Novel Coronavirus’ Effects on the Respiratory System and Potential Treatment Options

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain, has been demonstrated to cause many problems for the respiratory system. One such noticeable effect of this disease, as indicated in a study conducted by Luciano Gattinoni and colleagues, was hypoxemia being observed in lungs that were compliant¹. The researchers suggested that this could be due to an inability to regulate blood flow to the lungs (lung perfusion) and the constriction of pulmonary arteries in hypoxic conditions (hypoxic vasoconstriction). In another study done by Gattinoni, with Davide Chiumello and Sandra Rossi, hypoxemia of differing severity was also observed in patients inflicted with COVID-19².

In these cases, it was proposed that there are two types of patients, those with acute respiratory distress syndrome (ARDS) and those without. The two types of patients are easily recognizable based on CT scans, with the patients displaying ARDS having noticeably higher lung weight and percentage of non-aerated tissue, while possessing lower venous admixtures, oxygenation indexes, and respiratory system compliances². In a separate analysis conducted by John Marini and Gattinoni, a simple model was used to assign patients into two categories, type “L” and type “H”; type “L” patients were considered to have lower lung elastance, lung weight, and lower responses to positive end-expiratory pressure (PEEP) than their type “H” counterparts³. A similar study done by Gattinoni and colleagues elaborated more on methods that could be used to treat type “L” and type “H” patients.

It was recommended to first attempt to reverse the hypoxemia that occurs by increasing the concentration of oxygen inhaled (FiO₂). For patients experiencing dyspnea, noninvasive methods were said to be available, examples being high-flow nasal cannula (HFNC) or noninvasive ventilation (NIV), however, due to possibly having high failure rates these were not recommended. Upon sedation and intubation, the type “L” patients were recommended to be ventilated, if hypercapnic, with early intubation possibly preventing conversion from type “L” to type “H” phenotype.

 For type “H” patients, it was recommended that they should be treated similarly to patients suffering from severe ARDS, which includes prone positioning and higher PEEP⁴. As evident by the research done by Gattinoni and colleagues, it is imperative to determine the correct phenotype of patients inflicted with COVID-19, via CT scan and other medical testing, in order to determine appropriate treatment response.

Regarding treatment, several different potential solutions have been proposed and some have even been tested on patients with COVID-19, albeit not in a controlled, experimental setting. One such treatment that has demonstrated positive results was the usage of convalescent plasma by Chenguang Shen and colleagues to treat seriously ill patients that had COVID-19 and ARDS. The plasma from the donors all had high virus-specific immunoglobulin G (IgG) and immunoglobulin M (IgM) titers⁵. Following treatment with convalescent plasma, 4 of the 5 patients experienced a drop in their Sequential Organ Failure Assessment (SOFA) and an improvement in their Horowitz indexes (PaO₂/FiO₂). Also, four of the patients who had been being treated with mechanical ventilation did not require support after 9 days, following the treatment with convalescent plasma⁵. It was suggested by Shen and colleagues, that utilizing convalescent plasma containing neutralizing antibodies in treatment for patients with COVID-19 could potentially lead to an improved condition. Although, the small sample size and lack of controlled studies must be discussed and evaluated before determining the efficacy of this treatment.

With regards to pharmaceutical treatment, James M. Sanders and colleagues laid out a comprehensive review of a number of drugs that have been utilized to fight COVID-19; these range from drugs seen prominently in media, such as chloroquine and hydroxychloroquine, to antiretrovirals and other drugs that are currently being investigated. The treatment that appears to be most promising, according to Sanders and colleagues, is remdesivir, a monophosphate prodrug that was investigated closely during the Ebola outbreak in West Africa due to its ability to hinder viral replication. During single and multiple-dose phase 1 trials, infusions within a range of 3 mg and 225 mg via IV were demonstrated to be tolerated well and did not display damage or toxicity to the liver or kidney⁶. However, remdesivir has recently been approved by the FDA to treat severe patients with COVID-19. Overall, there is an apparent need to conduct more clinical trials for potential treatments for COVID-19 as few have demonstrated efficacy in combating the virus thus far.

References

1. Gattinoni, Luciano et al. “COVID-19 Does Not Lead to a ‘Typical’ Acute Respiratory Distress Syndrome”. American Journal of Respiratory and Critical Care Medicine vol.201, 10. Published online May 15, 2020. https://www.atsjournals.org/doi/pdf/10.1164/rccm.202003-0817LE
2. Gattinoni, Luciano et al. “COVID-19 pneumonia: ARDS or not?”. Critical Care vol. 24. Published online April 16, 2020. https://ccforum.biomedcentral.com/articles/10.1186/s13054-020-02880-z?utm_source=miragenews&utm_medium=miragenews&utm_campaign=news
3. Gattinoni, Luciano, Marini, John J. “Management of COVD-19 Respiratory Distress”. Published online April 24, 2020. https://jamanetwork.com/journals/jama/article-abstract/2765302
4. Gattinoni, Luciano et al. “COVID-19 pneumonia: different respiratory treatments for different phenotypes?”. Published online April 14, 2020. https://link.springer.com/content/pdf/10.1007/s00134-020-06033-2.pdf
5. Chenguang, Shen et al. “Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma”. Published online March 27, 2020. https://jamanetwork.com/journals/jama/article-abstract/2763983
6. Sanders, James M. et al. “Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19)”. Published online April 13, 2020. https://jamanetwork.com/journals/jama/article-abstract/2764727