TNFα aggravates detrimental effects of SARS-CoV-2 infection in the liver.

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus does not only lead to pulmonary infection but can also infect other organs such as the gut, the kidney, or the liver. Recent studies confirmed that severe cases of COVID-19 are often associated with liver damage and liver failure, as well as the systemic upregulation of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNFα). However, the impact these immune mediators in the liver have on patient survival during SARS-CoV-2 infection is currently unknown. Here, by performing a post-mortem analysis of 45 patients that died from a SARS-CoV-2 infection, we find that an increased expression of TNFA in the liver is associated with elevated mortality. Using publicly available single-cell sequencing datasets, we determined that Kupffer cells and monocytes are the main sources of this TNFα production. Further analysis revealed that TNFα signaling led to the upregulation of pro-inflammatory genes that are associated with an unfavorable outcome. Moreover, high levels of TNFA in the liver were associated with lower levels of interferon alpha and interferon beta. Thus, TNFα signaling in the infected SARS-CoV-2 liver correlates with reduced interferon levels and overall survival time.

"Too shocked to search" The COVID-19 shutdowns' impact on the search for apprenticeships.

Even though the recession in Switzerland triggered by COVID-19 ultimately remained without consequences for the apprenticeship market, significantly fewer apprenticeship contracts had been signed in the months of the first shutdown in 2020 than in the same months of the previous year. Using daily search queries on the national administrative platform for apprenticeship vacancies from February 2020 until April 2021 as a proxy for the supply of potential apprentices, we find a temporal pattern that coincides perfectly with the development of signed apprenticeship contracts. Furthermore, the analyses show that the initially very strong relationship between the intensity of the politically imposed restrictions to fight the COVID-19 pandemic and the daily search queries diminished over time, leading to a search intensity in March 2021 that was back at pre-pandemic level.