Longitudinal characterization of mixed-genotype SARS-CoV-2 infections in a military cohort reveals compartmentalized viral populations

{"Mixed-genotype":[0],"severe":[1,182],"acute":[2,183],"respiratory":[3,184],"syndrome":[4,185],"coronavirus":[5,186],"2":[6,187],"(SARS-CoV-2)":[7,188],"infections":[8,197,300],"are":[9,198],"a":[10,127,216,244,272,280],"concern":[11],"due":[12],"to":[13,23,94,100,113,144,204,229,321,328],"the":[14,39,107,162,333],"potential":[15,308],"generation":[16],"of":[17,49,109,164,181,268,277,288,294,335],"novel":[18],"recombinants":[19,180],"that":[20,121,246],"give":[21],"rise":[22],"new":[24],"variants.":[25],"To":[26,233],"better":[27],"understand":[28],"intra-host":[29,231],"viral":[30],"dynamics,":[31],"we":[32,69,152,242],"analyzed":[33,215],"specimens":[34,221],"from":[35,38,102,148,156,190,222,237],"24":[36,66],"participants":[37],"U.S.":[40],"Military":[41],"Health":[42],"System's":[43],"Epidemiology,":[44],"Immunology,":[45],"and":[46,75,89,116,169,207,255,279,291,301,314,331],"Clinical":[47],"Characteristics":[48],"Emerging":[50],"Infectious":[51],"Diseases":[52],"with":[53,58,192,220,240,257],"Pandemic":[54],"Potential":[55],"COVID-19":[56],"cohort":[57],"suspected":[59,67],"mixed-genotype":[60,97],"SARS-CoV-2":[61,296],"infections.":[62,98,177],"From":[63],"an":[64,140,227],"initial":[65],"cases,":[68,151],"confirmed":[70],"17":[71],"as":[72,130,132],"genuine":[73,154],"coinfections":[74,155,191],"graded":[76],"them":[77],"by":[78,126,252],"evidence:":[79],"7":[80,90],"were":[81,84,87,91],"\\"strong\\";":[82],"4":[83],"\\"moderate\\";":[85],"6":[86],"\\"weak\\";":[88],"deemed":[92],"unlikely":[93],"be":[95],"true":[96,235,304],"Access":[99],"swabs":[101],"multiple":[103,223],"body":[104,224],"sites":[105],"across":[106],"course":[108],"infection":[110,306],"allowed":[111,263],"us":[112],"observe":[114],"compartmentalization":[115,278],"shifts":[117],"in":[118,173,324],"variant":[119,260],"dominance":[120],"would":[122],"have":[123],"been":[124],"missed":[125],"single-timepoint":[128],"analysis,":[129],"well":[131],"one":[133],"recombinant":[134,281],"Omicron":[135],"BA.1/BA.2":[136],"genome.":[137],"By":[138],"using":[139],"evidence-based":[141],"bioinformatic":[142,157,171,238],"framework":[143,245],"assess":[145,230],"sequencing":[146],"data":[147,218],"well-characterized":[149],"clinical":[150,292],"distinguished":[153],"artifacts.":[158],"Our":[159],"findings":[160],"emphasize":[161],"importance":[163],"both":[165],"extensive":[166],"specimen":[167],"collection":[168],"careful":[170],"approaches":[172],"ascertaining":[174],"dual":[175],"genotype":[176],"IMPORTANCE:":[178],"Novel":[179],"arise":[189],"different":[193],"lineages,":[194],"but":[195],"mixed":[196,250,269,295],"not":[199],"screened":[200],"for":[201,249,332],"despite":[202],"risk":[203],"public":[205,312],"health,":[206],"most":[208],"surveillance":[209],"relies":[210],"on":[211],"single":[212,273],"swabs.":[213],"We":[214],"longitudinal":[217],"set":[219],"sites,":[225],"providing":[226],"opportunity":[228],"dynamics.":[232],"distinguish":[234],"coinfection":[236],"artifacts":[239,310],"confidence,":[241],"applied":[243],"grades":[247],"evidence":[248,320],"genotypes":[251,270],"incorporating":[253],"lineage":[254],"clade":[256],"manually":[258],"validated":[259],"calls.":[261],"This":[262,283],"investigation":[264],"beyond":[265],"abundance":[266],"levels":[267],"within":[271],"specimen,":[274],"including":[275],"observations":[276],"virus.":[282],"work":[284],"enables":[285],"further":[286],"study":[287],"evolutionary,":[289],"immunological,":[290],"implications":[293],"genotypes.":[297],"Detecting":[298],"dual-genotype":[299,305],"discriminating":[302],"between":[303],"vs":[307],"bioinformatics-based":[309],"support":[311],"health":[313],"military":[315],"readiness.":[316],"These":[317],"efforts":[318],"provide":[319],"bolster":[322],"decision-making":[323],"molecular":[325],"epidemiological":[326],"studies":[327],"track":[329],"transmission":[330],"choice":[334],"effective":[336],"countermeasures.":[337]}

Authors

Institutions

Publication Details

Journal
Microbiology Spectrum
Published
2026-09-14
DOI
https://doi.org/10.1128/spectrum.01806-26
Primary Topic
SARS-CoV-2 and COVID-19 Research
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
article

Longitudinal characterization of mixed-genotype SARS-CoV-2 infections in a military cohort reveals compartmentalized viral populations

Brian K. Agan, Kyle A. Long, Stephanie A Richard, Katrin Mende et al.
Microbiology Spectrum
SARS-CoV-2 and COVID-19 Research
article

Longitudinal characterization of mixed-genotype SARS-CoV-2 infections in a military cohort reveals compartmentalized viral populations

Brian K. Agan, Kyle A. Long, Stephanie A Richard, Katrin Mende, Anthony C Fries, Bishwo N. Adhikari, Logan J. Voegtly, Mark P. Simons, Robin H. Miller, Kimberly A. Bishop‐Lilly, Adrian C. Paskey, David R. Tribble, Francisco Malagón, J. Alexander Chitty, Regina Z. Cer, Charlotte Lanteri, Simon D. Pollett, Timothy H. Burgess, Haven Miner
article en

Abstract

Mixed-genotype severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are a concern due to the potential generation of novel recombinants that give rise to new variants. To better understand intra-host viral dynamics, we analyzed specimens from 24 participants from the U.S. Military Health System's Epidemiology, Immunology, and Clinical Characteristics of Emerging Infectious Diseases with Pandemic Potential COVID-19 cohort with suspected mixed-genotype SARS-CoV-2 infections. From an initial 24 suspected cases, we confirmed 17 as genuine coinfections and graded them by evidence: 7 were "strong"; 4 were "moderate"; 6 were "weak"; and 7 were deemed unlikely to be true mixed-genotype infections. Access to swabs from multiple body sites across the course of infection allowed us to observe compartmentalization and shifts in variant dominance that would have been missed by a single-timepoint analysis, as well as one recombinant Omicron BA.1/BA.2 genome. By using an evidence-based bioinformatic framework to assess sequencing data from well-characterized clinical cases, we distinguished genuine coinfections from bioinformatic artifacts. Our findings emphasize the importance of both extensive specimen collection and careful bioinformatic approaches in ascertaining dual genotype infections. IMPORTANCE: Novel recombinants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) arise from coinfections with different lineages, but mixed infections are not screened for despite risk to public health, and most surveillance relies on single swabs. We analyzed a longitudinal data set with specimens from multiple body sites, providing an opportunity to assess intra-host dynamics. To distinguish true coinfection from bioinformatic artifacts with confidence, we applied a framework that grades evidence for mixed genotypes by incorporating lineage and clade with manually validated variant calls. This allowed investigation beyond abundance levels of mixed genotypes within a single specimen, including observations of compartmentalization and a recombinant virus. This work enables further study of evolutionary, immunological, and clinical implications of mixed SARS-CoV-2 genotypes. Detecting dual-genotype infections and discriminating between true dual-genotype infection vs potential bioinformatics-based artifacts support public health and military readiness. These efforts provide evidence to bolster decision-making in molecular epidemiological studies to track transmission and for the choice of effective countermeasures.

Microbiology Spectrum
Leidos (United States) (US), Henry M. Jackson Foundation (US), Naval Medical Research Command (US), Defense Threat Reduction Agency (US), Uniformed Services University of the Health Sciences (US), United States Air Force (US), Joint Base San Antonio (US)
Good health and well-being
Openalex Percentile: Top 11%
SARS-CoV-2 and COVID-19 Research
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.