COVID-19 and Its Effects on Lungs

Introduction:

The COVID-19 pandemic is the most devastating healthcare crisis of recent times. Millions of people have lost their lives due to COVID-19 infection. Respiratory distress caused by the involvement of the upper respiratory tract is the major cause of death in such cases. Lung injury due to COVID-19 is known as COVID lung. Evaluation of lung pathology and its involvement in COVID-19 cases can prove to be decisive in curing patients.

What Is COVID-19 Infection?

COVID-19, a member of the Orthocoronaviridae subfamily, is an RNA virus. It typically causes mild to moderate self-limiting respiratory tract infections in humans. Usually, it is associated with mild cough and cold. The initial outbreak of COVID-19 occurred in China in late 2019. The genome of this novel coronavirus bears resemblance to other β-CoV strains found in bats, which are known to cause severe acute respiratory syndrome (SARS) infections.

In severe cases, COVID-19 can lead to fatal complications. Patients often experience severe breathing difficulties and exhibit various signs of complications, including:

1. Severe lung congestion is accompanied by the production of mucus-like substances.

2. Decreased oxygen saturation levels in the blood.

3. Severe pulmonary pneumonia.

4. Elevated heart rate.

5. High blood pressure.

Insufficient oxygen supply to the body and organs ultimately results in death. Individuals with compromised immune systems or underlying conditions like diabetes have weakened defense mechanisms, making them more susceptible to fatal outcomes in case of a coronavirus infection.

What Is the Pathophysiology of COVID Lung?

During infection, SARS-CoV-2 stimulates various cell types within the lungs, including lung epithelial cells, endothelial cells, and macrophages. This produces a range of cytokines such as interleukins (IL 1, 2,6,7, and 10), tumor necrosis factor-alpha, granulocyte colony-stimulating factor (GCSF), interferon-gamma-inducible protein 10 (CXCL10), monocyte chemoattractant protein 1 (MCP-1), and macrophage inflammatory protein 1-alpha (MIP-1). This cascade of cytokine production triggers a cytokine storm. This leads to the recruitment of macrophages, monocytes, and neutrophils from the bloodstream into the lungs. This influx of immune cells causes damage to the endothelial cells, vascular barrier, capillaries, and alveoli, ultimately resulting in acute lung injury.

Furthermore, SARS-CoV-2 interferes with the renin-angiotensin-aldosterone system (RAAS) by inhibiting the activity of angiotensin-converting enzyme 2 (ACE2). ACE2 is responsible for converting angiotensin (Ang) II to Ang 1–7, but when its function is hindered by the virus, Ang II levels in the plasma increase. Additionally, SARS-CoV-2 binds to angiotensin receptor type 1 (AT1R) in macrophages and monocytes. This leads to the activation of nuclear factor kappa B (NF-κB) and subsequent expression of different types of interleukins (IL-1 beta, 6, and 10) and tumor necrosis factor-alpha. The active AT1R also influences the release of other cytokines, such as IL-1, IL-10, and IL-12, through the different signaling pathways, further contributing to the cytokine storm.

Moreover, SARS-CoV-2 infection is associated with lymphocytopenia, which is characterized by a decrease in the number of memory helper T cells, CD4+ and CD8+ lymphocytes, and natural killer (NK) cells. This depletion of lymphocytes is responsible for decreased immune response against the virus.

What Are the COVID Lung Changes?

Pulmonary COVID-19 can be categorized into four primary morphological phases. These include;

1. Early stage (day 0 to 1) with edema (collection of fluid), incipient epithelial damage, and capillaritis or endothelialitis.

2. Stage of exudative diffuse alveolar damage (DAD) (days 1 to 7).

3. The organizing stage (one to several weeks).

4. The fibrotic change of diffuse alveolar damage.

Diffuse alveolar damage is a well-known histopathological pattern that is associated with respiratory distress and can be categorized into two distinct phases. The first phase, also known as the exudative phase, occurs during the initial 10 days of viral infection and is characterized by the formation of hyaline membranes due to fibrin polymerization in the plasma liquid that has leaked into the interstitial or alveolar space. Additionally, there is an injury to the alveolar-capillary barrier, which leads to red blood cell extravasation and a significant infiltration of inflammatory cells into the intra-alveolar space. The second phase is known as the proliferative phase. It is marked by an excessive proliferation of fibroblasts and myofibroblasts, which can result in acute fibrinous organizing pneumonia or organizing pneumonia.

During the organizing phase, there is a noticeable increase in cellular fibroblastic proliferation. Additionally, there is an occurrence of type 2 pneumocyte hyperplasia and squamous metaplasia (atypical cell changers), which can sometimes be quite pronounced. Furthermore, the hyaline membranes dissolve and merge with the alveolar septa. The radiological features are;

1. Chest radiography is the most common choice for imaging in such patients. However, in the early stages of COVID-19 infection, chest radiography often does not reveal any abnormalities. As a result, it is not recommended as the primary method for investigating chest abnormalities in patients with suspected COVID-19. However, in cases of mild COVID-19, chest radiography may exhibit localized irregular radiopacities in the outer regions of the lungs and the subpleural area. COVID-19 lung involvement typically manifests as bilateral involvement of the peripheral and lower lobe basal segments. In severe instances, there is widespread consolidation, sometimes appearing patchy, along with a small amount of pleural effusion. In critically ill patients, the entire lung may be covered with areas of consolidation, which is referred to as "white lung."

2. During active infection, COVID-19 can exhibit distinct characteristics on chest CT scans, which can aid in tracking the progression of the disease and administering prompt treatment. The presence of patchy ground glass appearances that merge into dense, consolidative lesions with a peripheral distribution in the subpleural areas and broncho-vascular bundles is a hallmark of COVID-19. As the disease advances, the number of lesions can escalate rapidly and spread to central regions. The reticular pattern, which is also seen in some cases, is characterized by an intricate arrangement of linear opacities, which are accompanied by thickening of the interlobular and intralobular septa. This pattern is attributed to the infiltration of lymphocytes and can also be observed.

What Are the Postmortem Findings of COVID Lungs?

The changes in the lungs that can be observed in the deceased persons are:

1. Many chemokines and macrophages can be found in the bronchoalveolar fluid of the lung samples. These macrophages contain SARS-CoV-2 nucleoprotein (NP).

2. Destruction of the alveolar epithelium and alveolar structure can be seen. Serous and fibrin exudation and hyaline membrane formation can also be observed.

3. The presence of macrophages and monocytes can be observed in the alveolar structure. Multinucleated giant cells, lymphocytes, eosinophils, and neutrophils are also present. The alveolar blood vessels exhibit congestion and are filled with infiltration of monocytes and lymphocytes, primarily macrophages and monocytes.

4. Coronavirus particles can be detected in the bronchial epithelium and type II alveolar epithelium. This epithelium shows positive findings for the 2019-nCoV antigen. 2019-nCoV nucleic acid can also be found in polymerase chain reactions.

5. Lung parenchymal cells show degeneration and necrosis.

6. Deep venous thrombosis can be found in the blood vessels. Also, intra-alveolar hemorrhage and vascular congestion are observed.

7. The occurrence of lung fibrosis is frequently observed in such instances. The manifestation of fibrosis is intricately linked to fibrinous organizing pneumonia, with the presence of intra-alveolar fibrin bodies and Masson bodies (spherical clusters of connective tissues) also being noted.

Conclusion:

COVID-19 infection mainly involves the upper respiratory tract and lungs. Involvement of lung cells by virus initiates inflammatory response. This is associated with the release of cytokines and inflammatory mediators. This is responsible for the destruction of lung cells, collection of fluid, cellular atypia, and lung congestion.