COVID Long-Haulers: Respiratory System 

Courtesy of Heramb Podar


The world, particularly our medical infrastructure, has been ravaged by the Coronavirus Disease of 2019 (COVID-19) like nothing we have witnessed before, with the limits in every sector and industry being tested. COVID-19 primarily affects the upper respiratory tract (sinuses, nose, and throat) and the lower respiratory tract (windpipe and lungs), forcing patients to be in need of ventilators and medical care. As we are seemingly coming out of the dark void of the pandemic, with vaccination drives coming to the rescue, it is worth noting that the bodies of some infected people may not recover fully, yielding long-term repercussions. 


 Anatomy of the Respiratory system  


Figure 1. Anatomy of Respiratory System. (Respiratory System, 2019)


The respiratory system is responsible primarily for delivering oxygen to the cells of the body. The system starts with the nose and the mouth, which take up oxygen from our surrounding atmosphere, aided by the sinuses in the gaps between our bones, regulating the temperature and humidity of the air we breathe. The pharynx (referred to as the windpipe) then carries the air to the trachea. The air is then delivered to the bronchioles and alveolar ducts, where the exchange of oxygen for carbon dioxide from the circulatory system occurs, providing the body with much-needed oxygen.

How COVID-19 virus attacks the respiratory system?


The SARS-CoV-2 virus can infect both lower and upper airways, making it more contagious while also wrecking internal damage deep in the lungs. SARS-CoV-2 may use Angiotensin Converting-Enzyme-2 (ACE 2)’s receptors to gain entry into human cells. ACE 2 proteins are essential to enzymatic functions influencing blood flow to the kidneys, heart, and lungs. ACE 2 receptors are present in abundance on the surface of lung tissue Spike (S) proteins protruding on the COVID-19 virus attack these receptors gaining access to the inside of human cells, taking control of the cell, and using them to manufacture more of themselves. It is speculated that this reduces the enzymatic functioning of the ACE 2 receptors themselves, dealing a double blow to the lungs (Ni et al., 2020).


Long term effects of COVID 19 on the Respiratory system 



Figure 2.The mechanism of COVID-19 attack on the body. (Ni et al., 2020)


The scarring of lung tissues can lead to long-term breathing problems. Coronaviruses like Severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS) typically have long-term effects on the respiratory system. Scarring of lung tissue, called fibrosis, is one of these effects that hamper the exchange of oxygen and carbon dioxide in the lungs and the overall flexibility of the tissue (Colombo et. al, 2020).


Additionally, pneumonia caused by COVID-19 can lead to severe breathing difficulties and long-standing damage to tiny air sacs (alveoli) in the lungs. This is a severe issue since it may take several months for normal breathing to be restored, even after the initial recovery from the disease. A study by the Hong Kong Hospital Authority conducted in March 2020 found that the virus can take a toll of as much as a decrease of 20-30% in lung capacity in some cases (South China Morning Post, March 2020). As COVID-19 pneumonia progresses, air sacs become filled with fluid leaking from the blood vessels in the lungs. Eventually, shortness of breath sets in, leading to acute respiratory distress syndrome (ARDS) (Fan et al.,2020). Patients with ARDS are often unable to breathe on their own and may require ventilator support to help circulate oxygen in the body (COVID-19 Lung Damage, 2021). 


Diffuse alveolar damage also seems to be a common form of lung injury associated with COVID-19 and usually evolves in a reasonably predictable manner. Pulmonary function, particularly diffusing capacity for Carbon Monoxide (DLCO), declined in COVID-19 survivors  (Qin et al., 2021). A study published in the Journal Radiology conducted in August-December 2020 noted that hyperpolarized xenon MRI (XeMRI) scans had found abnormalities in the lungs in COVID-19 patients with impaired oxygen uptake for more than three months and, in some cases, nine months after leaving the hospital when other clinical measurements were routine (Grist et al., 2021). 



Figure 3. Images at 172 days after discharge in a 60-year-old patient (top row) with a history of breathlessness after COVID-19. (A) CT, (B) ventilation, and (C) red blood cell (RBC) phases of hyperpolarized xenon 129 MRI (XeMRI). Images in healthy control volunteer (bottom row) at (D) gas and (E) RBC phases. Images from XeMRI are shown in coronal view for both individuals, with disrupted RBC being shown in the patient. (Grist et al., 2021).



Figure 4. Montage of images of all volunteers imaged in this study shows gas and red blood cell (RBC) phase images. Paired ventilation (gas) and RBC phase imaging are shown side by side. (Grist et al., 2021)


According to Xie et al., 2005, a number of patients recovering from acute viral illness may have significant impairment in overall functional capacity and their pulmonary function in the first few months. Residual abnormalities were also identified on chest radiographs and HRCT of about 20% of SARS patients, along with interstitial thickening, hypoinflation/volume loss, and bronchiectasis.


Exacerbations and further complications of pre-existing health conditions have emerged as unintended consequences of the pandemic. They must be taken into account when deciding any medical policy by the authorities. There is a higher mortality rate, greater need for ICU admission, and increased need for mechanical ventilation in such patients (Philip et al., 2020).



Figure 5. SARS pathology in the respiratory tract. (A) Lung of a SARS victim. The cut surface showed severe edema, consolidation, and hemorrhage. (Gu et al., 2005). 


Autopsies of SARS patients showed that SARS-CoV infection could cause injury to multiple organs, such as the heart, kidney, liver, skeletal muscle, central nervous system, and adrenal and thyroid glands, besides the lungs (Gu et al., 2005). In a meta-analysis of eight studies involving 46,248 patients infected with SARS-CoV-2, the most prevalent comorbidities were hypertension (17 ± 7, 95% CI 14–22%) and diabetes (8 ± 6, 95% CI 6–11%), followed by cardiovascular disease (5 ± 4, 95% CI 4–7%) and respiratory disease (2 ± 0, 95% CI 1–3%) (Yang et al., 2020). According to Lohia et al., 2021, patients with pre-existing respiratory diseases had significantly higher mortality. Thus, there is an increased need for ICU admission and a greater need for mechanical ventilation than patients without pre-existing respiratory conditions. Different factors such as patient’s age, comorbidities, history of cigarette smoking, length of hospital admission, and the severity of the acute disease (such as the need for ICU admission) and type and quality of treatment offered would play a role in the severity of residual functional abnormalities (Sorge and De Blieux, 2020). 


Limitations of the study


It must be noted that COVID-19 is a recent disease, thus facing an issue of limited studies. Sufficient time has not elapsed for a number of studies to be conducted focusing on the long-term effects of COVID-19. Extrapolations from other novel coronavirus diseases such as SARS were used to model potential long-term effects of COVID-19. It is still too early to tell, but continuous research efforts are being made to resolve these concerns. 


Looking towards the future


Long-term follow-up chest imaging of survivors is needed to better understand the possible irreversible pulmonary damages of SARS-CoV-2 pneumonia. Panagis Galiatsatos, M.D., M.H.S., an expert on lung disease at Johns Hopkins Bayview Medical Center, states that “Once the pandemic is over, there will be a group of patients with new health needs: the survivors. Doctors, respiratory therapists, and other health care providers will need to help these patients recover their lung function as much as possible.” Our society has to contend with the harsh medical reality that even long after the pandemic is done and the seemingly recurrent waves have passed, there will be a group of people in need of additional care while suffering from the effects of once having had the COVID-19 virus in their body.


About the Author


Heramb Podar is a sophomore student at the Indian Institute of Technology, Roorkee, studying chemistry. He is particularly interested in biochemistry and astrochemistry. Heramb likes to research historical events in his free time, observe the many immaculate wonders of the night sky, and read books.




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