Can FeNO be a biomarker in the post-COVID-19 patients monitoring?

Abstract

The nature of the inflammatory and fibrotic processes found in patients with post-COVID-19 syndrome makes it possible to speculate that in such patients fractional exhaled nitric oxide (FeNO) may be a useful biomarker. Consequently, we set out to verify the consistency of this hypothesis. We consecutively enrolled 68 post-COVID patients after being hospitalized for persistent clinical manifestations within 2 months from disease onset and 29 healthy volunteers as control group. None of post-COVID patients had bronchial asthma or were being treated with a corticosteroid. Only 19 out of 68 post-COVID-19 patients reported a FeNO value > 25 ppb. The mean FeNO value in post-COVID-19 patients was 18.55 ppb (95% CI: 15.50 to 21.58), while in healthy subjects it was 17.46 ppb (95% CI: 15.75 to 19.17). The mean difference was not statistically significant (P = 0.053). However, the mean FeNO value of post-COVID-19 patients was higher in men than in women (20.97 ppb; 95% CI: 16.61 to 25.33 vs 14.36 ppb; 95% CI: 11.11 to 17.61) with a difference between the two sexes that was statistically significant (P = 0.016). Mean FeNO was 14.89 ppb (95% CI: 10.90 to 18.89) in patients who had been treated with systemic corticosteroids because of their COVID-19, and 20.80 ppb (95% CI: 16.56 to 25.04) in those who had not taken them, with a difference that was statistically significant (P = 0.043). The data generated in this study suggest that measurement of FeNO is not useful as a biomarker in post-COVID-19 patient. However, this hypothesis needs solid validation with additional specifically designed studies.

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

“…Our results are consistent with recently published studies finding that FeNO values did not differ between COVID-19 patients with varying degrees of severity [ 34 , 35 , 36 , 37 ]. These observations have prompted some investigators to cast doubt on the need of measuring exhaled NO as a biomarker in post-COVID-19 patient monitoring [ 36 , 37 ]. As already discussed, a key feature related to the physiological meanings of different NO parameters must, however, constantly be emphasised [ 13 ].…”

“…As already discussed, a key feature related to the physiological meanings of different NO parameters must, however, constantly be emphasised [ 13 ]. Many already published studies only investigated FeNO [ 33 , 34 , 35 , 36 , 37 ], a biomarker of proximal bronchial inflammation [ 10 ], that is unlikely to occur 6 to 52 weeks after the acute phase in those COVID-19 patients without a medical history of asthma. That FeNO remained within normal ranges and did not differ between different groups of patients, as observed in our study and many others [ 7 , 8 , 33 , 34 , 35 , 36 , 37 ], is also consistent with the relatively low percentage of patients with bronchial obstructive patterns during COVID-19 follow-up studies [ 3 , 5 , 6 ], and the hypothesis that bronchial obstructive lung disease is an unlikely feature of PASC [ 3 ].…”

“…Many already published studies only investigated FeNO [ 33 , 34 , 35 , 36 , 37 ], a biomarker of proximal bronchial inflammation [ 10 ], that is unlikely to occur 6 to 52 weeks after the acute phase in those COVID-19 patients without a medical history of asthma. That FeNO remained within normal ranges and did not differ between different groups of patients, as observed in our study and many others [ 7 , 8 , 33 , 34 , 35 , 36 , 37 ], is also consistent with the relatively low percentage of patients with bronchial obstructive patterns during COVID-19 follow-up studies [ 3 , 5 , 6 ], and the hypothesis that bronchial obstructive lung disease is an unlikely feature of PASC [ 3 ]. Of greater concern, however, is the risk of pulmonary fibrosis that might occur as a long-term complication of COVID-19 even in those patients free of ILD prior to infection by SARS-CoV-2 [ 30 , 32 ].…”

Knowledge of fractional exhaled nitric oxide use among doctors working in a local respiratory department

“…The data generated in this study suggested that measurement of FeNO is not useful as a biomarker in post-COVID-19 patients. The final question of the questionnaire tackled this study with most experienced trainees responding correctly with a correct response rate of 84.6% (n=11) 14 .…”

Can Fractional Exhaled Nitric Oxide (FeNO) Serve as a Clinical Indicator for Patients Hospitalized with Crimean-Congo Hemorrhagic Fever?

“…This property of NOS2 has allowed FeNO level to play a significant role in the monitoring of patients with obstructive pulmonary diseases, particularly asthma (33)(34)(35). In studies regarding viral infections of the lower respiratory tract, it was found that FeNO levels were elevated in viral infections and decreased with treatment (36)(37)(38). This was interpreted as evidence that NO has a role in antiviral activity.…”