CLL Linked With Worse COVID-19 Outcomes in Early Pandemic

People with chronic lymphocytic leukemia (CLL) faced a significantly higher risk of severe disease and mortality in the early days of the coronavirus disease 2019 (COVID-19) pandemic, a Swedish study published in the journal Blood Advances found.

The study also highlighted a need for ongoing strategies to mitigate risk, as the data show the risk of mortality also spiked when the Omicron strain became predominant in late 2021.¹

People with CLL had significant mortality rates throughout the study years, which spanned the timeframe from the onset of the pandemic through February 2023. | Image credit: phonlamaiphoto - stock.adobe.com

It is well-documented that people with compromised immune systems were particularly vulnerable to the SARS-CoV-2 virus. In the case of CLL, that vulnerability can be attributed both to the immune dysfunction associated with the disease itself and the immunomodulatory effects associated with its treatments, noted corresponding author Lotta Hansson, MD, PhD, of Sweden’s Karolinska University Hospital, and colleagues.² For instance, a European study from September 2020 showed 79% of patients with CLL and COVID-19 had severe cases of the latter, and more than one-third (36.4%) of those patients died.³

However, Hansson and colleagues explained that Sweden represents a particularly intriguing case study because, compared with many of its peer countries, Sweden had relatively few public health interventions in the early months of the pandemic.¹ The authors noted that the country did not enact general lockdowns, and had no large-scale face mask regulations.

“A better understanding of outcomes for CLL in patients in such open society settings is warranted to inform future SARS-CoV-2 vaccination campaigns and epidemic preparedness for medical high-risk groups,” the authors wrote.

The investigators set out to examine how COVID-19 outcomes varied between people with CLL and those without CLL in the first 3 years of the pandemic. They consulted 10 nationwide registries to find COVID-19 cases in patients born between 1930 and 2003. The databases covered a population of more than 8 million people, of whom 6653 had CLL. Of those, 2.1 million first COVID-19 infections were catalogued, including 1289 first infections among people with CLL.

People with CLL had significant mortality rates throughout the study years, which spanned the timeframe from the onset of the pandemic through February 2023. During the wild-type phase of the pandemic, the mortality rate for all people with CLL was 24.8%, dropping to 17.2% during the Alpha phase. The rate dropped to 4.1% during the Delta period but spiked again in the Omicron phase, reaching 12.6%.

The adjusted relative risk (aRR) for 90-day mortality among individuals with CLL compared with those without CLL was 1.95 (95% CI, 1.58-2.41) for wild-type, 2.38 (95% CI, 1.58-3.57) for Alpha, 0.71 (95% CI, 0.24-2.08) for Delta, and 1.49 (95% CI, 1.24-1.78) for Omicron.

The authors found that during Omicron, the greatest risk of death was among those ages 75 years and older. Small molecule inhibitors (aRR, 1.56; 95% CI, 1.03-2.37) and corticosteroid usage (aRR, 1.45; 95% CI, 1.04-2.02) were both associated with an increased risk of death, the authors found.

When the investigators looked specifically at Stockholm, the country’s highly populated capital, they found people with CLL saw an all-cause mortality increase of 55% during the first half of 2020 compared with the previous year. During the same timeframe, the increase in all-cause mortality for the general population was 31%, they found.

Hansson and colleagues noted that the increase in all-cause mortality among people with CLL in Stockholm is significantly higher than what has been reported in other countries, which shows the need for further studies to see whether different policy measures in the pre-vaccine period led to higher mortality.

“Collectively, our study is valuable both in the continued COVID-19 era, but also provides important information for future viral outbreaks or pandemics,” the authors concluded.

References

1. Hedberg P, Blixt L, Eketorp Sylvan S, et al. Outcomes of the COVID-19 pandemic in chronic lymphocytic leukemia: Focus on the very early period and Omicron era. Blood Adv. Published online February 21, 2025. doi:10.1182/bloodadvances.2024015260

2. Yang S, Wei R, Shi H, et al. The impact of Bruton's tyrosine kinase inhibitor treatment on COVID-19 outcomes in Chinese patients with chronic lymphocytic leukemia. Front Oncol. 2024;14:1396913. doi:10.3389/fonc.2024.1396913

3. Scarfò L, Chatzikonstantinou T, Rigolin GM, et al. COVID-19 severity and mortality in patients with chronic lymphocytic leukemia: a joint study by ERIC, the European Research Initiative on CLL, and CLL Campus. Leukemia. 2020;34(9):2354-2363. doi:10.1038/s41375-020-0959-x