Inhalation of Low Molecular Weight Heparins as Prophylaxis against SARS-CoV-2
ABSTRACT New SARS-CoV-2 variants of concern and waning immunity demonstrate the need for a quick and simple prophylactic agent to prevent infection. Low molecular weight heparins (LMWH) are potent inhibitors of SARS-CoV-2 binding and infection in vitro. The airways are a major route for infection an...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2022-12-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mbio.02558-22 |
| _version_ | 1811289978437632000 |
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| author | Julia Eder Marta Bermejo-Jambrina Killian E. Vlaming Tanja M. Kaptein Viktoria Zaderer E. Marleen Kemper Doris Wilflingseder Sietze Reitsma Godelieve J. de Bree Danny M. Cohn Teunis B. H. Geijtenbeek |
| author_facet | Julia Eder Marta Bermejo-Jambrina Killian E. Vlaming Tanja M. Kaptein Viktoria Zaderer E. Marleen Kemper Doris Wilflingseder Sietze Reitsma Godelieve J. de Bree Danny M. Cohn Teunis B. H. Geijtenbeek |
| author_sort | Julia Eder |
| collection | DOAJ |
| description | ABSTRACT New SARS-CoV-2 variants of concern and waning immunity demonstrate the need for a quick and simple prophylactic agent to prevent infection. Low molecular weight heparins (LMWH) are potent inhibitors of SARS-CoV-2 binding and infection in vitro. The airways are a major route for infection and therefore inhaled LMWH could be a prophylactic treatment against SARS-CoV-2. We investigated the efficacy of in vivo inhalation of LMWH in humans to prevent SARS-CoV-2 attachment to nasal epithelial cells in a single-center, open-label intervention study. Volunteers received enoxaparin in the right and a placebo (NaCl 0.9%) in the left nostril using a nebulizer. After application, nasal epithelial cells were retrieved with a brush for ex-vivo exposure to either SARS-CoV-2 pseudovirus or an authentic SARS-CoV-2 isolate and virus attachment as determined. LMWH inhalation significantly reduced attachment of SARS-CoV-2 pseudovirus as well as authentic SARS-CoV-2 to human nasal cells. Moreover, in vivo inhalation was as efficient as in vitro LMWH application. Cell phenotyping revealed no differences between placebo and treatment groups and no adverse events were observed in the study participants. Our data strongly suggested that inhalation of LMWH was effective to prevent SARS-CoV-2 attachment and subsequent infection. LMWH is ubiquitously available, affordable, and easy to apply, making them suitable candidates for prophylactic treatment against SARS-CoV-2. IMPORTANCE New SARS-CoV-2 variants of concern and waning immunity demonstrate the need for a quick and simple agent to prevent infection. Low molecular weight heparins (LMWH) have been shown to inhibit SARS-CoV-2 in experimental settings. The airways are a major route for SARS-CoV-2 infection and inhaled LMWH could be a prophylactic treatment. We investigated the efficacy of inhalation of the LMWH enoxaparin in humans to prevent SARS-CoV-2 attachment because this is a prerequisite for infection. Volunteers received enoxaparin in the right and a placebo in the left nostril using a nebulizer. Subsequently, nasal epithelial cells were retrieved with a brush and exposed to SARS-CoV-2. LMWH inhalation significantly reduced the binding of SARS-Cov-2 to human nasal cells. Cell phenotyping revealed no differences between placebo and treatment groups and no adverse events were observed in the participants. Our data indicated that LMWH can be used to block SARS-CoV-2 attachment to nasal cells. LMWH was ubiquitously available, affordable, and easily applicable, making them excellent candidates for prophylactic treatment against SARS-CoV-2. |
| first_indexed | 2024-04-13T04:04:52Z |
| format | Article |
| id | doaj.art-be136ae2d1a34d2388548dd0bfd91721 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-04-13T04:04:52Z |
| publishDate | 2022-12-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-be136ae2d1a34d2388548dd0bfd917212022-12-22T03:03:22ZengAmerican Society for MicrobiologymBio2150-75112022-12-0113610.1128/mbio.02558-22Inhalation of Low Molecular Weight Heparins as Prophylaxis against SARS-CoV-2Julia Eder0Marta Bermejo-Jambrina1Killian E. Vlaming2Tanja M. Kaptein3Viktoria Zaderer4E. Marleen Kemper5Doris Wilflingseder6Sietze Reitsma7Godelieve J. de Bree8Danny M. Cohn9Teunis B. H. Geijtenbeek10Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam, The NetherlandsDepartment of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam, The NetherlandsDepartment of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam, The NetherlandsDepartment of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam, The NetherlandsInstitute of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, AustriaDepartment of Pharmacy and Clinical Pharmacology, Amsterdam UMC, University of Amsterdam, Amsterdam, The NetherlandsInstitute of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, AustriaDepartment of Otorhinolaryngology, Amsterdam UMC, University of Amsterdam, Amsterdam, The NetherlandsAmsterdam Institute for Infection and Immunity, Amsterdam, The NetherlandsDepartment of Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The NetherlandsDepartment of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam, The NetherlandsABSTRACT New SARS-CoV-2 variants of concern and waning immunity demonstrate the need for a quick and simple prophylactic agent to prevent infection. Low molecular weight heparins (LMWH) are potent inhibitors of SARS-CoV-2 binding and infection in vitro. The airways are a major route for infection and therefore inhaled LMWH could be a prophylactic treatment against SARS-CoV-2. We investigated the efficacy of in vivo inhalation of LMWH in humans to prevent SARS-CoV-2 attachment to nasal epithelial cells in a single-center, open-label intervention study. Volunteers received enoxaparin in the right and a placebo (NaCl 0.9%) in the left nostril using a nebulizer. After application, nasal epithelial cells were retrieved with a brush for ex-vivo exposure to either SARS-CoV-2 pseudovirus or an authentic SARS-CoV-2 isolate and virus attachment as determined. LMWH inhalation significantly reduced attachment of SARS-CoV-2 pseudovirus as well as authentic SARS-CoV-2 to human nasal cells. Moreover, in vivo inhalation was as efficient as in vitro LMWH application. Cell phenotyping revealed no differences between placebo and treatment groups and no adverse events were observed in the study participants. Our data strongly suggested that inhalation of LMWH was effective to prevent SARS-CoV-2 attachment and subsequent infection. LMWH is ubiquitously available, affordable, and easy to apply, making them suitable candidates for prophylactic treatment against SARS-CoV-2. IMPORTANCE New SARS-CoV-2 variants of concern and waning immunity demonstrate the need for a quick and simple agent to prevent infection. Low molecular weight heparins (LMWH) have been shown to inhibit SARS-CoV-2 in experimental settings. The airways are a major route for SARS-CoV-2 infection and inhaled LMWH could be a prophylactic treatment. We investigated the efficacy of inhalation of the LMWH enoxaparin in humans to prevent SARS-CoV-2 attachment because this is a prerequisite for infection. Volunteers received enoxaparin in the right and a placebo in the left nostril using a nebulizer. Subsequently, nasal epithelial cells were retrieved with a brush and exposed to SARS-CoV-2. LMWH inhalation significantly reduced the binding of SARS-Cov-2 to human nasal cells. Cell phenotyping revealed no differences between placebo and treatment groups and no adverse events were observed in the participants. Our data indicated that LMWH can be used to block SARS-CoV-2 attachment to nasal cells. LMWH was ubiquitously available, affordable, and easily applicable, making them excellent candidates for prophylactic treatment against SARS-CoV-2.https://journals.asm.org/doi/10.1128/mbio.02558-22low molecular weight heparinSARS-CoV-2infection preventionvirus-host interactions |
| spellingShingle | Julia Eder Marta Bermejo-Jambrina Killian E. Vlaming Tanja M. Kaptein Viktoria Zaderer E. Marleen Kemper Doris Wilflingseder Sietze Reitsma Godelieve J. de Bree Danny M. Cohn Teunis B. H. Geijtenbeek Inhalation of Low Molecular Weight Heparins as Prophylaxis against SARS-CoV-2 mBio low molecular weight heparin SARS-CoV-2 infection prevention virus-host interactions |
| title | Inhalation of Low Molecular Weight Heparins as Prophylaxis against SARS-CoV-2 |
| title_full | Inhalation of Low Molecular Weight Heparins as Prophylaxis against SARS-CoV-2 |
| title_fullStr | Inhalation of Low Molecular Weight Heparins as Prophylaxis against SARS-CoV-2 |
| title_full_unstemmed | Inhalation of Low Molecular Weight Heparins as Prophylaxis against SARS-CoV-2 |
| title_short | Inhalation of Low Molecular Weight Heparins as Prophylaxis against SARS-CoV-2 |
| title_sort | inhalation of low molecular weight heparins as prophylaxis against sars cov 2 |
| topic | low molecular weight heparin SARS-CoV-2 infection prevention virus-host interactions |
| url | https://journals.asm.org/doi/10.1128/mbio.02558-22 |
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