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1.
JMIR Public Health Surveill ; 8(6): e37377, 2022 06 03.
Article in English | MEDLINE | ID: covidwho-1881329

ABSTRACT

BACKGROUND: The Omicron variant of SARS-CoV-2 is more transmissible than prior variants of concern (VOCs). It has caused the largest outbreaks in the pandemic, with increases in mortality and hospitalizations. Early data on the spread of Omicron were captured in countries with relatively low case counts, so it was unclear how the arrival of Omicron would impact the trajectory of the pandemic in countries already experiencing high levels of community transmission of Delta. OBJECTIVE: The objective of this study is to quantify and explain the impact of Omicron on pandemic trajectories and how they differ between countries that were or were not in a Delta outbreak at the time Omicron occurred. METHODS: We used SARS-CoV-2 surveillance and genetic sequence data to classify countries into 2 groups: those that were in a Delta outbreak (defined by at least 10 novel daily transmissions per 100,000 population) when Omicron was first sequenced in the country and those that were not. We used trend analysis, survival curves, and dynamic panel regression models to compare outbreaks in the 2 groups over the period from November 1, 2021, to February 11, 2022. We summarized the outbreaks in terms of their peak rate of SARS-CoV-2 infections and the duration of time the outbreaks took to reach the peak rate. RESULTS: Countries that were already in an outbreak with predominantly Delta lineages when Omicron arrived took longer to reach their peak rate and saw greater than a twofold increase (2.04) in the average apex of the Omicron outbreak compared to countries that were not yet in an outbreak. CONCLUSIONS: These results suggest that high community transmission of Delta at the time of the first detection of Omicron was not protective, but rather preluded larger outbreaks in those countries. Outbreak status may reflect a generally susceptible population, due to overlapping factors, including climate, policy, and individual behavior. In the absence of strong mitigation measures, arrival of a new, more transmissible variant in these countries is therefore more likely to lead to larger outbreaks. Alternately, countries with enhanced surveillance programs and incentives may be more likely to both exist in an outbreak status and detect more cases during an outbreak, resulting in a spurious relationship. Either way, these data argue against herd immunity mitigating future outbreaks with variants that have undergone significant antigenic shifts.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , Disease Outbreaks , Humans , Pandemics , Public Health Surveillance/methods
2.
Anal Chem ; 94(23): 8105-8109, 2022 Jun 14.
Article in English | MEDLINE | ID: covidwho-1873391

ABSTRACT

New platforms for the rapid and sensitive detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern are urgently needed. Here we report the development of a nanomechanical sensor based on the deflection of a microcantilever capable of detecting the SARS-CoV-2 spike (S) glycoprotein antigen using computationally designed multivalent minibinders immobilized on a microcantilever surface. The sensor exhibits rapid (<5 min) detection of the target antigens down to concentrations of 0.05 ng/mL (362 fM) and is more than an order of magnitude more sensitive than an antibody-based cantilever sensor. Validation of the sensor with clinical samples from 33 patients, including 9 patients infected with the Omicron (BA.1) variant observed detection of antigen from nasopharyngeal swabs with cycle threshold (Ct) values as high as 39, suggesting a limit of detection similar to that of the quantitative reverse transcription polymerase chain reaction (RT-qPCR). Our findings demonstrate the use of minibinders and nanomechanical sensors for the rapid and sensitive detection of SARS-CoV-2 and potentially other disease markers.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/diagnosis , COVID-19 Testing , Clinical Laboratory Techniques , Humans , SARS-CoV-2/genetics , Sensitivity and Specificity
3.
Open forum infectious diseases ; 2022.
Article in English | EuropePMC | ID: covidwho-1824074

ABSTRACT

Background The global effort to vaccinate people against SARS-CoV-2 during an ongoing pandemic has raised questions about how vaccine breakthrough infections compare with infections in immunologically naive individuals, and the potential for vaccinated individuals to transmit the virus. Methods We examined viral dynamics and infectious virus shedding through daily longitudinal sampling in 23 adults infected with SARS-CoV-2 at varying stages of vaccination, including 6 fully vaccinated individuals. Results The durations of both infectious virus shedding and symptoms were significantly reduced in vaccinated individuals compared with unvaccinated individuals. We also observed that breakthrough infections are associated with strong tissue compartmentalization and are only detectable in saliva in some cases. Interpretation Vaccination shortens the duration of time of high transmission potential, minimizes symptom duration, and may restrict tissue dissemination.

4.
Placenta ; 121: 79-81, 2022 04.
Article in English | MEDLINE | ID: covidwho-1730029

ABSTRACT

SARS-CoV-2 infection in pregnancy and COVID placentitis are associated with an increased risk of stillbirth. We sought to investigate the presence of maternal viremia in people with SARS-CoV-2 infection during pregnancy who had histologic placentitis versus those without placentitis. SARS-CoV-2 qRT-PCR was performed on plasma from 6 patients with COVID placentitis and 12 matched controls without placentitis. SARS-CoV-2 infection occurred between 4/2020-1/2021; the latency between SARS-CoV-2 diagnosis and delivery was 0-76 days. Two placentitis cases demonstrated viremia (1 stillbirth and 1 well infant), while 12/12 controls were negative. Future research may consider viremia as a possible marker of COVID placentitis.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , COVID-19/complications , COVID-19 Testing , Female , Humans , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/pathology , SARS-CoV-2 , Stillbirth , Viremia
5.
Open Forum Infect Dis ; 9(3): ofac027, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1701028

ABSTRACT

BACKGROUND: While several demographic and clinical correlates of coronavirus disease 2019 (COVID-19) outcome have been identified, their relationship to virological and immunological parameters remains poorly defined. METHODS: To address this, we performed longitudinal collection of nasopharyngeal swabs and blood samples from a cohort of 58 hospitalized adults with COVID-19. Samples were assessed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load, viral genotype, viral diversity, and antibody titer. Demographic and clinical information, including patient blood tests and several composite measures of disease severity, was extracted from electronic health records. RESULTS: Several factors, including male sex, higher age, higher body mass index, higher 4C Mortality score, and elevated lactate dehydrogenase levels, were associated with intensive care unit admission. Of all measured parameters, only the retrospectively calculated median Deterioration Index score was significantly associated with death. While quantitative polymerase chain reaction cycle threshold (Ct) values and genotype of SARS-CoV-2 were not significantly associated with outcome, Ct value did correlate positively with C-reactive protein levels and negatively with D-dimer, lymphocyte count, and antibody titer. Intrahost viral genetic diversity remained constant through the disease course and resulted in changes in viral genotype in some participants. CONCLUSIONS: Ultimately, these results suggest that worse outcomes are driven by immune dysfunction rather than by viral load and that SARS-CoV-2 evolution in hospital settings is relatively constant over time.

6.
Nat Commun ; 13(1): 688, 2022 02 03.
Article in English | MEDLINE | ID: covidwho-1671561

ABSTRACT

Disparities in SARS-CoV-2 genomic surveillance have limited our understanding of the viral population dynamics and may delay identification of globally important variants. Despite being the most populated country in Africa, Nigeria has remained critically under sampled. Here, we report sequences from 378 SARS-CoV-2 isolates collected in Oyo State, Nigeria between July 2020 and August 2021. In early 2021, most isolates belonged to the Alpha "variant of concern" (VOC) or the Eta lineage. Eta outcompeted Alpha in Nigeria and across West Africa, persisting in the region even after expansion of an otherwise rare Delta sub-lineage. Spike protein from the Eta variant conferred increased infectivity and decreased neutralization by convalescent sera in vitro. Phylodynamic reconstructions suggest that Eta originated in West Africa before spreading globally and represented a VOC in early 2021. These results demonstrate a distinct distribution of SARS-CoV-2 lineages in Nigeria, and emphasize the need for improved genomic surveillance worldwide.


Subject(s)
COVID-19/virology , SARS-CoV-2/classification , SARS-CoV-2/genetics , Adolescent , Adult , Africa, Western , Aged , Aged, 80 and over , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/diagnosis , COVID-19/epidemiology , Child , Child, Preschool , Female , Genome, Viral , Humans , Male , Middle Aged , Mutation , Nigeria/epidemiology , Phylogeny , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Young Adult
7.
mBio ; : e0214121, 2022 Jan 25.
Article in English | MEDLINE | ID: covidwho-1650754

ABSTRACT

As public health guidelines throughout the world have relaxed in response to vaccination campaigns against SARS-CoV-2, it is likely that SARS-CoV-2 will remain endemic, fueled by the rise of more infectious SARS-CoV-2 variants. Moreover, in the setting of waning natural and vaccine immunity, reinfections have emerged across the globe, even among previously infected and vaccinated individuals. As such, the ability to detect reexposure to and reinfection by SARS-CoV-2 is a key component for global protection against this virus and, more importantly, against the potential emergence of vaccine escape mutations. Accordingly, there is a strong and continued need for the development and deployment of simple methods to detect emerging hot spots of reinfection to inform targeted pandemic response and containment, including targeted and specific deployment of vaccine booster campaigns. In this study, we identify simple, rapid immune biomarkers of reinfection in rhesus macaques, including IgG3 antibody levels against nucleocapsid and FcγR2A receptor binding activity of anti-RBD antibodies, that are recapitulated in human reinfection cases. As such, this cross-species analysis underscores the potential utility of simple antibody titers and function as price-effective and scalable markers of reinfection to provide increased resolution and resilience against new outbreaks. IMPORTANCE As public health and social distancing guidelines loosen in the setting of waning global natural and vaccine immunity, a deeper understanding of the immunological response to reexposure and reinfection to this highly contagious pathogen is necessary to maintain public health. Viral sequencing analysis provides a robust but unrealistic means to monitor reinfection globally. The identification of scalable pathogen-specific biomarkers of reexposure and reinfection, however, could significantly accelerate our capacity to monitor the spread of the virus through naive and experienced hosts, providing key insights into mechanisms of disease attenuation. Using a nonhuman primate model of controlled SARS-CoV-2 reexposure, we deeply probed the humoral immune response following rechallenge with various doses of viral inocula. We identified virus-specific humoral biomarkers of reinfection, with significant increases in antibody titer and function upon rechallenge across a range of humoral features, including IgG1 to the receptor binding domain of the spike protein of SARS-CoV-2 (RBD), IgG3 to the nucleocapsid protein (N), and FcγR2A receptor binding to anti-RBD antibodies. These features not only differentiated primary infection from reexposure and reinfection in monkeys but also were recapitulated in a sequencing-confirmed reinfection patient and in a cohort of putatively reinfected humans that evolved a PCR-positive test in spite of preexisting seropositivity. As such, this cross-species analysis using a controlled primate model and human cohorts reveals increases in antibody titers as promising cross-validated serological markers of reinfection and reexposure.

8.
JMIR Public Health Surveill ; 8(1): e35763, 2022 01 31.
Article in English | MEDLINE | ID: covidwho-1649375

ABSTRACT

BACKGROUND: Variants of the SARS-CoV-2 virus carry differential risks to public health. The Omicron (B.1.1.529) variant, first identified in Botswana on November 11, 2021, has spread globally faster than any previous variant of concern. Understanding the transmissibility of Omicron is vital in the development of public health policy. OBJECTIVE: The aim of this study is to compare SARS-CoV-2 outbreaks driven by Omicron to those driven by prior variants of concern in terms of both the speed and magnitude of an outbreak. METHODS: We analyzed trends in outbreaks by variant of concern with validated surveillance metrics in several southern African countries. The region offers an ideal setting for a natural experiment given that most outbreaks thus far have been driven primarily by a single variant at a time. With a daily longitudinal data set of new infections, total vaccinations, and cumulative infections in countries in sub-Saharan Africa, we estimated how the emergence of Omicron has altered the trajectory of SARS-CoV-2 outbreaks. We used the Arellano-Bond method to estimate regression coefficients from a dynamic panel model, in which new infections are a function of infections yesterday and last week. We controlled for vaccinations and prior infections in the population. To test whether Omicron has changed the average trajectory of a SARS-CoV-2 outbreak, we included an interaction between an indicator variable for the emergence of Omicron and lagged infections. RESULTS: The observed Omicron outbreaks in this study reach the outbreak threshold within 5-10 days after first detection, whereas other variants of concern have taken at least 14 days and up to as many as 35 days. The Omicron outbreaks also reach peak rates of new cases that are roughly 1.5-2 times those of prior variants of concern. Dynamic panel regression estimates confirm Omicron has created a statistically significant shift in viral spread. CONCLUSIONS: The transmissibility of Omicron is markedly higher than prior variants of concern. At the population level, the Omicron outbreaks occurred more quickly and with larger magnitude, despite substantial increases in vaccinations and prior infections, which should have otherwise reduced susceptibility to new infections. Unless public health policies are substantially altered, Omicron outbreaks in other countries are likely to occur with little warning.


Subject(s)
COVID-19 , Pandemics , Humans , Public Health , Public Health Surveillance , SARS-CoV-2
9.
Infect Control Hosp Epidemiol ; : 1-5, 2021 Oct 01.
Article in English | MEDLINE | ID: covidwho-1447267

ABSTRACT

OBJECTIVE: To identify the impact of universal masking on COVID-19 incidence and putative SARS-CoV-2 transmissions events among children's hospital healthcare workers (HCWs). DESIGN: Quasi-experimental study. SETTING: Single academic free-standing children's hospital. METHODS: We performed whole-genome sequencing of SARS-CoV-2- PCR-positive samples collected from HCWs 3 weeks before and 6 weeks after implementing a universal masking policy. Phylogenetic analyses were performed to identify clusters of clonally related SARS-CoV-2 indicative of putative transmission events. We measured COVID-19 incidence, SARS-CoV-2 test positivity rates, and frequency of putative transmission events before and after the masking policy was implemented. RESULTS: HCW COVID-19 incidence and test positivity declined from 14.3 to 4.3 cases per week, and from 18.4% to 9.0%, respectively. Putative transmission events were only identified prior to universal masking. CONCLUSIONS: A universal masking policy was associated with reductions in HCW COVID-19 infections and occupational acquisition of SARS-CoV-2.

10.
J Pediatr ; 239: 74-80.e1, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1433570

ABSTRACT

OBJECTIVES: To assess rates of asymptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) positivity in K-8 schools with risk mitigation procedures in place, and to evaluate SARS-CoV-2 transmission in school and household contacts of these positive individuals. STUDY DESIGN: In this prospective observational study, screening testing for SARS-CoV-2 was performed by oropharyngeal swabbing and polymerase chain reaction (PCR) analysis in students and staff at K-8 private schools in high-risk Chicago ZIP codes. New coronavirus disease 2019 (COVID-19) diagnoses or symptoms among participants, household contacts, and nonparticipants in each school were queried. RESULTS: Among 11 K-8 private schools across 8 Chicago ZIP codes, 468 participants (346 students, 122 staff members) underwent screening testing. At the first school, 17 participants (36%) tested positive, but epidemiologic investigation suggested against in-school transmission. Only 5 participants in the subsequent 10 schools tested positive for an overall 4.7% positivity rate (1.2% excluding school 1). All but 1 positive test among in-person students had high PCR cycle threshold values, suggesting very low SARS-CoV-2 viral loads. In all schools, no additional students, staff, or household contacts reported new diagnoses or symptoms of COVID-19 during the 2 weeks following screening testing. CONCLUSIONS: We identified infrequent asymptomatic COVID-19 in schools in high-risk Chicago communities and did not identify transmission among school staff, students, or their household contacts. These data suggest that COVID-19 mitigation procedures, including masking and physical distancing, are effective in preventing transmission of COVID-19 in schools. These results may inform future strategies for screening testing in K-8 schools.


Subject(s)
Asymptomatic Diseases/epidemiology , COVID-19/diagnosis , Mass Screening , Schools , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Testing , Chicago/epidemiology , Faculty , Humans , Prospective Studies , Students
11.
Biosens Bioelectron ; 195: 113647, 2022 Jan 01.
Article in English | MEDLINE | ID: covidwho-1415225

ABSTRACT

The rapid spread of COVID-19 including recent emergence of new variants with its extreme range of pathologies create an urgent need to develop a versatile sensor for a rapid, precise, and highly sensitive detection of SARS-CoV-2. Herein, we report a microcantilever-based optical detection of SARS-CoV-2 antigenic proteins in just few minutes with high specificity by employing fluidic-atomic force microscopy (f-AFM) mediated nanomechanical deflection method. The corresponding antibodies against the target antigens were first grafted on the gold-coated microcantilever surface pre-functionalized with EDC-NHS chemistry for a suitable antibody-antigen interaction. Rapid detection of SARS-CoV-2 nucleocapsid (N) and spike (S1) receptor binding domain (RBD) proteins was first demonstrated at a clinically relevant concentration down to 1 ng/mL (33 pM) by real-time monitoring of nanomechanical signal induced by antibody-antigen interaction. More importantly, we further show high specific detection of antigens with nasopharyngeal swab specimens from patients pre-determined with qRT-PCR. The results take less than 5 min (swab to signal ≤5 min) and exhibit high selectivity and analytical sensitivity (LoD: 100 copies/ ml; 0.71 ng/ml of N protein). These findings demonstrate potential for nanomechanical signal transduction towards rapid antigen detection for early screening of SARS-CoV-2 and its related mutants.


Subject(s)
Biosensing Techniques , COVID-19 , Gold , Humans , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
12.
Mol Cell ; 81(12): 2656-2668.e8, 2021 06 17.
Article in English | MEDLINE | ID: covidwho-1179919

ABSTRACT

A deficient interferon (IFN) response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been implicated as a determinant of severe coronavirus disease 2019 (COVID-19). To identify the molecular effectors that govern IFN control of SARS-CoV-2 infection, we conducted a large-scale gain-of-function analysis that evaluated the impact of human IFN-stimulated genes (ISGs) on viral replication. A limited subset of ISGs were found to control viral infection, including endosomal factors inhibiting viral entry, RNA binding proteins suppressing viral RNA synthesis, and a highly enriched cluster of endoplasmic reticulum (ER)/Golgi-resident ISGs inhibiting viral assembly/egress. These included broad-acting antiviral ISGs and eight ISGs that specifically inhibited SARS-CoV-2 and SARS-CoV-1 replication. Among the broad-acting ISGs was BST2/tetherin, which impeded viral release and is antagonized by SARS-CoV-2 Orf7a protein. Overall, these data illuminate a set of ISGs that underlie innate immune control of SARS-CoV-2/SARS-CoV-1 infection, which will facilitate the understanding of host determinants that impact disease severity and offer potential therapeutic strategies for COVID-19.


Subject(s)
Antigens, CD/genetics , Host-Pathogen Interactions/genetics , Interferon Regulatory Factors/genetics , Interferon Type I/genetics , SARS-CoV-2/genetics , Viral Proteins/genetics , Animals , Antigens, CD/chemistry , Antigens, CD/immunology , Binding Sites , Cell Line, Tumor , Chlorocebus aethiops , Endoplasmic Reticulum/genetics , Endoplasmic Reticulum/immunology , Endoplasmic Reticulum/virology , GPI-Linked Proteins/chemistry , GPI-Linked Proteins/genetics , GPI-Linked Proteins/immunology , Gene Expression Regulation , Golgi Apparatus/genetics , Golgi Apparatus/immunology , Golgi Apparatus/virology , HEK293 Cells , Host-Pathogen Interactions/immunology , Humans , Immunity, Innate , Interferon Regulatory Factors/classification , Interferon Regulatory Factors/immunology , Interferon Type I/immunology , Molecular Docking Simulation , Protein Binding , Protein Conformation, alpha-Helical , Protein Conformation, beta-Strand , Protein Interaction Domains and Motifs , SARS-CoV-2/immunology , Signal Transduction , Vero Cells , Viral Proteins/chemistry , Viral Proteins/immunology , Virus Internalization , Virus Release/genetics , Virus Release/immunology , Virus Replication/genetics , Virus Replication/immunology
13.
JCI Insight ; 6(9)2021 05 10.
Article in English | MEDLINE | ID: covidwho-1147004

ABSTRACT

BACKGROUNDEstimates of seroprevalence to SARS-CoV-2 vary widely and may influence vaccination response. We ascertained IgG levels across a single US metropolitan site, Chicago, from June 2020 through December 2020.METHODSParticipants (n = 7935) were recruited through electronic advertising and received materials for a self-sampled dried-blood spot assay through the mail or a minimal contact in-person method. IgG against the receptor-binding domain of SARS-CoV-2 was measured using an established highly sensitive and highly specific assay.RESULTSOverall seroprevalence was 17.9%, with no significant difference between method of contact. Only 2.5% of participants reported having had a diagnosis of COVID-19 based on virus detection, consistent with a 7-fold greater exposure to SARS-CoV-2 measured by serology than that detected by viral testing. The range of IgG level observed in seropositive participants from this community survey overlapped with the range of IgG levels associated with COVID-19 cases having a documented positive PCR test. From a subset of those who participated in repeat testing, half of seropositive individuals retained detectable antibodies for 3 to 4 months.CONCLUSIONQuantitative IgG measurements with a highly specific and sensitive assay indicated more widespread exposure to SARS-CoV-2 than observed by viral testing. The range of IgG concentrations produced from these asymptomatic exposures was similar to IgG levels occurring after documented nonhospitalized COVID-19, which were considerably lower than those produced from hospitalized COVID-19 cases. The differing ranges of IgG response, coupled with the rate of decay of antibodies, may influence response to subsequent viral exposure and vaccine.FundingNational Science Foundation grant 2035114, NIH grant 3UL1TR001422-06S4, NIH National Center for Advancing Translational Sciences grants UL1 TR001422 and UL1 TR002389, Dixon Family Foundation, Northwestern University Cancer Center (NIH grant P30 CA060553), and Walder Foundation's Chicago Coronavirus Assessment Network.


Subject(s)
COVID-19 Serological Testing/methods , COVID-19/epidemiology , Pandemics , SARS-CoV-2/immunology , Adolescent , Adult , Antibodies, Viral/blood , COVID-19/immunology , COVID-19/virology , COVID-19 Serological Testing/statistics & numerical data , Chicago/epidemiology , Cohort Studies , Dried Blood Spot Testing/methods , Dried Blood Spot Testing/statistics & numerical data , Female , Humans , Immunoglobulin G/blood , Male , Middle Aged , Sensitivity and Specificity , Seroepidemiologic Studies , Young Adult
14.
Cell Rep ; 34(2): 108628, 2021 01 12.
Article in English | MEDLINE | ID: covidwho-1036973

ABSTRACT

Recent studies have profiled the innate immune signatures in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and suggest that cellular responses to viral challenge may affect disease severity. Yet the molecular events that underlie cellular recognition and response to SARS-CoV-2 infection remain to be elucidated. Here, we find that SARS-CoV-2 replication induces a delayed interferon (IFN) response in lung epithelial cells. By screening 16 putative sensors involved in sensing of RNA virus infection, we found that MDA5 and LGP2 primarily regulate IFN induction in response to SARS-CoV-2 infection. Further analyses revealed that viral intermediates specifically activate the IFN response through MDA5-mediated sensing. Additionally, we find that IRF3, IRF5, and NF-κB/p65 are the key transcription factors regulating the IFN response during SARS-CoV-2 infection. In summary, these findings provide critical insights into the molecular basis of the innate immune recognition and signaling response to SARS-CoV-2.


Subject(s)
Immunity, Innate , Interferon-Induced Helicase, IFIH1/metabolism , SARS-CoV-2/physiology , COVID-19/pathology , COVID-19/virology , Cell Line , Epithelial Cells/cytology , Epithelial Cells/immunology , Epithelial Cells/virology , Humans , Induced Pluripotent Stem Cells/cytology , Interferon Regulatory Factor-3/genetics , Interferon Regulatory Factor-3/metabolism , Interferon Regulatory Factors/genetics , Interferon Regulatory Factors/metabolism , Interferons/genetics , Interferons/metabolism , RNA Helicases/metabolism , RNA Interference , RNA, Double-Stranded/metabolism , RNA, Small Interfering/metabolism , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Signal Transduction , Transcription Factor RelA/metabolism , Virus Replication
15.
EBioMedicine ; 62: 103112, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1023543

ABSTRACT

BACKGROUND: The rapid spread of SARS-CoV-2, the causative agent of Coronavirus disease 2019 (COVID-19), has been accompanied by the emergence of distinct viral clades, though their clinical significance remains unclear. Here, we aimed to investigate the phylogenetic characteristics of SARS-CoV-2 infections in Chicago, Illinois, and assess their relationship to clinical parameters. METHODS: We performed whole-genome sequencing of SARS-CoV-2 isolates collected from COVID-19 patients in Chicago in mid-March, 2020. Using these and other publicly available sequences, we performed phylogenetic, phylogeographic, and phylodynamic analyses. Patient data was assessed for correlations between demographic or clinical characteristics and virologic features. FINDINGS: The 88 SARS-CoV-2 genome sequences in our study separated into three distinct phylogenetic clades. Clades 1 and 3 were most closely related to viral sequences from New York and Washington state, respectively, with relatively broad distributions across the US. Clade 2 was primarily found in the Chicago area with limited distribution elsewhere. At the time of diagnosis, patients infected with Clade 1 viruses had significantly higher average viral loads in their upper airways relative to patients infected with Clade 2 viruses, independent of disease severity. INTERPRETATION: These results show that multiple variants of SARS-CoV-2 were circulating in the Chicago area in mid-March 2020 that differed in their relative viral loads in patient upper airways. These data suggest that differences in virus genotype can impact viral load and may influence viral spread. FUNDING: Dixon Family Translational Research Award, Northwestern University Clinical and Translational Sciences Institute (NUCATS), National Institute of Allergy and Infectious Diseases (NIAID), Lurie Comprehensive Cancer Center, Northwestern University Emerging and Re-emerging Pathogens Program.


Subject(s)
COVID-19/genetics , Genome, Viral , Genotype , Phylogeny , SARS-CoV-2/genetics , Viral Load , Female , Humans , Male , Whole Genome Sequencing
16.
Curr Opin HIV AIDS ; 16(1): 11-24, 2021 01.
Article in English | MEDLINE | ID: covidwho-927147

ABSTRACT

PURPOSE OF REVIEW: The aim of this review was to compare and contrast the application of molecular epidemiology approaches for the improved management and understanding of the HIV versus SARS-CoV-2 epidemics. RECENT FINDINGS: Molecular biology approaches, including PCR and whole genome sequencing (WGS), have become powerful tools for epidemiological investigation. PCR approaches form the basis for many high-sensitivity diagnostic tests and can supplement traditional contact tracing and surveillance strategies to define risk networks and transmission patterns. WGS approaches can further define the causative agents of disease, trace the origins of the pathogen, and clarify routes of transmission. When coupled with clinical datasets, such as electronic medical record data, these approaches can investigate co-correlates of disease and pathogenesis. In the ongoing HIV epidemic, these approaches have been effectively deployed to identify treatment gaps, transmission clusters and risk factors, though significant barriers to rapid or real-time implementation remain critical to overcome. Likewise, these approaches have been successful in addressing some questions of SARS-CoV-2 transmission and pathogenesis, but the nature and rapid spread of the virus have posed additional challenges. SUMMARY: Overall, molecular epidemiology approaches offer unique advantages and challenges that complement traditional epidemiological tools for the improved understanding and management of epidemics.


Subject(s)
COVID-19/virology , HIV Infections/virology , HIV/genetics , SARS-CoV-2/genetics , COVID-19/epidemiology , HIV/classification , HIV/isolation & purification , HIV Infections/epidemiology , Humans , Molecular Epidemiology , Pandemics , SARS-CoV-2/classification , SARS-CoV-2/isolation & purification
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