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

## TL;DR

This study shows that SARS-CoV-2 can trigger severe episodes of a rare condition called MG-CLS, leading to higher ICU mortality compared to other triggers.

## Contribution

The study identifies SARS-CoV-2 as a significant and dangerous trigger for MG-CLS episodes with increased mortality.

## Key findings

- SARS-CoV-2-triggered MG-CLS episodes had higher 28-day mortality (42%) compared to other triggers (17%).
- Episodes caused by SARS-CoV-2 required more mechanical ventilation and renal replacement therapy.
- Intravenous immunoglobulins did not improve survival in these patients.

## Abstract

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.

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.

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.

The online version contains supplementary material available at 10.1186/s13613-025-01483-7.