Single-cell multi-omics analysis of the immune response in COVID-19

Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy

A mechanistic approach for accurate simulation of village scale malaria transmission

Background: Malaria transmission models commonly incorporate spatial environmental and climate variability for making regional predictions of disease risk. However, a mismatch of these models' typical spatial resolutions and the characteristic scale of malaria vector population dynamics may confound disease risk predictions in areas of high spatial hydrological variability such as the Sahel region of Africa. Methods: Field observations spanning two years from two Niger villages are compared. The two villages are separated by only 30 km but exhibit a ten-fold difference in anopheles mosquito density. These two villages would be covered by a single grid cell in many malaria models, yet their entomological activity differs greatly. Environmental conditions and associated entomological activity are simulated at high spatial- and temporal resolution using a mechanistic approach that couples a distributed hydrology scheme and an entomological model. Model results are compared to regular field observations of Anopheles gambiae sensu lato mosquito populations and local hydrology. The model resolves the formation and persistence of individual pools that facilitate mosquito breeding and predicts spatio-temporal mosquito population variability at high resolution using an agent-based modeling approach. Results: Observations of soil moisture, pool size, and pool persistence are reproduced by the model. The resulting breeding of mosquitoes in the simulated pools yields time-integrated seasonal mosquito population dynamics that closely follow observations from captured mosquito abundance. Interannual difference in mosquito abundance is simulated, and the inter-village difference in mosquito population is reproduced for two years of observations. These modeling results emulate the known focal nature of malaria in Niger Sahel villages. Conclusion: Hydrological variability must be represented at high spatial and temporal resolution to achieve accurate predictive ability of malaria risk at the village scale, which can then be integrated appropriately to regional spatial scales and seasonal temporal scales. These results have important implications for models seeking to link the impacts of climate change and climate variability to malaria transmission. The highly focal nature of malaria in the Sahel makes detailed representation necessary to evaluate village-level risks associated with hydrology-related vector population variability.National Oceanic and Atmospheric Administration. Oceans and Human Health Initiativ