Severe COVID-19 patients have impaired plasmacytoid dendritic cell-mediated control of SARS-CoV-2.

Type I and III interferons (IFN-I/λ) are important antiviral mediators against SARS-CoV-2 infection. Here, we demonstrate that plasmacytoid dendritic cells (pDC) are the predominant IFN-I/λ source following their sensing of SARS-CoV-2-infected cells. Mechanistically, this short-range sensing by pDCs requires sustained integrin-mediated cell adhesion with infected cells. In turn, pDCs restrict viral spread by an IFN-I/λ response directed toward SARS-CoV-2-infected cells. This specialized function enables pDCs to efficiently turn-off viral replication, likely via a local response at the contact site with infected cells. By exploring the pDC response in SARS-CoV-2 patients, we further demonstrate that pDC responsiveness inversely correlates with the severity of the disease. The pDC response is particularly impaired in severe COVID-19 patients. Overall, we propose that pDC activation is essential to control SARS-CoV-2-infection. Failure to develop this response could be important to understand severe cases of COVID-19.

Measuring Intellectual and Emotional Health during COVID-19 Pandemic: Scale Development and Validation

Coronavirus disease (COVID-19) has proven itself a deadly pandemic and has not spared a single life on this planet. Every individual is bearing the brunt of this pandemic to a great extent in every possible way. The world is entering into the new normal where people have started living with the precautions. However, several stressors that emerged during COVID-19 are leaving not just a short term but also a long-term impact on the intellect and emotions of every single person. Measurement of intellectual and emotional health has become the need of the hour and will be very useful for analysing the effect of stress due to COVID-19, which will eventually help everyone identify and practice their coping strategies. The current study aims to develop and validate a scale for measuring the intellectual and emotional health of people. The data was collected from 364 respondents using convenience sampling. The validated scale has a total of 21 items, of which five items are for measuring intellectual health and 16 items for measuring emotional health. In addition, behaviour indicators identified during the research for both health types were categorised into eustress and distress. The developed scale can be useful for working and non-working individuals to understand their level of emotional and intellectual health and be proactive in protecting themselves from the continuous pain of depression, anxiety, or the tendency to engage in self-harm behaviours even after the COVID-19 era gets over.

SARS-CoV-2 spike E156G/Δ157-158 mutations contribute to increased infectivity and immune escape.

Breakthrough infections by emerging SARS-CoV-2 variants raise significant concerns. Here, we sequence-characterized the spike gene from breakthrough infections that corresponded to B.1.617 sublineage. Delineating the functional impact of spike mutations revealed that N-terminal domain (NTD)-specific E156G/Δ157-158 contributed to increased infectivity and reduced sensitivity to vaccine-induced antibodies. A six-nucleotide deletion (467-472) in the spike-coding region introduced this change in the NTD. We confirmed the presence of E156G/Δ157-158 from cases concurrently screened, in addition to other circulating spike (S1) mutations such as T19R, T95I, L452R, E484Q, and D614G. Notably, E156G/Δ157-158 was present in more than 90% of the sequences reported from the USA and UK in October 2021. The spike-pseudotyped viruses bearing a combination of E156G/Δ157-158 and L452R exhibited higher infectivity and reduced sensitivity to neutralization. Notwithstanding, the post-recovery plasma robustly neutralized viral particles bearing the mutant spike. When the spike harbored E156G/Δ157-158 along with L452R and E484Q, increased cell-to-cell fusion was also observed, suggesting a combinatorial effect of these mutations. Our study underscores the importance of non-RBD changes in determining infectivity and immune escape.