COVID-19-related end stage lung disease: two distinct phenotypes

Figures & data

Table 1. Different aspects of the two phenotypes of COVID associated lung fibrosis.

	COVID-19 related ARDS (CARDS)	post-COVID pulmonary fibrosis (PCPF)
Clinical features	7–14 days after initial symptoms secondary pulmonary hypertension +++	4–6 to 12 weeks after initial infection secondary pulmonary hypertension +
Mortality 90 days	30–50%	unknown
Risk factors	Mechanical ventilation, VILI, hyperoxia, prolonged hypoxia, increased BMI, elderly patients, possibly thromboembolism and hypercoagulability, possibly NETS	profound dyspnoea, higher respiratory rate, comorbid hypertension, ICU admission, hyperoxia, prolonged hypoxia, elderly patients, possibly thromboembolism and hypercoagulability, possibly NETS, higher CRP levels, lymphocytopenia, neutrophilia, eosinopenia lower baseline IFN-γ and MCP-3
Biomarkers	Classic “cytokine storm” not observed IL-6 moderately increased persistent deactivation of key immune cells e.g. reduced surface expression of the mHLA-DR	cytokine-driven: TGF-β and IL-1β longer telomere lengths appear to be protective, this genomic biomarker estimates balance of profibrotic and antifibrotic susceptibilities
Restrictive ventilatory defect	++	+++ (rib cage shrinkage)
Pneumothorax	+++	++
Pathophysiology	Severe pulmonary infiltration/edema and endothelitis	inflammation leading to impaired alveolar homeostasis, alteration of pulmonary physiology resulting in pulmonary fibrosis

ARDS = Acute Respiratory Distress Syndrome, CARDS = COVID-19 related ARDS, CRP = C-reactive protein, IFN-γ = interferon gamma, IL = interleukin, MCP-3 = monocyte chemoattractant protein 3, mHLA-DR = monocytic human leucocyte antigen-DR, NETS = neutrophil extracellular traps, PCPF = post-COVID pulmonary fibrosis, TGF = Tumour Growth Factor, VILI = mechanical ventilation-induced lung injury.