Thread by @ZdenekVrozina

Cardio-Pulmonary Features of Long COVID review.
From molecular pathways to clinical impact - and why heart and lung damage often go hand-in-hand.
Most mechanisms are variant-agnostic; prevalence numbers reflect the specific wave & vaccine context.🧵

Early imaging data was alarming.
In a JAMA Cardiology 2020 study (Wuhan strain, early 2020, pre-vaccine):
78% of recently recovered patients showed cardiac abnormalities on MRI
60% had signs of ongoing myocardial inflammation
These were not only patients with severe acute illness - many had mild initial COVID.

Histopathology tells the same story:
Endothelial damage in heart and lung microvasculature
Perivascular immune cell infiltration (lymphocytes, macrophages)
Microvascular thrombosis
SARS-CoV-2 RNA and proteins found in myocardial tissue months after infection - ongoing antigenic stimulation

Lungs show persistent structural injury across waves:
Organizing pneumonia, interstitial fibrosis, capillary congestion
In some transplant cases (various waves, mostly Alpha & Delta), end-stage fibrosis resembling idiopathic pulmonary fibrosis
Supports the rationale for lung transplantation in selected long COVID cases

Core mechanisms (all major variants):
Persistent low-grade inflammation (↑ IL-6, IL-1β, TNF-α, IFN-γ, CRP)
Endothelial dysfunction (↓ nitric oxide bioavailability, ↑ oxidative stress)
Coagulation cascade dysregulation (↑ platelet activation, ↑ D-dimer, ↑ PAI-1)
Microthrombosis in heart, lung, and brain microcirculation
Viral persistence in endothelial and immune cells

The vicious cycle:
Endothelial injury - chronic inflammation - more endothelial dysfunction - more thrombosis.
Chemokines (eg CCL2) and neutrophil extracellular traps (NETs) add fuel to the fire, damaging vessels and impairing tissue repair.

Myocardium (all waves, variable prevalence):
Chronic endotheliitis, perivascular fibrosis
Active lymphocytic or eosinophilic myocarditis in some cases
↑ anti-cardiac autoantibodies
Viral RNA detectable months post-infection

Lungs (all waves, worse in Delta & pre-vaccine):
Persistent inflammation, alveolar type II cell senescence
Vascular hyperplasia, fibrotic remodeling up to 1 year post-infection
TGF-β pathway activation - fibrosis and myocardial stiffening

Immune dysregulation:
Persistent CD8+T cell activation in lung tissue
Autoantibodies targeting GPCRs, endothelial antigens, phospholipids
Epigenetic reprogramming & altered miRNA expression - long-lasting changes in gene expression

Pro-thrombotic state (all waves, higher prevalence in severe acute illness):
Platelets remain activated for months
↑ P-selectin, ↑ tissue factor, ↑ factor VIII
Microthrombi resistant to breakdown - cerebral & pulmonary microcirculation damage
↑ D-dimer in 25–30% of patients 3–6 months post-infection (seen in Alpha, Delta, and early Omicron cohorts)

Clinical picture across variants:
Dyspnea on exertion
Chest pain, palpitations, tachycardia
Exercise intolerance & post-exertional symptom exacerbation
Silent ischemia - brain fog, fatigue

Key takeaways:
Heart and lung injury in long COVID share a vascular-immune mechanism
Endothelial dysfunction is the central hub linking inflammation, clotting, and fibrosis
Prevalence numbers vary by variant and vaccine era, but the core biology is consistent!
Management may require multi-specialty care: cardiology, pulmonology, hematology, immunology, rehab
Long-term monitoring is essential - even after mild acute COVID

Cimmino et al., Cardio-Pulmonary Features of Long COVID: From Molecular and Histopathological Characteristics to Clinical Implications. 2025. mdpi.com/1422-0067/26/1…