Is Altered Surfactant Protein Gene Expression in Peripheral Blood Associated with COVID-19 Disease Severity?
<b>Background/Objectives:</b> 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...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-07-01
|
| Series: | Diagnostics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2075-4418/15/13/1690 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849319833704857600 |
|---|---|
| author | Suna Koc Kamil Cankut Senturk Sefa Cetinkaya Guven Yenmis Hulya Arkan Mahmut Demirbilek Pinar Acar Erhan Arikan Mehmet Dokur |
| author_facet | Suna Koc Kamil Cankut Senturk Sefa Cetinkaya Guven Yenmis Hulya Arkan Mahmut Demirbilek Pinar Acar Erhan Arikan Mehmet Dokur |
| author_sort | Suna Koc |
| collection | DOAJ |
| description | <b>Background/Objectives:</b> 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. <b>Methods:</b> 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<sup>−ΔΔCt</sup> method. Outliers (Ct values > 3 SD from the mean) were excluded before analysis. <b>Results:</b> 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 (<i>p</i> < 0.0001), but then decreased by ~54-fold in severe cases relative to mild (<i>p</i> < 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 (<i>p</i> < 0.0001), and SFTPD was ~4346-fold higher in severe versus asymptomatic cases (<i>p</i> < 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. <b>Conclusions:</b> 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. |
| format | Article |
| id | doaj-art-2968036cdecb4ad5982bb7b918bca3fe |
| institution | Kabale University |
| issn | 2075-4418 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Diagnostics |
| spelling | doaj-art-2968036cdecb4ad5982bb7b918bca3fe2025-08-20T03:50:17ZengMDPI AGDiagnostics2075-44182025-07-011513169010.3390/diagnostics15131690Is Altered Surfactant Protein Gene Expression in Peripheral Blood Associated with COVID-19 Disease Severity?Suna Koc0Kamil Cankut Senturk1Sefa Cetinkaya2Guven Yenmis3Hulya Arkan4Mahmut Demirbilek5Pinar Acar6Erhan Arikan7Mehmet Dokur8Department of Anesthesia and Reanimation, School of Medicine, Biruni University, Istanbul 34015, TurkeySchool of Medicine, Biruni University, Istanbul 34015, TurkeyDepartment of Medical Genetics, School of Medicine, Biruni University, Istanbul 34015, TurkeyDepartment of Medical Biology, Tayfur Ata Sokmen School of Medicine, Hatay Mustafa Kemal University, Hatay 31060, TurkeyCenter for Nanotechnology and Biomaterials Applications and Research, Marmara University, Istanbul 34854, TurkeyDepartment of Emergency Medicine, School of Medicine, Biruni University, Istanbul 34015, TurkeyDepartment of Anesthesia and Reanimation, School of Medicine, Biruni University, Istanbul 34015, TurkeyDepartment of Emergency Medicine, Faculty of Medicine, Bilecik Seyh Edebali University, Bilecik 11230, TurkeyDepartment of Emergency Medicine, Faculty of Medicine, Bilecik Seyh Edebali University, Bilecik 11230, Turkey<b>Background/Objectives:</b> 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. <b>Methods:</b> 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<sup>−ΔΔCt</sup> method. Outliers (Ct values > 3 SD from the mean) were excluded before analysis. <b>Results:</b> 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 (<i>p</i> < 0.0001), but then decreased by ~54-fold in severe cases relative to mild (<i>p</i> < 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 (<i>p</i> < 0.0001), and SFTPD was ~4346-fold higher in severe versus asymptomatic cases (<i>p</i> < 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. <b>Conclusions:</b> 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.https://www.mdpi.com/2075-4418/15/13/1690COVID-19surfactant proteindisease severitygene expressionSFTPD |
| spellingShingle | Suna Koc Kamil Cankut Senturk Sefa Cetinkaya Guven Yenmis Hulya Arkan Mahmut Demirbilek Pinar Acar Erhan Arikan Mehmet Dokur Is Altered Surfactant Protein Gene Expression in Peripheral Blood Associated with COVID-19 Disease Severity? Diagnostics COVID-19 surfactant protein disease severity gene expression SFTPD |
| title | Is Altered Surfactant Protein Gene Expression in Peripheral Blood Associated with COVID-19 Disease Severity? |
| title_full | Is Altered Surfactant Protein Gene Expression in Peripheral Blood Associated with COVID-19 Disease Severity? |
| title_fullStr | Is Altered Surfactant Protein Gene Expression in Peripheral Blood Associated with COVID-19 Disease Severity? |
| title_full_unstemmed | Is Altered Surfactant Protein Gene Expression in Peripheral Blood Associated with COVID-19 Disease Severity? |
| title_short | Is Altered Surfactant Protein Gene Expression in Peripheral Blood Associated with COVID-19 Disease Severity? |
| title_sort | is altered surfactant protein gene expression in peripheral blood associated with covid 19 disease severity |
| topic | COVID-19 surfactant protein disease severity gene expression SFTPD |
| url | https://www.mdpi.com/2075-4418/15/13/1690 |
| work_keys_str_mv | AT sunakoc isalteredsurfactantproteingeneexpressioninperipheralbloodassociatedwithcovid19diseaseseverity AT kamilcankutsenturk isalteredsurfactantproteingeneexpressioninperipheralbloodassociatedwithcovid19diseaseseverity AT sefacetinkaya isalteredsurfactantproteingeneexpressioninperipheralbloodassociatedwithcovid19diseaseseverity AT guvenyenmis isalteredsurfactantproteingeneexpressioninperipheralbloodassociatedwithcovid19diseaseseverity AT hulyaarkan isalteredsurfactantproteingeneexpressioninperipheralbloodassociatedwithcovid19diseaseseverity AT mahmutdemirbilek isalteredsurfactantproteingeneexpressioninperipheralbloodassociatedwithcovid19diseaseseverity AT pinaracar isalteredsurfactantproteingeneexpressioninperipheralbloodassociatedwithcovid19diseaseseverity AT erhanarikan isalteredsurfactantproteingeneexpressioninperipheralbloodassociatedwithcovid19diseaseseverity AT mehmetdokur isalteredsurfactantproteingeneexpressioninperipheralbloodassociatedwithcovid19diseaseseverity |