Mannose binding lectin gene 2 (rs1800450) missense variant may contribute to development and severity of COVID-19 infection

Medetalibeyoğlu, Alpay; Bahat, Gülistan; Şenkal, Naci; Köse, Murat; Avci, Kader; Sayın, Gözde Yeşil; İşoğlu-Alkaç, Ümmühan; Tükek, Tufan; Pehlıvan, Sacide

doi:10.1016/j.meegid.2021.104717

Cited by 36 publications

(44 citation statements)

References 34 publications

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“…We investigated the possible role of MBL2 genetic variants in determining susceptibility to severe COVID-19 with respiratory failure, by exploiting the statistical power provided by haplotype analysis. Surprisingly and in contrast with a previous study (Medetalibeyoglu et al, 2021), we found only a borderline correlation between one haplotype of the 6 SNPs associated with MBL levels and frequency of severe COVID-19 cases. However, we found a total of 7 significantly associated haplotypes, distributed along the MBL2 genomic region, often mapping in correspondence of regulatory elements (such as enhancers, promoter region, histone marks; Figure 6).…”

Section: Discussioncontrasting

confidence: 99%

“…In SARS, conflicting results have been reported concerning the relevance of MBL2 genetic variants in this condition (Ip et al, 2005; Yuan et al, 2005; Zhang et al, 2005). In COVID-19, one MBL2 SNP has been associated with development and severity of the infection (Medetalibeyoglu et al, 2021). We investigated the possible role of MBL2 genetic variants in determining susceptibility to severe COVID-19 with respiratory failure, by exploiting the statistical power provided by haplotype analysis.…”

Section: Discussionmentioning

confidence: 99%

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Recognition and inhibition of SARS-CoV-2 by humoral innate immunity pattern recognition molecules

Stravalaci

Pagani

Paraboschi

et al. 2021

Preprint

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The humoral arm of innate immunity includes diverse molecules with antibody-like functions, some of which serve as disease severity biomarkers in COVID-19. The present study was designed to conduct a systematic investigation of the interaction of humoral fluid phase pattern recognition molecules (PRM) with SARS-CoV-2. Out of 10 PRM tested, the long pentraxin PTX3 and Mannose Binding Lectin (MBL) bound the viral Nucleoprotein and Spike, respectively. MBL bound trimeric Spike, including that of variants of concern, in a glycan-dependent way and inhibited SARS-CoV-2 in three in vitro models. Moreover, upon binding to Spike, MBL activated the lectin pathway of complement activation. Genetic polymorphisms at the MBL locus were associated with disease severity. These results suggest that selected humoral fluid phase PRM can play an important role in resistance to, and pathogenesis of, COVID-19, a finding with translational implications.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Recognition and inhibition of SARS-CoV-2 by humoral innate immunity pattern recognition molecules

Stravalaci

Pagani

Paraboschi

et al. 2021

Preprint

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“…In this context, Tu et al reported that the presence of the B allele of the MBL2 gene was significantly associated with an increased risk of SARS ( Tu et al, 2015 ), although in another study from Hong-Kong with 180 SARS patients, such an association was not confirmed ( Yuan et al, 2005 ). Considering COVID-19, Medetalibeyoglu et al recently reported that the presence of the B allele was significantly associated with a higher risk for severe disease and the need of ICU care ( Medetalibeyoglu et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…Conversely, the B allele of the MBL2 gene is the more common polymorphism affecting MBL serum levels in humans, leading several studies to focus solely in its study ( Medetalibeyoglu et al, 2021 , Tu et al, 2015 ). For example, while genetic MBL deficiency was not considered a major risk factor for chronic obstructive pulmonary disease (COPD) ( Dahl and Nordestgaard, 2009 ), the presence of the deficiency-causing B allele has been associated with 4.9 times increased odds of hospital admission due to infection-induced COPD exacerbations bearing a worse outcome ( Lin et al, 2011 , Yang et al, 2003 ).…”

Section: Discussionmentioning

confidence: 99%

MBL deficiency-causing B allele (rs1800450) as a risk factor for severe COVID-19

et al. 2021

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The COVID-19 pandemic represents one of the greatest challenges in modern medicine. The disease is characterized by a variable clinical phenotype, ranging from asymptomatic carriage to severe and/or critical disease, which bears poor prognosis and outcome because of the development of severe acute respiratory distress syndrome (SARS) requiring ICU hospitalization, multi-organ failure and death. Therefore, the determination of risk factors predisposing to disease phenotype is of outmost importance. The aim of our study was to evaluate which predisposing factors, including MBL2 genotyping, affected clinical phenotype in 264 COVID-19 patients. We demonstrated that older age along with underlying comorbidities, primarily obesity, chronic inflammatory disorders and diabetes mellitus, represent the most important risk factors related to hospitalization, the development of pneumonia and SARS. Moreover, we found that the presence of the MBL deficiency-causing B allele (rs1800450) was significantly associated with almost 2-fold increased risk for developing pneumonia and requiring hospitalization , suggesting its usage as a molecular predictor of severe disease in SARS-CoV-2 infected individuals.

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“…However, false-negative nasopharyngeal tests for SARS-CoV-2 were frequently reported during the early phases of the pandemic [ 25 ]. Individual susceptibility factors to severe clinical course, including genetic polymorphisms that have a known relationship with COVID-19-related mortality [ 51 , 52 ], were not investigated.…”

Section: Discussionmentioning

confidence: 99%

The Clinical Significance of Procalcitonin Elevation in Patients over 75 Years Old Admitted for COVID-19 Pneumonia

Ticinesi

Nouvenne

Prati

et al. 2021

Mediators of Inflammation

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Aim. To investigate the clinical significance of procalcitonin (PCT) elevation on hospital admission for coronavirus disease-19 (COVID-19) and its association with mortality in oldest old patients ( age > 75 years ). Methods. The clinical records of 1074 patients with chest high-resolution computed-tomography (HRCT) positive for interstitial pneumonia and symptoms compatible for COVID-19, hospitalized in medical wards during the first pandemic wave in a single academic center in Northern Italy, were retrospectively analyzed. All patients had serum PCT testing performed within six hours from admission. Information on COVID-19-related symptoms, comorbidities, drugs, autonomy in daily activities, respiratory exchanges, other routine lab tests, and outcomes were collected. Clinical characteristics were compared across different admission PCT levels and ages. The association of admission PCT with mortality was tested separately in participants aged > 75 and ≤75 years old by stepwise multivariate Cox regression model with forward selection. Results. With increasing classes of PCT levels (<0.05, 0.05-0.49, 0.5-1.99, and ≥2 ng/ml), there was a significant trend ( P < 0.0001 ) towards older age, male gender, wider extension of lung involvement on HRCT, worse respiratory exchanges, and several other laboratory abnormalities. Each incremental PCT class was associated with increased risk of hospital death at multivariate models in subjects older than 75 (hazard ratio for PCT ≥ 2 vs. <0.05 ng/ml: 30.629, 95% confidence interval 4.176-224.645, P = 0.001 ), but not in subjects aged 75 or younger. Conclusions. In patients admitted for COVID-19, PCT elevation was associated with several clinical, radiological, and laboratory characteristics of disease severity. However, PCT elevation was strongly associated with hospital mortality only in oldest old subjects ( age > 75 ).

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Mannose binding lectin gene 2 (rs1800450) missense variant may contribute to development and severity of COVID-19 infection

Cited by 36 publications

References 34 publications

Recognition and inhibition of SARS-CoV-2 by humoral innate immunity pattern recognition molecules

Recognition and inhibition of SARS-CoV-2 by humoral innate immunity pattern recognition molecules

MBL deficiency-causing B allele (rs1800450) as a risk factor for severe COVID-19

The Clinical Significance of Procalcitonin Elevation in Patients over 75 Years Old Admitted for COVID-19 Pneumonia

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