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1.
Signal Transduct Target Ther ; 7(1): 392, 2022 12 19.
Article in English | MEDLINE | ID: covidwho-2185768

ABSTRACT

Horseshoe bats host numerous SARS-related coronaviruses without overt disease signs. Bat intestinal organoids, a unique model of bat intestinal epithelium, allow direct comparison with human intestinal organoids. We sought to unravel the cellular mechanism(s) underlying bat tolerance of coronaviruses by comparing the innate immunity in bat and human organoids. We optimized the culture medium, which enabled a consecutive passage of bat intestinal organoids for over one year. Basal expression levels of IFNs and IFN-stimulated genes were higher in bat organoids than in their human counterparts. Notably, bat organoids mounted a more rapid, robust and prolonged antiviral defense than human organoids upon Poly(I:C) stimulation. TLR3 and RLR might be the conserved pathways mediating antiviral response in bat and human intestinal organoids. The susceptibility of bat organoids to a bat coronavirus CoV-HKU4, but resistance to EV-71, an enterovirus of exclusive human origin, indicated that bat organoids adequately recapitulated the authentic susceptibility of bats to certain viruses. Importantly, TLR3/RLR inhibition in bat organoids significantly boosted viral growth in the early phase after SARS-CoV-2 or CoV-HKU4 infection. Collectively, the higher basal expression of antiviral genes, especially more rapid and robust induction of innate immune response, empowered bat cells to curtail virus propagation in the early phase of infection.


Subject(s)
COVID-19 , Chiroptera , Virus Diseases , Animals , Humans , Chiroptera/genetics , Antiviral Agents/pharmacology , Toll-Like Receptor 3/genetics , SARS-CoV-2 , Organoids , Immunosuppression Therapy
2.
Biomed Res Int ; 2020: 6342598, 2020.
Article in English | MEDLINE | ID: covidwho-955428

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children accounts for a small proportion of all infections and is usually mild or asymptomatic. There are few studies on the clinical characteristics of SARS-CoV-2 infection in children, and the causes of the low prevalence in children remain unclear. Herein, we compared the epidemiological and clinical characteristics of SARS-CoV-2 infection between adults and children. Fifty-two patients with Coronavirus Disease 2019 (COVID-19) were retrospectively analyzed, including 38 adults and 14 children. Their clinical information such as epidemiological exposure history, laboratory indicators, chest computed tomography (CT) performance, and number of SARS-CoV-2 positive days were analyzed and compared. In children, 5 (35.71%) had mild COVID-19 and 9 (64.29%) had common type, while, in adults, 9 (23.68%) cases were mild, and 29 (76.32%) were common COVID-19. Among them, family clustering infection accounted for 50% (7/14) of child cases and 23.68% (9/36) of adult cases. Epidemiological exposure history, clinical classification, clinical symptoms, chest CT manifestations, and number of SARS-CoV-2-positive days were not significantly different between children and adults. However, the percentage of neutrophils in adults was significantly higher than that in children (P < 0.05). The percentage and absolute value of lymphocytes, platelet counts, aspartate aminotransferase, and aspartate aminotransferase/alanine aminotransferase in adults were lower than those in children (P < 0.05). Conclusively, children infected with SARS-CoV-2 show the characteristics of family clustering, and the proportion of mild and asymptomatic infections is higher. For families with a history of epidemiological exposure, routine SARS-CoV-2 nucleic acid testing and chest CT examination should be performed in asymptomatic children to determine whether they are infected. Unlike adults, although the reduction of lymphocytes and platelets in children is not common, it is necessary to be alert to the increased risk of liver damage in children.


Subject(s)
COVID-19 , Tomography, X-Ray Computed , Adolescent , Adult , Aged , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Blood Platelets/metabolism , COVID-19/blood , COVID-19/diagnostic imaging , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Leukocyte Count , Male , Middle Aged , Neutrophils/metabolism , Platelet Count , SARS-CoV-2
3.
Physiol Meas ; 41(8): 085008, 2020 09 10.
Article in English | MEDLINE | ID: covidwho-690496

ABSTRACT

OBJECTIVE: Patients with the novel coronavirus disease (COVID-19) often have airway secretions that severely compromise ventilation. This study investigates electrical impedance tomography (EIT) monitoring of a therapeutic bronchoalveolar lavage (BAL) in a patient with COVID-19. APPROACH: A patient with COVID-19 developed acute respiratory distress syndrome requiring mechanical ventilation. He received regional BAL to remove mucus in the small airways (20 ml × 5). Regional ventilation changes before BAL, 30 min after and in the following days, were monitored with EIT. MAIN RESULTS: Regional ventilation worsened shortly after BAL and improved in the following days. The improvement of the oxygenation did not exactly match the ventilation improvement, which indicated a possible ventilation/perfusion mismatch. SIGNIFICANCE: Therapeutic BAL might improve regional ventilation for COVID-19 and EIT could be a useful tool at the bedside to monitor the ventilation treatment of COVID-19.


Subject(s)
Betacoronavirus , Bronchoalveolar Lavage/methods , Coronavirus Infections/therapy , Electric Impedance/therapeutic use , Monitoring, Physiologic/methods , Pneumonia, Viral/therapy , Respiration, Artificial/methods , Aged , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/diagnostic imaging , Humans , Male , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/diagnostic imaging , Respiratory Distress Syndrome/diagnostic imaging , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/therapy , SARS-CoV-2 , Tomography/methods
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