Retrospective Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Crit Care Med. Sep 9, 2023; 12(4): 226-235
Published online Sep 9, 2023. doi: 10.5492/wjccm.v12.i4.226
Delayed inflammatory pulmonary syndrome: A distinct clinical entity in the spectrum of inflammatory syndromes in COVID-19 infection?
Prithviraj Bose, Binila Chacko, Ashwin Oliver Arul, Leena Robinson Vimala, Balamugesh Thangakunam, George M Varghese, Mohan Jambugulam, Audrin Lenin, John Victor Peter
Prithviraj Bose, Binila Chacko, Ashwin Oliver Arul, John Victor Peter, Department of Medical Intensive Care, Christian Medical College, Vellore 632004, Tamil Nadu, India
Leena Robinson Vimala, Department of Radiodiagnosis, Christian Medical College, Vellore 632004, Tamil Nadu, India
Balamugesh Thangakunam, Department of Pulmonary Medicine, Christian Medical College, Vellore 632004, Tamil Nadu, India
George M Varghese, Department of Infectious Disease, Christian Medical College, Vellore 632004, Tamil Nadu, India
Mohan Jambugulam, Audrin Lenin, Department of Medicine, Christian Medical College, Vellore 632004, Tamil Nadu, India
Author contributions: Bose P, Chacko B, Oliver A, and Peter JV designed and performed the research and wrote the paper, performed literature search, reviewed the final manuscript, and approved for publication; Leena RV, Balamugesh T, George MV, Mohan J, and Audrin L provided clinical advice, literature review, reviewed the final manuscript and approved the manuscript for publication; Peter JV designed the research and supervised the report.
Institutional review board statement: The study was approved by the Institutional Review Board of the institution, (CDSCO- Ethics Committee Registration number: ECR/326/INST/TN/2013/RR-2019; DHR provisional registration number: EC/NEW/INST//2020/818; IRB Min No. 14513, approval date 23.02.2021, study title: “Pulmonary hyperinflammation syndrome in survivors of critically ill COVID-19 Long stayers in ICU – a case series”).
Informed consent statement: In view of the retrospective nature of the study, the large number of COVID-19 patients admitted in the ICU, and deidentification of clinical data, informed consent waiver was obtained from the institutional review board.
Conflict-of-interest statement: There was no conflict of interest or any financial disclosure for all the authors listed in the manuscript.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: John Victor Peter, DNB, FRACP, MAMS, MD, Professor, Department of Medical Intensive Care, Christian Medical College, Division of Critical Care Christian Medical College Vellore, Vellore 632004, Tamil Nadu, India.
Received: May 11, 2023
Peer-review started: May 11, 2023
First decision: June 15, 2023
Revised: June 24, 2023
Accepted: July 6, 2023
Article in press: July 6, 2023
Published online: September 9, 2023
Research background

Delayed deterioration in pulmonary function, following initial improvement, was seen in a subset of patients admitted to the intensive care unit (ICU) during the coronavirus disease 2019 (COVID-19) pandemic. These patients had no evidence of ongoing infection, fluid overload or cardiac dysfunction, but had elevated systemic inflammatory markers. They did not satisfy the diagnostic criteria for Multisystem Inflammatory Syndrome- Adults (MIS-A) due to the paucity of extrapulmonary organ manifestations (mainly cardiac, gastrointestinal and mucocutaneous), but responded well to immunmodulation.

Research motivation

Delayed worsening of respiratory function in the ICU is generally attributable to infection, cardiac dysfunction, or fluid overload. But non-infectious inflammatory complications of post COVID-19 immune dysregulation is a distinct clinical entity that may play a role in worsening organ dysfunction in patients who have no evidence of the above.

Research objectives

The objectives of the current study were to describe the clinical and laboratory characteristics of post COVID-19 delayed inflammatory pulmonary syndrome (DIPS), the outcomes and management caveats encountered in the management of these patients, and to contrast DIPS with other post COVID-19 immune dysregulation related inflammatory disorders.

Research methods

This was a retrospective observational study of adult patients admitted to the medical ICU of a 2200-bed university affiliated teaching hospital, between May and August 2021, who fulfilled clearly defined inclusion and exclusion criteria. Outcome was assessed by a change in PaO2/FiO2 ratio and levels of inflammatory markers before and after immunomodulation, duration of mechanical ventilation after starting treatment, and survival to discharge.

Research results

Five patients developed delayed respiratory deterioration in the absence of new infection, fluid overload or extra-pulmonary organ dysfunction at a median interquartile range (IQR) duration of 32 (23-35) d after the onset of symptoms. These patients had elevated inflammatory markers, required mechanical ventilation for 13 (IQR 10-23) d, and responded to glucocorticoids and/or intravenous immunoglobulin. One patient died (20%).

Research conclusions

This delayed respiratory worsening with elevated inflammatory markers and clinical response to immunomodulation appears to contrast the well described MIS-A by the paucity of extrapulmonary organ involvement. The diagnosis can be considered in patients presenting with delayed respiratory worsening, that is not attributable to cardiac dysfunction, fluid overload or ongoing infections, and associated with an increase in systemic inflammatory markers like C-reactive protein, inteleukin-6 and ferritin. A good response to immunomodulation can be expected. This delayed inflammatory pulmonary syndrome may represent a distinct clinical entity in the spectrum of inflammatory syndromes in COVID-19 infection.

Research perspectives

Larger prospective studies are required to validate these preliminary observations and formulate treatment guidelines for this inherently reversible entity.