Gas exchange abnormalities in Long COVID are driven by the alteration of the vascular component, 2024, Imeri et al.

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Gas exchange abnormalities in Long COVID are driven by the alteration of the vascular component
Gianluca Imeri; Caterina Conti; Anna Caroli; Alberto Arrigoni ; Pietro Bonaffini; Sandro Sironi; Luca Novelli; Federico Raimondi; Greta Chiodini; Simone Vargiu; Fabiano Di Marco

BACKGROUND
There are uncertainties whether the impairment of lung diffusing capacity in COVID-19 is due to an alteration in the diffusive conductance of the alveolar membrane (Dm), or an alteration of the alveolar capillary volume (Vc), or a combination of both. The combined measurement DLNO and DLCO diffusion, owing to NO higher affinity and faster reaction rate with haemoglobin compared to CO, enables the simultaneous and rapid determination of both Vc and Dm. The aim of the present study was to better identify the precise cause of post-COVID-19 diffusion impairment.

METHODS
Using the combined NO and CO gas transfer techniques (DLNO and DLCO), it is possible to better understand whether gas exchange abnormalities are due to membrane or alveolar capillary volume components. The present study was aimed at evaluating pulmonary gas exchange one year after severe COVID-19.

RESULTS
The cohort included 33 survivors to severe COVID-19 (median age 67 years, 70% male) with no pre-existing lung disease, who underwent clinical, lung function and imaging assessments at 12 months due to persistence of respiratory symptoms or radiological impairment. The gas exchange abnormalities were mainly determined by the compromise of the vascular component as demonstrated by vascular pattern of gas exchange impairment (i.e., DLNO/DLCO≥110%, 76% of the sample), and by a reduction of the Vc (73%), while the Dm was reduced only in 9% of the entire sample. We did not find a correlation between the gas exchange impairment and the extent of the chest CT alterations (DLCO p = 0.059 and DLNO p = 0.054), which on average were found to be mild (11% of the parenchyma).

CONCLUSIONS
In COVID-19 survivors who are still symptomatic or have minimal CT findings at one year, gas exchange abnormalities are determined by impairment of the vascular component, rather than the diffusive component of the alveolar membrane.

Link | PDF (Multidisciplinary Respiratory Medicine) [Open Access]

 

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Hospitalised cohort without pre-existing pulmonary disease 12 months on from severe infection but little abnormality on chest CT.

 

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The pulmonary diffusing capacity of carbon monoxide (DLCO) is the most sensitive pulmonary function test in the assessment of gas exchange at the alveolar-capillary membrane. Specifically, this examination is determined by two resistances arranged in series: the pulmonary membrane diffusing capacity (Dm) for carbon monoxide (CO) and the rate of carbon monoxide uptake by blood in the alveolar capillary volume (Vc). Notably, both components are involved in SARS-CoV-2 infection.

However, a reduction of the classical DLCO is mainly driven by the vascular compartment, with the potential risk of shadowing alterations of Dm in the study of COVID-19 sequelae. This is, because DLCO can better measure the defects in microvascular alterations while DLNO is affected more by the membrane defects. To overcome this limitation, it is possible to evaluate the transfer of nitric oxide (DLNO) in association with DLCO. Indeed, nitric oxide (NO) has a higher affinity and faster reaction with haemoglobin than CO, making the contribution of the second resistance negligible (i.e., NO uptake by blood) and eventually allowing the isolated measurement of the diffusive component (i.e., Dm).

The aim of the present study was to evaluate gas exchange one year after COVID-19, using the combined DLNO/DLCO technique in patients with radiological abnormalities or symptoms that persist 12 months after discharge; moreover, the correlation between gas exchange impairment and CT radiological findings was investigated.

 

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The main findings [...] can be summarized as follows:

(a) DLCO has a high sensitivity in the assessment of long-term COVID-19 sequelae, with 54% of patients either symptomatic or with radiological abnormalities 12 months after infection still having impairment of this test;

(b) however, most patients (76%) demonstrates a vascular pattern of gas exchange (i.e., DLNO/DLCO ≥ 110%) and there are patients with normal DLCO showing a significant decrease in capillary volume, which is the most common impairment in these patients (73%), while Dm is reduced only in 9% of the whole sample;

(c) there is no correlation between gas exchange abnormalities and the extent of CT abnormal involvement which was on average mild.

The predominant histological pattern of lung injury in COVID-19 deceased patients is diffuse alveolar damage, often associated with hyaline membrane formation and atypical hyperplasia of pneumocytes. However, capillary endothelitis and fibrinous microthrombi with angiogenesis within the interalveolar septa are also described. An analysis of morpho-phenotypic changes by transbronchial lung cryobiopsy in patients with persistent symptoms and residual parenchymal lung disease on average 3 months after recovery from COVID-19 revealed three different clusters of cases: chronic fibrosing, acute/subacute and a vascular form. The latter cluster was characterized by diffuse vascular increase and dilatation or distortion (capillaries and venules) within the otherwise normal parenchyma.

we found that capillary volume impairment is the predominant alteration in long COVID-19.

in a study including long-term COVID-19 patients with persisting symptoms, population was evaluated by sublingual video microscopy. The Authors found that COVID-19 leaves a persistent capillary rarefaction up to 18 months after infection. Our results are consistent with this hypothesis. In fact, more than seven out of ten patients show a reduction in capillary volume, and most patients (76%) demonstrates a vascular pattern of gas exchange (i.e., DLNO /DLCO ≥ 110%) despite nonspecific imaging and a DLCO sometimes within normal limits. In these cases, we can hypothesize that the reduction in capillary volume is balanced by an increase in membrane conductance, in terms of efficiency or surface area.