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. 2025 May 26;15(1):72.
doi: 10.1186/s13613-025-01483-7.

Characteristics of SARS-CoV-2-associated severe episodes of monoclonal gammopathy-associated capillary leak syndrome (Clarkson disease)

Nissim Grinberg #  1 , Maddalena Alessandra Wu #  2 , Quentin Moyon  1   3   4 , Sybille Merceron  5 , Yannick Fedun  6 , Marie Gousseff  7 , Romain Sonneville  8 , François Lhote  9 , Elie Azoulay  10 , Jean-Herlé Raphalen  11 , David Saadoun  12 , Ygal Benhamou  13 , Jean-Paul Mira  14 , Guillaume Dumas  15 , Pierre Bay  16 , Jérôme Devaquet  17 , Laurent Argaud  18 , Marc Lambert  19 , Avinash Aujayeb  20 , Basile Henriot  21 , Amandine Bichon  22 , Thomas Bocar  23 , John Harty  24 , Remo Melchio  25 , Franck Leibinger  26 , Laure Calvet  27 , Tomas Urbina  28 , Laurent Bodson  29 , Jean-Marie Tonnelier  30 , Danielle Reuter  31 , Emmanuel Canet  32 , Gilles Blaison  33 , Julien Maizel  34 , Nicholas Sedillot  35 , Laurence Dangers  36 , Vincent Eble  37 , Franco Verlicchi  38 , Stanislas Faguer  39 , Jonathan Montomoli  40 , Geoffroy Dingemans  41 , Marc Mikulski  42 , Jonas Pochard  43 , Fabrice Uhel  44 , Fleur Cohen-Aubart  2   45 , Charles-Edouard Luyt  1   3 , Alexis Mathian  2   45 , Alain Combes  1   3 , Riccardo Colombo  46 , Zahir Amoura #  2   45 , Marc Pineton de Chambrun #  47   48   49 ; EurêClark Study Group
Affiliations

Characteristics of SARS-CoV-2-associated severe episodes of monoclonal gammopathy-associated capillary leak syndrome (Clarkson disease)

Nissim Grinberg et al. Ann Intensive Care. .

Abstract

Background: Monoclonal gammopathy-associated capillary leak syndrome (MG-CLS) is a rare condition characterized by recurrent episodes of hypovolemic shock caused by a sudden increase in capillary permeability. The COVID-19 pandemic has been associated with a rise in MG-CLS episodes and increased mortality. We aimed to explore the association between MG-CLS and SARS-CoV-2 infection. We conducted a multicenter retrospective observational study involving MG-CLS patients who were admitted to the intensive care unit (ICU). The primary endpoint was 28-day mortality according to whether SARS-CoV-2 was identified as a trigger.

Results: The study included 84 patients (44% women) with a median age of 55 years [IQR 46-62], accounting for 127 ICU admissions. Most patients (88%) had monoclonal gammopathy, predominantly with an IgG heavy chain (98%). A trigger was identified in 63% of cases, primarily suspected or confirmed viral infections, including 26 episodes of SARS-CoV-2 infection. Within 28 days of ICU admission, 32% of patients died. Episodes triggered by SARS-CoV-2 were associated with a higher need for mechanical ventilation (69% vs. 38%, p = 0.004), renal replacement therapy (54% vs. 31%, p = 0.03), and increased 28-day mortality (42% vs. 17%, p = 0.005). Multivariable analysis revealed that SARS-CoV-2 infection was independently associated with 28-day mortality (OR 4.67 [1.08-20.1], p = 0.04). The use of intravenous immunoglobulins did not improve 28-day survival.

Conclusion: In this large cohort of MG-CLS episodes requiring ICU admission, SARS-CoV-2as a trigger was associated with significantly higher 28-day mortality compared to other triggers. Further research is essential to elucidate the specific mechanisms by which SARS-CoV-2 impacts MG-CLS patients.

Keywords: Clarkson disease; Intensive care unit; Monoclonal gammopathy; Monoclonal gammopathy-associated capillary-leak syndrome; SARS-CoV-2.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The database is registered with the “Commission Nationale de l’Informatique et des Libertés” (n°1950673). In accordance with the ethical standards of our hospital’s institutional review board, the Committee for the Protection of Human Subjects, and French law, written informed consent was not needed for demographic, physiological and hospital-outcome data analyses because this observational study did not modify existing diagnostic or therapeutic strategies; however, patients were informed of their inclusion in the study. Consent for publication: All authors significantly contributed to study design, data collection, manuscript drafting, critical evaluation and/or final approval. Competing interests: Jonathan Montomoli is a co-founder and shareholder of Callisia srl University Spin-off at Università Politecnica delle Marche developing a smart bracelet collecting patient data intelligently for real-time visualization and data analysis.

Figures

Fig. 1
Fig. 1
Total number of flares per patient stratified by SARS-CoV-2 status. COVID-19, coronavirus disease 2019
Fig. 2
Fig. 2
Day 1-to-10 In-ICU urine output with comparison by SARS-CoV-2 Status. ICU, intensive care unit; CLS, capillary-leak syndrome; COVID-19, coronavirus disease 2019. Box-plots values: internal horizontal line = median; lower and upper box limit = 25 th–75 th percentiles; whiskers = 0 th-100 th percentiles
Fig. 3
Fig. 3
Cumulated fluid therapy on first ICU day with comparison by SARS-CoV-2 status. ICU, intensive care unit; COVID-19, coronavirus disease 2019. Box-plots values: internal horizontal line = median; lower and upper box limit = 25 th–75 th percentiles; whiskers = 0 th-100 th percentiles; black dots = outliers
Fig. 4
Fig. 4
Kaplan–Meier Curves representation of the cumulative probability of survival until 28 days after ICU admission with comparison by COVID-19 status. ICU, intensive care unit; COVID-19, coronavirus disease 2019. Comparison According COVID-19 Status performed with the Log-Rank Test
See this image and copyright information in PMC

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