Systems-level immunomonitoring from acute to recovery phase of severe COVID-19 (original) (raw)

, Pirkka Pekkarinen, Tadepally Lakshmikanth, Ziyang Tan, Camila Rosat Consiglio, Christian Pou, Yang Chen, Constantin Habimana Mugabo, Anh Nguyen Quoc, Kirsten Nowlan, Tomas Strandin, Lev Levanov, Jaromir Mikes, Jun Wang, Anu Kantele, Jussi Hepojoki, Olli Vapalahti, Santtu Heinonen, Eliisa Kekäläinen, Petter Brodin

doi: https://doi.org/10.1101/2020.06.03.20121582

SUMMARY

The immune response to SARS-CoV2 is under intense investigation, but not fully understood att this moment. Severe disease is characterized by vigorous inflammatory responses in the lung, often with a sudden onset after 5–7 days of stable disease. Efforts to modulate this hyperinflammation and the associated acute respiratory distress syndrome, rely on the unraveling of the immune cell interactions and cytokines that drive such responses. Systems-level analyses are required to simultaneously capture all immune cell populations and the many protein mediators by which cells communicate. Since every patient analyzed will be captured at different stages of his or her infection, longitudinal monitoring of the immune response is critical. Here we report on a systems-level blood immunomonitoring study of 39 adult patients, hospitalized with severe COVID-19 and followed with up to 14 blood samples from acute to recovery phases of the disease. We describe an IFNγ – Eosinophil axis activated prior to lung hyperinflammation and changes in cell-cell coregulation during different stages of the disease. We also map an immune trajectory during recovery that is shared among patients with severe COVID-19.

HIGHLIGHTS Systems-level immunomonitoring from acute to recovery in severe COVID-19

An IFNγ - Eosinophil axis involved in lung hyperinflammation

Cell-cell coregulation differ during four disease stages

Basophils and hyperinflammation modulate humoral responses

A shared trajectory of immunological recovery in severe COVID-19

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

The authors are grateful to private donations to Karolinska Institutet from Bure Equity AB (Stockholm, Sweden) and Af Jochnick Foundation. The study was also supported by grants from Academy of Finland to E.K. (308913) and S.H. (323499) and Helsinki University Hospital (project M7100YLIT2) to P.P as well as funding from Juho Vainio Foundation to O.V and A.K.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study was approved by the Ethics Committee of the Hospital District of Helsinki and Uusimaa (HUS/853/2020) and conducted in accordance with the Declaration of Helsinki.

All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.

Yes

The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.