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1.
Open Forum Infect Dis ; 8(11): ofab518, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1528171

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) has had high incidence rates at institutions of higher education (IHE) in the United States, but the transmission dynamics in these settings are poorly understood. It remains unclear to what extent IHE-associated outbreaks have contributed to transmission in nearby communities. METHODS: We implemented high-density prospective genomic surveillance to investigate these dynamics at the University of Michigan and the surrounding community during the Fall 2020 semester (August 16-November 24). We sequenced complete severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from 1659 individuals, including 468 students, representing 20% of cases in students and 25% of total cases in Washtenaw County over the study interval. RESULTS: Phylogenetic analysis identified >200 introductions into the student population, most of which were not related to other student cases. There were 2 prolonged student transmission clusters, of 115 and 73 individuals, that spanned multiple on-campus residences. Remarkably, <5% of nonstudent genomes were descended from student clusters, and viral descendants of student cases were rare during a subsequent wave of infections in the community. CONCLUSIONS: The largest outbreaks among students at the University of Michigan did not significantly contribute to the rise in community cases in Fall 2020. These results provide valuable insights into SARS-CoV-2 transmission dynamics at the regional level.

2.
J Infect Dis ; 224(8): 1287-1293, 2021 10 28.
Article in English | MEDLINE | ID: covidwho-1505875

ABSTRACT

BACKGROUND: Previous studies demonstrated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA can be detected for weeks after infection. The significance of this finding is unclear and, in most patients, does not represent active infection. Detection of subgenomic RNA has been proposed to represent productive infection and may be a useful marker for monitoring infectivity. METHODS: We used quantitative reverse-transcription polymerase chain reaction (RT-qPCR) to quantify total and subgenomic nucleocapsid (sgN) and envelope (sgE) transcripts in 185 SARS-CoV-2-positive nasopharyngeal swab samples collected on hospital admission and to relate to symptom duration. RESULTS: We find that all transcripts decline at the same rate; however, sgE becomes undetectable before other transcripts. The median duration of symptoms to a negative test is 14 days for sgE and 25 days for sgN. There is a linear decline in subgenomic compared to total RNA, suggesting that subgenomic transcript copy number is dependent on copy number of total transcripts. The mean difference between total and sgN is 16-fold and the mean difference between total and sgE is 137-fold. This relationship is constant over duration of symptoms, allowing prediction of subgenomic copy number from total copy number. CONCLUSIONS: Subgenomic RNA may be no more useful in determining infectivity than a copy number threshold determined for total RNA.


Subject(s)
COVID-19 Nucleic Acid Testing/methods , COVID-19/diagnosis , RNA, Viral/isolation & purification , SARS-CoV-2/isolation & purification , Viral Load , Aged , COVID-19/transmission , COVID-19/virology , COVID-19 Nucleic Acid Testing/standards , COVID-19 Nucleic Acid Testing/statistics & numerical data , Coronavirus Envelope Proteins/genetics , Coronavirus Nucleocapsid Proteins/genetics , Feasibility Studies , Female , Humans , Male , Middle Aged , Nasopharynx/pathology , Nasopharynx/virology , Phosphoproteins/genetics , Real-Time Polymerase Chain Reaction/statistics & numerical data , Reference Values , Retrospective Studies , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity
3.
Open Forum Infect Dis ; 8(7): ofab268, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1320320

ABSTRACT

Monoclonal antibodies targeting the receptor binding domain (RBD) of severe acute respiratory syndrome coronavirus 2 spike protein are important outpatient treatment options in coronavirus disease 2019 to mitigate progression of disease and prevent hospitalization. The impact of different RBD mutations on the efficacy of the available monoclonal antibodies and processes for incorporating this impact into treatment algorithms are ill defined. Herein, we synthesize the data surrounding the impact of key RBD mutations on the efficacy of US Food and Drug Administration Emergency Use Authorized monoclonal antibodies and describe our approach at Michigan Medicine at monitoring mutation frequency in circulating virus and developing an algorithm that incorporates these data into outpatient treatment pathways.

4.
PLoS Pathog ; 17(4): e1009499, 2021 04.
Article in English | MEDLINE | ID: covidwho-1171175

ABSTRACT

Analysis of SARS-CoV-2 genetic diversity within infected hosts can provide insight into the generation and spread of new viral variants and may enable high resolution inference of transmission chains. However, little is known about temporal aspects of SARS-CoV-2 intrahost diversity and the extent to which shared diversity reflects convergent evolution as opposed to transmission linkage. Here we use high depth of coverage sequencing to identify within-host genetic variants in 325 specimens from hospitalized COVID-19 patients and infected employees at a single medical center. We validated our variant calling by sequencing defined RNA mixtures and identified viral load as a critical factor in variant identification. By leveraging clinical metadata, we found that intrahost diversity is low and does not vary by time from symptom onset. This suggests that variants will only rarely rise to appreciable frequency prior to transmission. Although there was generally little shared variation across the sequenced cohort, we identified intrahost variants shared across individuals who were unlikely to be related by transmission. These variants did not precede a rise in frequency in global consensus genomes, suggesting that intrahost variants may have limited utility for predicting future lineages. These results provide important context for sequence-based inference in SARS-CoV-2 evolution and epidemiology.


Subject(s)
COVID-19/virology , Mutation Accumulation , SARS-CoV-2/genetics , Aged , Base Sequence , COVID-19/metabolism , Female , Genetic Variation , Genome, Viral , Host Microbial Interactions , Humans , Male , Middle Aged , Mutation/genetics , Phylogeny , RNA, Viral/genetics , Sequence Analysis, RNA/methods
5.
Cell ; 184(10): 2595-2604.e13, 2021 05 13.
Article in English | MEDLINE | ID: covidwho-1163482

ABSTRACT

The emergence and spread of SARS-CoV-2 lineage B.1.1.7, first detected in the United Kingdom, has become a global public health concern because of its increased transmissibility. Over 2,500 COVID-19 cases associated with this variant have been detected in the United States (US) since December 2020, but the extent of establishment is relatively unknown. Using travel, genomic, and diagnostic data, we highlight that the primary ports of entry for B.1.1.7 in the US were in New York, California, and Florida. Furthermore, we found evidence for many independent B.1.1.7 establishments starting in early December 2020, followed by interstate spread by the end of the month. Finally, we project that B.1.1.7 will be the dominant lineage in many states by mid- to late March. Thus, genomic surveillance for B.1.1.7 and other variants urgently needs to be enhanced to better inform the public health response.


Subject(s)
COVID-19 Testing , COVID-19 , Models, Biological , SARS-CoV-2 , COVID-19/genetics , COVID-19/mortality , COVID-19/transmission , Female , Humans , Male , SARS-CoV-2/genetics , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , United States/epidemiology
6.
Am J Transplant ; 21(8): 2885-2889, 2021 08.
Article in English | MEDLINE | ID: covidwho-1075766

ABSTRACT

We describe a case of proven transmission of SARS-CoV-2 from lung donor to recipient. The donor had no clinical history or findings suggestive of infection with SARS-CoV-2 and tested negative by reverse transcriptase polymerase chain reaction (RT-PCR) on a nasopharyngeal (NP) swab obtained within 48 h of procurement. Lower respiratory tract testing was not performed. The recipient developed fever, hypotension, and pulmonary infiltrates on posttransplant day (PTD) 3, and RT-PCR testing for SARS-CoV-2 on an NP swab specimen was non-reactive, but positive on bronchoalveolar lavage (BAL) fluid. One thoracic surgeon present during the transplantation procedure developed COVID-19. Sequence analysis of isolates from donor BAL fluid (obtained at procurement), the recipient, and the infected thoracic surgeon proved donor origin of recipient and health-care worker (HCW) infection. No other organs were procured from this donor. Transplant centers and organ procurement organizations should perform SARS-CoV-2 testing of lower respiratory tract specimens from potential lung donors, and consider enhanced personal protective equipment for HCWs involved in lung procurement and transplantation.


Subject(s)
COVID-19 , Lung Transplantation , COVID-19 Testing , Humans , Lung , Lung Transplantation/adverse effects , SARS-CoV-2
7.
J Infect Dis ; 223(1): 23-27, 2021 01 04.
Article in English | MEDLINE | ID: covidwho-1066344

ABSTRACT

We describe a case of chronic coronavirus disease 2019 (COVID-19) in a patient with lymphoma and associated B-cell immunodeficiency. Viral cultures and sequence analysis demonstrate ongoing replication of infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for at least 119 days. The patient had 3 admissions related to COVID-19 over a 4-month period and was treated twice with remdesivir and convalescent plasma with resolution of symptoms. The patient's lack of seroconversion and prolonged course illustrate the importance of humoral immunity in resolving SARS-CoV-2 infection. This case highlights challenges in managing immunocompromised hosts, who may act as persistent shedders and sources of transmission.


Subject(s)
COVID-19/virology , SARS-CoV-2/physiology , Virus Replication , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Antibodies, Viral/blood , COVID-19/diagnosis , Hospitalization , Humans , Immunity, Humoral , Immunocompromised Host , Lymphoma, Mantle-Cell/complications , Male , Middle Aged , Primary Immunodeficiency Diseases/complications , Seroconversion
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