Distal Lung Inflammation Assessed by Alveolar Concentration of Nitric Oxide Is an Individualised Biomarker of Severe COVID-19 Pneumonia

Abstract

Pulmonary sequelae as assessed by pulmonary function tests (PFTs) are often reported in patients infected by SARS-CoV-2 during the post-COVID-19 period. Little is known, however, about the status of pulmonary inflammation during clinical recovery after patients’ discharge from the hospitals. We prospectively measured PFTs coupled with the exhaled nitric oxide (NO) stemming from the proximal airways (FeNO) and the distal lung (CaNO) in 169 consecutive patients with varying degrees of the severity of COVID-19 six weeks to one year after acute infection by SARS-CoV-2. The proportions of patients with abnormal PFTs, defined as the presence of either obstructive/restrictive patterns or impaired lung gas transfer, or both, increased with the severity of the initial lung disease (15, 30, and 52% in patients with mild, moderate, and severe COVID-19). FeNO values remained within normal ranges and did not differ between the three groups of patients. CaNO, however, was significantly higher in patients with severe or critical COVID-19, compared with patients with milder forms of the disease. There was also an inverse relationship between CaNO and DLCO. We conclude that the residual inflammation of the distal lung is still present in the post-COVID-19 follow-up period, in particular, in those patients with an initially severe form of COVID-19. This long-lasting alveolar inflammation might contribute to the long-term development of pulmonary fibrosis and warrants the regular monitoring of exhaled NO together with PFTs in patients with COVID-19.

Lung function assessment in children with Long‐Covid syndrome

“…Specifically, Cameli et al 40 observed higher values of CaNO about 90 days after the hospital discharge in 20 post‐COVID‐19 patients than healthy gender‐ and‐age matched controls, although FeNO levels were normal in both. Similarly, Hua‐Huy et al 41 found no different FeNO levels among patients with mild, moderate and severe COVID‐19‐related lung disease 5 months after acute infection. However,, the authors observed increased CaNO levels in the severe/critical disease group compared to the mild disease one.…”

“…In 82 adult patients hospitalized for COVID-19, Betancor et al 38 Adult patients with a history of severe COVID-19 showed higher CaNO values but normal FeNO levels a few months after hospital discharge. 40,41 Specifically, Cameli et al 40 COVID-19 at 3-6 months from the recovery. 36 Nitric oxide has an antimicrobial action versus bacteria, fungi, parasites and selected viral species, and its production increases during viral infections.…”

“…The authors attributed this fluctuation to the administration of corticosteroids during acute infection, which inhibit nitric oxide production by iNOS. Adult patients with a history of severe COVID‐19 showed higher CaNO values but normal FeNO levels a few months after hospital discharge 40,41 . Specifically, Cameli et al 40 observed higher values of CaNO about 90 days after the hospital discharge in 20 post‐COVID‐19 patients than healthy gender‐ and‐age matched controls, although FeNO levels were normal in both.…”

Persisting Shadows: Unraveling the Impact of Long COVID-19 on Respiratory, Cardiovascular, and Nervous Systems

“…Additionally, research on exhaled nitric oxide in patients recovering from COVID-19 has shown that residual inflammation in the distal lung (including the alveoli) can persist, particularly in those who initially had a severe form of the disease. This ongoing alveolar inflammation might contribute to the long-term development of pulmonary fibrosis, underscoring the need to regularly monitor pulmonary function and inflammation in COVID-19 patients [161].…”

In Situ Noninvasive Observation of Nitric Oxide Fluctuation in SARS-CoV-2 Infection In Vivo by Organic Near-Infrared-II Fluorescent Molecular Nanoprobes

“…Notably, nitric oxide (NO) in the lungs is a key signal transduction molecule involved in many functions, including selective pulmonary vasodilator effects, bronchodilator effects, increased blood flow to the alveoli, and antithrombotic effects. − Meanwhile, NO in the lungs is an important immune regulator to perform anti-inflammatory effects and anti-SARS-CoV-2 virus effects. − The role of NO hinges on its location of production and concentration. In fact, the exhaled NO stemming from the proximal airways and the distal lung in SARS-COV-2 infection has been studied, − but these outcomes do not directly uncover the real in situ NO level of SARS-COV-2 infection in the lung at the cellular level due to the short half-life of NO in water (the order of 0.1 s) and exhaled NO possibly from airways, tracheobronchial tissues, mouth, or nose rather than from lung tissues. Thus, the in situ, noninvasive, and real-time monitoring of endogenous NO levels to understand its underlying pathogenesis holds promise for managing SARS-CoV-2 infections and providing insight into therapeutical interventions.…”