SARS-CoV-2 vaccine in patients with systemic sclerosis: impact of disease subtype and therapy

Abstract

Objective To analyse the safety, immunogenicity and factors affecting antibody response to Severe Acute Respiratory Syndrome–Coronavirus–2(SARS-CoV-2) vaccination in patients with systemic sclerosis (SSc). Methods This is a phase 4 prospective study within a larger trial of two doses of inactivated SARS-CoV-2 vaccine (CoronaVac) in 51 SSc patients compared with 153 controls. Anti-SARS-CoV-2-IgG and neutralizing antibodies (NAb) were assessed at each vaccine shot (D0/D28) and 6 weeks after the 2nd dose(D69), only in individuals with negative baseline IgG/NAb and those who did not have coronavirus-19(COVID19) during follow-up. Vaccine safety was also assessed in all participants. Results Patients and controls had comparable median ages [48(38.5–57) vs 48(38–57) years, p= 0.945]. Patients had mostly diffuse SSc (68.6%) and the majority (74.5%) had interstitial lung disease. Most patients were under immunosuppressive therapy (72.5%), mainly mycophenolate mofetil (MMF) (52.9%). After full vaccination (D69), anti-SARS-CoV-2-IgG frequency (64.1% vs 94.2%, p< 0.001) and NAb positivity (53.8% vs 76.9%; p= 0.006) were moderate, although lower than controls. The first dose response (D28) was low and comparable for both SC (p= 0.958) and NAb positivity (p= 0.537). SSc patients under MMF monotherapy vs other (no therapy/other DMARDs) had lower immunogenicity (SC : 31.3% vs 90%, p< 0.001) and NAb : 18.8% vs 85%, p< 0.001). Multiple regression analysis confirmed that MMF use, but not disease subtype, is associated with insufficient seroconversion [odds ratio (OR)=0.056(95%CI 0.009–0.034), p= 0.002] and NAb positivity [OR = 0.047(95%CI 0.007–0.036), p= 0.002]. No moderate/severe side-effects were observed. Conclusion CoronaVac has an excellent safety profile and moderate response to anti-SARS-CoV-2 vaccine in SSc. Vaccine antibody response is not influenced by disease subtype and is greatly affected by MMF, reinforcing the need for additional strategies to up-modulate vaccine response in this subgroup of patients. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov, NCT04754698

Impact of COVID-19 and vaccination campaign on 1,755 systemic sclerosis patients during first three years of pandemic. Possible risks for individuals with impaired immunoreactivity to vaccine, ongoing immunomodulating treatments, and disease-related lung involvement during the next pandemic phase

“…4 ). As suggested by the clinical history of individual patients here described and by other observations [ 31 , 37 , 38 ], not infrequently we will have to manage patients with only the first 2–3 doses of COVID-19 vaccine but needing long-term treatment with immunomodulatory drugs; in these instances, it would be highly recommendable to verify their actual anti-COVID-19 immunogenic condition starting with the serum NAb level detection ( Fig. 4 ).…”

“…The effects of anti-COVID-19 vaccination are reported in small patients' series [ [31] , [32] , [33] , [34] , [35] , [36] ], showing a generally good tolerability to different anti-COVID-19 vaccines, mostly mRNA types [ [19] , [20] , [21] , 35 , 37 ]. The percentage of impaired seroconversion largely varied among different patients’ series [ 19 , 31 , 34 , 37 , 38 ]. It was frequently evaluated after the first two doses of vaccine [ 31 , 32 , 34 , 39 ] and in only two reports after the booster dose [ 19 , 21 ]; one of them included the detection of the T-cell immunoreactivity [ 21 ].…”

“…In the majority of previous investigations, the ongoing or recent administration of immunomodulating drugs, mainly anti-CD20 cycles, seems to exert a negative role on the humoral immunogenecity of anti-COVID-19 vaccines [ 19 , 20 , 38 ]. In this context, an increasing number of studies suggested a possible role of genetic factors on the impaired response to vaccines [ 40 , 41 ].…”

“…From one side, ongoing immunomodulating treatments at the time of SARS-CoV2 infection, such as conventional disease-modifying antirheumatic drugs, seemed to be able to contrast the strong immunoreactivity to virus, the so-called ‘cytokine storm’, observed in those patients who developed rapidly severe COVID-19 inflammatory manifestations and worst outcomes [ 16 ]. From the other side, these drugs may weaken the immunogenicity of COVID-19 vaccines, especially if used closely to vaccine administration [ 19 , 20 , 38 ]. Given the divergent effects of immunomodulating drugs, their balanced use may be decisive in immunocompromised patients during the pandemic.…”

Systemic sclerosis in the time of COVID-19

“…International scientific initiatives are ongoing and will provide robust evidence on the effect of COVID-19 on the disease course of systemic sclerosis and the development and management of complications related to the disease. Similarly, data on the use of the COVID-19 vaccines in patients with systemic sclerosis continue to accrue [9][10][11] and will provide evidence for the most appropriate timing of vaccination as a preventive measure. As it is clear that we have to learn to live with the SARS-CoV-2 virus, the data being collected during the pandemic will support rheumatologists in continuing to improve approaches to the future care of patients with systemic sclerosis.…”