What are the respiratory implications of COVID-19?

By Charlene Mhangami, Vitalograph

Published 21 December 2021

Clinical presentation

COVID-19 is mainly spread by respiratory droplets, transmission can occur from a symptomatic or asymptomatic person. In those who are symptomatic the most common symptoms are highlighted in figure 1. About 80% of people who contract COVID-19 get mild to moderate symptoms such as dry cough or a sore throat, some may present with pneumonia, a lung condition which affects the alveoli. Approximately 14% of people get severe symptoms and 5% end up with very severe symptoms1 .

Figure 1 – Symptoms of COVID-19 2

How does it end up in the respiratory system?

COVID-19 can affect both the upper and lower part of the respiratory tract. The virus meets the mucous membranes that lines the nose, mouth, and eyes. The virus enters a healthy cell and uses the cell to multiply the virus and the infects nearby cells. As the cells are infected, the lining in the airways become irritated and inflamed as the immune system begins to fight back, the more severe the infection becomes the more it spreads in the respiratory tract and where the problems in the respiratory system begin to arise.

Effect on the lungs

COVID-19 can cause complications in the lung such as pneumonia, this where the lungs become filled with fluid and inflamed leading to breathing difficulties. The pneumonia that COVID -19 causes affects both lungs. When someone contracts pneumonia caused by other diseases such as flu, they may recover without lasting lung damage, however the pneumonia associated with COVID-19 can be severe, even after recovery from the disease, the lung injury may take months to improve.

When the alveolus within the lungs gets filled with fluid it limits the gas exchange process causing symptoms such as dyspnea and cough Normally the relationship between capillaries and the alveolar epithelium is closely connected. The alveolar epithelium (which covers 95% of the alveolar membrane) contains Alveolar Type II (AT II) cells. COVID-19 infects AT II cells which normally would function to secrete pulmonary surfactant: primarily responsible for reducing the surface tension between the tissue in the alveoli of the lungs to prevent atelectasis which is collapse of the lung. However, COVID-19, kills the AT II cells and flood the alveolus (figure 2).

Pathological changes in the lung parenchyma due to COVID-19. (A) Normal alveolus surrounded by capillaries containing red blood cells. Oxygen is exchanged with carbon dioxide in the capillaries. The alveolar membrane contains Type I and Type II cells. (B) Moderately infected lung. Alveolar Type II cells are inflamed resulting in reduced pulmonary surfactant. Surface tension and pressure increase inside the alveolus affecting the gas exchange. Vasodilation of the capillary occurs resulting in release of inflammatory cytokines and accumulation of protein-rich fluid inside the alveolus. (C) Severely infected lung, alveolar type II cells become more inflamed, resulting in complete loss of pulmonary surfactant and scar tissue on the alveolar surface begins to form, inflammatory cytokines are increased, and more protein-rich fluid accumulates inside the alveolus. Gas exchange process is affected resulting in difficulty breathing3 .

Figure 2

In more severe cases of COVID-19, where pneumonia has progressed further the capillaries leak more fluid into the alveoli. Overtime, this leads to acute respiratory distress syndrome (ARDS) which is a form of lung failure. Patients with ARDS are often unable to breathe on their own and may require ventilatory support to help oxygenate the body. Another possible complication of severe COVID-19 is sepsis, this occurs when an infection within the lung spreads through the blood stream causing tissue damage all over the body. The cooperation between the organs falls apart, in some cases even after recovery from sepsis a patient can have lasting damage to the lungs and other organs.

(Borczuk et al.,2020) performed a multi—institutional autopsy cohort study in Italy and New York, to evaluate lungs of 68 patients who had received an autopsy following the contraction of COVID-19. They looked at several compartments of the respiratory system (airways, alveolar walls, airspaces, and vasculature) to observe the extent of COVID-19. From this they identified COVID-19 as heterogenous meaning it affects various parts of the respiratory system. They found evidence of bronchitis, alveolar damage, and vascular injury.

Usefulness of testing

Various studies have been performed to assess how much of the damage caused by COVID-19 can be picked up by pulmonary function testing. A retrospective multi-center cohort study by (Lewis et al,2021) looked at patients who had a lung function test preinfection and post-infection within one year of the infection, during March 2020 and November 2020. They tested a total of 80 patients with an even split between males and females, who had a mild to moderate COVID-19 requiring hospitalization. The main findings where there was no difference between pre and post-PFT data, when looking at spirometry, DLCO and lung volumes. They observed there was no difference in PFT data when analyzed by hospitalization and disease severity.

Although those who had pre-existing comorbidity such as interstitial lung disease (ILD) was independently associated with a decreased FEV1 and those with cystic fibrosis were associated with having a deteriorating FVC when comparing the pre and post infection PFT. Only increasing age was independently associated with a reduction in TLC and DLCO pre and post infection. Overall, the study is suggestive in those who don’t have underlying disease there isn’t a difference between pre and post PFT.

Another study by (Eksombatchai et al., 2021) looked at spirometry, six-minute walk test and chest x-ray among those who had recovered from COVID-19. The study included 87 patients who had recovered and been discharged from the infection. Testing was performed on day 60 after the onset of symptoms. They were 35 men and 52 women, 45 patients had mild symptoms, 35 had non-severe pneumonia and 7 had severe pneumonia. When evaluating test data 15 patients (17.2%) had abnormal spirometry, with 8% having a restrictive defect and 9.2% having an obstructive defect. The patients with abnormal spirometry where mainly those with severe pneumonia. The other tests shown those with severe pneumonia had shorter mean 6-min walking distance and chest abnormalities visible on x-ray was present in those with severe pneumonia.

A study by (Wu et al., 2021) looked at the consequences of COVID-19 in 83 patients that were admitted with severe case but did not require mechanical ventilation. Patients included had no underlying respiratory conditions. Patients had followed up hospital at 3 months, 6 months, 9 months, and 12 months after discharge from hospital. During the visits they had a full PFT test, blood tests, CT scan, 6-minute walk test and filled out the medical research council dyspnea scale (MRC). Overall, they observed improvement.

“Pulmonary function tests (PFTs) are noninvasive tests that show how well the lungs are working. The test measure lung volume, capacity, rates of flow, and gas exchange.”
“Spirometry, also known as dynamic lung volumes, is used to measure forced expiratory flow rates and volumes. It is the most used pulmonary function test to evaluate subjects at risk of lung disease.”
“DLCO – Diffusing lung capacity for carbon monoxide. Also known was “Gas Transfer” this test measures the extent to which oxygen passes from the air sacs of the lungs into the blood. It is one of the most clinically valuable tests of lung function.”
“Lung volumes measurements also known as static lung volumes, measure or calculate the volumes and capacities of air within the lungs that cant be measured by spirometry, such as FRC.”

 

What does the future look like?

A patient’s recovery and long -term lung heath is dependent on what kind of care they get and how quickly, especially those with are critically ill with the condition. The prognosis is approximately 25 to 50 percent which is mainly caused by severe ARDS, mortality can be higher in those with existing lung conditions. The highest mortality rates occur in those 65 years and older (Yanez, Weiss, Romand and Treggiari, 2020).

For those who recover from the disease some people may still present with prolonged post-acute symptoms, often described as “Long Covid”. The symptoms are mainly respiratory (breathlessness, cough, chest-tightness, chest pain ), but also include neurology, cardiovascular complications, and chronic fatigue. It has been suggested that abnormalities are still visible in those who are not critically ill4.

When looking at long covid and assessing symptoms overtime with pulmonary function testing. Spirometry indices appear to be preserved but DLCO abnormality has been identified on follow-up lung function, present in 20- 30% with mild to moderate disease and 60% of those with severe disease. Also, reductions in total lung capacity were commonly reported (Thomas, Price and Hull, 2021).

Clinical rehabilitation is being considered in helping patients improve symptoms as those with severe cases requiring ventilation may have high levels of deconditioning Follow up care should be considered for those patients with persisting clinical symptoms, this may include serial measurements of lung function, echocardiography, and CT scans of the chest.

“Post COVID-19 or “Long Covid” syndrome is defined signs and symptoms that develop during or following an infection consistent with Covid-19, continue for more than 12 weeks and are not explained by an alternative diagnosis.”

Other treatment options are being investigated. An observational study by (Myall et al., 2021) looked at progression of persistent inflammatory interstitial lung disease (ILD) associated with COVID-19 and whether a corticosteroid such as prednisolone is effective in treating pneumonia associated with the disease. The outcome was early intervention with corticosteroids is well tolerated and can improve lung function as they observed increase in DLCO and FVC. As this is a novel virus, further research is still needed as to whether the effects of COVID-19 are permanent or whether they will heal over time.

References

1. https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200306-sitrep-46-covid- 19.pdf

2. Clerkin, K., Fried, J., Raikhelkar, J., Sayer, G., Griffin, J., Masoumi, A., Jain, S., Burkhoff, D., Kumaraiah, D., Rabbani, L., Schwartz, A. and Uriel, N., 2020. COVID-19 and Cardiovascular Disease. Circulation, 141(20), pp.1648- 1655.

3.Wang, S., Li, Z., Wang, X., Zhang, S., Gao, P. and Shi, Z., 2021. The Role of Pulmonary Surfactants in the Treatment of Acute Respiratory Distress Syndrome in COVID-19. Frontiers in Pharmacology, 12.

4. Nice.org.uk. 2021. [online] Available at: https://www.nice.org.uk/guidance/ng188 [Accessed 29 November 2021]

Borczuk, A.C., Salvatore, S.P., Seshan, S.V. et al. COVID-19 pulmonary pathology: a multi-institutional autopsy cohort from Italy and New York City. Mod Pathol 33, 2156–2168 (2020)

Dhont, S., Derom, E., Van Braeckel, E., Depuydt, P. and Lambrecht, B., 2020. The pathophysiology of ‘happy’ hypoxemia in COVID-19. Respiratory Research, 21(1).

Mallea, J., Baig, H. and Patel, N., 2021. COVID-19 and the effects on pulmonary function following infection: A retrospective analysis. EClinicalMedicine, 39, p.101079.

Myall, K., Mukherjee, B., Castanheira, A., Lam, J., Benedetti, G., Mak, S., Preston, R., Thillai, M., Dewar, A., Molyneaux, P. and West, A., 2021. Persistent Post–COVID-19 Interstitial Lung Disease. An Observational Study of Corticosteroid Treatment. Annals of the American Thoracic Society, 18(5), pp.799-806.

Thomas, M., Price, O. and Hull, J., 2021. Pulmonary function and COVID- 19. Current Opinion in Physiology, 21, pp.29-35.

Wu, X., Liu, X., Zhou, Y., Yu, H., Li, R., Zhan, Q., Ni, F., Fang, S., Lu, Y., Ding, X., Liu, H., Ewing, R., Jones, M., Hu, Y., Nie, H. and Wang, Y., 2021. 3-month, 6- month, 9-month, and 12-month respiratory outcomes in patients following COVID-19-related hospitalisation: a prospective study. The Lancet Respiratory Medicine,.

Yanez, N., Weiss, N., Romand, J. and Treggiari, M., 2020. COVID-19 mortality risk for older men and women. BMC Public Health, 20(1).

Lewis, K., Helgeson, S., Tatari, M., Mallea, J., Baig, H. and Patel, N., 2021. COVID-19 and the effects on pulmonary function following infection: A retrospective analysis. EClinicalMedicine, 39, p.101079.

Lewis, K., Helgeson, S., Tatari, M.,

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