Background: There is ongoing uncertainty regarding transmission chains and the respective roles of healthcare workers (HCWs) and elderly patients in nosocomial outbreaks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in geriatric settings.
Methods: We performed a retrospective cohort study including patients with nosocomial coronavirus disease 2019 (COVID-19) in four outbreak-affected wards, and all SARS-CoV-2 RT-PCR positive HCWs from a Swiss university-affiliated geriatric acute-care hospital that admitted both Covid-19 and non-Covid-19 patients during the first pandemic wave in Spring 2020. We combined epidemiological and genetic sequencing data using a Bayesian modelling framework, and reconstructed transmission dynamics of SARS-CoV-2 involving patients and HCWs, to determine who infected whom. We evaluated general transmission patterns according to case type (HCWs working in dedicated Covid-19 cohorting wards: HCWcovid; HCWs working in non-Covid-19 wards where outbreaks occurred: HCWoutbreak; patients with nosocomial Covid-19: patientnoso) by deriving the proportion of infections attributed to each case type across all posterior trees and comparing them to random expectations.
Results: During the study period (March 1 to May 7, 2020) we included 180 SARS-CoV-2 positive cases: 127 HCWs (91 HCWcovid, 36 HCWoutbreak) and 53 patients. The attack rates ranged from 10-19% for patients, and 21% for HCWs. We estimated that 16 importation events occurred with high confidence (four patients, 12 HCWs) that jointly led to up to 41 secondary cases; in six additional cases (five HCWs, one patient), importation was possible with a posterior between 10-50%. Most patient-to-patient transmission events involved patients having shared a ward (95.2%, 95% credible interval [CrI] 84.2-100%), in contrast to those having shared a room (19.7%, 95%CrI 6.7-33.3%). Transmission events tended to cluster by case type: patientnoso were almost twice as likely to be infected by other patientnoso than expected (observed:expected ratio 2.16, 95%CrI 1.17 - 4.20, p = 0.006); similarly, HCWoutbreak were more than twice as likely to be infected by other HCWoutbreak than expected (2.72, 95%CrI 0.87-9.00, p = 0.06). The proportion of infectors being HCWcovid was as expected as random. We found a trend toward a greater proportion of high transmitters (≥2 secondary cases) among HCWoutbreak than patientnoso in the late phases (28.6% vs. 11.8%) of the outbreak, although this was not statistically significant.
Conclusions: Most importation events were linked to HCW. Unexpectedly, transmission between HCWcovid was more limited than transmission between patients and HCWoutbreak. This finding highlights gaps in infection control and suggests possible areas of improvements to limit the extent of nosocomial transmission.
Funding: This work was supported by a grant from the Swiss National Science Foundation under the NRP78 funding scheme (Grant no. 4078P0_198363).
Due to small size of the various clusters, the raw clinical data will not be shared to safeguard anonymity of patients and healthcare workers. Processed data of the output of the model, which will comprise the posterior distribution of infectors, will be made available in an anonymized version. This will allow reproducing the analyses looking at the proportion of healthcare workers among infectors, and the number of secondary infections. This data will not allow reconstruction of the transmission tree, which would require the raw data. The raw data in an anonymized format will be made available upon reasonable and justified request, subject to approval by the project's Senior Investigator. The genomic sequencing data have been submitted to the Genbank repository (GenBank accession numbers: ON209723-ON209871).
- Mohamed Abbas
- Dr Anne Cori
- Samuel Cordey
- Florian Laubscher
- Tomás Robalo Nunes
- Anne Iten
- Stephan Harbarth
- Mohamed Abbas
- Dr Anne Cori
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Human subjects: The Ethics Committee of the Canton of Geneva (CCER), Switzerland, approved this study (CCER no. 2020-01330 and CCER no. 2020-00827). Written informed consent was obtained from HCWs. Written informed consent was not required for patients as data were generated in a context of mandatory surveillance.
- Joshua T Schiffer, Fred Hutchinson Cancer Research Center, United States
© 2022, Abbas et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Aristolochic acid nephropathy (AAN) is a progressive kidney disease caused by herbal medicines. Proline–serine–threonine phosphatase-interacting protein 2 (PSTPIP2) and neutrophil extracellular traps (NETs) play important roles in kidney injury and immune defense, respectively, but the mechanism underlying AAN regulation by PSTPIP2 and NETs remains unclear. We found that renal tubular epithelial cell (RTEC) apoptosis, neutrophil infiltration, inflammatory factor, and NET production were increased in a mouse model of AAN, while PSTPIP2 expression was low. Conditional knock-in of Pstpip2 in mouse kidneys inhibited cell apoptosis, reduced neutrophil infiltration, suppressed the production of inflammatory factors and NETs, and ameliorated renal dysfunction. Conversely, downregulation of Pstpip2 expression promoted kidney injury. In vivo, the use of Ly6G-neutralizing antibody to remove neutrophils and peptidyl arginine deiminase 4 (PAD4) inhibitors to prevent NET formation reduced apoptosis, alleviating kidney injury. In vitro, damaged RTECs released interleukin-19 (IL-19) via the PSTPIP2/nuclear factor (NF)-κB pathway and induced NET formation via the IL-20Rβ receptor. Concurrently, NETs promoted apoptosis of damaged RTECs. PSTPIP2 affected NET formation by regulating IL-19 expression via inhibition of NF-κB pathway activation in RTECs, inhibiting RTEC apoptosis, and reducing kidney damage. Our findings indicated that neutrophils and NETs play a key role in AAN and therapeutic targeting of PSTPIP2/NF-κB/IL-19/IL-20Rβ might extend novel strategies to minimize Aristolochic acid I-mediated acute kidney injury and apoptosis.
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