The experience of European hospital-based health care workers on following infection prevention and control procedures and their wellbeing during the first wave of the COVID-19 pandemic.

BACKGROUND: Working under pandemic conditions exposes health care workers (HCWs) to infection risk and psychological strain. A better understanding of HCWs' experiences of following local infection prevention and control (IPC) procedures during COVID-19 is urgently needed to inform strategies for protecting the psychical and psychological health of HCWs. The objective of this study was therefore to capture the perceptions of hospital HCWs on local IPC procedures and the impact on their emotional wellbeing during the first wave of the COVID-19 pandemic in Europe. METHODS: Participants were recruited in two sampling rounds of an international cross-sectional survey. Sampling took place between 31 March and 17 April 2020 via existing research networks and between 14 May and 31 August 2020 via online convenience sampling. Main outcome measures were behavioural determinants of HCWs' adherence to IPC guidelines and the WHO-5 Well-Being Index, a validated scale of 0-100 reflecting emotional wellbeing. The WHO-5 was interpreted as a score below or above 50 points, a cut-off score used in previous literature to screen for depression. RESULTS: 2289 HCWs from 40 countries in Europe participated. Mean age was 42 (±11) years, 66% were female, 47% and 39% were medical doctors and nurses, respectively. 74% (n = 1699) of HCWs were directly treating patients with COVID-19, of which 32% (n = 527) reported they were fearful of caring for these patients. HCWs reported high levels of concern about COVID-19 infection risk to themselves (71%) and their family (82%) as a result of their job. 40% of HCWs considered that getting infected with COVID-19 was not within their control. This feeling was more common among junior than senior HCWs (46% versus 38%, P value < .01). Sufficient COVID-19-specific IPC training, confidence in PPE use and institutional trust were positively associated with the feeling that becoming infected with COVID-19 was within their control. Female HCWs were more likely than males to report a WHO-5 score below 50 points (aOR 1.5 (95% confidence interval (CI) 1.2-1.8). CONCLUSIONS: In Europe, the COVID-19 pandemic has had a differential impact on those providing direct COVID-19 patient care, junior staff and women. Health facilities must be aware of these differential impacts, build trust and provide tailored support for this vital workforce during the current COVID-19 pandemic.

The Fc-mediated effector functions of a potent SARS-CoV-2 neutralizing antibody, SC31, isolated from an early convalescent COVID-19 patient, are essential for the optimal therapeutic efficacy of the antibody.

Although SARS-CoV-2-neutralizing antibodies are promising therapeutics against COVID-19, little is known about their mechanism(s) of action or effective dosing windows. We report the generation and development of SC31, a potent SARS-CoV-2 neutralizing antibody, isolated from a convalescent patient. Antibody-mediated neutralization occurs via an epitope within the receptor-binding domain of the SARS-CoV-2 Spike protein. SC31 exhibited potent anti-SARS-CoV-2 activities in multiple animal models. In SARS-CoV-2 infected K18-human ACE2 transgenic mice, treatment with SC31 greatly reduced viral loads and attenuated pro-inflammatory responses linked to the severity of COVID-19. Importantly, a comparison of the efficacies of SC31 and its Fc-null LALA variant revealed that the optimal therapeutic efficacy of SC31 requires Fc-mediated effector functions that promote IFNγ-driven anti-viral immune responses, in addition to its neutralization ability. A dose-dependent efficacy of SC31 was observed down to 5mg/kg when administered before viral-induced lung inflammatory responses. In addition, antibody-dependent enhancement was not observed even when infected mice were treated with SC31 at sub-therapeutic doses. In SARS-CoV-2-infected hamsters, SC31 treatment significantly prevented weight loss, reduced viral loads, and attenuated the histopathology of the lungs. In rhesus macaques, the therapeutic potential of SC31 was evidenced through the reduction of viral loads in both upper and lower respiratory tracts to undetectable levels. Together, the results of our preclinical studies demonstrated the therapeutic efficacy of SC31 in three different models and its potential as a COVID-19 therapeutic candidate.

Label-free quantitative lymphocyte activation profiling using microfluidic impedance cytometry

Circulating lymphocytes are integral components of our adaptive immunity with emerging clinical applications in immune status monitoring in infectious diseases and cell-mediated cancer immunotherapies. Herein we present a novel impedance-based microfluidic assay for label-free lymphocyte activation profiling based on native or antigen-specific T-lymphocyte biophysical responses. Single cell impedance profiling of T-lymphocytes first revealed distinct biophysical differences in cell size and membrane electrical impedance of healthy, activated (CD3/CD28) and dead lymphocyte populations. Impedance characterization of peripheral blood mononuclear cells (PBMCs) stimulated with mitogen phytohemagglutinin (PHA) or Tuberculin Purified Protein Derivative antigen (PPD) after 24 hours also showed an increase in lymphocyte cell size (∼8 to 10 µm) which corresponded to activated lymphocytes (CD69+CD137+). We next developed a spiral inertial microfluidics cell sorter integrated with coplanar electrodes for direct impedance quantification of activated lymphocytes. By removing non-activated smaller lymphocytes (< 8 µm) and employing hydrodynamic-based single stream particle focusing, we demonstrated significant enrichment of activated lymphocytes (∼11.7-fold) to electrically detect low levels of lymphocyte activation (< 5%). Finally, the developed biochip is coupled with magnetic activated cell sorting (MACS) to quantify CD4+ T-lymphocytes response in PBMCs stimulated with PPD. A differential impedance cell count ratio (stimulated/unstimulated) was defined to distinguish activated T-lymphocytes, which showed better sensitivity as compared to immunophenotyping by flow cytometry. Taken together, the integrated impedance biosensor can be further developed as a rapid multiplexed screening assay to detect antigen-specific T-lymphocyte responses to characterize host immunity and diagnosis of infectious diseases (e.g tuberculosis, dengue and COVID-19).