The ongoing pandemic of SARS-CoV-2 presents novel challenges and opportunities for the use of phylogenetics to understand and control its spread. Here, we analyze the emergence of SARS-CoV-2 in Russia in March and April 2020. Combining phylogeographic analysis with travel history data, we estimate that the sampled viral diversity has originated from at least 67 closely timed introductions into Russia, mostly in late February to early March. All but one of these introductions were not from China, suggesting that border closure with China has helped delay establishment of SARS-CoV-2 in Russia. These introductions resulted in at least 9 distinct Russian lineages corresponding to domestic transmission. A notable transmission cluster corresponded to a nosocomial outbreak at the Vreden hospital in Saint Petersburg; phylodynamic analysis of this cluster reveals multiple (2-3) introductions each giving rise to a large number of cases, with a high initial effective reproduction number of 3.0 [1.9, 4.3].

Evolution of SARS-CoV-2 in immunocompromised hosts may result in novel variants with changed properties. While escape from humoral immunity certainly contributes to intra-host evolution, escape from cellular immunity is poorly understood. Here, we report a case of long-term COVID-19 in an immunocompromised patient with non-Hodgkin’s lymphoma who received treatment with rituximab and lacked neutralizing antibodies. Over the 318 days of the disease, the SARS-CoV-2 genome gained a total of 40 changes, 34 of which were present by the end of the study period. Among the acquired mutations, 12 reduced or prevented the binding of known immunogenic SARS-CoV-2 HLA class I antigens. By experimentally assessing the effect of a subset of the escape mutations, we show that they resulted in a loss of as much as ~1% of effector CD8 T cell response. Our results indicate that CD8 T cell escape represents a major underappreciated contributor to SARS-CoV-2 evolution in humans.

Background Marinobufagenin (MBG), a bufadienolide cardiotonic steroid, induces cardiovascular fibrosis. Because levels of MBG in preeclampsia are increased, and anti-MBG monoclonal antibody reduces blood pressure (BP) in a rat model of preeclampsia, we hypothesized that in preeclampsia, elevated MBG levels would be associated with the development of fibrosis in feto-placental circulation and with impairment of vascular relaxation. Method We studied 16 patients with preeclampsia (systolic BP = 150 ± 4 mmHg; 28 ± 2 years, 37 ± 1 weeks gestational age) and 14 gestational age-matched normal pregnant women (systolic BP = 112 ± 2 mmHg). Results Preeclampsia was associated with a rise in plasma and placental levels of MBG. In preeclamptic umbilical arteries, the expression of Fli-1, a transcription factor and a negative regulator of fibrosis, was significantly reduced (P < 0.001), whereas procollagen-1 expression was increased (P < 0.01). As compared to control vessels, isolated rings of umbilical arteries from patients with preeclampsia demonstrated unaltered responsiveness to endothelin-1 (EC₅₀ = 2.2 and 3.2 nmol/l, respectively), but exhibited an impaired response to the relaxant effect of sodium nitroprusside (EC₅₀ = 1.5 vs. 32.4 nmol/l, P < .001) following endothelin-1-induced constriction. Ex-vivo treatment of normal umbilical arteries explants with 1 and 10 nmol/l MBG for 24 h mimicked the effects of preeclampsia, specifically suppressed Fli-1 and increased collagen-1 expression while impairing vasorelaxation. Conclusion Our results indicate that in preeclampsia, elevated levels of MBG induce vascular fibrosis via a Fli-1-dependent mechanism which leads to an impairment of vasorelaxation, and suggest that MBG represents a potential target for therapy of this syndrome.

New strategies providing protection against tuberculosis (TB) are still pending. The airborne nature of Mycobacterium tuberculosis (M.tb) infection assumes that the mucosal delivery of the TB vaccine could be a more promising strategy than the systemic route of immunization. We developed a mucosal TB vaccine candidate based on recombinant attenuated influenza vector (Flu/THSP) co-expressing truncated NS1 protein NS1(1–124) and a full-length TB10.4 and HspX proteins of M.tb within an NS1 protein open reading frame. The Flu/THSP vector was safe and stimulated a systemic TB-specific CD4+ and CD8+ T-cell immune response after intranasal immunization in mice. Double intranasal immunization with the Flu/THSP vector induced protection against two virulent M.tb strains equal to the effect of BCG subcutaneous injection in mice. In a guinea pig TB model, one intranasal immunization with Flu/THSP improved protection against M.tb when tested as a vaccine candidate for boosting BCG-primed immunity. Importantly, enhanced protection provided by a heterologous BCG-prime → Flu/THSP vector boost immunization scheme was associated with a significantly reduced lung and spleen bacterial burden (mean decrease of 0.77 lg CFU and 0.72 lg CFU, respectively) and improved lung pathology 8.5 weeks post-infection with virulent M.tb strain H37Rv.

A dramatic increase of influenza activity in Russia since week 3 of 2016 significantly differs from previous seasons in terms of the incidence of influenza and acute respiratory infection (ARI) and in number of lethal cases. We performed antigenic analysis of 108 and whole‐genome sequencing of 77 influenza A(H1N1)pdm09 viruses from Moscow and Saint Petersburg. Most of the viruses were antigenically related to the vaccine strain. Whole‐genome analysis revealed a composition of specific mutations in the internal genes (D2E and M83I in NEP, E125D in NS1, M105T in NP, Q208K in M1, and N204S in PA‐X) that probably emerged before the beginning of 2015/2016 epidemic season.