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

ARTICLE HIGHLIGHTS

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.