COVID-19 and the lungs: A review

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) attacks pulmonary alveolar cells via angiotensin-converting enzyme 2 (ACE2) receptors and causes pulmonary infections that result in coronavirus disease (COVID-19), inducing immune responses that can result in severe pneumonia. We reviewed the clinical experiences of lung diseases during the COVID-19 pandemic to offer insights into the adaptations made by experts in the diagnosis and treatment of these comorbidities. Various lung comorbidities increase the severity of COVID-19 and associated mortality by amplifying ACE2 expression. Additionally, the COVID-19 pandemic has changed the use of routine diagnostic pulmonary imaging methods, making chest sonography scoring the most convenient, as it can be conducted bedside. Treatment protocols for SARS-CoV-2 infection and the underlying lung diseases are also affected owing to potential interactions. The optimal diagnostic methods and treatment protocols for lung diseases have been adapted worldwide to increase survival rates and attenuate acute lung injuries during the COVID-19 pandemic.

Keywords: Angiotensin-converting enzyme 2; Coronavirus disease-19; Lung comorbidities; Pathophysiology; Pulmonary images; Severe acute respiratory syndrome coronavirus-2.

Fig. 1

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection of lung cells and the associated complications. The SARS-CoV-2 surface spike protein, S glycoprotein, can act through two pathways to enter the host cells, such as lung epithelial cells, endothelial cells, and type 2 alveolar cells. (1) One is via the spike protein binding to the angiotensin-converting enzyme 2 (ACE2) receptor, (2) using endocytosis to enter the cell, whereas (1’) the other is through the activation of the host cell surface type 2 transmembrane serine protease (TMPRSS2) by the spike protein, (2’) leading to SARS-CoV-2 fusion into the host cells. (3) Thereafter, SARS-CoV-2 replicates its RNA, synthesizes proteins, and assembles, resulting in the multiplication of viruses that spread to other host cells. Clinical statistical analysis showed that chronic obstructive pulmonary disease (COPD) and smoking are risk factors of SARS-CoV-2 infection as they can cause epithelial cells and type 2 alveolar cells to express more ACE2 receptors at the gene, mRNA, and protein levels. In addition, smoke could also pass through the renin-angiotensin system to enhance the pathogenicity of SARS-CoV-2. The same result was observed in human ACE2 over-expressing transgene mice, which had more severe SARS-CoV-2 pathogenicity.

Fig. 2

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection induces immune reaction. The innate immune system includes macrophages, monocytes, dendritic cells, and neutrophils, which act through pattern recognition receptors (PRRs), detecting virus-induced pathogen-associated molecular patterns (PAMPs). PRRs included TLRs 3, 7, and 8, which can induce the production of cytokines such as IL-6, IL-10, and TNF-α. Other PRRs, retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5), could induce interferon response factor 3 (IRF3) or activation protein 1 (AP-1) producing type I IFNs (T1IFN) to inhibit infection. Nucleotide-binding domain leucine-rich repeat (NLR) proteins also act as PRRs, which can detect endogenous danger-associated molecular patterns (DAMPs), activate inflammasomes, and covert pro-caspase-1 to AP-1, which then induces the conversion of pro-IL-1β to IL-1β. In adaptive immunity, SARS-CoV-2 induced CD4⁺ T cell differentiation to pathogenic Th1 cells, which produced IL-6 and granulocyte macrophage-colony-stimulating factor (GM-CSF) stimulating the recruitment of CD14⁺ CD16⁺ monocytes to the lungs. In addition, pro-inflammatory bioactive mediators such as eicosanoids, prostaglandins, and leukotrienes activate an inflammasome-induced eicosanoid storm. However, specialized pro-resolution mediators (SPMs) may mediate macrophage clearance of pro-inflammatory cytokine production, and soluble epoxide hydrolase (sEH) which could degrade arachidonic acid-derived epoxyeicosatrienoic acids (EETs) to inhibit inflammation.

Fig. 3

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections induces cytokine storm. During infection, SARS-CoV-2 induces lung epithelial cells, endothelial cells, and macrophages to produce cytokines such as IL-1, IL-2, IL-6, IL-7, IL-10, TNF-α, granulocyte colony-stimulating factor (GCSF), interferon-gamma-inducible protein 10 (CXCL10), monocyte chemoattractant protein 1 (MCP-1), and macrophage inflammatory protein 1-alpha (MIP-1α). This causes a cytokine storm, leading to macrophage, monocyte, and neutrophil recruitment from circulation into the lungs inducing endothelial cell, vascular barrier, capillary, and alveolar damage, resulting in acute lung injury. SARS-CoV-2, through the renin-angiotensin-aldosterone system (RAAS), inhibits angiotensin-converting enzyme 2 (ACE2) convert angiotensin (Ang) II to Ang 1–7, resulting in higher Ang II levels in the plasma, and through AT1R binding to macrophages and monocytes, results in NF-κB-induced IL-1β, IL-6, IL-10, and TNF-α expression. Active AT1R through the MAPK-ERK1/2, JNK, and p38MPK pathways regulates IL-1, IL-10, IL-12, and TNF-α release, causing a cytokine storm. In addition, SARS-CoV-2 causes lymphocytopenia, decreasing memory helper T, CD4⁺ and CD8⁺ lymphocytes, and NK cells.