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Multicenter Study
. 2023 May;43(4):680-691.
doi: 10.1007/s10875-023-01444-4. Epub 2023 Feb 16.

COVID-19 and Mixed Cryoglobulinemia Syndrome: Long-Term Survey Study on the Prevalence and Outcome, Vaccine Safety, and Immunogenicity

Laura Gragnani  1 , Marcella Visentini  2 , Serena Lorini  1 , Stefano Angelo Santini  3   4 , Gianfranco Lauletta  5 , Cesare Mazzaro  6 , Teresa Urraro  7 , Luca Quartuccio  8 , Fabio Cacciapaglia  9 , Piero Ruscitti  10 , Antonio Tavoni  11 , Silvia Marri  1 , Giuseppina Cusano  2 , Luisa Petraccia  1 , Caterina Naclerio  7 , Elena Treppo  8 , Giulia Del Frate  8 , Ilenia Di Cola  10 , Vincenzo Raimondo  12 , Daniela Scorpiniti  12 , Monica Monti  1 , Lorenzo Puccetti  11 , Giusy Elia  13 , Poupak Fallahi  14 , Stefania Basili  2 , Salvatore Scarpato  7 , Florenzo Iannone  9 , Milvia Casato  2 , Alessandro Antonelli  13 , Anna Linda Zignego  1 , Clodoveo Ferri  15   16
Affiliations
Multicenter Study

COVID-19 and Mixed Cryoglobulinemia Syndrome: Long-Term Survey Study on the Prevalence and Outcome, Vaccine Safety, and Immunogenicity

Laura Gragnani et al. J Clin Immunol. 2023 May.

Abstract

Purpose: Mixed cryoglobulinemia syndrome (MCs) is a rare immunoproliferative systemic disorder with cutaneous and multiple organ involvement. Our multicenter survey study aimed to investigate the prevalence and outcome of COVID-19 and the safety and immunogenicity of COVID-19 vaccines in a large MCs series.

Methods: The survey included 430 unselected MCs patients (130 M, 300 F; mean age 70 ± 10.96 years) consecutively collected at 11 Italian referral centers. Disease classification, clinico-serological assessment, COVID-19 tests, and vaccination immunogenicity were carried out according to current methodologies.

Results: A significantly higher prevalence of COVID-19 was found in MCs patients compared to Italian general population (11.9% vs 8.0%, p < 0.005), and the use of immunomodulators was associated to a higher risk to get infected (p = 0.0166). Moreover, higher mortality rate was recorded in MCs with COVID-19 compared to those without (p < 0.01). Patients' older age (≥ 60 years) correlated with worse COVID-19 outcomes. The 87% of patients underwent vaccination and 50% a booster dose. Of note, vaccine-related disease flares/worsening were significantly less frequent than those associated to COVID-19 (p = 0.0012). Impaired vaccination immunogenicity was observed in MCs patients compared to controls either after the first vaccination (p = 0.0039) and also after the booster dose (p = 0.05). Finally, some immunomodulators, namely, rituximab and glucocorticoids, hampered the vaccine-induced immunogenicity (p = 0.029).

Conclusions: The present survey revealed an increased prevalence and morbidity of COVID-19 in MCs patients, as well an impaired immunogenicity even after booster vaccination with high rate of no response. Therefore, MCs can be included among frail populations at high risk of infection and severe COVID-19 manifestations, suggesting the need of a close monitoring and specific preventive/therapeutical measures during the ongoing pandemic.

Keywords: COVID-19 vaccine; SARS-CoV-2; cryoglobulinemic vasculitis; immunogenicity; mixed cryoglobulinemia.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
A COVID-19 prevalence; B asymptomatic infection; C mild-moderate disease; D severe disease. **p < 0.001
Fig. 2
Fig. 2
A COVID-19 prevalence; B asymptomatic infection; C mild-moderate disease; D severe disease. *p < 0.05
Fig. 3
Fig. 3
A Median levels of IgG neutralizing antibody (NAb) against SARS-CoV-2 trimeric spike S1/S2 glycoproteins in mixed cryoglobulinemia patients and healthy controls, at 3 and 24 weeks after a complete vaccination and 2–4 weeks after the booster shot; results are expressed in binding antibody unit/mL (BAU/mL); interquartile range: 25–75th percentile. B Rate of no response at 3 and 24 weeks after a complete vaccination and 2 weeks after the booster shot in mixed cryoglobulinemia patients and healthy controls. *p < 0.05, **p < 0.001, ***p < 0.0001
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References

    1. Meltzer M, Franklin EC, Elias K, McCluskey RT, Cooper N. Cryoglobulinemia--a clinical and laboratory study. II. Cryoglobulins with rheumatoid factor activity. Am J Med. 1966;40(6):837–856. doi: 10.1016/0002-9343(66)90200-2. - DOI - PubMed
    1. Ferri C, Zignego AL, Pileri SA. Cryoglobulins. J Clin Pathol. 2002;55(1):4–13. doi: 10.1136/jcp.55.1.4. - DOI - PMC - PubMed
    1. Zignego AL, Ferri C, Giannini C, La Civita L, Careccia G, Longombardo G, et al. Hepatitis C virus infection in mixed cryoglobulinemia and B-cell non-Hodgkin's lymphoma: evidence for a pathogenetic role. Arch Virol. 1997;142(3):545–555. doi: 10.1007/s007050050100. - DOI - PubMed
    1. Ferri C, Sebastiani M, Giuggioli D, Colaci M, Fallahi P, Piluso A, et al. Hepatitis C virus syndrome: a constellation of organ- and non-organ specific autoimmune disorders, B-cell non-Hodgkin's lymphoma, and cancer. World J Hepatol. 2015;7(3):327–343. doi: 10.4254/wjh.v7.i3.327. - DOI - PMC - PubMed
    1. Desbois AC, Cacoub P, Saadoun D. Cryoglobulinemia: an update in 2019. Joint Bone Spine. 2019;86(6):707–713. doi: 10.1016/j.jbspin.2019.01.016. - DOI - PubMed

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