Do JAK inhibitors affect immune response to COVID-19 vaccination? Data from the MAJIK-SFR Registry.
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ABSTRACT:
SUBMITTER: Seror R
PROVIDER: S-EPMC8494471 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:During SARS-CoV-2 infection, the innate immune response can be inhibited or delayed, and the subsequent persistent viral replication can induce emergency signals that may culminate in a cytokine storm contributing to the severe evolution of COVID-19. Cytokines are key regulators of the immune response and virus clearance, and, as such, are linked to the-possibly altered-response to the SARS-CoV-2. They act via a family of more than 40 transmembrane receptors that are coupled to one or several of the 4 Janus kinases (JAKs) coded by the human genome, namely JAK1, JAK2, JAK3, and TYK2. Once activated, JAKs act on pathways for either survival, proliferation, differentiation, immune regulation or, in the case of type I interferons, antiviral and antiproliferative effects. Studies of graft-versus-host and systemic rheumatic diseases indicated that JAK inhibitors (JAKi) exert immunosuppressive effects that are non-redundant with those of corticotherapy. Therefore, they hold the potential to cut-off pathological reactions in COVID-19. Significant clinical experience already exists with several JAKi in COVID-19, such as baricitinib, ruxolitinib, tofacitinib, and nezulcitinib, which were suggested by a meta-analysis (Patoulias et al.) to exert a benefit in terms of risk reduction concerning major outcomes when added to standard of care in patients with COVID-19. Yet, only baricitinib is recommended in first line for severe COVID-19 treatment by the WHO, as it is the only JAKi that has proven efficient to reduce mortality in individual randomized clinical trials (RCT), especially the Adaptive COVID-19 Treatment Trial (ACTT-2) and COV-BARRIER phase 3 trials. As for secondary effects of JAKi treatment, the main caution with baricitinib consists in the induced immunosuppression as long-term side effects should not be an issue in patients treated for COVID-19.We discuss whether a class effect of JAKi may be emerging in COVID-19 treatment, although at the moment the convincing data are for baricitinib only. Given the key role of JAK1 in both type I IFN action and signaling by cytokines involved in pathogenic effects, establishing the precise timing of treatment will be very important in future trials, along with the control of viral replication by associating antiviral molecules.
| S-EPMC9035837 | biostudies-literature
Project description: Not available
| S-EPMC8975261 | biostudies-literature
Project description:Introduction La réponse vaccinale chez les patients atteints de maladies auto-immunes et inflammatoires peut être fortement impactée sous certains traitements de fond, tels que le RTX. À ce jour, peu de données sont disponibles concernant les JAK inhibiteurs (JAKi), et aucune en lien avec la vaccination anti-SARS-CoV-2. L’objectif de cette étude était d’étudier la réponse vaccinale anti-SARS-CoV-2 chez des patients sous JAKi. Patients et méthodes Dans cette étude ancillaire du registre MAJIK-SFR (NCT04602091), les patients toujours sous anti-JAKi au moment de la vaccination et ayant eu une sérologie anti-SARS-CoV-2 effectuée au moins 2 semaines après un schéma vaccinal complet (2 injections du vaccin Pfizer, Moderna ou AstraZeneca, ou 1 injection du vaccin Janssen, ou infection COVID-19 suivi d’une injection de n’importe quel vaccin). Les taux d’anticorps IgG ou totaux anti-protéine spike (S1, S1/S2 ou RBD) ont été détectés à l’aide de kits commerciaux utilisant majoritairement la technique d’immunoanalyse par chimiluminescence, ou dans 4 cas par ELISA ou enzyme linked fluorescence assay (ELFA). Le patient était considéré répondeur si le taux d’anticorps détecté était ≥ au seuil de positivé du kit. Les caractéristiques des patients ont été comparées entre les répondeurs et non-répondeurs afin d’identifier les facteurs associés a la non-réponse. Résultats Cent treize patients ont été inclus (98 [86,7 %] atteints de PR, 15 [13,4 %] de PsA) dont 56 (49,6 %) sous baricitinib, 30 (26,5 %) sous tofacitinib et 27 (23,9 %) sous upadacitinib. Quatre-vingt-dix-sept (85,8 %) patients ont reçu une vaccination par vaccin à ARNm (Pfizer ou Moderna). Neuf patients avaient eu une infection COVID avant la vaccination. Cinq patients ont reçu une 3e dose. La réponse vaccinale a été évaluée en moyenne 8,7 semaines (±5,2) après la dernière injection. Le taux de séroconversion était de 88,5 %. Le taux de non-réponse était plus élevé sous upadacitinib (n = 7/27, 25,9 %, p = 0,013) comparé au baricitinib (n = 5/56, 8,9 %) ou tofacitinib (n = 1/30, 3,3 %). Les non-répondeurs étaient plus âgés que les répondeurs (p = 0,02), mais l’âge moyen à la vaccination était similaire pour chaque JAKi. Sous barictinib et tofacitinib les non-répondeurs avaient tous ≥ 65 ans ; 4 des 7 non-répondeurs sous upadacitinib avaient moins de 65 ans. L’intervalle entre la dernière injection et la sérologie était légèrement plus long chez les non-répondeurs (11,25 ± 5,94 vs 8,32 ± 5,01, p = 0,099). Aucun autre paramètre (utilisation concomitante de MTX ou corticostéroïdes, dose de JAKi, activité de la maladie, type de vaccin) n’était associé à une non-réponse. Un antécédent de traitement par RTX (n = 18, 15,9 %) n’avait pas non plus d’impact sur la réponse vaccinale ; néanmoins, la dernière injection datait de ≥ 6 mois avant la vaccination chez tous les patients. Conclusion Le taux de séroconversion après vaccination anti-SARS-CoV-2 chez les patients traités par JAKi reste élevé (88,5 %). Cependant, la non-réponse peut survenir principalement chez les patients âgés ≥ 65 ans. De plus, l’upadacitinib était associé à un taux de non-réponse plus élevé (25,9 %). Ces résultats doivent être confirmés mais suggèrent que chez les patients sous JAKi de ≥ 65 ans ou traités par upadacitinib, une évaluation sérologique pourrait être discuter pour guider la décision clinique (3e dose de vaccin et/ou vaccination familiale). L’évaluation de la réponse immunitaire cellulaire chez les non-répondeurs sera également intéressante pour déterminer si une autre forme d’immunité peut avoir été acquise.
| S-EPMC8626125 | biostudies-literature
Project description:ObjectiveThe current study aimed to identify the association between COVID-19 vaccination and prolonged post-COVID symptoms (long-COVID) in adults who reported suffering from this condition.MethodsThis was a retrospective follow-up study of adults with long-COVID syndrome. The data were collected during a phone call to the participants in January-February 2022. We inquired about their current health status and also their vaccination status if they agreed to participate.ResultsIn total, 1236 people were studied; 543 individuals reported suffering from long long- COVID (43.9%). Chi square test showed that 15 out of 51 people (29.4%) with no vaccination and 528 out of 1185 participants (44.6%) who received at least one dose of any vaccine had long long- COVID symptoms (p = 0.032).ConclusionsIn people who have already contracted COVID-19 and now suffer from long-COVID, receiving a COVID vaccination has a significant association with prolonged symptoms of long-COVID for more than one year after the initial infection. However, vaccines reduce the risk of severe COVID-19 (including reinfections) and its catastrophic consequences (e.g., death). Therefore, it is strongly recommended that all people, even those with a history of COVID-19, receive vaccines to protect themselves against this fatal viral infection.
| S-EPMC10849259 | biostudies-literature
Project description:In India, COVID-19 (Corona Virus Disease-2019) continues to this day, although with subdued intensity, following two major waves of viral infection. Despite ongoing vaccination drives to curb the spread of COVID-19, the relative potential of the administered vaccines to render immune protection to the general population and their advantage over natural infection remain undocumented. In this study, we examined the humoral and cell-mediated immune responses induced by the two vaccines Covishield and Covaxin, in individuals living in and around Kolkata, India. We also compared the immune responses induced separately by vaccination and natural infection. Our results indicate that although Covishield generates a better humoral immune response toward SARS-CoV-2, both vaccines are almost equivalent in terms of cell-mediated immune response to the virus. Both Covishield and Covaxin, however, are more effective toward the wild-type virus than the Delta variant. Additionally, the overall immune response resulting from natural infection in and around Kolkata is not only similar to that generated by vaccination but the cell-mediated immune response to SARS-CoV-2 also lasts for at least ten months in some individuals after the viral infection.
| S-EPMC10257406 | biostudies-literature
Project description:COVID-19 vaccinations are recommended for children with cancer but data on their vaccination response is scarce. This study assesses the antibody and T-cell response following a 2- or 3-dose vaccination with BNT162b2 mRNA COVID-19 vaccine in children (5-17 years) with cancer. For the antibody response, participants with a serum concentration of anti-SARS-CoV-2 spike 1 antibodies of >300 binding antibody units per milliliter were classified as good responders. For the T-cell response, categorization was based on spike S1 specific interferon-gamma release with good responders having >200 milli-international units per milliliter. The patients were categorized as being treated with chemo/immunotherapy for less than 6 weeks (Tx < 6 weeks) or more than 6 weeks (Tx > 6 weeks) before the first immunization event. In 46 patients given a 2-dose vaccination series, the percentage of good antibody and good T-cell responders was 39.3% and 73.7% in patients with Tx < 6 weeks and 94.4% and 100% in patients with Tx > 6 weeks, respectively. An additional 3rd vaccination in 16 patients with Tx < 6 weeks, increased the percentage of good antibody responders to 70% with no change in T-cell response. A 3-dose vaccination series effectively boosted antibody levels and is of value for patients undergoing active cancer treatment.
| S-EPMC10177402 | biostudies-literature
Project description:BackgroundInnate immune cells play a crucial role in the pathophysiology of rheumatoid arthritis (RA) via release of cytokines. Small-molecule inhibitors of Janus kinases (JAKi) are clinically efficacious in patients with RA. However, the isoform-specific action of each JAKi is difficult to assess, since JAKs form heterodimeric complexes with cytokine receptors. We assessed the effects of several JAKi on GM-CSF-primed human innate immune cells.ResultsTreatment with JAKi (tofacitinib, baricitinib, upadacitinib) prevented GM-CSF-induced JAK2/STAT5 phosphorylation at higher concentrations (400 nM) in THP-1 cells. Whereas compared with baricitinib or upadacitinib, the inhibitory effects of tofacitinib on the GM-CSF-induced JAK2/STAT5 phosphorylation were weak at lower concentrations (≤ 100 nM). All JAKi inhibited GM-CSF-induced IL-1β production by human neutrophils. However, the inhibitory effects of baricitinib on IL-1β production were larger compared to those of tofacitinib or upadacitinib at lower concentrations (≤ 100 nM). Similarly, all JAKi inhibited GM-CSF-induced caspase-1(p20) production by human neutrophils.ConclusionWe conclude that incubation with JAKi prevents GM-CSF-mediated JAK2/STAT5 activation in human innate immune cells. Although baricitinib and upadacitinib almost completely blocked GM-CSF-mediated JAK2/STAT5 signaling, the inhibitory effects of tofacitinib were weaker at lower concentrations suggesting that variation exists among these JAKi in the inhibition of JAK2 signaling pathways.
| S-EPMC7296727 | biostudies-literature
Project description:Background and aimImmune status profile can predict response to vaccination, while lymphocyte phenotypic alterations represent its effectiveness. We prospectively evaluated these parameters in kidney transplant recipients (KTRs) regarding Tozinameran (BNT162b2) vaccination.MethodIn this prospective monocenter observational study, 39 adult KTRs, on stable immunosuppression, naïve to COVID-19, with no protective humoral response after two Tozinameran doses, received the third vaccination dose, and, based on their immunity activation, they were classified as responders or non-responders. Humoral and cellular immunities were assessed at predefined time points (T0: 48 h before the first, T1: 48 h prior to the third and T2: three weeks after the third dose).ResultsResponders, compared to non-responders, had a higher total and transitional B-lymphocyte count at baseline (96.5 (93) vs. 51 (52)cells/μL, p: 0.045 and 9 (17) vs. 1 (2)cells/μL, p: 0.031, respectively). In the responder group, there was a significant increase, from T0 to T1, in the concentrations of activated CD4+ (from 6.5 (4) to 10.08 (11)cells/μL, p: 0.001) and CD8+ (from 8 (19) to 14.76 (16)cells/μL, p: 0.004) and a drop in CD3+PD1+ T-cells (from 130 (121) to 30.44 (25)cells/μL, p: 0.001), while naïve and transitional B-cells increased from T1 to T2 (from 57.55 (66) to 1149.3 (680)cells/μL, p < 0.001 and from 1.4 (3) to 17.5 (21)cells/μL, p: 0.003). The percentages of memory and marginal zone B-lymphocytes, and activated CD4+, CD8+ and natural killer (NK) T-cells significantly increased, while those of naïve B-cells and CD3+PD1+ T-cells reduced from T0 to T1.ConclusionsResponders and non-responders to the third BNT162b2 dose demonstrated distinct initial immune cell profiles and changes in cellular subpopulation composition following vaccination.
| S-EPMC10611345 | biostudies-literature
Project description:The essential trace element selenium (Se) is of central importance for human health and particularly for a regular functioning of the immune system. In the context of the current pandemic, Se deficiency in patients with COVID-19 correlated with disease severity and mortality risk. Selenium has been reported to be associated with the immune response following vaccination, but it is unknown whether this also applies to SARS-CoV-2 vaccines. In this observational study, adult health care workers (n = 126) who received two consecutive anti-SARS-CoV-2 vaccinations by BNT162b2 were followed for up to 24 weeks, with blood samples collected at the first and second dose and at three and 21 weeks after the second dose. Serum SARS-CoV-2 IgG titres, neutralising antibody potency, total Se and selenoprotein P concentrations, and glutathione peroxidase 3 activity were quantified. All three biomarkers of Se status were significantly correlated at all the time points, and participants who reported supplemental Se intake displayed higher Se concentrations. SARS-CoV-2 IgG titres and neutralising potency were highest three weeks after the second dose and decreased towards the last sampling point. The humoral immune response was not related to any of the three Se status biomarkers. Supplemental Se intake had no effect at any time point on the vaccination response as measured by serum SARS-CoV-2 IgG levels or neutralising potency. Overall, no association was found between Se status or supplemental Se intake and humoral immune response to COVID-19 mRNA vaccination.
| S-EPMC8810594 | biostudies-literature
Project description:SARS-CoV-2 variants of concern (VOCs) can trigger severe endemic waves and vaccine breakthrough infections (VBI). We analyzed the cellular and humoral immune response in 8 patients infected with the alpha variant, resulting in moderate to fatal COVID-19 disease manifestation, after double mRNA-based anti-SARS-CoV-2 vaccination. In contrast to the uninfected vaccinated control cohort, the diseased individuals had no detectable high-avidity spike (S)-reactive CD4+ and CD8+ T cells against the alpha variant and wild type (WT) at disease onset, whereas a robust CD4+ T-cell response against the N- and M-proteins was generated. Furthermore, a delayed alpha S-reactive high-avidity CD4+ T-cell response was mounted during disease progression. Compared to the vaccinated control donors, these patients also had lower neutralizing antibody titers against the alpha variant at disease onset. The delayed development of alpha S-specific cellular and humoral immunity upon VBI indicates reduced immunogenicity against the S-protein of the alpha VOC, while there was a higher and earlier N- and M-reactive T-cell response. Our findings do not undermine the current vaccination strategies but underline a potential need for the inclusion of VBI patients in alternative vaccination strategies and additional antigenic targets in next-generation SARS-CoV-2 vaccines.
| S-EPMC8821964 | biostudies-literature