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

Table 1 Patient characteristics

Baseline characteristics of the study cohort (n = 5)
Age (mean ± SD) yr	48.2 (14.2)
Male: Female ratio	4: 1
APACHE-II score at admission (median, IQR)	19 (10-21)
Day of worsening from date of onset of symptoms (Median, IQR)	32 (23-35)
Oxygenation parameters (median, IQR) PF ratio
Peak PF ratio prior to onset of DIPS	326 (243-329)
PF ratio at onset of DIPS	182 (156-190)
Peak PF ratio after immunomodulation	353 (327-353)
Ventilation data (median, IQR) d
Duration of mechanical ventilationa prior to the onset of DIPS	9 (2-16)
Duration of mechanical ventilation after the onset of DIPS	13 (10-23)
Inflammatory markers (median, IQR)
CRP (mg/L) at baseline	142 (113-182)
CRP (mg/L) at onset of DIPS	165.5 (157-212)
Ferritin (ng/mL) at baseline	270.2 (191-349)
Ferritin (ng/mL) at onset of DIPS	677.5 (382-1893)
IL-6 (pg/mL) at onset of DIPS (median, IQR)	207.4 (163-311)

^aMechanical ventilation includes both invasive and non-invasive ventilation.

SD: Standard deviation; APACHE: Acute Physiology and Chronic Health Evaluation; PF: (PaO₂/FIO₂); IQR: Interquartile range; DIPS: Delayed inflammatory pulmonary syndrome; CRP: C reactive protein (reference range: < 6 mg/L). Ferritin reference range (male: 22-322 ng/mL; female: 10-291 ng/mL); IL: Interleukin (reference range: < 7 pg/mL);

Table 2 Comparison of characteristics of coronavirus disease 2019 (COVID-19) associated acute respiratory distress syndrome, multisystem inflammatory syndrome Adults, multisystem inflammatory syndrome Children, post COVID-19 secondary organising pneumonia, post COVID-19 interstitial lung disease and Delayed Inflammatory Pulmonary Syndrome

Syndrome	Time of onset (Median, IQR) d	Primary organ affected	Other organs affected	Inflammatory markers	Treatment	Intensive care required (%)	Mortality, %
CARDS[11,12]	8 (5-13) d from onset of infection	Lungs	Gastro-intestinal	Elevated IL-2, IL7, TNF-α	Corticosteroids, Baricitinib (JAK-2 inhibitor) and Tocilizumab (IL-6 inhibitor) in severe hypoxia and evidence of hyperinflammation	Yes (17)	39
MIS-A[6]	28 (20-36) d after SARS-CoV-2 infection	Cardio-vascular	Gastro-intestinal, muco-cutaneous, haematological	Fibrinogen, D-dimer, CRP, ferritin, IL-6 elevated in > 90%	IVIG (55%), corticosteroids (74%), IL-6 inhibitors (21%)	Yes (57)	7
MIS-C[2]	Within 4 wk of SARS-CoV-2 infection (13)	Gastro-intestinal tract	Muco-cutaneous	CRP, ferritin, procalcitonin, IL-6 elevated	IVIG (76.4%) and corticosteroids (52.3%), IL-1ra inhibitor (8.5%) and IL-6 inhibitors (6%)	Yes (73.8)	1.9
Secondary OP[7,8]	Beyond 4 wk of SARS-CoV-2 infection	Lungs	Nil	CRP (mild elevation: 3.45 to 11.7 mg/dL)	Corticosteroids	No	Nil
Secondary ILD[9]	6 wk after discharge from hospital	Lungs	Uncommon	CRP and ferritin significantly elevated	Corticosteroids	No	Nil
DIPS (Current study)	32 (23-35) d after symptom onset	Lungs	Uncommon	Elevated CRP, ferritin, and IL-6	Good response to IVIG/steroids	Yes (100)	20

CARDS: COVID-19 associated acute respiratory distress syndrome; MIS-A: Multisystem inflammatory syndrome Adults; MIS-C: Multisystem inflammatory syndrome Children; OP: Organising pneumonia; ILD: Interstitial lung disease; DIPS: Delayed inflammatory pulmonary syndrome; IQR: Interquartile range; equivalent of dexamethasone 6 mg once daily recommended in hypoxic patients; IVIG: Intravenous immunoglobulin; CRP: C-reactive protein.