THE HISTOLOGICAL EFFECTS OF COVID-19 ON THE LOWER RESPIRATORY SYSTEM

Both histologically and anatomically, the respiratory system is a compound system having diverse functions. It fulfills the process of respiration that is regarded as gas exchange through conduction and filtration of air. The respiratory system is functionally divided into conducting and respiratory parts.Anatomically, the respiratory tract is categorized into the upper and lower respiratory tract. The lower respiratory tract represents the organs within the thorax such as the trachea, bronchi, bronchioles, alveolar duct, and alveoli which make up the lungs.The paired lungs are parts of the lower respiratory tract which are regularly presented microorganisms.Although COVID-19 affects different organs simultaneously it seriously affects the lower respiratory system, produces respiratory distress to affected individuals, and mostly produces histological changes in the respiratory tract. In terms of COVID-19 effects on the lower respiratory tract, the lungs are affected in most cases, and the review is largely focused on the lungs. The histological effects of COVID-19 on the lungs are different and reveal a broad spectrum of abnormalities.Diffuse alveolar damage (DAD) remained the principal lung histopathological finding in patients with COVID-19. DAD results from damage of the covering cells of the alveoli and endothelium ending with disarrangement of the blood-air barrier. Concerning the event of pulmonary injury, DAD is classified into three histopathological stages that are acute (exudative), subacute (organizing), and chronic (fibrotic) stage.Since there is no adequate information about the histological effects of COVID-19 on the lower respiratory system, this article aimed to review what is known about the histological effects of COVID-19 on the lower respiratory system. It summarizes the previous literature of published articles that examined the histological effects of COVID-19 on the lower respiratory system to display the present understanding of histological changes of the lower respiratory system associated with COVID-19. Further data about the histological effects of COVID-19 on the lower respiratory system is needed to adequately define the histopathological changes of the lower respiratory system associated with COVID-19.

Both histologically and anatomically, the respiratory system is a compound system having diverse functions. It fulfills the process of respiration that is regarded as gas exchange through conduction and filtration of air. The respiratory system is functionally divided into conducting and respiratory parts.Anatomically, the respiratory tract is categorized into the upper and lower respiratory tract. The lower respiratory tract represents the organs within the thorax such as the trachea, bronchi, bronchioles, alveolar duct, and alveoli which make up the lungs.The paired lungs are parts of the lower respiratory tract which are regularly presented microorganisms.Although COVID-19 affects different organs simultaneously; it seriously affects the lower respiratory system, produces respiratory distress to affected individuals, and mostly produces histological changes in the respiratory tract. In terms of COVID-19 effects on the lower respiratory tract, the lungs are affected in most cases, and the review is largely focused on the lungs. The histological effects of COVID-19 on the lungs are different and reveal a broad spectrum of abnormalities.Diffuse alveolar damage (DAD) remained the principal lung histopathological finding in patients with COVID-19. DAD results from damage of the covering cells of the alveoli and endothelium ending with disarrangement of the blood-air barrier. Concerning the event of pulmonary injury, DAD is classified into three histopathological stages that are acute (exudative), subacute (organizing), and chronic (fibrotic) stage.Since there is no adequate information about the histological effects of COVID-19 on the lower respiratory system, this article aimed to review what is known about the histological effects of COVID-19 on the lower respiratory system. It summarizes the previous literature of published articles that examined the histological effects of COVID-19 on the lower respiratory system to display the present understanding of histological changes of the lower respiratory system associated with COVID-19. Further data about the histological effects of COVID-19 on the lower respiratory system is needed to adequately define the histopathological changes of the lower respiratory system associated with COVID-19.

ISSN: 2320-5407
Int. J. Adv. Res. 9(10), 127-135 128 Introduction:-Both histologically and anatomically, the respiratory system is a compound system having diverse functions (Haschek, Rousseaux, and Wallig, 2010).It fulfills the process of respiration that is regarded as gas exchange through conduction and filtration of air (Ross, 2011).The respiratory system is divided into conducting and respiratory parts (figures 1 and 2). The conducting part starts from the nasal cavity to the nasopharynx, larynx, trachea, primary bronchi, secondary bronchi, tertiary bronchi and ends in the terminal bronchiole. The respiratory part begins from the respiratory bronchiole to the alveolar ducts, alveolar sacs, and alveoli which are the site of gas exchange. The respiratory bronchiole is the midway between the conductingand respiratory parts (figure 2)(Alkanlı and Koroglu, 2019).
Anatomically, the respiratory tract is categorized into the upper and lower respiratory tract.The lower respiratory tract represents the organs within the thorax such as the trachea, bronchi, bronchioles, alveolar duct, and alveoli which make up the lungs (Patwa and Shah, 2015). The paired lungs are parts of the lower respiratory tract which are regularly presented microorganisms.Fortunately, lungs possess a major character to identify the serious materials exposed to them(Alkanlı and Koroglu, 2019).Within these lungs, the airways bifurcate into frequently smaller tubes to give the smallest air spaces, called the alveoli. Alveoli are the most terminal segment of the respiratory passage. The Groups of alveoli gathered collectively and having a common opening are termed as an alveolar sac. Alveoli that make a tube are termed as alveolar ducts (Ross, 2011).
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) appeared in late 2019, producing the disease coronavirus disease 2019 (COVID-19) (Brosnahan, Jonkman, Kugler, Munger, and Kaufman, 2020). The disease spread rapidly in China and brought many lives to death and created a rise in global cases.COVID-19 is severe in the elderly and in chronically ill individuals. Treatment was supportive to manage symptoms and complications, and vaccines for COVID-19 were not ready during that time. This gave COVID-19 global attention and World Health Organization declared COVID-19 as a global public health crisis (Mead, 2020).During this pandemic period, COVID-19 was accountable for a number of respiratory problems (Tamburello, Bruno, and Marando, 2020).

Normal Histological Structure of the Lower Respiratory System
The lower respiratory tract starts from the trachea to the paired lungs.The trachea and bronchi are lined by a pseudostratified epithelium (figure 3), where the ciliated columnar cell is the principal cell (French, 2009).The entire bronchi are enclosed by unique lung tissue (LT) manifesting blank spaces of lung alveoli.The epithelium is also lined by ciliated pseudostratified columnar in the larger bronchioles (figure 4); however, this diminishes in the smallest terminal bronchioles as well as respiratory bronchioles and begins to be ciliated simple columnar or simple cuboidal epithelium.The cuboidal epithelium of terminal and respiratory bronchioles consistschieflyof Clara cells. Respiratory bronchioles' distal ends (figure 5) divide into tubes termed as alveolar ducts which are fully lined by alveoli openings.The ends of the alveolar ducts are distally constituted by larger groups of alveoli which are termed as alveolar sacs (Mescher, 2013

Histological effects of COVID-19 on the lower respiratory system
Although COVID-19 affects different organs simultaneously, it seriously affects the lower respiratory system, produces respiratory distress to affected individuals, and mostly produces histological changes in the respiratory tract(Alsaad, Arabi, and Hajeer, 2020; Rajaa and Nada, 2020). In terms of COVID-19 effects on the lower respiratory tract, the lungs are affected in most cases, and the review is largely focused on the lungs ( The subacute phase ( figure 9B) of DAD happens about one week following the primary pulmonary injury and is delineated by the microscopic structure of the fibrin accompanied by migration fibroblast and secretion of loose collagen. Hyaline membranes become slowly organized into organizing fibrotic tissue, which starts to be visible in airspaces, alveolar ducts, and alveolar walls. Unusual variations in type II pneumocytes and squamous metaplasia may be initiated. In a few situations, DAD finally resolves, whereas others develop into a chronic fibrotic phase 132 following weeks to months of the initial injury with increasing structural reconstruction and interstitial fibrosis (Hariri et al., 2021).
Acute fibrinous and organizing pneumonia (AFOP) is identified by the formation of fibrin balls inside the alveolar spaces. The organization follows the migration of fibroblast and the production of young collagen within fibrin aggregates ( figure 9C). The appearance of hyaline membranes implies DAD. Organizing pneumonia (OP) is observed as isolation or in union with DAD or AFOP and is distinguished by intraluminal tufts of plump fibroblasts and immature tissue of collagen in alveolar ducts and distal airspaces ( figure 9D) (Hariri et al., 2021).

Conclusion:-
The lower respiratory tract starts from the trachea to the paired lungs. It is the main respiratory center of histological and pathological diagnosis.The review is largely focused on the histological effects of COVID-19 on the lower respiratory tract. Diffusealveolar damage (DAD) remained the principal lung histopathological finding in patients with COVID-19. DAD results from damage of the covering cells of the alveoli and endothelium ending with disarrangement of the blood-air barrier. About the event of pulmonary injury, DAD is classified into three histopathological stages that are acute (exudative), subacute (organizing), and chronic (fibrotic) stage.
Since there is no adequate information about the histological effects of COVID-19 on the lower respiratory system, a perfect understanding of histological changes of the respiratory tract is of great significance especially in the area of pulmonology. Histological changes occurring after COVID-19 are important and may give histologists and pathologists to possess a deep understanding of the respiratory system.
This article may assist internists, pulmonologists, and researchers to understand the effects or histopathological changes of COVID-19 on the lower respiratory system, which may improve the approach of the disease and its prevention.Further data regarding the histological effects of COVID-19 on the lower respiratory tract is needed to adequately define the histopathological changes of the lower respiratory tract associated with COVID-19.Additional comprehensive research concerning histopathological findings is also needed and is important for a comprehensive understanding of the effort to manufacture effective vaccines. Progress done in the area of histology and pathology may help to manage the diagnosis, prevention, and treatment of COVID-19 as well as any similar upcoming diseases.