Pulmonary Surfactant Proteins Are Inhibited by Immunoglobulin A Autoantibodies in Severe COVID-19

Sinnberg, Tobias; Lichtensteiger, Christa; Ali, Omar Hasan; Pop, Oltin T.; Jochum, Ann-Kristin; Risch, Lorenz; Brugger, Silvio D.; Velić, Ana; Bomze, David; Köhler, Philipp; Vernazza, Pietro; Albrich, Werner C.; Kahlert, Christian; Abdou, Maire-Therese; Wyss, Nina; Hofmeister, Kathrin; Niessner, Heike; Zinner, Carl; Gilardi, Mara; Tzankov, Alexandar; Röcken, Martin; Dulovic, Alex; Shambat, Srikanth Mairpady; Ruétalo, Natalia; Buehler, Philipp K.; Scheier, Thomas; Jochum, Wolfram; Kern, Lukas; Henz, Samuel; Schneider, Tino; Kuster, Gabriela M.; Lampart, Maurin; Siegemund, Martin; Bingisser, Roland; Schindler, Michael; Schneiderhan‐Marra, Nicole; Kalbacher, Hubert; McCoy, Kathy D.; Spengler, Werner; Brutsche, Martin; Maček, Boris; Twerenbold, Raphael; Penninger, Josef; Matter, Matthias S.; Flatz, Lukas

doi:10.1164/rccm.202201-0011oc

Cited by 19 publications

(15 citation statements)

References 44 publications

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“…There are some reports that surfactant production is altered during COVID-19 infection (56,57). Sinnberg et al demonstrated that IgA autoantibodies to pulmonary surfactant proteins B and C are detectable in patients with COVID-19 and that these autoantibodies impair the ability of pulmonary surfactant to decrease surface tension (56). However, we do not know if such a phenomenon is present after COVID-19 vaccination.…”

Section: Discussionmentioning

confidence: 99%

Exhaled aerosols among PCR-confirmed SARS-CoV-2-infected children

Schuchmann

Scheuch²,

Naumann³

et al. 2023

Front. Pediatr.

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BackgroundAvailable data on aerosol emissions among children and adolescents during spontaneous breathing are limited. Our aim was to gain insight into the role of children in the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and whether aerosol measurements among children can be used to help detect so-called superspreaders—infected individuals with extremely high numbers of exhaled aerosol particles.MethodsIn this prospective study, the aerosol concentrations of SARS-CoV-2 PCR-positive and SARS-CoV-2 PCR-negative children and adolescents (2–17 years) were investigated. All subjects were asked about their current health status and medical history. The exhaled aerosol particle counts of PCR-negative and PCR-positive subjects were measured using the Resp-Aer-Meter (Palas GmbH, Karlsruhe, Germany) and compared using linear regression.ResultsA total of 250 children and adolescents were included in this study, 105 of whom were SARS-CoV-2 positive and 145 of whom were SARS-CoV-2 negative. The median age in both groups was 9 years (IQR 7–11 years). A total of 124 (49.6%) participants were female, and 126 (50.4%) participants were male. A total of 81.9% of the SARS-CoV-2-positive group had symptoms of viral infection. The median particle count of all individuals was 79.55 particles/liter (IQR 44.55–141.15). There was a tendency for older children to exhale more particles (1–5 years: 79.54 p/L; 6–11 years: 77.96 p/L; 12–17 years: 98.63 p/L). SARS-CoV-2 PCR status was not a bivariate predictor (t = 0.82, p = 0.415) of exhaled aerosol particle count; however, SARS-CoV-2 status was shown to be a significant predictor in a multiple regression model together with age, body mass index (BMI), COVID-19 vaccination, and past SARS-CoV-2 infection (t = 2.81, p = 0.005). COVID-19 vaccination status was a highly significant predictor of exhaled aerosol particles (p < .001).ConclusionDuring SARS-CoV-2 infection, children and adolescents did not have elevated aerosol levels. In addition, no superspreaders were found.

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Section: Discussionmentioning

confidence: 99%

Exhaled aerosols among PCR-confirmed SARS-CoV-2-infected children

Schuchmann

Scheuch²,

Naumann³

et al. 2023

Front. Pediatr.

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“…588,589 Antibodies against these proteins can also interfere with surfactant function. 590 Large amounts of surfactant are taken up and degraded by invading neutrophils, further increasing the deficit. 591 One of the complicating factors translating these mechanisms to the in vivo situation is that measurements of inhibition include the formation of a surface film, whereas, as noted above in our model of surfactant function, within the lungs the surface film is generated during adsorption at birth and maintained throughout life.…”

Section: 541mentioning

confidence: 99%

“…This then leads to the altered biophysical properties of this material, which are detectable in vitro. The synthesis and turnover of surfactant components such as SP-B and SP-C can be altered, leading to lower levels. , Antibodies against these proteins can also interfere with surfactant function . Large amounts of surfactant are taken up and degraded by invading neutrophils, further increasing the deficit .…”

Section: What Do Physiological and Pathophysiological Studies Teach U...mentioning

confidence: 99%

Pulmonary Surfactant: A Mighty Thin Film

Possmayer,

Zuo,

Veldhuizen

et al. 2023

Chem. Rev.

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Pulmonary surfactant is a critical component of lung function in healthy individuals. It functions in part by lowering surface tension in the alveoli, thereby allowing for breathing with minimal effort. The prevailing thinking is that low surface tension is attained by a compression-driven squeeze-out of unsaturated phospholipids during exhalation, forming a film enriched in saturated phospholipids that achieves surface tensions close to zero. A thorough review of past and recent literature suggests that the compression-driven squeeze-out mechanism may be erroneous. Here, we posit that a surfactant film enriched in saturated lipids is formed shortly after birth by an adsorptiondriven sorting process and that its composition does not change during normal breathing. We provide biophysical evidence for the rapid formation of an enriched film at high surfactant concentrations, facilitated by adsorption structures containing hydrophobic surfactant proteins. We examine biophysical evidence for and against the compressiondriven squeeze-out mechanism and propose a new model for surfactant function. The proposed model is tested against existing physiological and pathophysiological evidence in neonatal and adult lungs, leading to ideas for biophysical research, that should be addressed to establish the physiological relevance of this new perspective on the function of the mighty thin film that surfactant provides.

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“…How ALF influences SARS-CoV-2 infection is mostly unknown. However, patients with severe COVID-19 sometimes harbor IgA autoantibodies against pulmonary SP-B and SP-C, blocking the function of the lung surfactant lipid layer and potentially contributing to alveolar collapse and poor oxygenation ( 125 ). Other studies indicate that levels of SP-D in blood could be used as a biomarker for COVID-19 severity as a result of the impairment of the pulmonary barrier caused by prolonged inflammation ( 126 ).…”

Section: Lung Environment In the Elderly In The Context Of Tb And Cov...mentioning

confidence: 99%

Tuberculosis and COVID-19 in the elderly: factors driving a higher burden of disease

Allué-Guardia,

Torrelles,

Sigal

2023

Front. Immunol.

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Mycobacterium tuberculosis (M.tb) and SARS-CoV-2 are both infections that can lead to severe disease in the lower lung. However, these two infections are caused by very different pathogens (Mycobacterium vs. virus), they have different mechanisms of pathogenesis and immune response, and differ in how long the infection lasts. Despite the differences, SARS-CoV-2 and M.tb share a common feature, which is also frequently observed in other respiratory infections: the burden of disease in the elderly is greater. Here, we discuss possible reasons for the higher burden in older adults, including the effect of co-morbidities, deterioration of the lung environment, auto-immunity, and a reduced antibody response. While the answer is likely to be multifactorial, understanding the main drivers across different infections may allow us to design broader interventions that increase the health-span of older people.

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Pulmonary Surfactant Proteins Are Inhibited by Immunoglobulin A Autoantibodies in Severe COVID-19

Cited by 19 publications

References 44 publications

Exhaled aerosols among PCR-confirmed SARS-CoV-2-infected children

Exhaled aerosols among PCR-confirmed SARS-CoV-2-infected children

Pulmonary Surfactant: A Mighty Thin Film

Tuberculosis and COVID-19 in the elderly: factors driving a higher burden of disease

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