Although PF may be seen in other respiratory viral diseases as well, it is more common after SARS-CoV infection [2]. However, the mechanisms of SARS-CoV infection-related PF remain to be fully understood. Activation of Transforming Growth Factor b (TGFb) pathway and increased degradation of Angiotensin-Converting Enzyme2 (ACE2) or angiotensinogen system-mediated lung fibrosis may play major roles [2].

COVID-19 mainly affects the respiratory system resulting in pulmonary fibrosis, based on clinical, radiographic, and autopsy reports. Though patients survive the acute phase of the disease and are even discharged, a major proportion of the affected individuals die from pulmonary fibrosis [1]. In the inflammatory phase of ARDS, there is dysregulation of matrix metalloproteinase, which can cause epithelial and endothelial damage, resulting in uncontrolled fibrosis [5]. The continuous activation of epithelial cells may contribute to cellular senescence and overproduction of chemokines, vascular inhibitors, pro-fibrotic growth factors, and coagulation factors. These kinds of factors are collectively called Senescence Associated Secretory Phenotype factors (SASP) [1]. In fibrotic lungs, the fibroblasts and myofibroblasts are the markers of stress and senescence, causing resistance to apoptosis and excessive production of Extra Cellular Matrix components (ECM) [1].

Although PF may be seen in other respiratory viral diseases as well, it is more common after SARS-CoV infection. However, the mechanisms of SARS-CoV infection-related. Moreover, PF is more common after SARS-CoV infection than other respiratory viral diseases. However, the mechanisms of SARS-CoV infection-related PF remain to be fully understood [2]. In addition to activating the Transforming Growth Factor (TGF) pathway and increasing degradation of the Angiotensin-Converting Enzyme 2 (ACE2), the angiotensinogen system may play an important role in lung fibrosis [2]. During the early phase of SARS infection, elevated levels of TGFb1 have been reported [6]. Besides, TGFb pathway activation leads to fibrin, collagen, and matrix metalloproteinases (MMPs). According to further studies, TGFb induces lung fibroblasts to differentiate into myofibroblasts after lung injury, which is crucial for pulmonary tissue repair [2].

Among the explanations for aggravated severe illness in COVID-19 patients is the excessive immune response associated with Cytokine Release Syndrome (CRS), which contributes to lung tissue damage, repair imbalance, and respiratory failure [7]. Eventually, the patient may die from multiple organ failure [8]. Chronic inflammatory syndrome, or CRS, is an aberrant systemic inflammatory response triggered by numerous factors including severe infections and certain drugs. Clinically, the condition is characterized by the rapid appearance of a large number of cytokines within a short period of time. According to an analysis of plasma cytokine levels in 41 confirmed cases of COVID-19 in China, levels of IP-10, MCP-1, MIP-1A, MIP-1B, PDGF, TNF-α, and VEGF were significantly higher in ICU and non-ICU patients [9]. High concentrations of IL-6, GCSF, CRP, and TNF-α have been found in COVID-19 patients [10].

ARDS is associated with hyperproliferation of matrix metalloproteinases, leading to epithelial and endothelial damage, and ultimately uncontrolled fibrosis [11]. These factors are collectively called senescence-associated secretory phenotypes (SASP) [12]. SASP factors can lead to abnormal wound healing, characterized by abnormal crosstalk between epithelial and mesenchymal cells, and the subsequent accumulation of myofibroblasts [6]. It has been observed that fibroblasts and myofibroblasts in fibrotic lungs show signs of stress and senescence, including resistance to apoptosis and excessive production of extracellular matrix components [13]. Moreover, fibrosis could result from this increase in matrix stiffness, which leads to irreversible tissue damage [14].

Collectively stating that fibrosis of the lungs is a chronic, progressive, fibrotic interstitial disease with a poor prognosis [15]. Currently, it has no effective treatment. Based on previous coronavirus infections, such as Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS), as well as current clinical evidence from Coronavirus disease 2019, SARS-CoV-2 infection is likely to cause PF, which has a negative impact on patient prognosis and quality of life [15]. Hence, PF prevention and treatment can not only aid in improving the overall well-being of patient’s outcomes after SARS-COV-2 but also reduce overall social and economic burdens.