COVID-19 primarily affects the alveoli, as the virus targets type II pneumocytes. This can lead to abnormalities in the alveolar-capillary membrane, a condition referred to as post-COVID syndrome.
Patients with this condition often report symptoms such as shortness of breath (dyspnea) and fatigue, even though spirometry results are often within normal ranges. Â In such cases, the diffusion capacity test is the ideal method to confirm a post-COVID syndrome diagnosis and is useful for monitoring pulmonary rehabilitation following the disease.
In this blog we delve into a clinical report that intends to shed some light to the causes why symptomatic post COVID patients present no only impaired alveolar capillary membrane function but also high VE/VCO2 (minute ventilation/carbon dioxide production relationship slope).
By América Torres
What is the Post-COVID Syndrome?
Some clinical studies report reduced diffusion capacity in COVID-19 survivors at three and twelve months after discharge1. Researchers observed that while part of the patients recovers during the acute phase half of the patients admitted at the hospital due to COVID-19 still experience symptoms three months after the acute infection. Researchers call this persistence of symptoms long COVID or Post-COVID Syndrome.Â
Long-term Lung Effects of COVID-19: Alveolar-Capillary Membrane Dysfunction
Even one year after infection, one-third of the hospitalized COVID-19 patients report that they do no feel recovered. Three months after discharge, survivors most commonly report the following persisting symptoms1:
- Fatigue
- Dyspnoea
- Muscle weakness
- Sleep- problems
- Memory  problems
These symptoms greatly affect their QOL (quality of life), but researchers have yet to determine their cause.
Pulmonary sequelae of COVID-19
Some post-COVID-19 symptoms result from pulmonary function impairments. Long-term pulmonary function impairments mainly include a reduced diffusion capacity. Studies report this finding in 52–56% of hospitalized COVID-19 patients three months after discharge.1
Even one year after discharge, COVID-19 survivors report abnormal diffusion capacity  (39%) and declined total lung capacity (TLC) (42%). Although in the majority of the patients, these pulmonary function impairments improve over time, still one-third of the COVID-19 patients that were hospitalized during the acute phase of the infection have a reduced diffusion capacity one year  later.1
Persistent Pulmonary Impairment in Post-COVID Patients
Patients hospitalized with COVID-19 who had acute disease, were female, or had co-morbidities such as chronic respiratory disease, diabetes, or hypertension showed worse long-term pulmonary function outcomes. 1 However, apparently, the severity of the infection does noy to play a role in the frequency and intensity of post COVID-19 symptoms.2
Alveolar-capillary membrane dysfunction after COVID-19
In the clinical trial Symptomatic Post-COVID Patients Have Impaired Alveolar-Capillary Membrane Function and High VE/VCOâ‚‚ by Piergiuseppe Agostoni et al.2, researchers applied several tests to assess cardiorespiratory function in patients with post-COVID-19 syndrome.
The cohort reported symptoms such as tiredness, exercise-induced fatigability and dyspnea in 60%, 75% and 45% of cases; besides, they described a variety of cardiorespiratory complaints . The participants had the following characteristics:2
- 204 post COVID-19 patients
- 93 patients of them were hospitalized for acute COVID-19 syndrome
- Age 56.5 ± 14.5 years
- 44% females, 56% males
- 28% of subjects declared previous cardiovascular disease with symptoms
- BMI 25.7 ± 4.0
- 11 active smokers (6%)
- Researchers evaluated patients an average of 171 ± 85 days after they recovered from acute COVID-19 infection (it always included pneumonia)
- 55 out of 198 cases had a prior, non-severe cardiorespiratory disease and experienced only mild symptoms.
- 143 reported being in good clinical condition before their COVID-19 infection.
Gas exchange impairment after COVID-19
The researchers used various tests to assess the pulmonary condition of the patients. These included CT scans, transthoracic echocardiography, cardiopulmonary exercise tests (CPETs), standard spirometry, diffusing capacity of the lungs for carbon monoxide (DLCO), and SPB (surfactant binding protein B). This section focuses on the patients’ diffusion capacity results. The researchers found the following averages:2
- On the average DLCO was 22.2 ± 6.8 mL/min/mmHg (82 ± 19%pred)
- DM (membrane diffusion) 47.6 ± 14.8 mL/min/mmHg (107 ± 23%pred)
- Vcap (capillary volume) 59 ± 17 mL (85 ± 22%pred).
- VA (alveolar volume) 5.2 L [IQR (Interquartile Range)5–5.9], 93% pred [84–102].
- In patients with DLCO < 80% (39%), VA, DM and Vcap were 84% [IQR 76–93], 89 ± 22% and 65 ± 17%, respectively.
- In patients with DLCO ≥ 80%, VA, DM and Vcap were 98% [IQR 91–106], 117 ± 17% and 96 ± 16%, respectively, (p < 0.001 for all).
Alveolar dysfunction in long COVID syndrome
Agostoni et al. believe that the data indicate ventilation inefficiency plays a central role in post-COVID-19 syndrome, along with a reduced capillary volume (Vcap) at the alveolar-capillary membrane level.
High levels of SPB (surfactant binding protein B) indicate dysregulation of alveolar cells. However, it remains uncertain whether capillary volume can recover over time in post-COVID-19 syndrome. The elevated immature SPB levels, though, suggest that the alveolar-capillary membrane remains in a dynamic state, with ongoing dysfunction of the alveolar cells.
Patients with post-COVID-19 syndrome experience cardiorespiratory symptoms that correlate with their breathing patterns during exercise (VE/VCO₂ slope). In these patients, alveolar cells show dysregulation, and capillary volume (Vcap) is markedly reduced, as indicated by very high SPB levels. The study’s authors suggest that the low Vcap likely results from post-COVID-19 damage to the pulmonary endothelium and vasculature. However, DLCO is only slightly impaired, as DM (membrane diffusion) remains preserved.
Researchers conclude that it is necessary to conduct more studies to evaluate the long-term course of post-COVID symptoms and functional abnormalities, including lung parenchyma damage, standard spirometry results, alveolar-capillary function, SPB levels, and CPET data.
Managing post-COVID lung complications
The diffusion capacity test (DLCO) is a valuable tool for confirming a post-COVID syndrome diagnosis and monitoring patients during pulmonary rehabilitation. Accurate assessment of lung function is essential to guide therapy and track these patients response to treatment.
SCHILLER-GANSHORN equips clinicians with advanced devices designed to support high-quality patient care. The PowerCube Diffusion+ System features a multi-gas sensor that analyzes diffusion capacity, delivering fast and precise carbon monoxide (CO) measurements. Its high-speed, long-life sensor requires no maintenance and allows adjustment of discard and sampling volumes, enabling measurements even in patients with a vital capacity as low as 0.5 liters.
The system’s high-precision analyzers provide detailed CO and helium washout curves, while its efficient demand valve optimizes sample gas usage, helping reduce operating costs. Importantly, the PowerCube Diffusion+ was the first CO diffusion system on the market to integrate SharpFlow (ultrasonic) technology, offering a level of innovation and accuracy that sets it apart.
The PowerCube Diffusion+ system can be integrated into the PowerCube Body+ plethysmograph. This makes it an excellent solution for clinics or pulmonary function labs that want to assess lung volume but have limited space.
Experience the benefits of this advanced technology firsthand—click the button to request a no-obligation demo today and discover how SCHILLER-GANSHORN’s PowerCube Diffusion+ can enhance your care for post-COVID patients.
FAQ Alveolar-Capillary Membrane and Post-COVID Syndrome
What is alveolar-capillary membrane dysfunction after COVID-19?
It’s impaired gas exchange between alveoli and capillaries, often causing fatigue, dyspnea, and exercise intolerance in post-COVID patients.
How does COVID-19 affect the alveoli?
The virus targets type II pneumocytes, causing alveolar damage, reduced diffusion capacity, and persistent long-term pulmonary sequelae.
What are the long-term lung effects of COVID-19?
Patients can experience reduced diffusion capacity, alveolar dysfunction, fatigue, and dyspnea even one year post-infection.
How is alveolar dysfunction in long COVID diagnosed?
Using DLCO, CPET, and SPB measurements to detect impaired gas exchange and ongoing alveolar-cell dysregulation.
How can post-COVID alveolar-capillary membrane dysfunction be managed?
Pulmonary rehabilitation and monitoring with advanced devices like the PowerCube Diffusion+ enable clinicians to track recovery and guide therapy effectively.
REFERENCES
[1] Gach, D., Beijers, R.J.H.C.G., van Zeeland, R. et al. Pulmonary function trajectories in COVID-19 survivors with and without pre-existing respiratory disease. Sci Rep 14, 16571 (2024). https://doi.org/10.1038/s41598-024-67314-0
 [2] Agostoni, P., Mapelli, M., Salvioni, E. et al. Symptomatic post COVID patients have impaired alveolar capillary membrane function and high VE/VCO2. Respir Res 25, 82 (2024). https://doi.org/10.1186/s12931-023-02602-3