ABSTRACT
The current pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and outbreaks of new variants highlight the need for preventive treatments. Here, we identified heparan sulfate proteoglycans as attachment receptors for SARS-CoV-2. Notably, neutralizing antibodies against SARS-CoV-2 isolated from COVID-19 patients interfered with SARS-CoV-2 binding to heparan sulfate proteoglycans, which might be an additional mechanism of antibodies to neutralize infection. SARS-CoV-2 binding to and infection of epithelial cells was blocked by low molecular weight heparins (LMWH). Although dendritic cells (DCs) and mucosal Langerhans cells (LCs) were not infected by SARS-CoV-2, both DC subsets efficiently captured SARS-CoV-2 via heparan sulfate proteoglycans and transmitted the virus to ACE2-positive cells. Notably, human primary nasal cells were infected by SARS-CoV-2, and infection was blocked by pre-treatment with LMWH. These data strongly suggest that heparan sulfate proteoglycans are important attachment receptors facilitating infection and transmission, and support the use of LMWH as prophylaxis against SARS-CoV-2 infection.
Subject(s)
COVID-19/transmission , Heparan Sulfate Proteoglycans/metabolism , Heparin, Low-Molecular-Weight/pharmacology , SARS-CoV-2/pathogenicity , Angiotensin-Converting Enzyme 2/immunology , Angiotensin-Converting Enzyme 2/metabolism , Animals , Antibodies, Neutralizing/metabolism , Antibodies, Neutralizing/pharmacology , Chlorocebus aethiops , Dendritic Cells/metabolism , Dendritic Cells/virology , Epithelial Cells/metabolism , Epithelial Cells/virology , Host-Pathogen Interactions , Humans , Mucous Membrane/cytology , Mucous Membrane/virology , SARS-CoV-2/metabolism , Syndecan-1/metabolism , Syndecan-4/metabolism , Vero Cells , COVID-19 Drug TreatmentABSTRACT
Our study intended to longitudinally explore the prediction effect of immunoglobulin A (IgA) on pulmonary exudation progression in COVID-19 patients. The serum IgA was tested with chemiluminescence method. Autoregressive moving average model was used to extrapolate the IgA levels before hospital admission. The positive rate of IgA and IgG in our cohort was 97% and 79.0%, respectively. In this study, the IgA levels peaks within 10-15 days after admission, while the IgG levels peaks at admission. We found that the time difference between their peaks was about 10 days. Viral RNA detection results showed that the positive rate in sputum and feces were the highest. Blood gas analysis showed that deterioration of hypoxia with the enlargement of pulmonary exudation area. And alveolar-arterial oxygen difference and oxygenation index were correlated with IgA and IgG. The results of biopsy showed that the epithelium of lung was exfoliated and the mucosa was edematous. In severe COVID-19 patients, the combination of IgA and IgG can predict the progress of pulmonary lesions and is closely related to hypoxemia and both also play an important defense role in invasion and destruction of bronchial and alveolar epithelium by SARS-CoV-2.
Subject(s)
COVID-19/pathology , COVID-19/virology , Immunoglobulin A/blood , Immunoglobulin G/blood , Sputum/virology , Aged , Alveolar Epithelial Cells/metabolism , Alveolar Epithelial Cells/virology , Antibodies, Viral/blood , Bronchi/metabolism , Bronchi/virology , COVID-19/blood , COVID-19/metabolism , Female , Humans , Hypoxia/blood , Hypoxia/metabolism , Male , Middle Aged , Mucous Membrane/metabolism , Mucous Membrane/virology , Oxygen/metabolism , Pulmonary Alveoli/metabolism , Pulmonary Alveoli/virology , RNA, Viral/genetics , SARS-CoV-2/geneticsABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic, in part due to the highly infectious nature of the disease. Because SARS-CoV-2 is new, much is unknown regarding mechanisms of transmission, and such information is urgently needed. Here, based on previous findings from related human betacoronaviruses, it is suggested that one possible route of transmission may be via infectious sweat. It is suggested that research be conducted in order to determine whether sweat in SARS-CoV-2 infected individuals harbors virus in quantities that can infect others. Findings could be used for formulations of mitigation strategies and empirically based public health messaging.