Effect of The Coronavirus Disease on Respiratory System

The Coronavirus Disease 2019 or COVID-19 caused by SARS-CoV-2 is a respiratory illness which has been declared as a pandemic by the World Health Organization in March 2020. Several studies including the 10 articles chosen have found that the virus may impact human organ physiology that may result to death in Covid-19 patients. As the pandemic is continuously evolving, and more data are made available every day and even every hour, this article highlights and emphasize the best evidence and practices with regard to the effects of the SARS-CoV-2 virus to human organ physiology. Published clinical studies have supported that SARS-CoV-2 affects the respiratory system, nervous system, cardiovascular system, digestive system, and even the reproductive system which may cause organs in that particular system to malfunction due to virus infection. Herein, a brief summary of literature data around the world was analyzed, examine, and compile for future research and therapeutic development

Introduction and Background

“Every day, COVID-19 seems to reach a new and tragic milestone. There’s still a lot we don’t know, but every day we’re learning more, and we’re working around the clock to fill in the gaps in our knowledge. Ultimately, how deadly this virus will depend not only on the virus itself but on how we respond to it.” -WHO Director-General Dr. Tedros Adhanom Ghebreyesus

Over the past few months, the world has witnessed the emergence of a previously unknown pathogen that originated in Wuhan, China in December 2019 causing an outbreak and rapid viral transmission over the country and later globally as the rapid spread of the disease have caused the world leaders to be alarmed and close their nation’s boundaries, limitation of any travels, and imposing strict quarantine for precautionary measures. On March 11, 2020, the pathogen which is SARS-CoV-2 also called Covid-19 can be transmitted through human-to-human droplets and close contact have caused diseases with an estimated mortality rate for about 0.19% with 150,000 confirmed while more and more countries have affected, hence, it has been declared by World Health Organization (WHO) as Pandemic. According to worldmeter.info/coronavirus (1), as of November 10, 2020, which is shortly 9 months after the outbreak declared a pandemic, there are over 51,785,368 confirmed cases with a mortality rate of 2.5% that account for 1,278,394 deaths and 600,000+ daily cases worldwide affecting 216 countries and territories worldwide.

SARS-CoV-2 or Covid-19 is a strain of virus that can trigger respiratory tract infection and in worse cases severe acute respiratory syndrome due to the fact that the viral transmission is through droplet or aerosol (airborne transmission) released into the air when an infected person sneezes or cough and person-to-person contact (within about 6 feet, or 2 meters). Since the carrier may symptomatic or asymptotic and the severity of disease caused by the virus varies that range from mild, to moderate, to severe, hence, there is no wonder why the virus is known as fatal. Additionally, SARS-CoV-2 is a virus belonging to the family of coronaviruses such as SARS-CoV and MERS-CoV. Covid-19 is mainly composed of densely glycosylated spike proteins which enables it to penetrate and bind to the angiotensin-converting enzyme 2 receptors (ACE2) of the human host cell, similar to studies found previously in SARS-CoV [1-10]

As an effort to formulate the vaccine and minimize the spread and infection, the world’s known pharmaceutical companies such as Pfizer and BioNTech, researchers and scientists united to eradicate the virus once and for all, yet, there is no assurance of how and until when, relying solely on further researches, studies, and experiment. Although the world seems winning with 36,350,516 recovered patients or a 70.2% recovery rate over 1,278,394 deaths or 2.5% death rate (1), Increasing evidence in numerous studies and research found out that respiratory systems is not just the only organ system that may be affected by the virus and diseases caused by the pathogen but also the almost all organ system in the human body together with its function or physiology due to virus mechanism which binds to angiotensin-converting enzyme (ACE2) in a host cell. Furthermore, the brain, lungs, heart, blood vessels, intestines, and testis happen to be abundant with ACE2 [1,2], therefore, the organs mentioned are more vulnerable (lungs: most vulnerable) to SARS-CoV-2 infection.

Lastly, due to the manifestation of Covid-19 to human physiology, it will cause a major public health crisis not only for acute effects on the interconnected structure (anatomy) and physiology of the human organs system but also for the long-term harm and restriction to its function. In this regard, we will focus on the impacts of Covid-19 to different organ system physiology together with the virus mechanism and pathogenesis, and on how this virus may affect the physiology, particularly in long-term, short-term, and post-effects.

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Effects of COVID-19 on the Organs system and physiology

1. Nervous System

Numerous patients hospitalized due to Covid-19 around the world as observed by doctors, epidemiologists, scientists, and researchers proves that the nervous system is frequently involved and affected by the infection, the worst case is the long-term effects brought by the virus in people who have severe symptoms [6]. Neurological effects are common and not surprising because infection from other respiratory viruses such as the Coronavirus family has been also described to affect the nervous system [8]. Similar to other strains of viruses such as SARS-CoV-1, SARS-CoV-2 or Covid-19, also use the angiotensin-converting enzyme 2 (ACE2) which can also be found and abundant in the brain stem and cerebral cortex making them vulnerable to infection. The densely glycosylated spike proteins of Covid-19 enable it for efficient cell entry, the virus utilizes the ACE2 as the primary docking receptor and needs proteolytic processing of the spike protein by transmembrane protease serine 2 or TMPRSS2. The infection and invasion of SARS-CoV-2 in the nervous system and nerve cells have been reported and this strain of the virus can infect neurons that cause nerve damage or neuronal death. [8,5]

The mentioned infection mechanism of the virus (Covid-19) in the nervous system particularly in the brain can be therefore concluded that the physiological function of the nervous system is at risk of disturbance and damage since the virus itself has been reported to cause nerve damage and neuronal death. In two correlative articles which are titled “effects of Covid-19 on the nervous system” by (Costantino Ladecola et al., 2020) [8] and “intact brain network function in an unresponsive patient with covid-19” by (Fischer D. et al., 2020) [6] they focused and analyzed the virus pathogenicity and mechanism, the updated neurological manifestation, and comparative involvement of respiratory and nervous virus. From here, the authors managed to collect and provide clinical data including figures and illustrations of the virus mechanism of vascular damage and brain entry, and MRI data photographs, additionally, the authors attempt to flesh out caveats and unanswered questions regarding the critical aspects of the Covid-19 were profoundly achieved and may help to gain a better understanding to minimized the virus harmful impact to the nervous system. The findings of the two articles are the following:

• The ACE2 present in vascular wall cells in the human brain is at level, however, non-canonical SARS-CoV-2 receptors are present in several types of brain cells making them vulnerable to virus (Covid-19) pathogenicity.
• The potential routes of virus invasion are through the olfactory route, the blood-brain barrier, and infected immune cells.
• The indirect brain effects of systematic factors include lung damage and respiratory failure that cause neuronal damage in brain regions through hypoxia that is induced by respiratory failure; and systematic inflammation and immune dysregulation which damage the hypothalamus due to maladaptive immune response and hyperactivity of the immune system.
• The patients with mild Covid-19 symptoms are mostly confined to malaise, dizziness, headache, and loss of smell and taste while the patients with severe symptoms are associated with higher mortality. Encephalopathy, encephalitis, and ischemic stroke is also risk for patients with severe Covid-19.
• Post-infectious neurological complications are also possible since SARS-CoV-2 can cause dysregulation of systemic immune response which can have delayed effects on the nervous system.
• rs-fMRI data showed that intact brain network connectivity suggests that the neurologic prognosis may not be as severe as the conventional prognostic biomarkers implied.

2. Respiratory system

Coronaviruses including SARS-CoV-1 and SARS-CoV-2 are a family of viruses known to be transmitted through human-to-human respiratory droplets (direct and indirect) and contact routes primarily the nose and mouth routes, airborne transmission is maybe possible but in specific circumstances, these are the reason why the respiratory system is the most vulnerable organ in all organ system in the human body. Moreover, angiotensin-converting enzyme 2 receptors or ACE2 is primarily present and abundant in the lungs enabling the virus to dock in the host cell and later reproduce by injecting its genetic material [1,2,5].

In the article titled impact of Covid-19 on the histological structure of respiratory system” by (Al-Tree and Al-khaki, 2020) [3], the authors described the morphological structure of the virus and analyzes its impacts to the respiratory system. Al-Taee and Al-khfaji argue that both anatomical and physiological structure/function of the respiratory system including the respiratory tract, lung tissue, epithelium, and pulmonary alveoli may be damaged by the SARS-CoV-2 (Covid-19) pathogenicity, additionally, they focused on the microscopical changes and damages that affect the epithelium lining in the respiratory system, and provide an assessment of up-to-date histological understanding in relation with the disease caused by a coronavirus that may provide another guide in prevention and treatment of SARS-CoV-2.

To address the argument, Al-Taee and Al-khfaji provide several updated reports and studies to support their argument and met the aims of their article which is assessing the effects of Covid-19 infection to the respiratory system together with the microscopic structure of the respiratory tract especially the tissues and epithelium of the respiratory system. Although the article is lack of figures, charts, or tables for better understanding of readers, the authors managed to profoundly describe and explain the content of the article. According to them, the respiratory epithelia are primarily considered to be the first tissue that is vulnerable to the virus pathogenicity and the major target for respiratory infection and since SARS-CoV-2 binds it densely glycosylated spike proteins to ACE2 receptors which is abundant in alveolar cells, physiological functions of the respiratory system may be disrupted due to the formation of hyaline membranes, damage to all types of epithelia, and diffuse hyperplasia which features alveolar damage and mild alveolar wall thickening that refers to more complicated and severe stage of the disease. Since all the objectives of the study were met despite of little issue in visuals, the information and findings of this study will surely contribute for a better understanding of the impacts of Covid-19 to the structure and function of the respiratory system.

The organ's structure and function are known to be interconnected and we might say “one cannot exist without the other”, since the above article mostly evaluates the impacts of the SARS-CoV-2 to structure of the respiratory system, the article “respiratory physiology of covid-19- induced respiratory failure compared to ARDS of other etiologies” by (Domenico Luca Grieco et al., 2020) [7] primarily focused on the effects of the virus to the physiology of the respiratory system and from here, the methods were also presented which 30 consecutive patients in intensive care unit in Rome, Italy with Covid-19 were observed. Domenico Luca Grieco et al., 2020 suggest that around 5 percent of the patients who is affected by the Coronavirus disease or Covid-19 require ICU or intensive care unit admission due to ARDS or acute respiratory disease syndrome which is the result of the damaged respiratory system which accounts for 30 and 60 percent of mortality rate. Additionally, since the virus accounts for the destruction of alveoli cells in the lungs, patients will need invasive mechanical ventilation to treat gas exchange abnormalities and support the mainstay of therapy. Meanwhile, Grieco et al., 2020 screened all the consecutive adult patients who are admitted to the ICU due to respiratory failure with a positive molecular diagnosis of SARS-CoV-2 infection, from here, patients who passed the criteria for moderate and severe ARDS were enrolled within 24 hours from endotracheal intubation. Every patient’s demographics, other medical conditions, and 28 days of clinical results were recorded. After the assessments of the potential for lung recruitment, respiratory mechanics, and tidal volume, positive end-expiratory pressure or PEEP effects in 30 consecutive mechanically ventilated patients, Grieco et al., 2020 suggest that in Covid-19 patients, lungs were damaged causing the whole respiratory system to malfunction due to hypoxemia. With all of these in mind, the article is very relevant for those researchers, scientists, and doctors who are working to create the vaccine because the physiology of Covid-19 and ARDS-causing viruses were also compared and differentiated, and virus impacts to physiology were clearly explained including its caused were presented excellently. Moreover, since the authors have met their objectives with complete illustration and the process of investigation, methods, procedures and measurements, and findings there is no wonder that this article will contribute to the medical field knowledge against the Covid-19 virus.