Background/Objectives: Severe COVID-19 pneumonia damages alveolar type II cells and disrupts surfactant homeostasis, contributing to acute respiratory distress syndrome (ARDS). Surfactant proteins (SP-A, SP-B, SP-C, SP-D) are critical for reducing alveolar surface tension and for innate immune defense. We aimed to evaluate whether surfactant protein gene expression varies with the severity of COVID-19. Methods: Peripheral blood was collected from 122 adults with confirmed COVID-19, categorized as asymptomatic (no symptoms), mild (requiring hospitalization), or severe (requiring ICU admission). We quantified mRNA expression of surfactant protein genes (SFTPA1, SFTPA2, SFTPB, SFTPC, SFTPD) in blood cells using RT-qPCR. Relative expression was normalized to GAPDH and compared among the groups using the 2^−ΔΔCt method. Outliers (Ct values > 3 SD from the mean) were excluded before analysis. Results: Distinct surfactant gene expression patterns were markedly associated with disease severity. Transcripts of SFTPB and SFTPC decreased with increasing severity of the disease. Notably, SFTPC expression was ~49-fold higher in mild cases compared to asymptomatic COVID-19-positive patients (p < 0.0001), but then decreased by ~54-fold in severe cases relative to mild (p < 0.0001), returning to near-baseline levels. In contrast, SFTPA2 and SFTPD were dramatically upregulated in severe cases. SFTPA2 was ~50-fold higher in severe versus mild cases (p < 0.0001), and SFTPD was ~4346-fold higher in severe versus asymptomatic cases (p < 0.0001; ~9.6-fold higher than in mild). SFTPA1 showed only a modest ~1.4-fold decrease in severe cases (vs. mild). All noted differences remained statistically significant after outlier exclusion. Conclusions: COVID-19 severity is correlated with profound changes in surfactant gene expression in blood. Critically ill patients exhibit loss of key surfactant components (SP-B and SP-C transcripts) alongside an excessive SP-D response. These preliminary findings suggest an imbalance that may contribute to lung injury in severe disease. However, further validation is needed to establish surfactant proteins, such as SP-D, as biomarkers of COVID-19 severity.

Background/Objectives: Since its emergence in 2020, researchers worldwide have been collaborating to better understand the SARS-CoV-2 disease’s pathophysiology. Disease severity can vary based on several factors, including comorbidities and genetic variations. Notably, recent studies have highlighted the role of genes associated with athletic performance, such as ACE, ACTN3, and PPARGC1A, in influencing muscle function, cardiovascular health, and the body’s metabolic response. Given that these genes also impact oxidative metabolism, inflammation, and respiratory efficiency, we hypothesized that they might play a critical role in the host’s response to SARS-CoV-2 infection. This study aimed to investigate the association between disease severity and genetic polymorphisms in these sport performance-related genes, specifically ACE rs4646994, ACTN3 rs1815739, and PPARGC1A rs8192678. Methods: A total of 422 COVID-19-positive patients were included in this study. The participants were divided into three groups: a severe group (77 patients) requiring intensive care unit (ICU) admission, a mild group (300 patients) exhibiting at least one symptom, and an asymptomatic control group. Genotyping was performed using restriction fragment length polymorphism PCR. Results: The D allele and DD genotype of ACE and the T allele and TT genotype of ACTN3 were found to confer protective effects against severe SARS-CoV-2 infection. Conversely, the PPARGC1A TC genotype and the ACE-PPARGC1A ins/ins + TC combined genotype were associated with increased disease severity (p < 0.05). Conclusions: Although vaccination has reduced the severity of SARS-CoV-2, the virus continues to impact human health. Inter-individual differences due to these genetic variations will broaden the horizon of knowledge on the pathophysiology of the disease.

Background/Objectives: Severe COVID-19 pneumonia causes alveolar type II cell damage and surfactant dysfunction, contributing to acute respiratory distress syndrome (ARDS). Surfactant proteins (SP-A, SP-B, SP-C, SP-D) are critical for reducing alveolar surface tension and defending against infection. We aimed to evaluate how surfactant protein gene expression affects COVID-19 severity Methods: Peripheral blood was collected from 122 adults with confirmed COVID-19, categorized as asymptomatic (no symptoms), mild (hospitalized), or severe (ICU admission). We quantified mRNA expression of surfactant protein genes (SFTPA1, SFTPA2, SFTPB, SFTPC, SFTPD) by RT-qPCR and compared relative expression levels between groups. Results: Surfactant gene expression patterns differed markedly with disease severity. SFTPB and SFTPC transcripts decreased as severity increased. Notably, SFTPC was ~49-fold higher in mild cases than asymptomatic controls, but then dropped ~54-fold in severe cases relative to mild, returning to near-baseline levels. In contrast, SFTPA2 and SFTPD were dramatically upregulated in severe illness. SFTPD expression in severe patients was ~4346-fold higher than in asymptomatic individuals (and ~9.6-fold higher than in mild cases). SFTPA2 was ~50-fold higher in severe versus mild cases. By comparison, SFTPA1 showed a modest ~1.4-fold decrease in severe cases (vs. mild). All noted differences were statistically significant (p < 0.05). Conclusion: COVID-19 severity is associated with distinct surfactant gene expression changes. Critically ill patients exhibited loss of key surfactant components (SP-B and SP-C) alongside an excessive SP-D response. This imbalance in the surfactant system likely contributes to alveolar collapse in severe COVID-19, and elevated SP-D may serve as a biomarker of lung injury severity.