immunosuppressionstates. This readily allows comparisons between specific patient groups and healthy controls. Administration oftwo consecutive doses, 3 weeks apart,of BNT162b2 wasoverall safe. Therate of seroconversion was generally lowerinimmunocompromised patientscompared to healthy controls with the lowest responses intheSOT and CLL patientgroups. The prospective design of the study furthermore allowedanalyses of risk factors for seroconversion failure, in addition toprospective analysis of safety.SOT patients showed the lowest overall seroconversion with only 43·4%responding. Receiving MMF as a part of the immunosuppressive treatment was strongly associated with low seroconversion, which is in line with previous studies 10,12,13. A recently published report found that a third vaccine dose increased the seroconversion rate in SOT patients from 40% to 68% 14. This, however,still leaves almost one third of SOT patients without a serologicalresponse. As the present resultsindicate, a possible strategy might be to temporarily discontinue MMF to increase the chance of a vaccine response. This intervention must be weighed against the risk of development of donor specific antibodiesor even T-cell mediated rejectionof the graft.The first reportson COVID-19 vaccination in CLLpatientsfound that only 39·5% of included patients seroconverted 15. The corresponding ratein our clinical trial was 63·3%.Seroconversion was generally low (26·9%)in patients with ongoing ibrutinibtherapy,but nearly doubled in those who had stopped/paused this therapy, in line with previous reports In contrast, >80% of the patients who had indolent CLL or were long-term off anti-CD20 based chemoimmunotherapy responded to the vaccine. Previous anti-CD20 therapy has been associated with poor responses to vaccines. In the present study, however, most patients responded after a median time of 13 months between anti-CD20 therapy and vaccination. Hence, actions may berequired, particularly in those who are on treatment with ibrutinibwhere temporary cessation of ibrutinib-treatmentbefore vaccinationcould be warranted.With respect topatients with PID,alowseroconversion ratewas found in patients with CVID. Interestingly, all but one ofthe patients with idiopathic CD4 cytopenia seroconverted.In addition,a patientwith hypomorphic SCID due to amutation affecting the Artemisgene and apatient with a CARD11-mutationdid not respond to vaccination, supportingtheimportance of these genes for antibody responses 17,18. The resultsare in line with a previous studyin whichseroconversion was observed in18/26 (69·2%)PID patients after vaccination with BNT162b28. Overall, we observedthat most PID-patients respondedto vaccination and the number of AEswas low.In HSCTpatients, the results are concordant with studies of other vaccines. Some of the present findings are also similar to other reports of COVID-19 vaccines in this patient group. Time after HSCT had a significant impact on the likelihood of seroconversionsimilar to findings in other studies 19-21. However, it was observed thatseverity of chronic GvHD impacted negatively on seroconversionin univariate analysis. Seroconversion failure was furthermore found to be associated with ongoingsecond line treatments for chronic GvHD, such as ruxolitinib and photophoresis,andadministration of anti-CD20 therapygiven several months priorto vaccination. An effect of the severity of chronic GvHD has not been reported previously but is not unexpected considering what has been observed for other vaccines. None of the two assessablepatients receivingCD19 CART cell therapy seroconverted, likely due to the persistent depletion of B cells after successful therapy. People living withHIVresponded well to the vaccine, with high seroconversion rates and antibody titresregardlessoflow (<300cells/μl) orhigh (>300cells/μl) CD4 counts. These resultsare in line with recent reportsthat demonstratedrobust humoral BNT162b2 vaccination response in this group11,22,23. However, the durability of the antibody responsein PLWHwill be important to followsince,despiteeffective antiviral therapy, full immune reconstitution is not achievedin many PLWH. These individuals can have diminished or less durable response to vaccination, which is particularly relevant to monitor in those with low CD4 cell-counts24-26.This is to our knowledge the firstprospective, clinical trial performed in several immunocompromised patient groups allowing careful assessment of safety. Reactogenicity was comparable to previous reports5, and other AEwere also generallymild. However, a few immune activation phenomenawere observed,such as fourcases of GvHD among the HSCT patients. Similarly, Ali et al.reported recently in a retrospective study that 9·7% of HSCT patients developed new chronic GvHD and 3·5% experienced worsened chronic GvHD after vaccination with mRNA vaccines27. Moreover, Ram et al.reported in a prospective cohort study three cases of worsened GvHD (5%) after each dose of BNT162b2 vaccine among 66 allogenic HSCT recipients20. Of note, the traditional adjuvanted pandemic H1N1 influenza vaccine has also beenreported to aggravate chronic GvHD28.Taken together, these observations indicate the necessity for careful monitoring and evaluation infuture prospectivestudiesand clinical routine. One case ofSUSAR with progressive respiratory failure and fatal outcomeoccurred. This case will need further evaluation. It is possible that mRNA-vaccines, by virtue of their potent immunogenicity, may precipitate dysfunctional immune-responses inparticularly vulnerable patientsand/or patient groups. As wouldbe expected in a large clinical trial comprising of more than 500 individuals during the third wave of COVID-19 infectionin Sweden, a few COVID-19caseswere documented duringthe study.In this respect, the presentstudy was not powered to evaluate a potentiallyprotective effect on the number and severity of COVID-19cases.Aparticular strength of the presentstudy isthe clinical trial settingwith careful prospective safety evaluation. In addition, the study comprises arelatively large participant number, with a prioridefined monitoring and analyses of the data. The study clearlyshowsthat not all patientgroupshave the same risk for poor response to COVID-19 vaccination. For example, HSCT patients at a late stage after transplantation and without chronic GvHD respondedwell to two doses of vaccine. It is unknown, however, whether the duration of immunity will be similar to healthy controls,whichrequires further studies with a longer follow-up time. In contrast, we also identifiedsubgroups of patients responding poorly,or very poorly,to vaccination. Some of these risk factors have been previously identified,such as ibrutinibin CLL patients and the use of MMF in SOTpatients and such patients might benefit from a 3rddoseof vaccine. There are severallimitations ofthis study. Thetrial hadan open-label and non-randomized design. n conclusion, this prospective clinical trial showed that the mRNA BNT162b2 vaccine issafe to administer toimmunocompromised patients. However, the rate of seroconversion issubstantially lower compared tohealthy controls, with a wide range of seroconversion rates and titreswithin the patient groupsand subgroupsat risk. This knowledge can form the basis for individually adaptedvaccination schedules. This might require specificvaccination strategies in differentgroups of immunosuppressed patients such as subsequent vaccinations for boost, pausing of concomitant immunosuppression, and/or in some cases pre-interventional vaccination.
Tags: вакцина, здоровье, иммунитет, коронавирус, статья

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