Subclass-switched anti-spike IgG3 oligoclonal cocktails strongly enhance Fc-mediated opsonization.

Antibodies play a central role in the immune defense against SARS-CoV-2. Emerging evidence has shown that nonneutralizing antibodies are important for immune defense through Fc-mediated effector functions. Antibody subclass is known to affect downstream Fc function. However, whether the antibody subclass plays a role in anti-SARS-CoV-2 immunity remains unclear. Here, we subclass-switched eight human IgG1 anti-spike monoclonal antibodies (mAbs) to the IgG3 subclass by exchanging their constant domains. The IgG3 mAbs exhibited altered avidities to the spike protein and more potent Fc-mediated phagocytosis and complement activation than their IgG1 counterparts. Moreover, combining mAbs into oligoclonal cocktails led to enhanced Fc- and complement receptor-mediated phagocytosis, superior to even the most potent single IgG3 mAb when compared at equivalent concentrations. Finally, in an in vivo model, we show that opsonic mAbs of both subclasses can be protective against a SARS-CoV-2 infection, despite the antibodies being nonneutralizing. Our results suggest that opsonic IgG3 oligoclonal cocktails are a promising idea to explore for therapy against SARS-CoV-2, its emerging variants, and potentially other viruses.

The value of data privacy during the COVID-19 pandemic: a new set of survey questions

Contact-tracing smartphone apps that rely on users’ private data have been proposed as important tools in fighting the COVID-19 pandemic. The use of these apps, however, has sparked new debates on the value of data privacy. Several earlier studies have investigated citizens’ willingness to use such apps. We propose a set of questions as a new measurement instrument that goes beyond eliciting acceptance and aims at quantifying users’ willingness to pay (WTP) for data privacy. We assess some aspects of the measurement instrument pertaining to its validity. We find central assumptions of our theoretical model met, suggesting that the instrument serves as a good starting point for measuring WTP. For example, we found a rather low WTP for data privacy in times of a pandemic, with high consent rates to data sharing and a majority of people who would pay amounts of up to 10€ only to not have to share data. Nevertheless, there are several improvements to the instrument possible that should be addressed by future research. We also encourage researchers to field the refined version in larger samples including the offline population.Supplementary Information: The online version contains supplementary material available at 10.1186/s42409-022-00037-y.

[Impact of the COVID-19 lockdown on emergency medical service operations]. / Auswirkung des COVID-19-Lockdowns auf Rettungseinsätze.

Background: As a response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, extensive contact restrictions were imposed by law in Germany as in other European countries. The present study intends to clarify the effect of these restrictions on emergency medical service (EMS) operations. Materials and methods: Retrospective chart review of EMS operation protocols over the first 6 months of 2020 (n = 6668 rescue missions) in four rescue stations in eastern Lower Saxony (Germany). Description and statistical comparison of operations 6 weeks before the restrictions with an equally long period after the order of the restrictions ("lockdown"). Results: During the 6 weeks after the lockdown the frequency of rescue operations decreased by 17.7%. In particular, there was a 40.6% (n = 91) decrease of emergency cases with respiratory diseases, mainly due to a decline of pneumonia and exacerbated chronic-obstructive pulmonary disease (COPD). At the same time, patients' mean age increased with fewer patients under 65 years. There were no changes in the frequency of psychiatric disorders, deceased or injured patients, or refusal of treatment and transport. A total of 67 patients with suspected or confirmed SARS-CoV­2 infection (1.0%) were observed during this period. Discussion: EMS experienced a reduction of operations as a result of contact restrictions, although not as pronounced as was recently described for emergency rooms. This supports the hypothesis that the reduction is particularly evident in less severe cases and in younger patients. The reduction in pneumonia and COPD cases is striking. On the one hand, this could indicate that contact restrictions reduce the incidence of other respiratory infections and their impact on chronic respiratory disorders, but it could also mean that patients try to avoid hospital treatment.

Mismatch between circulating cytokines and spontaneous cytokine production by leukocytes in hyperinflammatory COVID-19.

The disease COVID-19 has developed into a worldwide pandemic. Hyperinflammation and high levels of several cytokines, for example, IL-6, are observed in severe COVID-19 cases. However, little is known about the cellular origin of these cytokines. Here, we investigated whether circulating leukocytes from patients with COVID-19 had spontaneous cytokine production. Patients with hyperinflammatory COVID-19 (n = 6) and sepsis (n = 3) were included at Skåne University Hospital, Sweden. Healthy controls were also recruited (n = 5). Cytokines were measured in COVID-19 and sepsis patients using an Immulite immunoassay system. PBMCs were cultured with brefeldin A to allow cytokine accumulation. In parallel, LPS was used as an activator. Cells were analyzed for cytokines and surface markers by flow cytometry. High levels of IL-6 and measurable levels of IL-8 and TNF, but not IL-1ß, were observed in COVID-19 patients. Monocytes from COVID-19 patients had spontaneous production of IL-1ß and IL-8 (P = 0.0043), but not of TNF and IL-6, compared to controls. No spontaneous cytokine production was seen in lymphocytes from either patients or controls. Activation with LPS resulted in massive cytokine production by monocytes from COVID-19 patients and healthy controls, but not from sepsis patients. Finally, monocytes from COVID-19 patients produced more IL-1ß than from healthy controls (P = 0.0087) when activated. In conclusion, monocytes contribute partly to the ongoing hyperinflammation by production of IL-1ß and IL-8. Additionally, they are responsive to further activation. This data supports the notion of IL-1ß blockade in treatment of COVID-19. However, the source of the high levels of IL-6 remains to be determined.

Navigating the Clean Energy Transition in the COVID-19 Crisis.

Bjarne Steffen is a senior researcher at ETH Zurich's Energy Politics Group. His research addresses policies related to energy innovation and the role of finance in the energy transition. He previously worked at MIT's Center for Energy and Environmental Policy Research, the World Economic Forum, and a strategy consultancy. Bjarne holds a Master's in economics from the University of Mannheim and a PhD in energy economics from the University of Duisburg-Essen. Florian Egli is a PhD candidate at ETH Zurich's Energy Politics Group. His research focuses on the role of finance in the energy transition and climate finance more generally. He is a World Economic Forum Global Shaper, is associated with the think tank foraus as its former vice president, and held a Mercator Fellowship on International Affairs in 2015 and 2016. Florian holds a Master's in International Economics from the Graduate Institute of International and Development Studies (IHEID) in Geneva. Michael Pahle is head of the working group "Climate and Energy Policy" at the Potsdam-Institute for Climate Impact Research. His research focuses on carbon pricing and power market design. He holds a Master's in Physics from Potsdam University and a PhD in economics from TU Berlin. Tobias S. Schmidt is Assistant Professor and the head of ETH Zurich's Energy Politics Group, an interdisciplinary group analyzing the interaction of energy policy and its underlying politics with technological change in the energy sector. His research covers both developed and developing countries. Tobias holds a Bachelor's and Master's of Science in electrical engineering (energy focus) from the Technical University Munich and a PhD from ETH Zurich in management, technology, and economics.