Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Sep 9;12(4):226-235.
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  1 , Binila Chacko  1 , Ashwin Oliver Arul  1 , Leena Robinson Vimala  2 , Balamugesh Thangakunam  3 , George M Varghese  4 , Mohan Jambugulam  5 , Audrin Lenin  5 , John Victor Peter  6
Affiliations

Delayed inflammatory pulmonary syndrome: A distinct clinical entity in the spectrum of inflammatory syndromes in COVID-19 infection?

Prithviraj Bose et al. World J Crit Care Med. .

Abstract

Background: During the second wave of the coronavirus disease 2019 (COVID-19) pandemic, a subset of critically ill patients developed delayed respiratory deterioration in the absence of new infection, fluid overload or extra-pulmonary organ dysfunction.

Aim: To describe the clinical and laboratory characteristics, outcomes, and management of these patients, and to contrast this entity with other post COVID-19 immune dysregulation related inflammatory disorders.

Methods: This was a retrospective observational study of adult patients admitted to the medical intensive care unit 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.

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%).

Conclusion: This delayed respiratory worsening with elevated inflammatory markers and clinical response to immunomodulation appears to contrast the well described Multisystem Inflammatory Syndrome - Adults 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.

Keywords: ARDS; COVID-19; Long COVID; Multisystem Inflammatory Syndrome in Adults; Organizing pneumonia.

PubMed Disclaimer

Conflict of interest statement

Conflict-of-interest statement: There was no conflict of interest or any financial disclosure for all the authors listed in the manuscript.

Figures

Figure 1
Figure 1
Sequential Organ Failure Assessment score representing degree of organ involvement in Delayed Inflammatory Pulmonary Syndrome. The contribution of respiratory Sequential Organ Failure Assessment (SOFA) to the overall SOFA score is depicted for all the five patients. It is evident that in all patients, respiratory SOFA contributed to > 50% of the total SOFA score. In two patients, there was no extrapulmonary organ dysfunction, while in the remaining three patients, there was some hepatic, renal and cardiovascular dysfunction. DIPS: Delayed Inflammatory Pulmonary Syndrome; SOFA: Sequential Organ Failure Assessment.
Figure 2
Figure 2
Representative Cross sectional computed tomography and plain radiograph images of patients with Delayed Inflammatory Pulmonary Syndrome. A: High resolution transverse computed tomography (CT) sections of patient 4, showing the evolution of infiltrates from day -2 of Delayed Inflammatory Pulmonary Syndrome (DIPS) (A1) till day +15 (A2). The diffuse ground glass opacities seen in A1 have reduced, while the areas of consolidation (marked with yellow arrows) have increased slightly, along with features of tractional bronchiectasis, suggestive of coronavirus disease (COVID) sequelae. The overall improvement in clinical status from A1 to A2 could suggest that the ground glass opacities were part of the inflammatory changes in the lungs and responded to immunomodulation; B: Representative plain radiographs (portable) of patient 1 showing the evolution of infiltrates from day -7 of DIPS (B1) till day 0 (B2), followed by improvement on day +1 (B3), after the initiation of glucocorticoids; C: Representative chest radiograph and coronal high resolution CT sections on day -26 (C1, taken in the index admission for mild COVID on day 10 of symptom onset) before the onset of DIPS, significant increase in diffuse ground glass opacities on day 0 of DIPS (C2), followed by improvement on day +1 of DIPS (C3).
Figure 3
Figure 3
PaO2/FiO2 ratio trends of patients prior to, during and post Delayed Inflammatory Pulmonary Syndrome. The PaO2/FiO2 (PF) ratio of the individual patients is shown in the y-axis. The x-axis depicts day 0 as the day of onset of Delayed Inflammatory Pulmonary Syndrome (DIPS). The highest PF ratio of each patient in the period prior to DIPS and following recovery from DIPS is plotted. The figure shows that the respiratory deterioration occurred gradually over several days in 3 patients and acutely over a day in 2 patients. Recovery was gradual over 5 to 10 d. DIPS: Delayed Inflammatory Pulmonary Syndrome; SOFA: Sequential Organ Failure Assessment.
See this image and copyright information in PMC

References

    1. Marini JJ, Gattinoni L. Management of COVID-19 Respiratory Distress. JAMA. 2020;323:2329–2330. - PubMed
    1. Feldstein LR, Tenforde MW, Friedman KG, Newhams M, Rose EB, Dapul H, Soma VL, Maddux AB, Mourani PM, Bowens C, Maamari M, Hall MW, Riggs BJ, Giuliano JS Jr, Singh AR, Li S, Kong M, Schuster JE, McLaughlin GE, Schwartz SP, Walker TC, Loftis LL, Hobbs CV, Halasa NB, Doymaz S, Babbitt CJ, Hume JR, Gertz SJ, Irby K, Clouser KN, Cvijanovich NZ, Bradford TT, Smith LS, Heidemann SM, Zackai SP, Wellnitz K, Nofziger RA, Horwitz SM, Carroll RW, Rowan CM, Tarquinio KM, Mack EH, Fitzgerald JC, Coates BM, Jackson AM, Young CC, Son MBF, Patel MM, Newburger JW, Randolph AG Overcoming COVID-19 Investigators. Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19. JAMA. 2021;325:1074–1087. - PMC - PubMed
    1. Morris SB, Schwartz NG, Patel P, Abbo L, Beauchamps L, Balan S, Lee EH, Paneth-Pollak R, Geevarughese A, Lash MK, Dorsinville MS, Ballen V, Eiras DP, Newton-Cheh C, Smith E, Robinson S, Stogsdill P, Lim S, Fox SE, Richardson G, Hand J, Oliver NT, Kofman A, Bryant B, Ende Z, Datta D, Belay E, Godfred-Cato S. Case Series of Multisystem Inflammatory Syndrome in Adults Associated with SARS-CoV-2 Infection - United Kingdom and United States, March-August 2020. MMWR Morb Mortal Wkly Rep. 2020;69:1450–1456. - PMC - PubMed
    1. Spalding MC, Cripps MW, Minshall CT. Ventilator-Associated Pneumonia: New Definitions. Crit Care Clin. 2017;33:277–292. - PMC - PubMed
    1. Cardone M, Yano M, Rosenberg AS, Puig M. Lessons Learned to Date on COVID-19 Hyperinflammatory Syndrome: Considerations for Interventions to Mitigate SARS-CoV-2 Viral Infection and Detrimental Hyperinflammation. Front Immunol. 2020;11:1131. - PMC - PubMed