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Decomposing the sources of SARS-CoV-2 fitness variation in the United States.

ABSTRACT: The fitness of a pathogen is a composite phenotype determined by many different factors influencing growth rates both within and between hosts. Determining what factors shape fitness at the host population-level is especially challenging because both intrinsic factors like pathogen genetics and extrinsic factors such as host behavior influence between-host transmission potential. This challenge has been highlighted by controversy surrounding the population-level fitness effects of mutations in the SARS-CoV-2 genome and their relative importance when compared against non-genetic factors shaping transmission dynamics. Building upon phylodynamic birth-death models, we develop a new framework to learn how hundreds of genetic and non-genetic factors have shaped the fitness of SARS-CoV-2. We estimate the fitness effects of all amino acid variants and several structural variants that have circulated in the United States between February 2020 and March 2021 from viral phylogenies. We also estimate how much fitness variation among pathogen lineages is attributable to genetic versus non-genetic factors such as spatial heterogeneity in transmission rates. Before September 2020, most fitness variation between lineages can be explained by background spatial heterogeneity in transmission rates across geographic regions. Starting in late 2020, genetic variation in fitness increased dramatically with the emergence of several new lineages including B.1.1.7, B.1.427, B.1.429 and B.1.526. Our analysis also indicates that genetic variants in less well-explored genomic regions outside of Spike may be contributing significantly to overall fitness variation in the viral population.

SUBMITTER: Kepler L

PROVIDER: S-EPMC8499931 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:INTRODUCTION:Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has infected >6 million people worldwide since December 2019. Global reports of HIV/SARS-CoV-2 coinfection are limited. To better understand the impact of the coronavirus disease 2019 (COVID-19) pandemic on persons with HIV and improve their care, we present an outpatient and inpatient clinical experience of HIV/SARS-CoV-2 coinfection from Rhode Island, US. METHODS:We describe outpatient and inpatient preparedness for the COVID-19 pandemic, and present a case series of all known patients with HIV/SARS-CoV-2 coinfection at The Miriam Hospital and Rhode Island Hospital, and The Miriam Hospital Infectious Diseases and Immunology Center, in Providence, Rhode Island, US. RESULTS AND DISCUSSION:The Infectious Diseases and Immunology Center rapidly prepared for outpatient and inpatient care of persons with HIV and SARS-CoV-2. Between 30 March and 20 May 2020, 27 patients with HIV were diagnosed with SARS-CoV-2. Twenty were male, six female and one transgender female; average age was 49 years; 13/27 were Hispanic and 6/27 were African American. All had HIV viral load <200 copies/mL and were on antiretroviral therapy with CD4 count range 87 to 1441 cells/µL. Twenty-six of the 27 had common COVID-19 symptoms for one to twenty-eight days and most had other co-morbidities and/or risk factors. Nine of the 27 were hospitalized for one to thirteen days; of those, three lived in a nursing home, six received remdesivir through a clinical trial or emergency use authorization and tolerated it well; eight recovered and one died. Overall, 17% of known Center people had HIV/SARS-CoV-2 coinfection, whereas the comparable state-wide prevalence was 9%. CONCLUSIONS:We highlight challenges of outpatient and inpatient HIV care in the setting of the COVID-19 pandemic and present the largest detailed case series to date from the United States on HIV/SARS-CoV-2 coinfection, adding to limited global reports. The aggregated clinical findings suggest that the clinical presentation and outcomes of COVID-19 appear consistent with those without HIV. Whether SARS-CoV-2 infection is more frequent among persons with HIV remains to be determined. More data are needed as we develop our understanding of how HIV and antiretroviral therapy are affected by or have an impact on this pandemic.

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Decomposing the sources of SARS-CoV-2 fitness variation in the United States.

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