Challenges to Vaccination against SARS-CoV-2 in Patients with Immune-Mediated Diseases

Ramirez, Giuseppe A.; Asperti, Chiara; Cucca, Valentina; Yacoub, Mona‐Rita

doi:10.3390/vaccines9101147

Cited by 10 publications

(8 citation statements)

References 90 publications

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“…It should be added that in times of broad vaccination against COVID-19 in Western countries, one study demonstrated that the overall response rate to COVID-19 vaccine in patients suffering from systemic rheumatic diseases treated with JAKi remained high, 109 in line with rates reported with other immunosuppressants. 110 …”

Section: Introductionmentioning

confidence: 99%

JAK inhibitors and COVID-19

Levy

Guglielmelli

Langmuir

et al. 2022

J Immunother Cancer

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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.

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Section: Introductionmentioning

confidence: 99%

JAK inhibitors and COVID-19

Levy

Guglielmelli

Langmuir

et al. 2022

J Immunother Cancer

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“… 22 Consistent immunogenicity and safety findings were reported in two meta-analyses, however, studies focusing primarily on SLE patients were scarce and data of in-activated vaccines was very limited. 23 , 24 In a recent phase 4 trial conducted in Brazil comparing 910 adults with ARD (25.5% with SLE, 38.2% on glucocorticoids, 13.1% on myophenolate) and 182 matched healthy controls, both the rates of anti-SAR-CoV-2 IgG seroconversion (70.4% vs 95.5%, p < 0.001) and neutralizing antibody positivity (56.3% vs 79.3%, p < 0.001) were significantly lower in the ARD group 6 weeks after the second dose of CoronaVac. 15 The short-term immunogenicity overall was regarded acceptable.…”

Section: Discussionmentioning

confidence: 99%

Immunogenicity and safety of inactivated and mRNA COVID-19 vaccines in patients with systemic lupus erythematosus

Chan

et al. 2022

Therapeutic Advances in Musculoskeletal

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Objective: To evaluate the effects and side effects of both inactivated and mRNA COVID-19 vaccines in patients with systemic lupus erythematosus (SLE). Methods: This was a prospective, single-center, observational study. Patients with SLE planning to receive COVID-19 vaccines were recruited and matched 1:1 with healthy controls. The immunogenicity of the COVID-19 vaccines was assessed by a surrogate neutralization assay at 28 days after the second dose. The main outcome was the antibody response comparing SLE patients and controls. Other outcomes included reactogenicity, disease activity and predictors of antibody responses in patients with SLE. Results: Sixty-five SLE patients received 2 doses of COVID-19 vaccines (Comirnaty: 38; CoronaVac: 27) were recruited. Many of them were on systemic glucocorticoids (76%) and immunosuppressants (55%). At day 28 after the second dose of vaccines, 92% (Comirnaty: 100% vs CoronaVac: 82%, p = 0.01) of the patients had positive neutralizing antibody. However, compared to the age, gender, vaccine type matched controls, the level of neutralizing antibody was significantly lower ( p < 0.001). The self-reported adverse reactions after vaccines in lupus patients were common but mild, and were more frequent in the Comirnaty group. There was no significant change in lupus disease activity up to 28 days after vaccination. The independent predictors of neutralizing antibody level included the dosage of systemic glucocorticoids, use of mycophenolate and type of vaccines. Conclusions: COVID-19 vaccines produced satisfactory but impaired humoral response in SLE patients compared to controls which was dependent on the immunosuppressive medications use and type of vaccines received. There was no new short-term safety signal noted. Booster dose is encouraged.

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“…These observations are in line with previous studies, both considering patients with SLE and other RDs. Most studies reported a rate of flare ranging from 3% to 12%, with a preponderance of musculoskeletal and constitutional involvement [ 21 , 22 , 23 , 24 ]. Interestingly, patients, who experienced an adverse reaction, also had a higher disease flare rate.…”

Section: Discussionmentioning

confidence: 99%

The Impact of Anti-SARS-CoV-2 Vaccine in Patients with Systemic Lupus Erythematosus: A Multicentre Cohort Study

Gerosa

Schioppo²,

Argolini

et al. 2022

Vaccines

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Vulnerable subjects, including systemic lupus erythematosus (SLE) patients, have been prioritised to receive anti-SARS-CoV-2 vaccines. Few data about the safety of these vaccines in SLE are available. The aim of our study is to investigate the safety of anti-SARS-CoV-2 vaccines in SLE. We included 452 SLE patients, referring to seven tertiary centres, who were immunised. A total of 119 (26%) reported side effects (SE) after the first and/or the second shot (the most frequent SE were fever, local reaction, fatigue, and arthralgia). Patients with constitutional symptoms and those on an immunosuppressive regimen (especially belimumab) showed more SE. In addition, 19 (4%) had a flare after the immunisation (flares classified by organ involvement: six musculoskeletal with constitutional symptoms, four renal, three cardio-respiratory, three haematological, two mucocutaneous). None of the patients needed hospitalisation and none died. Moreover, 15 required a transient increase in corticosteroids and four were treated with steroid pulses. One patient required an additional rituximab course. Anti-dsDNA, moderate/high DAS before vaccine, and belimumab were found more frequently in patients with disease flare. Anti-SARS-CoV-2 vaccines are safe in SLE patients, and they should be recommended in these patients, as the potential benefits widely outweigh the risk of SE. Treatment adjustment might be considered with the aim of minimising SE risk and flare.

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Challenges to Vaccination against SARS-CoV-2 in Patients with Immune-Mediated Diseases

Cited by 10 publications

References 90 publications

JAK inhibitors and COVID-19

JAK inhibitors and COVID-19

Immunogenicity and safety of inactivated and mRNA COVID-19 vaccines in patients with systemic lupus erythematosus

The Impact of Anti-SARS-CoV-2 Vaccine in Patients with Systemic Lupus Erythematosus: A Multicentre Cohort Study

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