ABSTRACT
Background An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection occurred in a medical ward involving patients and hospital staff from May to June 2020. Aim The aim of this study is to determine risk factors related to the outbreak of SARS-CoV-2 in six healthcare workers (HCWs) in a medical ward with initially unrecognized coronavirus disease 2019 (COVID-19) positive patients. Methods A retrospective cross-sectional study was conducted using a comprehensive questionnaire and personal interviews to determine the risk factors for COVID-19 infection in HCWs. Findings A total of 6/34 HCWs were diagnosed with COVID-19 in a medical ward. There were no differences between COVID-19 negative HCWs and COVID-19 positive HCWs in terms of mean duration of hours worked in the unit during the cluster event (180.2 vs 177.5 hours) (p>0.05), mean total time spent in contact with COVID-19 positive patients (12.8 vs 10.5 hours) (p>0.05), mean total time spent on aerosol-generating procedures (1.9 vs 0.9 hours) (p>0.05), and mean total time spent on non-aerosol generating procedures (10.9 vs 9.6 hours ) (p>0.05). There was no difference in exposure to COVID-19 positive family members among the HCWs (33% vs 3.7%, p=0.08). In contrast, exposure to COVID-19 positive contacts in the community was significantly greater in infected vs non-infected HCWs (16.7% vs 0%, p=0.03). Conclusion There was no significant difference in risk factors for contracting SARs-CoV2 among HCWs due to hospital exposures. COVID-19 positive HCWs were more likely to be exposed to positive individuals in their households and community, indicating that the source of SARS-CoV-2 infection came from outside the hospital.
ABSTRACT
Rift Valley Fever Virus is a mosquito-borne phlebovirus causing febrile or haemorrhagic illness in ruminants and humans. The virus can prevent the induction of the antiviral interferon response through its NSs proteins. Mutations in the NSs gene may allow the induction of innate proinflammatory immune responses and lead to attenuation of the virus. Upon infection, virus-specific antibodies and T cells are induced that may afford protection against subsequent infections. Thus, all arms of the adaptive immune system contribute to prevention of disease progression. These findings will aid the design of vaccines using the currently available platforms. Vaccine candidates have shown promise in safety and efficacy trials in susceptible animal species and these may contribute to the control of RVFV infections and prevention of disease progression in humans and ruminants.
ABSTRACT
Recently emerged severe acute respiratory syndrome coronavirus (SARS-CoV)-1 and -2 initiate virus infection by binding of their spike glycoprotein with the cell-surface receptor angiotensin-converting enzyme 2 (ACE2) and enter into the host cells mainly via the clathrin-mediated endocytosis pathway. However, the internalization process post attachment with the receptor is not clear for both SARS-CoV-1 and -2. Understanding the cellular factor/s or pathways used by these CoVs for internalization might provide insights into viral pathogenesis, transmission, and development of novel therapeutics. Here, we demonstrated that the cytoplasmic tail of ACE2 is not essential for the entry of SARS-CoV-1 and -2 by using bioinformatics, mutational, confocal imaging, and pseudotyped SARS-CoVs infection studies. ACE2 cytoplasmic domain (cytACE2) contains a conserved internalization motif and eight putative phosphorylation sites. Complete cytoplasmic domain deleted ACE2 (∆cytACE2) was properly synthesized and presented on the surface of HEK293T and BHK21 cells like wtACE2. The SARS-CoVs S1 or RBD of spike protein binds and colocalizes with the receptors followed by internalization into the host cells. Moreover, pseudotyped SARS-CoVs entered into wtACE2- and ∆cytACE2-transfected cells but not into dipeptidyl peptidase 4 (DPP4)-expressing cells. Their entry was significantly inhibited by treatment with dynasore, a dynamin inhibitor, and NH4Cl, an endosomal acidification inhibitor. Furthermore, SARS-CoV antibodies and the soluble form of ACE2-treated pseudotyped SARS-CoVs were unable to enter the wtACE2 and ∆cytACE2-expressing cells. Altogether, our data show that ACE2 cytoplasmic domain signaling is not essential for the entry of SARS-CoV-1 and -2 and that SARS-CoVs entry might be mediated via known/unknown host factor/s.
