9Pandemics originating from pathogen transmission between animals and humans 10 highlight the broader need to understand how natural hosts have evolved in response to 11 emerging human pathogens and which groups may be susceptible to infection. Here, we 12 investigate angiotensin-converting enzyme 2 (ACE2), the host protein bound by SARS-CoV and 13 SARS-CoV-2. We find that the ACE2 gene is under strong selection pressure in bats, the group 14 in which the progenitors of SARS-CoV and SARS-CoV-2 are hypothesized to have evolved, 15 particularly in residues that contact SARS-CoV and SARS-CoV-2. We detect positive selection 16 in non-bat mammals in ACE2 but in a smaller proportion of branches than in bats, without 17 enrichment of selection in residues that contact SARS-CoV or SARS-CoV-2. Additionally, we 18 evaluate similarity between humans and other species in residues that contact SARS-CoV or 19 SARS-CoV-2, revealing potential susceptible species but also highlighting the difficulties of 20 predicting spillover events. This work increases our understanding of the relationship between 21 mammals, particularly bats, and coronaviruses, and provides data that can be used in functional 22 studies of how host proteins are bound by SARS-CoV and SARS-CoV-2 strains.23 24 Main: 25 The recent coronavirus pandemic has highlighted the disastrous impacts of zoonotic 26 spillovers and underscores the need to understand how pathogens and hosts evolve in 27 response to one another. Evolutionary analyses of host proteins targeted by infections reveal 28 the pressures that hosts have faced from pathogens and how they have evolved to resist 29 disease, informing predictions about spread of infections and how to counter them. The virus, 30SARS-CoV-2, the causative virus of COVID-19, like its close relative SARS-CoV, is thought to 31 have its progenitor origins in bats 1-3 . Bats have been suggested to be "special" reservoirs of 32 emerging infectious viruses 4 and of coronaviruses in particular 5 . However, often this species-33 rich, ecologically diverse clade is treated as a homogenous group, represented by one or two 34 was not certified by peer review) : bioRxiv preprint species, particularly when considering the interaction of SARS-CoV and SARS-CoV-2 with host 35 proteins (but see Hou et al. 6 and Demogines et al. 7 which consider multiple bat species). 36Examination of host proteins bound by potential zoonoses can be used not only to infer 37 past and current evolutionary pressure but to inform the likelihood of cross-species 38 transmission. One major barrier to cross-species transmission is the ability of the virus, adapted 39 to one host protein, to bind another species' protein 8,9 . Accordingly, many studies have 40 examined the ACE2 sequence of suspected disease reservoirs to understand how different viral 41 strains bind different species' ACE2 and where zoonotic spillover may have originated 6,8,10-12 . 42These studies, especially ones involving functional assays or in-depth modeling of virus-host 43 contacts, are usual...

Background There is increasing concern that persistent infection of SARS-CoV-2 within immunocompromised hosts could serve as a reservoir for mutation accumulation and subsequent emergence of novel strains with the potential to evade immune responses. Methods We describe three patients with acute lymphoblastic leukemia who were persistently positive for SARS-CoV-2 by real-time polymerase chain reaction. Viral viability from longitudinally-collected specimens was assessed. Whole-genome sequencing and serological studies were performed to measure viral evolution and evidence of immune escape. Findings We found compelling evidence of ongoing replication and infectivity for up to 162 days from initial positive by subgenomic RNA, single-stranded RNA, and viral culture analysis. Our results reveal a broad spectrum of infectivity, host immune responses, and accumulation of mutations, some with the potential for immune escape. Interpretation Our results highlight the need to reassess infection control precautions in the management and care of immunocompromised patients. Routine surveillance of mutations and evaluation of their potential impact on viral transmission and immune escape should be considered.

The immunological picture of how different patients recover from COVID-19, and how those recovery trajectories are influenced by infection severity, remain unclear. We investigated 140 COVID-19 patients from diagnosis to convalescence using clinical data, viral load assessments, and multi-omic analyses of blood plasma and circulating immune cells. Immune-phenotype dynamics resolved four recovery trajectories. One trajectory signals a return to pre-infection healthy baseline, while the other three are characterized by differing fractions of persistent cytotoxic and proliferative T cells, distinct B cell maturation processes, and memory-like innate immunity. We resolve a small panel of plasma proteins that, when measured at diagnosis, can predict patient survival and recovery-trajectory commitment. Our study offers novel insights into post-acute immunological outcomes of COVID-19 that likely influence long-term adverse sequelae.

Background: To estimate seroprevalence of SARS-CoV-2 antibodies in the US, the country with largest absolute numbers of COVID19 cases and deaths in the world, we conducted a cross-sectional assessment from a sample of patients receiving dialysis in January 2021. Methods: We tested remainder plasma of 21,424 patients receiving dialysis through the third-largest US dialysis organization, with facilities located nationwide. We used the Siemens spike protein receptor binding domain total antibody assay to estimate crude SARS-CoV-2 seroprevalence, and then estimated seroprevalence for the US dialysis and adult population by standardizing by age, sex and region. We also compared January 2021 seroprevalence and case-detection rates to that from a similar subsample of patients receiving dialysis who had been tested in July 2020. Results: Patients in the sample were disproportionately from older age and minority race/ethnic groups. Seroprevalence of SARS-CoV-2 was 18.9% (95% CI: 18.3-19.5%) in the sample, 18.7% (18.1-19.2%) standardized to the US dialysis population, and 21.3% (20.3-22.3%) standardized to the US adult population (range 15.3-20.8% in the Northeast and South respectively). Younger age groups (18-44 years), and persons self-identifying as Hispanic or living in Hispanic neighborhoods, and persons living in the poorest neighborhoods were among the subgroups with the highest seroprevalence (25.9% (24.1-27.8%), 25.1% (23.6-26.4%), 24.8% (23.2-26.5%) respectively). Compared to data from July 2020, we observed diminished variability in seroprevalence by geographic region and urban-rural status. Estimated case detection rate increased from 14% to 23% in July 2020 to January 2021. Conclusions: A year after the first case of SARS-CoV-2 infection was detected in the US, fewer than one in four adults have evidence of SARS-CoV-2 antibodies. Vaccine roll out to majority minority neighborhoods and poorer neighborhoods will be critical to disrupting the spread of infection.