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1.
Commun Biol ; 5(1): 439, 2022 05 11.
Article in English | MEDLINE | ID: covidwho-1839575

ABSTRACT

SARS-CoV-2 variants shaped the second year of the COVID-19 pandemic and the discourse around effective control measures. Evaluating the threat posed by a new variant is essential for adapting response efforts when community transmission is detected. In this study, we compare the dynamics of two variants, Alpha and Iota, by integrating genomic surveillance data to estimate the effective reproduction number (Rt) of the variants. We use Connecticut, United States, in which Alpha and Iota co-circulated in 2021. We find that the Rt of these variants were up to 50% larger than that of other variants. We then use phylogeography to show that while both variants were introduced into Connecticut at comparable frequencies, clades that resulted from introductions of Alpha were larger than those resulting from Iota introductions. By monitoring the dynamics of individual variants throughout our study period, we demonstrate the importance of routine surveillance in the response to COVID-19.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , Genomics , Humans , Pandemics , SARS-CoV-2/genetics , United States/epidemiology
2.
J Infect Dis ; 225(3): 374-384, 2022 02 01.
Article in English | MEDLINE | ID: covidwho-1672205

ABSTRACT

BACKGROUND: The underlying immunologic deficiencies enabling severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection are currently unknown. We describe deep longitudinal immune profiling of a transplant recipient hospitalized twice for coronavirus disease 2019 (COVID-19). METHODS: A 66-year-old male renal transplant recipient was hospitalized with COVID-19 March 2020 then readmitted to the hospital with COVID-19 233 days after initial diagnosis. Virologic and immunologic investigations were performed on samples from the primary and secondary infections. RESULTS: Whole viral genome sequencing and phylogenetic analysis revealed that viruses causing both infections were caused by distinct genetic lineages without evidence of immune escape mutations. Longitudinal comparison of cellular and humoral responses during primary SARS-CoV-2 infection revealed that this patient responded to the primary infection with low neutralization titer anti-SARS-CoV-2 antibodies that were likely present at the time of reinfection. CONCLUSIONS: The development of neutralizing antibodies and humoral memory responses in this patient failed to confer protection against reinfection, suggesting that they were below a neutralizing titer threshold or that additional factors may be required for efficient prevention of SARS-CoV-2 reinfection. Development of poorly neutralizing antibodies may have been due to profound and relatively specific reduction in naive CD4 T-cell pools. Seropositivity alone may not be a perfect correlate of protection in immunocompromised patients.


Subject(s)
COVID-19 , Reinfection , Transplant Recipients , Aged , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , Humans , Male , Organ Transplantation , Phylogeny , Reinfection/immunology , Reinfection/virology , SARS-CoV-2/genetics
3.
J Infect Dis ; 225(3): 374-384, 2022 02 01.
Article in English | MEDLINE | ID: covidwho-1493831

ABSTRACT

BACKGROUND: The underlying immunologic deficiencies enabling severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection are currently unknown. We describe deep longitudinal immune profiling of a transplant recipient hospitalized twice for coronavirus disease 2019 (COVID-19). METHODS: A 66-year-old male renal transplant recipient was hospitalized with COVID-19 March 2020 then readmitted to the hospital with COVID-19 233 days after initial diagnosis. Virologic and immunologic investigations were performed on samples from the primary and secondary infections. RESULTS: Whole viral genome sequencing and phylogenetic analysis revealed that viruses causing both infections were caused by distinct genetic lineages without evidence of immune escape mutations. Longitudinal comparison of cellular and humoral responses during primary SARS-CoV-2 infection revealed that this patient responded to the primary infection with low neutralization titer anti-SARS-CoV-2 antibodies that were likely present at the time of reinfection. CONCLUSIONS: The development of neutralizing antibodies and humoral memory responses in this patient failed to confer protection against reinfection, suggesting that they were below a neutralizing titer threshold or that additional factors may be required for efficient prevention of SARS-CoV-2 reinfection. Development of poorly neutralizing antibodies may have been due to profound and relatively specific reduction in naive CD4 T-cell pools. Seropositivity alone may not be a perfect correlate of protection in immunocompromised patients.


Subject(s)
COVID-19 , Reinfection , Transplant Recipients , Aged , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , Humans , Male , Organ Transplantation , Phylogeny , Reinfection/immunology , Reinfection/virology , SARS-CoV-2/genetics
4.
Emerg Infect Dis ; 27(10): 2669-2672, 2021.
Article in English | MEDLINE | ID: covidwho-1486740

ABSTRACT

In fall 2020, a coronavirus disease cluster comprising 16 cases occurred in Connecticut, USA. Epidemiologic and genomic evidence supported transmission among persons at a school and fitness center but not a workplace. The multiple transmission chains identified within this cluster highlight the necessity of a combined investigatory approach.


Subject(s)
COVID-19 , Fitness Centers , Connecticut/epidemiology , Genomics , Humans , SARS-CoV-2
5.
Hum Genomics ; 15(1): 27, 2021 05 10.
Article in English | MEDLINE | ID: covidwho-1221746

ABSTRACT

COVID-19 has engulfed the world and it will accompany us all for some time to come. Here, we review the current state at the milestone of 1 year into the pandemic, as declared by the WHO (World Health Organization). We review several aspects of the on-going pandemic, focusing first on two major topics: viral variants and the human genetic susceptibility to disease severity. We then consider recent and exciting new developments in therapeutics, such as monoclonal antibodies, and in prevention strategies, such as vaccines. We also briefly discuss how advances in basic science and in biotechnology, under the threat of a worldwide emergency, have accelerated to an unprecedented degree of the transition from the laboratory to clinical applications. While every day we acquire more and more tools to deal with the on-going pandemic, we are aware that the path will be arduous and it will require all of us being community-minded. In this respect, we lament past delays in timely full investigations, and we call for bypassing local politics in the interest of humankind on all continents.


Subject(s)
COVID-19/genetics , COVID-19/virology , Pandemics , Antibodies, Monoclonal/therapeutic use , COVID-19/prevention & control , COVID-19/therapy , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , Genetic Predisposition to Disease , Health Policy , Humans , Population Health , SARS-CoV-2 , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/immunology
6.
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
7.
PLoS Biol ; 18(8): e3000869, 2020 08.
Article in English | MEDLINE | ID: covidwho-727315

ABSTRACT

Genomic epidemiology can provide a unique, real-time understanding of SARS-CoV-2 transmission patterns. Yet the potential for genomic analyses to guide local policy and community-based behavioral decisions is limited because they are often oriented towards specially trained scientists and conducted on a national or global scale. Here, we propose a new paradigm: Phylogenetic analyses performed on a local level (municipal, county, or state), with results communicated in a clear, timely, and actionable manner to strengthen public health responses. We believe that presenting results rapidly, and tailored to a non-expert audience, can serve as a template for effective public health response to COVID-19 and other emerging viral diseases.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/epidemiology , Information Dissemination , Pneumonia, Viral/epidemiology , Public Health , COVID-19 , Genomics , Humans , Pandemics , Phylogeny , SARS-CoV-2
8.
Nat Microbiol ; 5(10): 1299-1305, 2020 10.
Article in English | MEDLINE | ID: covidwho-638387

ABSTRACT

The recent spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exemplifies the critical need for accurate and rapid diagnostic assays to prompt clinical and public health interventions. Currently, several quantitative reverse transcription-PCR (RT-qPCR) assays are being used by clinical, research and public health laboratories. However, it is currently unclear whether results from different tests are comparable. Our goal was to make independent evaluations of primer-probe sets used in four common SARS-CoV-2 diagnostic assays. From our comparisons of RT-qPCR analytical efficiency and sensitivity, we show that all primer-probe sets can be used to detect SARS-CoV-2 at 500 viral RNA copies per reaction. The exception for this is the RdRp-SARSr (Charité) confirmatory primer-probe set which has low sensitivity, probably due to a mismatch to circulating SARS-CoV-2 in the reverse primer. We did not find evidence for background amplification with pre-COVID-19 samples or recent SARS-CoV-2 evolution decreasing sensitivity. Our recommendation for SARS-CoV-2 diagnostic testing is to select an assay with high sensitivity and that is regionally used, to ease comparability between outcomes.


Subject(s)
Betacoronavirus/genetics , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , RNA, Viral/analysis , RNA, Viral/genetics , Reverse Transcriptase Polymerase Chain Reaction/methods , Betacoronavirus/isolation & purification , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques/statistics & numerical data , Coronavirus Infections/epidemiology , Genetic Variation , Genome, Viral , Humans , Molecular Probe Techniques/statistics & numerical data , Pandemics , Pneumonia, Viral/epidemiology , RNA/genetics , RNA Probes/genetics , Reverse Transcriptase Polymerase Chain Reaction/statistics & numerical data , SARS-CoV-2 , Sensitivity and Specificity
9.
J Clin Invest ; 130(9): 4947-4953, 2020 09 01.
Article in English | MEDLINE | ID: covidwho-611525

ABSTRACT

BACKGROUNDThe effects of the novel coronavirus disease 2019 (COVID-19) in pregnancy remain relatively unknown. We present a case of second trimester pregnancy with symptomatic COVID-19 complicated by severe preeclampsia and placental abruption.METHODSWe analyzed the placenta for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through molecular and immunohistochemical assays and by and electron microscopy and measured the maternal antibody response in the blood to this infection.RESULTSSARS-CoV-2 localized predominantly to syncytiotrophoblast cells at the materno-fetal interface of the placenta. Histological examination of the placenta revealed a dense macrophage infiltrate, but no evidence for the vasculopathy typically associated with preeclampsia.CONCLUSIONThis case demonstrates SARS-CoV-2 invasion of the placenta, highlighting the potential for severe morbidity among pregnant women with COVID-19.FUNDINGBeatrice Kleinberg Neuwirth Fund and Fast Grant Emergent Ventures funding from the Mercatus Center at George Mason University. The funding bodies did not have roles in the design of the study or data collection, analysis, and interpretation and played no role in writing the manuscript.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Placenta/pathology , Placenta/virology , Pneumonia, Viral/complications , Pregnancy Complications, Infectious/etiology , Pregnancy Complications, Infectious/virology , Abortion, Therapeutic , Abruptio Placentae/etiology , Abruptio Placentae/pathology , Abruptio Placentae/virology , Adult , Betacoronavirus/genetics , Betacoronavirus/isolation & purification , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus Infections/pathology , Coronavirus Infections/virology , Female , Humans , Microscopy, Electron, Transmission , Pandemics , Phylogeny , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Pre-Eclampsia/etiology , Pre-Eclampsia/pathology , Pre-Eclampsia/virology , Pregnancy , Pregnancy Complications, Infectious/pathology , Pregnancy Trimester, Second , RNA, Viral/genetics , RNA, Viral/isolation & purification , SARS-CoV-2 , Viral Load
10.
Cell ; 181(5): 990-996.e5, 2020 05 28.
Article in English | MEDLINE | ID: covidwho-60444

ABSTRACT

The novel coronavirus SARS-CoV-2 was first detected in the Pacific Northwest region of the United States in January 2020, with subsequent COVID-19 outbreaks detected in all 50 states by early March. To uncover the sources of SARS-CoV-2 introductions and patterns of spread within the United States, we sequenced nine viral genomes from early reported COVID-19 patients in Connecticut. Our phylogenetic analysis places the majority of these genomes with viruses sequenced from Washington state. By coupling our genomic data with domestic and international travel patterns, we show that early SARS-CoV-2 transmission in Connecticut was likely driven by domestic introductions. Moreover, the risk of domestic importation to Connecticut exceeded that of international importation by mid-March regardless of our estimated effects of federal travel restrictions. This study provides evidence of widespread sustained transmission of SARS-CoV-2 within the United States and highlights the critical need for local surveillance.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/transmission , Pneumonia, Viral/transmission , Travel , Betacoronavirus/isolation & purification , COVID-19 , Connecticut/epidemiology , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Epidemiological Monitoring , Humans , Likelihood Functions , Pandemics , Phylogeny , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , SARS-CoV-2 , Travel/legislation & jurisprudence , United States/epidemiology , Washington/epidemiology
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