Genomic surveillance reveals dynamic shifts in the connectivity of COVID-19 epidemics.

The maturation of genomic surveillance in the past decade has enabled tracking of the emergence and spread of epidemics at an unprecedented level. During the COVID-19 pandemic, for example, genomic data revealed that local epidemics varied considerably in the frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage importation and persistence, likely due to a combination of COVID-19 restrictions and changing connectivity. Here, we show that local COVID-19 epidemics are driven by regional transmission, including across international boundaries, but can become increasingly connected to distant locations following the relaxation of public health interventions. By integrating genomic, mobility, and epidemiological data, we find abundant transmission occurring between both adjacent and distant locations, supported by dynamic mobility patterns. We find that changing connectivity significantly influences local COVID-19 incidence. Our findings demonstrate a complex meaning of "local" when investigating connected epidemics and emphasize the importance of collaborative interventions for pandemic prevention and mitigation.

Epidemiology of COVID-19 in Mexico: Symptomatic profiles and presymptomatic people.

OBJECTIVES: The COVID-19 diagnosis is difficult and ambiguous due to nonspecific symptoms. Further, data from Mexico arehospitable population-based without signs and symptoms information. Thus, this work aims to provide epidemiology information about the burden of COVID-19 in Mexican outpatients and to identify symptomatic COVID-19 profiles that could help in the early diagnosis of the disease. METHODS: From June to September, epidemiological, clinical, and demographic data of 482,413 individuals diagnosed by RT-PCR test for SARS-CoV-2 in Salud Digna clinics were collected. RESULTS: We observed a 41% incidence of SARS-CoV-2 infections with a mean age of 36 years and with young adults (20-40 years) being the most affected. Among occupations, delivery persons (OR 1.38) or informal traders (OR 1.33) had a higher risk of COVID-19. Moreover, 13% of SARS-CoV-2 infections were in presymptomatic patients. Finally, we identified three different symptomatic profiles (common, respiratory, and gastrointestinal) associated with COVID-19. CONCLUSION: The incidence of SARS-CoV-2 was high among outpatients with a significant proportion of presymptomatic carriers, and thus it is necessary to increase testing and continue SARS-CoV-2 surveillance with a better description of signs and symptoms; in this regard, we identified three symptomatic profiles that could help in the diagnosis of COVID-19.

Beyond the antibody: B cells as a target for bacterial infection.

It is well established that B cells play an important role during infections beyond antibody production. B cells produce cytokines and are APCs for T cells. Recently, it has become clear that several pathogenic bacterial genera, such as Salmonella, Brucella, Mycobacterium, Listeria, Francisella, Moraxella, and Helicobacter, have evolved mechanisms such as micropinocytosis induction, inflammasome down-regulation, inhibitory molecule expression, apoptosis induction, and anti-inflammatory cytokine secretion to manipulate B cell functions influencing immune responses. In this review, we summarize our current understanding of B cells as targets of bacterial infection and the mechanisms by which B cells become a niche for bacterial survival and replication away from extracellular immune responses such as complement and antibodies.

SopB activates the Akt-YAP pathway to promote Salmonella survival within B cells.

B cells are a target of Salmonella infection, allowing bacteria survival without inducing pyroptosis. This event is due to downregulation of Nlrc4 expression and lack of inflammasome complex activation, which impairs the secretion of IL-1ß. YAP phosphorylation is required for downregulation of Nlrc4 in B cells during Salmonella infection; however, the microorganism's mechanisms underlying the inhibition of the NLRC4 inflammasome in B cells are not fully understood. Our findings demonstrate that the Salmonella effector SopB triggers a signaling cascade involving PI3K, PDK1 and mTORC2 that activates Akt with consequent phosphorylation of YAP. When we deleted sopB in Salmonella, infected B cells that lack Rictor, or inhibited the signaling cascade using a pharmacological approach, we were able to restore the function of the NLRC4 inflammasome in B cells and the ability to control the infection. Furthermore, B cells from infected mice exhibited activation of Akt and YAP phosphorylation, suggesting that Salmonella also triggers this pathway in vivo. In summary, our data demonstrate that the Salmonella effector inositide phosphate phosphatase SopB triggers the PI3K-Akt-YAP pathway to inhibit the NLRC4 inflammasome in B cells. This study provides further evidence that Salmonella triggers cellular mechanisms in B lymphocytes to manipulate the host environment by turning it into a survival niche to establish a successful infection.