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Eur Rev Med Pharmacol Sci ; 25(13): 4639-4643, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1319966


OBJECTIVE: Acute respiratory distress syndrome (ARDS) is characterized by quantitative and qualitative changes in surfactant composition, leading to surfactant dysregulation with alveolar collapse and acute respiratory hypoxic failure. Recently, surfactant has been hypothesized to play a relevant role in COVID-19, representing a strong defender against SARS-CoV-2 infection. The aim of our work was the study of immunohistochemical surfactant expression in the lungs of patients died following SARS-CoV-2 ARDS, in order to shed light on a possible therapeutic surfactant administration. PATIENTS AND METHODS: We investigated four patients who died due to ARDS following SARS-COV-2 infection and four patients submitted to lung biopsy, in the absence of SARS-CoV-2 infection. In all 8 cases, lung specimens were immunostained with anti-surfactant protein A (SP-A) and B (SP-B). RESULTS: In control subjects, reactivity for SP-B was restricted to type II alveolar cells. Immunostaining for SP-A was observed on the surface of alveolar spaces. In the COVID-19 positive lungs, immunoreactivity for SP-B was similar to that observed in control lungs; SP-A was strongly expressed along the alveolar wall. Moreover, dense aggregates of SP-A positive material were observed in the alveolar spaces. CONCLUSIONS: Our immunohistochemical data show the dysregulation of surfactant production in COVID-19 patients, particularly regarding SP-A expression. The increased presence of SP-A in condensed masses inside alveolar spaces could invalidate the therapeutic efficacy of the treatment with exogenous surfactant.

COVID-19/metabolism , Immunohistochemistry , Protein Precursors/analysis , Pulmonary Surfactant-Associated Protein A/analysis , Pulmonary Surfactant-Associated Proteins/analysis , COVID-19/diagnostic imaging , Humans , Protein Precursors/genetics , Protein Precursors/metabolism , Pulmonary Alveoli/diagnostic imaging , Pulmonary Alveoli/metabolism , Pulmonary Surfactant-Associated Protein A/genetics , Pulmonary Surfactant-Associated Protein A/metabolism , Pulmonary Surfactant-Associated Proteins/genetics , Pulmonary Surfactant-Associated Proteins/metabolism , Retrospective Studies , SARS-CoV-2/isolation & purification , SARS-CoV-2/metabolism
Front Immunol ; 12: 637654, 2021.
Article in English | MEDLINE | ID: covidwho-1138709


A coronavirus SARS-CoV-2, which has caused the pandemic viral pneumonia disease COVID-19, significantly threatens global public health, highlighting the need to develop effective and safe vaccines against its infection. In this study, we developed a novel DNA vaccine candidate against SARS-CoV-2 by expressing a chimeric protein of its receptor-binding domain (RBD) fused to a 33-bp sequence (11 aa) from the hepatitis B virus (HBV) preS1 region with a W4P mutation (W4P-RBD) at the N-terminal region and evaluated its immunogenicity. In vitro transfection experiments in multiple cell lines demonstrated that W4P-RBD vs. wild-type RBD protein (W-RBD) led to enhanced production of IL-6 and TNFα at the transcription and translation levels, suggesting the adjuvant potential of N-terminal HBV preS1 sequences for DNA vaccines against SARS-CoV-2. W4P-RBD also led to enhanced production of IgG and IgA, which can neutralize and block SARS-CoV-2 infection in both blood sera and bronchoalveolar lavage (BAL) fluid from the lung in vaccinated mice. Additionally, W4P-RBD led to an enhanced T-cell-mediated cellular immune response under S1 protein stimulation. In summary, W4P-RBD led to robust humoral and cell-mediated immune responses against SARS-CoV-2 in vaccinated mice, highlighting its feasibility as a novel DNA vaccine to protect against SARS-CoV-2 infection.

COVID-19 Vaccines/immunology , COVID-19/prevention & control , Hepatitis B Surface Antigens/genetics , Hepatitis B Surface Antigens/immunology , Mutation , Protein Domains/immunology , Protein Precursors/genetics , Protein Precursors/immunology , Recombinant Fusion Proteins/immunology , SARS-CoV-2/immunology , Vaccines, DNA/immunology , Animals , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/virology , Cell Line, Tumor , Chlorocebus aethiops , HEK293 Cells , Humans , Immunogenicity, Vaccine , Male , Mice , Mice, Inbred C57BL , Vaccination/methods , Vero Cells