IL-33 expression in response to SARS-CoV-2 correlates with seropositivity in COVID-19 convalescent individuals
clinical immunology/immunity inflammation
Authors:Stanczak, Sanin, Apostolova et al.
Link to paper: https://doi.org/10.1101/2020.07.09.20148056
Journal/ Pre-Print:MedXriv
Tags: Clinical, Immunology/Immunity, Inflammation
Research Highlights
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Professional rather than household exposure as determinant for transmission.
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Serum conversion correlates with innate inflammatory cytokine signature.
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IL-33 correlates with antibody titres and is expressed in BALF cell subsets.
Summary
This study investigated common immunological features associated with serum conversion in SARS-CoV2 patients. For this purpose, the authors looked at blood samples of 155 individuals and characterised lymphoid and myeloid cells several weeks post-infection. In their cohort, serum converted individuals maintained high titre of anti-Spike/-RBD IgG antibodies over a ~2-month period. The authors found that most SARS-CoV2 transmission occurs in professional rather than household settings. Lastly, although most immunological characteristics did not correlate with serum conversion, the authors found that serum converted individuals show a higher inflammatory signature when circulating immune cells are re-activated ex vivo. In this setting, IL-33 showed the strongest correlation with activated (CD69+) CD4+ T cells. Using publicly available scRNAseq data of cells from BALF, the authors found a subset cluster producing increased levels of IL-33. Though many results are not necessarily surprising, the implication of IL-33 in COVID19 with the associated pulmonary tissue damage may be a valuable insight for further investigation.
Impact for SARS-CoV2/COVID19 research efforts
Understand the immune response to SARS-CoV2/COVID19
Using their cohort, the authors dissect the immune phenotype in recovered vs. non-infected individuals and look at potential long-term effects on the state of the immune system. This may help to understand the recovery process and the determinants involved in successful serum conversion.
Study Type
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In vivo study
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Clinical Cohort study
Strengths and limitations of the paper
Novelty: IL-33 implication in COVID-19 pathology
Standing in the field:Thus far IL33 has not been identified as a major player in SARS-CoV2
pathology, as most papers looking at serum cytokines did not detect any increases systemically of IL33. However, IL-33 is usually found to be released locally in damaged tissues, including the lung. However, its role in potentially skewing the immune response during SARS-CoV2 infection remains unclear at the present.
Appropriate statistics:Yes, appropriate statistics were used
Viral model used:Blood from SARS-CoV2 infected patients and non-infected controls
(tested by PCR weeks before blood donation) were used in this study
Translatability:Low translatability. At present this study presents very much
descriptive information without providing much mechanistical insights.
Main limitations: The paper looks at individuals at one time point after they recovered from their infection. It would have been nice to get a more longitudinal perspective. This would have given more insights into persistence of antibody responses.
The paper does not include many hospitalised, hence correlation with disease severity is difficult.
Using serum-conversion as a classifier, rather than a positive PCR test, is potentially misleading as other studies show the emergence of SARS-CoV2-specific T cells upon infection without strong IgG responses.
Although out of scope of this paper, it would have been great to gain more mechanistical insight to the role of IL-33 during this viral infection.