Discussion
Our study showed that COVID-19 patients’ CRP, ferritin, and fibrinogen
levels decreased with treatment, consistent with previous studies, while
FEV1 and FVC values increased. The symptoms of
restrictive lung disease observed at the start of treatment were
improved on day 7 of treatment. Correlation analysis between the 7-day
changes in laboratory parameters and pulmonary function tests showed
that FEV1 and FVC values increased in correlation with
the change in CRP and fibrinogen levels.
On March 11, 2020, the World Health Organization (WHO) declared the
COVID-19 a pandemic and as of December 15, 2020, more than 72 million
cases had been confirmed worldwide [1]. Large-scale studies on
COVID-19 have documented extensive lung damage both during and after the
disease. In a recent report it was determined that COVID-19 pneumonia
patients still showed abnormalities in lung CT scans after discharge,
with ground-glass opacities being the most common pulmonary sequelae7. Survivors of other coronavirus pneumonias (SARS and
MERS) are known to have pulmonary function and exercise capacity
impairments persisting for months or even years5,8-10. To date, however, there have been few studies
examining loss of pulmonary function in discharged COVID-19 patients.
SARS-CoV-2 infects the human airway and the vascular and immune cells,
potentially leading to severe damage to the respiratory tract,
especially within the lungs. Disease severity depends on the
effectiveness of the immune system. Current evidence suggests that in
some cases, viral infection can cause an exaggerated immune reaction in
the host that is severe enough to be classified as the hyperinflammatory
condition referred to as macrophage activation syndrome11.
Numerous proinflammatory cytokines are released in COVID-19 patients,
primarily tumor necrosis factor alpha, interleukins 1, 2, 6 and 18, and
nitric oxide. These cytokines can increase vascular permeability,
resulting in impaired tissue perfusion, endothelial damage, and
microthrombus formation. Increased vascular permeability causes fluid
accumulation in the lung tissue and interstitial spaces, which manifests
clinically with acute respiratory failure 2,3.
Suppression of these proinflammatory cytokines has proven to be
therapeutically beneficial in many inflammatory conditions, including
viral infections. Increased cytokine levels in the lung cause alveolar
epithelial damage, alveolar septal fibrous proliferation, hyaline
membrane formation, and the development of pulmonary consolidation12. This is the main cause of the restrictive
pathology and reduced diffusion capacity seen in the lungs of COVID-19
patients. Studies have shown that this process continues in association
with regression even after discharge 13. In a study
including 110 COVID-19 patients, evaluation of pulmonary function tests
at discharge showed a reduction in diffusion capacity that was
correlated with disease severity. However, a striking aspect of the
study was that the diffusing capacity of the lung for carbon monoxide
(DLCO) decreased more than the diffusing capacity divided by alveolar
volume (DLCO/VA), suggesting that impairment of the diffusion membrane
was a more important issue than low lung volume 6.
It was also observed that levels of D-dimer and acute phase reactants
such as CRP, ferritin, and fibrinogen were elevated in COVID-19 patients
after intense inflammatory cytokine discharge and that these parameters
may be associated with morbidity and mortality 14.
Among these parameters, levels of CRP, fibrinogen, and ferritin levels
were found to be high and inversely correlated with FEV1and FVC levels 15-17. These acute phase reactants are
elevated in most inflammatory diseases, and studies evaluating the
relationship with parenchymal fibrosis in interstitial lung diseases
have demonstrated increases in correlation with the extent of
parenchymal fibrosis, highlighting their potential usefulness in
follow-up 18,19.
In the present study, we observed that the restrictive pattern initially
presented by COVID-19 patients due to parenchymal infiltration in the
lungs resolved during follow-up with regression of the lung
consolidation. Pulmonary function values increased with the decline in
CRP and fibrinogen levels, suggesting the improvement was secondary to
reduced inflammation. However, consistent with our experience with
COVID-19, fibrosis may be permanent and patients may show a restrictive
pattern with reduced diffusion in long-term follow-up. Plasma fibrogen
level has been associated with increased parenchymal fibrosis in
previous studies. Therefore, the decline in plasma fibrinogen levels
during follow-up in COVID-19 suggests that this parameter may be useful
in evaluating progression to parenchymal fibrosis in this disease, which
is characterized by pathologies also observed in interstitial lung
diseases, such as hyaline membrane formation and alveolar septal fibrous
proliferation.
The most important limitation of our study was the inability to evaluate
diffusion capacities and total lung capacities when evaluating the
etiology of the restrictive pathology observed in pulmonary function
tests. However, this was a result of the fact that only portable
pulmonary function testing equipment could be placed in the negative
pressure room established to minimize the chance of transmission.
In conclusion, although the assessment of laboratory parameters and
radiological findings has become a convenient method for evaluating
COVID-19 patients, the inability to evaluate patients’ pulmonary
function due to risk prevention measures has become the biggest problem
in follow-up and discharge. In this study examined the guiding potential
of some of these easily obtained parameters, we observed that decline in
both CRP and fibrinogen levels may be associated with improved pulmonary
functional capacity.