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
Tags: Clinical, Immunology/Immunity, Inflammation
Professional rather than household exposure as determinant for transmission.
Serum conversion correlates with innate inflammatory cytokine signature.
IL-33 correlates with antibody titres and is expressed in BALF cell subsets.
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.
In vivo study
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.