ABSTRACT
Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1, OAS2, or RNASEL in five unrelated children with MIS-C. The cytosolic dsRNA-sensing OAS1 and OAS2 generate 2'-5'-linked oligoadenylates (2-5A) that activate the ssRNA-degrading RNase L. Consistent with the absence of pneumonia in these patients, epithelial cells and fibroblasts defective for this pathway restricted SARS-CoV-2 normally. This contrasted with IFNAR1-deficient cells from patients prone to hypoxemic pneumonia without MIS-C. Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNASEL deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or SARS-CoV- 2 stimulation. Exogenous 2-5A suppresses cytokine production in OAS1-but not RNase L- deficient cells. Cytokine production in RNase L-deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by MAVS deficiency. Recessive OAS-RNase L deficiencies in these patients unleash the production of SARS-CoV-2-triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C.Copyright © 2023 Elsevier Inc.
ABSTRACT
Outbreaks of chilblains, a hallmark sign of type I interferonopathies, have been reported during the COVID-19 pandemic. These cases occurred mostly in patients who were asymptomatic and showed negative results from PCR and serology tests for SARS-CoV-2. We hypothesized that chilblain patients are predisposed to mount a robust innate immunity against the virus, which clinically manifests as chilblains and promotes early viral clearance, thereby preventing pulmonary disease and precluding adaptive responses. By profiling skin lesions in the early stage following chilblain onset, we uncover a transient IRF7-dependent type I interferon (IFN) signature that is driven by the acral infiltration of systemically activated plasmacytoid dendritic cells (pDCs). Patients' peripheral blood mononuclear cells (PBMCs) demonstrate increased production of IFNalpha when exposed to SARS-CoV-2 and influenza A, but not herpes simplex virus 1 (HSV-1), indicating a heightened ability to detect RNA -but not DNA- viruses. Further investigations revealed enhanced responsiveness of pDCs in chilblain patients to the RNA sensor TLR7, but not the DNA sensor TLR9. Collectively, our study establishes a two-step model for the immunopathology of SARS-CoV-2-related chilblains: enhanced TLR7 immunity in pDCs, likely triggered by SARS-CoV-2 exposure at the mucosal site, leads to prompt viral clearance, which explains the lack of infection markers in most cases. Subsequently, systemic spread of activated pDCs and infiltration of the toes in response to mechanical stress or acral coldness, may result in IFN-mediated tissue damage with development of chilblains.Copyright © 2023
ABSTRACT
A proper ventilation strategy in an isolation ward could promote better indoor air quality for the occupants. This could also reduce the risk of immunocompromised patients contracting healthcare-associated infections (HAI) or airborne diseases such as COVID-19, tuberculosis, and measles among others. This study aims to propose and examine appropriate ventilation strategies in a single-patient isolation ward that can reduce particle settlement in patients. A simplified CFD model of the isolation ward was developed and well-validated against established data. An RNG k-ε model and discrete phase model (DPM) were used to simulate airflow and particle transportation. The study examined the airflow and particle dispersion under a baseline case and four proposed ventilation strategies. Results showed that the baseline case study, which used the ceiling-mounted air curtain was insufficient to prevent the particles from dispersing into the vicinity of the patient. Likewise, the dilution effect under the baseline case and case 4 (wall-mounted air supply diffuser) were relatively weak due to the low air change rate (ACH) of 4/hr and 9/hr respectively. The ventilation strategy in case 4 has a negligible effect on reducing the particles (14%) settling on the patient although the ACH in case 4 was 2-times the baseline case. The present finding ascertains that utilising the combination of ceiling-mounted air diffuser and air curtain jet (case 3) results in zero particle settlement on both patient's and the patient's bed. It also reduced 57% of particles in the vicinity of the medical staff's breathing zone compared to the baseline case. © 2023 Elsevier Ltd
ABSTRACT
Air quality plays a significant role during the coronavirus pandemic. Air acts as a spreading media as well as a control measure for infection in polluted spaces. Insufficient ventilation around the building may lead to a rise of pollutants carrying the virus. One way to improve ventilation is by increasing the air change rate. This study investigates the air change rate effectiveness in reducing droplets spreading in a classroom. Cases with various layouts of inlet and outlet vents are considered, and the spread of droplets is studied. The airflow analysis shows the impact of the different ventilation layout configurations. The results show that the CFD model simulation indicates an optimum ventilation configuration to decrease the droplet spread. The discrete phase model results also determine the trajectory of droplets spread along the classroom. CFD results show that in the selected configuration, a significant number of droplets are expelled to the outside and reduce their concentration inside the classroom. © 2023, Penerbit Akademia Baru. All rights reserved.
ABSTRACT
Since the beginning of the COVID-19 pandemic, dermatologists around the world have reported patients with chilblain-like skin lesions on their toes, called COVID-toes. Surprisingly, the majority of these patients do not develop COVID-19 symptoms, and their nasal swabs and serological tests are unable to confirm SARS-CoV-2 infection, despite a clear exposure to the virus. Recent evidence suggests that these patients mount a robust type I interferon response to SARS-CoV-2, making them resistant to the infection. Because chilblains are hallmarks of excessive type I interferons, COVID-toes may represent the skin expression of interferon-mediated resistance to SARS-CoV-2. Uncovering the molecular patho-mechanisms of COVID-toes may provide new avenues to promote SARS-CoV-2 resistance and control the COVID-19 pandemic.