Cytokine profile in plasma of severe COVID-19 does not differ from ARDS and sepsis

Authors: Wilson et al.

Link to paper: https://doi.org/10.1101/2020.05.15.20103549

Journal/ Pre-Print: MedRxiv

Tags: Clinical, Immunology/Immunity, Inflammation

Research Highlights

1. Levels of IL-1b, IL-1RA, IL-6, IL-8, IL-18 and TNF (inflammatory cytokines associated with cytokine storm in COVID-19) do not differ between moderate COVID-19, severe COVID-19 and ARDS/sepsis patients.

2. It is unlikely that the cytokine storm observed in COVID-19 is distinct from other critical illness (e.g. sepsis and ARDS).

Summary 

Cytokine levels in 15 hospitalised COVID-19 patients (6 non-ICU, 9 ICU) were measured in their plasma samples and compared to cytokine levels in 28 critically ill patients (ICU) with ARDS or sepsis. No significant differences were found in levels of IL-1b, IL-1RA, IL-6, IL-8, IL-18 and TNF (inflammatory cytokines associated with cytokine storm in COVID-19) were found between moderate COVID-19, severe COVID-19 and ARDS/sepsis patients. Therefore, it is unlikely that the cytokine storm observed in COVID-19 is distinct from other critical illness (e.g. sepsis and ARDS) and that immunosuppressive therapies will be beneficial in unselected COVID-19 patients.

Impact for SARS-CoV2/COVID19 research efforts

Understand the immune response to SARS-CoV2/COVID19

There were no significant differences between cytokine levels in moderate COVID-19, sever COVID-19 and sepsis/ARDS patients. Altogether, the authors conclude that it is unlikely that the cytokine storm in COVID-19 is distinct from other critical illness.

Treat of SARS-CoV2/COVID19 positive individuals

Because there was no difference between the cytokine storm in COVID-19 compared to other critical illness, the authors says that broad testing of immunosuppressive therapies in unselected COVID-19patients may face the same difficulties as trails with immunosuppressants in unselected ARDS and sepsis patients: inconclusive results and a lack of understanding why it works for some patients, but not for others.

Study Type

· Patient Case study

Strengths and limitations of the paper

Novelty: Cytokine levels were not previously compared between moderate/severe COVID-19 patients and ARDS/sepsis patients. Therefore, the “cytokine storm” in COVID-19 may not differ from that in other critical illness (e.g. sepsis and ARDS).

Standing in the field: Previous reports have shown that cytokine levels in severe COVID-19 patients are elevated compared to moderate COVID-19 patients. This study showed a trend towards higher levels of IL-1RA and IL-6 in severe COVID-19 patients, which is consistent with previous study. The lack of statistically significant differences can be explained by a lack of power, as the patient groups were very small in this study.

Appropriate statistics: Good statistics

Viral model used: SARS-CoV2 infected patients

Translatability: Translatability is good, as this is a patient case study, where moderate/severe COVID-19 patients are compared with ARDS/sepsis patients. This study suspects the use of immunosuppressive therapies in unselected COVID-19 patients may not be successful, as the “cytokine storm” in COVID-19 seems similar to that in ARDS or sepsis and many clinical trials of immunosuppressive therapies in these diseases have failed.

Main limitations: First of all, the group sizes are very small (6 moderate COVID-19 patients, 9 severe COVID-19 patients and 28 sepsis/ARDS patients), leading to a lack of power to detect differences between groups. Furthermore, cytokines are measured at only one time point, there is no data on changes of cytokine levels over time. Finally, cytokine levels are reported as MFI per recommended Luminex analysis methods, precluding direct comparison of our values to previously published data that report cytokine levels in pg/mL.