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. 2023 Jul 3;37(4):1721–1728. doi: 10.21873/invivo.13259

The Soluble Lectin Families as Novel Biomarkers for COVID-19 Pneumonia

HARUKA TAKENAKA 1,#, ATSUSHI SAITO 1,#, KOJI KURONUMA 1, KEIGO MONIWA 1, HIROTAKA NISHIKIORI 1, SATOSHI TAKAHASHI 2, HIROFUMI CHIBA 1
PMCID: PMC10347912  PMID: 37369511

Abstract

Background/Aim: The lung-specific soluble lectins, SP-A and SP-D have been clinically used to diagnose interstitial lung disease, but their clinical significance in COVID-19 remains controversial. This study was undertaken to determine their association with other lectins (MBL and FCN1), disease severity, and radiographs in COVID-19 patients.

Patients and Methods: A total of 131 patients with COVID-19 admitted in the Sapporo Medical University Hospital between May 22 and September 19, 2021, were enrolled in the study. Data including demographics, medical history, symptoms, signs, laboratory findings, and radiological images were collected from the patients’ medical records. Chest computed tomography (CT) scanning was performed at admission. Serum levels of surfactant protein A and D (SP-A and SP-D), mannose-binding lectin (MBL) and ficolin1 (FCN1) were measured using enzyme-linked immunosorbent assay (ELISA) kits.

Results: Compared to the control group, the COVID-19 group had significantly higher serum SP-A and FCN1 levels on admission (SP-A: 59.60±38.89 vs. 35.61±11.22 ng/ml; p<0.01, FCN1: 542.45±506.04 vs. 250.6±161.1 ng/ml; p<0.01). The severe group in COVID-19 had significantly higher serum SP-D and lower MBL levels than the non-severe group (SP-D: 141.7±155.7 vs. 61.41±54.54 ng/ml; p<0.01, MBL: 1,670±1,240 vs. 2,170±1,140 ng/ml; p<0.05). SP-D strongly reflected the degree of imaging findings, whereas SP-A showed a significant correlation, albeit slightly weaker than SP-D. Conversely, MBL and FNC1 were not significantly correlated with imaging findings.

Conclusion: Among soluble serum lectins, SP-A and SP-D may be more sensitive to CT findings than reported disease biomarkers such as IL-6, LDH, and CRP due to their lung-specific characteristics.

Keywords: COVID-19, lectin, pulmonary collectin, SP-A, SP-D, mannose-binding lectin, FCN1, biomarker

It has already been 2 years since the first case of coronavirus disease 2019 (COVID-19) was reported, and its pathology is gradually becoming clear. However, COVID-19 is continuously threatening our lives. To date, the number of patients with COVID-19 is very large; thus, the medical care burden is a social problem. Therefore, the existence of biomarkers to easily grasp the clinical condition of patients is considered very important. Previous studies have shown that increased leukocyte count and blood urea nitrogen, creatinine, aspartate transaminase, alanine transaminase, lactate dehydrogenase, C-reactive protein (CRP), and interleukin-6 levels are useful biomarkers for COVID-19 severity.

The hydrophilic surfactant proteins A and D (SP-A and SP-D) are members of the collectin subgroup in the C-type lectin superfamily. As produced by epithelial alveolar type II and club cells, these pulmonary collectins play important roles in the innate immunity of the lungs (1-4) and have been used as prognostic biomarkers for interstitial lung diseases (ILDs) (5-10) and acute respiratory distress syndrome (11-14). As acute respiratory distress syndrome (11) is the severe complication of COVID-19 pneumonia, serum SP-A and SP-D concentrations may serve as biomarkers for predicting the prognosis. Further, the alveolar type II cells and club cells express the angiotensin converting enzyme ii (ACE2) receptor (15), the target receptor used by severe acute respiratory syndrome–coronavirus-2 (SARS-CoV-2) (16) and SARS-related coronaviruses for entry into the cells (17). Based on these findings, we hypothesized that the serum pulmonary collectin protein levels might change based on the severity of COVID-19 pneumonia. Therefore, this retrospective, single-center study aimed to determine whether SP-A and SP-D concentrations are associated with COVID-19 pneumonia progression and severity and whether they could be used clinically as biomarkers for COVID-19 treatment guidelines. Furthermore, several studies have shown that mannose-binding lectin (MBL) and ficolin, which are similar in vivo soluble lectins, may be related to COVID-19 pathophysiology and are expected as useful biomarkers.

Since laboratory data have always supported clinical decision-making in various infectious diseases, laboratory-based biomarkers should be identified to assess COVID-19. Therefore, this study assessed the association between different lectins, disease severity, and radiographs in patients with COVID-19.

Patients and Methods

Study population. A total of 131 patients with COVID-19 who had been admitted to the Sapporo Medical University Hospital between May 22 and September 19, 2021, were enrolled. A patient with a confirmed COVID-19 diagnosis was defined as positive for real-time reverse-transcriptase polymerase chain reaction assay of nasal swab specimens according to the World Health Organization (WHO) guidelines. The control group comprised 31 healthy volunteers showing no evidence of respiratory disease following a Shihoro-cho health check. This study was conducted following the Declaration of Helsinki and was approved by the hospital’s ethical board (approval number: 322-17), and informed consent was obtained in the form of opt-out on the website.

Data including demographics, medical history, symptoms, signs, laboratory findings, and radiological images were collected from the patients’ medical records. Chest computed tomography (CT) scanning was performed at admission. Patients with COVID-19 were classified into two groups based on the WHO’s categorization of COVID-19 severity.

Samples. SP-A and SP-D were measured based on Shimizu et al. (18) and Nagae et al. (19) methods using commercially available enzyme-linked immunosorbent assay (ELISA) kits purchased from BioVendor (Brno, Czech Republic) and Yamasa Co. (Choshi, Japan), respectively. Moreover, the serum MBL and Ficolin1 (FCN1) levels were measured using ELISA kits purchased from R&D Systems Inc. (Minneapolis, MN, USA) and Hycult Biotech Inc. (Wayne, PA, USA) following the manufacturer’s instructions.

High-resolution computed tomography (HRCT) images were obtained from the lung apex to the base at 5-mm intervals during a suspended full inspiration with participants in a supine position. All HRCT data were reconstructed using a high spatial-frequency algorithm and displayed on the lung parenchymal window [level, −700 Hounsfield units (HU); width, 1,500 HU]. CT images were evaluated in two ways. First, HRCT images were scored for severity using a commercially available three-dimensional medical image processing workstation Ziostation2 purchased from Ziosoft (Tokyo, Japan). The lungs were automatically extracted from CT images using the software, and −700 HU or more was defined as a pneumonia image, and the volume ratio was calculated (Figure 1). Second, HRCT images were scored for severity using a semiquantitative scoring system designed to quantitatively estimate the pulmonary involvement of all abnormalities based on the area involved, as described in previous studies (20,21). Each of the five lung lobes was visually scored from 0 to 5 based on the % involvement as follows: 0, no involvement; 1, <5%; 2, 25%; 3, 26-49%; 4, 50-75%; and 5, >75%. The total CT score was the sum of individual lobar scores, with a range of 0 (no involvement) to 25 (maximum involvement). Among these methods, chest CTs were evaluated by two pulmonologists.

Figure 1. HRCT images were scored for severity using commercially available three-dimensional medical image processing workstation Ziostation2 purchased from Ziosoft (Tokyo, Japan). (A) Raw image data, (B) The lungs were automatically extracted from CT images using the software, (C) −700 HU or more was defined as a pneumonia image, and the volume ratio was calculated. HRCT: High resolution computed tomography.

Figure 1

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Statistical analysis. All statistical analyses were performed using the JMP 15.0 (SAS Institute, Cary, NC, USA) and GraphPad Prism v8 software (GraphPad, Inc., San Diego, CA, USA). Between-group differences were analyzed using the Mann-Whitney U-test. Categorical variables were analyzed using the Chi-squared test. Serum SP-D was further analyzed via the receiver operating characteristic (ROC) curve to determine the appropriate cut-off level using the JMP 13.0, allowing for optimal diagnostic accuracy. To identify correlations between two datasets, simple regression analysis (ρ) was calculated using the JMP 15.0. For all analyses, p<0.05 was considered statistically significant.

Results

The study cohort included 131 patients with COVID-19 admitted to the Sapporo Medical University Hospital from May 22 to September 19, 2021. Blood samples collected from all 131 patients were analyzed. Case severity was classified as severe for patients treated with oxygen therapy and non-severe for those without based on Japan’s original severity classification (19). The median age of patients with COVID-19 was 50 years [interquartile ratio (IQR)=37-60], and 69 (52.7%) of them were men (Table I). The variants included 61 alpha, 41 deltas, and 10 unknown. The number of days since the disease onset is shown in Figure 2. The median was the seventh day, with a delayed tendency for several days in severe patients (Table I). Radiologically, nearly all patients had multilobular ground-glass opacification with a peripheral or posterior distribution. In severe cases, ARDS-like findings, mainly consolidation, were observed in images. To identify any relationships between soluble serum lectins and chest CT images, images were taken on the same day that blood samples were drawn. CT images were evaluated using two evaluation methods described in the Materials and Methods section. The percentage of lung areas of pneumonia evaluated on CT images [CT area (%)] was significantly higher in patients with severe COVID-19 than those with non-severe (19.7±13.3 vs. 4.2±4.6 %, respectively; p<0.01). Similarly, the CT score was significantly higher in the severe group (13.2±4.9 vs. 5.2±3.5, respectively; p<0.01) (Table I).

Table I. Patient characteristics.

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Age is presented as the median [IQR], and other data are presented as mean±SD. The two groups were compared using the Mann-Whitney U-test. Between-group differences in sex were assessed using the chi-squared test. *p<0.05; **p<0.01. IQR, Interquartile range; IFN-λ3, interferon-λ3; IL- 6, interleukin-6; LDH, lactate dehydrogenase; CRP, C-reactive protein.

Figure 2. The number of days since the onset of disease. Right graph showing them separately for non-severe and severe groups.

Figure 2

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Compared to the control group, the COVID-19 group had significantly higher serum SP-A and FCN1 levels on admission (SP-A: 59.60±38.89 vs. 35.61±11.22 ng/ml; p<0.01, FCN1: 542.45±506.04 vs. 250.6±161.1; p<0.01) (Table I and Figure 3A). In analyzing the severe and non-severe groups, the former had significantly higher serum SP-D and lower MBL levels than the latter group (SP-D: 141.7±155.7 vs. 61.41±54.54 ng/ml; p<0.01, MBL: 1,670±1,240 vs. 2,170±1,140 ng/ml; p<0.05) (Figure 3B). Additionally, serum SP-D levels were compared between patients with non-severe and severe COVID-19 using ROC curves. Results of the area under the curve (AUC) comparison between severe and non-severe cases were 0.692. Using ROC curves, the diagnostic cut-off levels were set at 96.1 ng/ml (Figure 4).

Figure 3. Comparison of serum SP-A, SP-D, MBL, and FCN1 levels: (A) between the COVID-19 (closed circle) and control groups (closed square), (B) between non-severe (closed circle) and severe (closed square). Serum SP-A, SP-D, MBL, and FCN1 levels from healthy volunteers and patients with COVID-19 were assessed using ELISA as described in the Materials and Methods section. Data are expressed as mean±SD. Between-group differences were compared using the Mann-Whitney U-test. *p<0.05; **p<0.01. COVID-19: Coronavirus disease 2019; SP-A: surfactant protein A; SP-D: surfactant protein D; MBL: mannose-binding protein; FCN1: ficolin1, M-ficolin.

Figure 3

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Figure 4. ROC curves of the serum SP-D level associated with COVID-19 severity. ROC, Receiver operating characteristic; SP-D: surfactant protein D; COVID-19: coronavirus disease 2019; AUC: area under the curve.

Figure 4

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SP-A and SP-D are lung-specific lectins, and we hypothesized that they might show changes in the degree of COVID-19 pneumonia, as in interstitial pneumonia. To examine the relationship between chest CT images and soluble serum lectins, a simple regression analysis was performed. In this study, two imaging evaluation methods were examined (Figure 5A and B), and SP-D reflected the degree of imaging findings very well using both methods, whereas SP-A showed a significant correlation, albeit slightly weaker than SP-D. Conversely, MBL and FNC1 were not significantly correlated with imaging findings.

Figure 5. (A) Correlation between the lung areas of pneumonia evaluated on CT images [CT area (%)] and serum level of SP-A, SP-D, MBL, and FCN1 as determined by the Simple regression analysis (ρ). (B) HRCT was scored as mentioned in Materials and Methods and examined in the same way above. SP-A: Surfactant protein A; SP-D: surfactant protein D; MBL: mannose-binding protein; FCN1: ficolin1, M-ficolin; HRCT: high resolution computed tomography.

Figure 5

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Discussion

It has been 2 years since COVID-19 affected the world, affecting the lives of many patients and people. COVID-19 infection causes the body to produce many proteins. In fact, Bereabu et al. have shown that administration of convalescent serum improves the clinical findings of COVID-19 (22). Also, several studies on COVID-19 markers have been conducted and published. Since we investigated serum SP-A and SP-D for interstitial pneumonia, these lectins might be useful as COVID-19 markers since the beginning and reported their usefulness as markers worldwide, albeit in a preprint. Therefore, the usefulness of SP-A and SP-D was also discussed in this report. SP-A and SP-D are proteins existing in the alveolar space and are thought to strongly reflect inflammation and increased lung permeability (2), and as shown in the present results, they are particularly strongly associated with CT images compared to other lectins (Figure 5A and B). Moreover, serum SP-D concentrations were significantly higher in severe than in non-severe cases (Figure 3). Pulmonary collectins are lung-specific proteins that may be more sensitive to imaging findings than several reported disease biomarkers (23). Although the timing of the increase was different between SP-A and SP-D, SP-A increases relatively early in interstitial pneumonia; however, its high lipid solubility binds to surfactant lipids and leaks less into the serum (24), and a similar mechanism was considered for COVID-19. Furthermore, it has been reported that inflammation caused by COVID-19 elevates serum IL-6 and IL-6 induces the release of SP-D into the circulation (25). In addition, SP-D has also been reported to eliminate SARS-CoV through direct interaction with viral spike glycoproteins (26). Although these results suggest that SP-D may have a molecular effect on the pathogenesis of COVID-19, the molecular mechanism remains a subject for further investigation.

MBL is a protein produced in the liver affecting innate immunity in the lungs (27). In this study, MBL was lower in patients with severe COVID-19 (Figure 3B). However, it was not correlated with imaging findings as SP-A and SP-D did with results indicating that MBL is a protein produced and secreted by the liver and plays a different role than pulmonary collectin, leaking into the blood due to increased lung permeability. Several reports demonstrated associations between MBL deficiency and increased susceptibility to various infections in newborns, older children/adolescents, and adults (27). Regarding viral infections, Gupta A et al. suggested that antiviral mannose-binding lectins offer potential applications in the prevention and control of viral infections (28). As shown in this study, patients with more severe diseases had lower MBL levels upon admission. MBL is possibly consumed by activating the complement system, resulting in low levels, or low MBL levels may be a factor in COVID-19 severity. Although this point needs further verification, Speletas et al. interestingly reported that the MBL deficiency-causing B allele is a risk factor for severe COVID-19 (29).

Ficolins are collectins structurally and functionally associated with MBL and are either present in the serum or expressed in tissues, including the lung (27). Ficolins play a role in the innate immune defense as pathogen-associated molecular pattern recognition molecules (30). Three ficolins are found in humans: M-ficolin (FCN1), L-ficolin (FCN2) and H-ficolin (FCN3). The cells producing them differ, and their role in innate immunity is slightly different. In infectious diseases, many studies reported FCN2 and FCN3; however, only a few studies have been conducted on FCN1. In our preliminary experiment, serum FCN2 levels were examined in patients with COVID-19; however, no significant correlation was observed between the disease severity and CT images (data not shown). FCN1 is a lectin produced and secreted by macrophages. The fact that serum FCN1 levels were higher than that of healthy patients is highly suggestive of inflammatory changes associated with viral infection. However, its level is not significantly increased even in patients with severe COVID-19, and its clinical significance needs further investigation.

The current study had certain limitations. First, the study population was small, and the study design was retrospective. Second, as the study was conducted using surplus clinical specimens, the association between additional complement systems and various cytokines was not examined. We hope to clarify these in future studies.

Although the omicron variant has become the mainstream and the COVID-19 severity is trending downwards, infection epidemics will continue to recur. Therefore, we believe that these disease markers should be used to assess disease status and provide patients with the treatment they need. Thus, serum SP-A and SP-D levels were significantly correlated with CT findings for each patient, whereas that of MBL and FCN1 did not. Among the soluble serum lectins, pulmonary collectins are useful biomarkers of COVID-19.

Conflicts of Interest

None of the Authors have conflicts of interest to declare.

Authors’ Contributions

AS and KK developed the study design. HT and AS performed the experiments, analyzed and interpreted the data, and wrote the manuscript. KM, ST, and HC assisted with data analysis and interpretation and supervised the statistical analysis. All Authors read and approved the final manuscript.

Acknowledgements

This work was supported by Sapporo Medical University research grant 2020 (to A.S.)

References

  • 1.Kuroki Y, Voelker DR. Pulmonary surfactant proteins. J Biol Chem. 1994;269(42):25943–25946. [PubMed] [Google Scholar]
  • 2.Kuroki Y, Takahashi M, Nishitani C. Pulmonary collectins in innate immunity of the lung. Cell Microbiol. 2007;9(8):1871–1879. doi: 10.1111/j.1462-5822.2007.00953.x. [DOI] [PubMed] [Google Scholar]
  • 3.Sawada K, Ariki S, Kojima T, Saito A, Yamazoe M, Nishitani C, Shimizu T, Takahashi M, Mitsuzawa H, Yokota S, Sawada N, Fujii N, Takahashi H, Kuroki Y. Pulmonary collectins protect macrophages against pore-forming activity of Legionella pneumophila and suppress its intracellular growth. J Biol Chem. 2010;285(11):8434–8443. doi: 10.1074/jbc.M109.074765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Ariki S, Kojima T, Gasa S, Saito A, Nishitani C, Takahashi M, Shimizu T, Kurimura Y, Sawada N, Fujii N, Kuroki Y. Pulmonary collectins play distinct roles in host defense against Mycobacterium avium. J Immunol. 2011;187(5):2586–2594. doi: 10.4049/jimmunol.1100024. [DOI] [PubMed] [Google Scholar]
  • 5.Kohno N, Awaya Y, Oyama T, Yamakido M, Akiyama M, Inoue Y, Yokoyama A, Hamada H, Fujioka S, Hiwada K. KL-6, a mucin-like glycoprotein, in bronchoalveolar lavage fluid from patients with interstitial lung disease. Am Rev Respir Dis. 1993;148(3):637–642. doi: 10.1164/ajrccm/148.3.637. [DOI] [PubMed] [Google Scholar]
  • 6.Kuroki Y, Tsutahara S, Shijubo N, Takahashi H, Shiratori M, Hattori A, Honda Y, Abe S, Akino T. Elevated levels of lung surfactant protein A in sera from patients with idiopathic pulmonary fibrosis and pulmonary alveolar proteinosis. Am Rev Respir Dis. 1993;147(3):723–729. doi: 10.1164/ajrccm/147.3.723. [DOI] [PubMed] [Google Scholar]
  • 7.Takahashi H, Kuroki Y, Tanaka H, Saito T, Kurokawa K, Chiba H, Sagawa A, Nagae H, Abe S. Serum levels of surfactant proteins A and D are useful biomarkers for interstitial lung disease in patients with progressive systemic sclerosis. Am J Respir Crit Care Med. 2000;162(1):258–263. doi: 10.1164/ajrccm.162.1.9903014. [DOI] [PubMed] [Google Scholar]
  • 8.Takahashi H, Fujishima T, Koba H, Murakami S, Kurokawa K, Shibuya Y, Shiratori M, Kuroki Y, Abe S. Serum surfactant proteins A and D as prognostic factors in idiopathic pulmonary fibrosis and their relationship to disease extent. Am J Respir Crit Care Med. 2000;162(3 Pt 1):1109–1114. doi: 10.1164/ajrccm.162.3.9910080. [DOI] [PubMed] [Google Scholar]
  • 9.Takahashi H, Imai Y, Fujishima T, Shiratori M, Murakami S, Chiba H, Kon H, Kuroki Y, Abe S. Diagnostic significance of surfactant proteins A and D in sera from patients with radiation pneumonitis. Eur Respir J. 2001;17(3):481–487. doi: 10.1183/09031936.01.17304810. [DOI] [PubMed] [Google Scholar]
  • 10.Okamoto T, Fujii M, Furusawa H, Tsuchiya K, Miyazaki Y, Inase N. The usefulness of KL-6 and SP-D for the diagnosis and management of chronic hypersensitivity pneumonitis. Respir Med. 2015;109(12):1576–1581. doi: 10.1016/j.rmed.2015.10.005. [DOI] [PubMed] [Google Scholar]
  • 11.Dhindsa S, Zhang N, McPhaul MJ, Wu Z, Ghoshal AK, Erlich EC, Mani K, Randolph GJ, Edwards JR, Mudd PA, Diwan A. Association of circulating sex hormones with inflammation and disease severity in patients with COVID-19. JAMA Netw Open. 2021;4(5):e2111398. doi: 10.1001/jamanetworkopen.2021.11398. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Sato H, Callister ME, Mumby S, Quinlan GJ, Welsh KI, duBois RM, Evans TW. KL-6 levels are elevated in plasma from patients with acute respiratory distress syndrome. Eur Respir J. 2004;23(1):142–145. doi: 10.1183/09031936.03.00070303. [DOI] [PubMed] [Google Scholar]
  • 13.Greene KE, Wright JR, Steinberg KP, Ruzinski JT, Caldwell E, Wong WB, Hull W, Whitsett JA, Akino T, Kuroki Y, Nagae H, Hudson LD, Martin TR. Serial changes in surfactant-associated proteins in lung and serum before and after onset of ARDS. Am J Respir Crit Care Med. 1999;160(6):1843–1850. doi: 10.1164/ajrccm.160.6.9901117. [DOI] [PubMed] [Google Scholar]
  • 14.Eisner MD, Parsons P, Matthay MA, Ware L, Greene K, Acute Respiratory Distress Syndrome Network Plasma surfactant protein levels and clinical outcomes in patients with acute lung injury. Thorax. 2003;58(11):983–988. doi: 10.1136/thorax.58.11.983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Wiener RS, Cao YX, Hinds A, Ramirez MI, Williams MC. Angiotensin converting enzyme 2 is primarily epithelial and is developmentally regulated in the mouse lung. J Cell Biochem. 2007;101(5):1278–1291. doi: 10.1002/jcb.21248. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL, Chen HD, Chen J, Luo Y, Guo H, Jiang RD, Liu MQ, Chen Y, Shen XR, Wang X, Zheng XS, Zhao K, Chen QJ, Deng F, Liu LL, Yan B, Zhan FX, Wang YY, Xiao GF, Shi ZL. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270–273. doi: 10.1038/s41586-020-2012-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Mossel EC, Wang J, Jeffers S, Edeen KE, Wang S, Cosgrove GP, Funk CJ, Manzer R, Miura TA, Pearson LD, Holmes KV, Mason RJ. SARS-CoV replicates in primary human alveolar type II cell cultures but not in type I-like cells. Virology. 2008;372(1):127–135. doi: 10.1016/j.virol.2007.09.045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Shimizu H, Hosoda K, Mizumoto M, Kuroki Y, Sato H, Kataoka K, Hagisawa M, Fujimoto S, Akino T. Improved immunoassay for the determination of surfactant protein A (SP-A) in human amniotic fluid. Tohoku J Exp Med. 1989;157(3):269–278. doi: 10.1620/tjem.157.269. [DOI] [PubMed] [Google Scholar]
  • 19.Nagae H, Takahashi H, Kuroki Y, Honda Y, Nagata A, Ogasawara Y, Abe S, Akino T. Enzyme-linked immunosorbent assay using F(ab’)2 fragment for the detection of human pulmonary surfactant protein D in sera. Clin Chim Acta. 1997;266(2):157–171. doi: 10.1016/s0009-8981(97)00124-1. [DOI] [PubMed] [Google Scholar]
  • 20.Chang YC, Yu CJ, Chang SC, Galvin JR, Liu HM, Hsiao CH, Kuo PH, Chen KY, Franks TJ, Huang KM, Yang PC. Pulmonary sequelae in convalescent patients after severe acute respiratory syndrome: evaluation with thin-section CT. Radiology. 2005;236(3):1067–1075. doi: 10.1148/radiol.2363040958. [DOI] [PubMed] [Google Scholar]
  • 21.Pan F, Ye T, Sun P, Gui S, Liang B, Li L, Zheng D, Wang J, Hesketh RL, Yang L, Zheng C. Time course of lung changes at chest CT during recovery from Coronavirus disease 2019 (COVID-19) Radiology. 2020;295(3):715–721. doi: 10.1148/radiol.2020200370. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Bereanu A, Crisan O, Constantin AM, Cainap S, Cainap C, Dragulescu R, Bereanu R, Vintila B, Roman C, Sava M. The effect of convalescent plasma in patients with Covid-19 in intensive care unit. In Vivo. 2022;36(3):1342–1348. doi: 10.21873/invivo.12836. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Tong M, Xiong Y, Zhu C, Xu H, Zheng Q, Jiang Y, Zou L, Xiao X, Chen F, Yan X, Hu C, Zhu Y. Serum surfactant protein D in COVID-19 is elevated and correlated with disease severity. BMC Infect Dis. 2021;21(1):737. doi: 10.1186/s12879-021-06447-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Nishikiori H, Chiba H, Ariki S, Kuronuma K, Otsuka M, Shiratori M, Ikeda K, Watanabe A, Kuroki Y, Takahashi H. Distinct compartmentalization of SP-A and SP-D in the vasculature and lungs of patients with idiopathic pulmonary fibrosis. BMC Pulm Med. 2014;14:196. doi: 10.1186/1471-2466-14-196. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Kurt A, Turut H, Acipayam A, Kirbas A, Yuce S, Cumhur Cure M, Cure E. Investigation of surfactant protein-D and interleukin-6 levels in patients with blunt chest trauma with multiple rib fractures and pulmonary contusions: a cross-sectional study in Black Sea Region of Turkey. BMJ Open. 2016;6(10):e011797. doi: 10.1136/bmjopen-2016-011797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Leth-Larsen R, Zhong F, Chow VT, Holmskov U, Lu J. The SARS coronavirus spike glycoprotein is selectively recognized by lung surfactant protein D and activates macrophages. Immunobiology. 2007;212(3):201–211. doi: 10.1016/j.imbio.2006.12.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Eisen DP. Mannose-binding lectin deficiency and respiratory tract infection. J Innate Immun. 2010;2(2):114–122. doi: 10.1159/000228159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Gupta A, Gupta GS. Status of mannose-binding lectin (MBL) and complement system in COVID-19 patients and therapeutic applications of antiviral plant MBLs. Mol Cell Biochem. 2021;476(8):2917–2942. doi: 10.1007/s11010-021-04107-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Speletas M, Dadouli K, Syrakouli A, Gatselis N, Germanidis G, Mouchtouri VA, Koulas I, Samakidou A, Nikolaidou A, Stefos A, Mimtsoudis I, Hatzianastasiou S, Koureas M, Anagnostopoulos L, Tseroni M, Tsinti G, Metallidis S, Dalekos G, Hadjichristodoulou C. MBL deficiency-causing B allele (rs1800450) as a risk factor for severe COVID-19. Immunobiology. 2021;226(6):152136. doi: 10.1016/j.imbio.2021.152136. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Endo Y, Matsushita M, Fujita T. Role of ficolin in innate immunity and its molecular basis. Immunobiology. 2007;212(4-5):371–379. doi: 10.1016/j.imbio.2006.11.014. [DOI] [PubMed] [Google Scholar]

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