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1.
JAMA Netw Open ; 5(3): e220935, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1849927

ABSTRACT

Importance: The emergence of the B.1.617.2 (Delta) variant of SARS-CoV-2 has led to increases in both infections and hospitalizations among adolescents. Little is known about the effectiveness of the BNT162b2 vaccine in adolescents in the general population, as opposed to a clinical trial population. Objective: To estimate the effectiveness of the BNT162b2 vaccine in adolescents aged 12 to 18 years. Design, Setting, and Participants: This was a matched case-control study among adolescents (aged 12-18 years) who had results from a SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) test. Immunization histories, relevant clinical data, and RT-PCR test results were obtained from the Yale New Haven Health System's medical records between June 1, 2021, and August 15, 2021, when the Delta variant caused 92% of infections in Connecticut. Case participants were defined as adolescents who had a positive test result and an associated medical encounter. Control participants were defined as those who had a negative test result and were matched to a case participant by age, county of residence, and date of testing. Exposures: Adolescents were defined as fully immunized if they had received 2 doses of vaccine at least 14 days before focal time. Main Outcomes and Measures: The primary outcome measured was SARS-CoV-2 infection confirmed by RT-PCR. The vaccine's effectiveness (VE) was estimated using matched odds ratios from conditional logistic regression models. Secondary measures included estimated VE by clinical symptoms, number of vaccine doses received, and elapsed time from immunization. Results: A total of 6901 adolescents were tested for SARS-CoV-2. The final sample comprised 186 case participants and 356 matched control participants. The median age was 14 (IQR, 13-16) years, 262 (48%) identified as female, 81 (15%) as Black, 82 (15%) as Hispanic, and 297 (55%) as White. Overall, 134 (25%) were fully immunized (case participants, 10 [5%]; control participants, 124 [35%]). The median time between immunization and the SARS-CoV-2 test was 62 days (range, 17-129 days). Within 4 months of receiving 2 doses, VE against any infection was estimated to be 91% (95% CI, 80%-96%); against asymptomatic infection, 85% (95% CI, 57%-95%). Effectiveness after a single dose was estimated to be 74% (95% CI, 18%-92%). Conclusions and Relevance: In this retrospective case-control study of US adolescents, 2 doses of BNT162b2 vaccine appeared to provide excellent protection for at least 4 months after immunization against both symptomatic and asymptomatic SARS-CoV-2 infections.


Subject(s)
BNT162 Vaccine/administration & dosage , COVID-19/prevention & control , SARS-CoV-2/immunology , Vaccine Efficacy , Adolescent , COVID-19/diagnosis , COVID-19 Nucleic Acid Testing , Case-Control Studies , Connecticut , Female , Humans , Male , Retrospective Studies , United States/epidemiology
2.
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
3.
Med (N Y) ; 3(5): 325-334.e4, 2022 05 13.
Article in English | MEDLINE | ID: covidwho-1773641

ABSTRACT

Background: The SARS-CoV-2 Omicron variant became a global concern due to its rapid spread and displacement of the dominant Delta variant. We hypothesized that part of Omicron's rapid rise was based on its increased ability to cause infections in persons that are vaccinated compared to Delta. Methods: We analyzed nasal swab PCR tests for samples collected between December 12 and 16, 2021, in Connecticut when the proportion of Delta and Omicron variants was relatively equal. We used the spike gene target failure (SGTF) to classify probable Delta and Omicron infections. We fitted an exponential curve to the estimated infections to determine the doubling times for each variant. We compared the test positivity rates for each variant by vaccination status, number of doses, and vaccine manufacturer. Generalized linear models were used to assess factors associated with odds of infection with each variant among persons testing positive for SARS-CoV-2. Findings: For infections with high virus copies (Ct < 30) among vaccinated persons, we found higher odds that they were infected with Omicron compared to Delta, and that the odds increased with increased number of vaccine doses. Compared to unvaccinated persons, we found significant reduction in Delta positivity rates after two (43.4%-49.1%) and three vaccine doses (81.1%), while we only found a significant reduction in Omicron positivity rates after three doses (62.3%). Conclusion: The rapid rise in Omicron infections was likely driven by Omicron's escape from vaccine-induced immunity. Funding: This work was supported by the Centers for Disease Control and Prevention (CDC).


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , COVID-19 Vaccines , Hospitalization , Humans , SARS-CoV-2/genetics
4.
Lancet Infect Dis ; 22(2): e52-e58, 2022 02.
Article in English | MEDLINE | ID: covidwho-1751515

ABSTRACT

As the number of individuals vaccinated against SARS-CoV-2 rises worldwide, population-level data regarding the vaccines' ability to reduce infection are being generated. Randomised trials have shown that these vaccines dramatically reduce symptomatic COVID-19; however, less is known about their effects on transmission between individuals. The natural course of infection with SARS-CoV-2 involves infection of the respiratory epithelia and replication within the mucosa to sufficient viral titres for transmission via aerosol particles and droplets. Here we discuss the available data on the existing, approved SARS-CoV-2 vaccines' capacity to reduce transmissibility by reducing primary infection, viral replication, capacity for transmission, and symptomaticity. The potential for mucosal-targeted SARS-CoV-2 vaccine strategies to more effectively limit transmission than intramuscular vaccines is considered with regard to known immunological mechanisms. Finally, we enumerate the population-level effects of approved vaccines on transmission through observational studies following clinical trials and vaccine distribution in real-world settings.


Subject(s)
COVID-19 Vaccines , COVID-19/prevention & control , COVID-19/transmission , Antibodies, Viral/biosynthesis , Antibodies, Viral/immunology , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , Humans , Immunoglobulin A/biosynthesis , Immunoglobulin A/immunology , Immunoglobulin G/biosynthesis , Immunoglobulin G/immunology , Virus Replication/immunology
5.
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
7.
Open forum infectious diseases ; 8(Suppl 1):S284-S284, 2021.
Article in English | EuropePMC | ID: covidwho-1565017

ABSTRACT

Background Quickly detecting and isolating individuals positive for SARS-CoV-2 is essential for limiting virus spread. Policy makers rely on the number of active cases to make decisions, and individuals use this information to evaluate risk should they return to public spaces. Robust testing strategies have been plagued with limited authorized diagnostic assays and high test prices, with large-scale implementation hampered by worldwide supply chain issues. Methods Having identified its potential early in the pandemic, we simplified saliva-based COVID-19 diagnostic testing by (1) not requiring collection tubes with preservatives, (2) replacing nucleic acid extraction with a simple enzymatic and heating step, and (3) testing specimens for SARS-CoV-2 in dualplex RT-qPCR. Moreover, we validated this approach (“SalivaDirect”) with reagents and instruments from multiple vendors to circumvent supply chain disruptions. Results SalivaDirect’s simplified protocol does not compromise on sensitivity. In our hospital cohort, we found a high positive agreement (94%) between saliva tested with SalivaDirect and nasopharyngeal swabs tested with a commercial RT-qPCR kit. With the National Basketball Association we tested 3,779 saliva specimens from healthy individuals and detected low rates of invalid (0.3%) and false-positive (< 0.05%) results. Using comparative assays and sample types, we also demonstrated SalivaDirect to efficiently detect SARS-CoV-2 in asymptomatic individuals. SalivaDirect is a simplified method for SARS-CoV-2 detection (A) Schematic overview of SalivaDirect workflow depicting the main steps of mixing saliva with proteinase K, heat inactivation, and dualplex qRT-PCR testing. Figure created with Biorender.com. (B) SARS-CoV-2 is stable in saliva for at least 7 days at 4C, room temperature (RT;19C), and 30C without addition of stabilizing buffers. Spiked-in saliva samples of low virus concentrations (12, 25, and 50 SARS-CoV-2 copies/mL) were kept at the indicated temperature for 7 days and then tested with SalivaDirect. N1 cycle threshold (Ct) values were lower when kept for 7 days at 30C as compared to fresh specimens (Kruskal-Wallis;p = 0.03). Horizontal bars indicate the median. (C) Comparing Ct values for saliva treated with proteinase K and heat as compared to nucleic extraction yields higher N1 Ct values without extraction (Wilcoxon;p < 0.01). (D) Testing extracted nucleic acid from saliva with the N1 primer-probe set (singleplex) as compared to a multiplex assay showed stronger N1 detection in multiplex (Wilcoxon;p < 0.01). The dotted line in (B)–(D) indicates the limit of detection. Conclusion Saliva is a valid alternative to swabs for SARS-CoV-2 screening. Importantly, SalivaDirect enables labs to utilize existing infrastructure, improving test implementation time and requiring limited investment to scale-up to meet mass testing needs. With the safe and reliable self-collection of saliva, our vision is to help provide accessible and equitable testing solutions, especially in low-resource and remote settings. Disclosures Anne Wyllie, PhD, Global Diagnostic Systems (Consultant)Pfizer (Advisor or Review Panel member, Research Grant or Support)PPS Health (Consultant)Tempus Labs, Inc (Research Grant or Support) Nathan D. Grubaugh, PhD, Tempus Labs (Consultant)

8.
Emerg Infect Dis ; 27(11): 2971-2973, 2021 11.
Article in English | MEDLINE | ID: covidwho-1559753

ABSTRACT

We reconstructed the 2016-2017 Zika virus epidemic in Puerto Rico by using complete genomes to uncover the epidemic's origin, spread, and evolutionary dynamics. Our study revealed that the epidemic was propelled by multiple introductions that spread across the island, intricate evolutionary patterns, and ≈10 months of cryptic transmission.


Subject(s)
Epidemics , Zika Virus Infection , Zika Virus , Evolution, Molecular , Humans , Puerto Rico/epidemiology , Zika Virus/genetics , Zika Virus Infection/epidemiology
9.
[Unspecified Source]; 2020.
Preprint in English | [Unspecified Source] | ID: ppcovidwho-292787

ABSTRACT

Most currently approved strategies for the collection of saliva for COVID-19 diagnostics require specialized tubes containing buffers promoted for the stabilization of SARS-CoV-2 RNA and virus inactivation. Yet many of these are expensive, in limited supply, and not necessarily validated specifically for viral RNA. While saliva is a promising sample type as it can be reliably self-collected for the sensitive detection of SARS-CoV-2, the expense and availability of these collection tubes are prohibitive to mass testing efforts. Therefore, we investigated the stability of SARS-CoV-2 RNA and infectious virus detection from saliva without supplementation. We tested RNA stability over extended periods of time (2-25 days) and at temperatures representing at-home storage and elevated temperatures which might be experienced when cold chain transport may be unavailable. We found SARS-CoV-2 RNA in saliva from infected individuals is stable at 4°C, room temperature (~19°C), and 30°C for prolonged periods and found limited evidence for viral replication in saliva. This work demonstrates that expensive saliva collection options involving RNA stabilization and virus inactivation buffers are not always needed, permitting the use of cheaper collection options. Affordable testing methods are urgently needed to meet current testing demands and for continued surveillance in reopening strategies.

10.
Non-conventional in English | MEDLINE, Grey literature | ID: grc-750483

ABSTRACT

BACKGROUND: Highly sensitive, non-invasive, and easily accessible diagnostics for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are essential for the control of the Coronavirus Disease 2019 (COVID-19) pandemic. There is a clear need to establish a gold standard diagnostic for SARS-CoV-2 infection in humans using respiratory tract specimens. METHODS: Searches will be conducted in the bibliographic databases Medline, Embase, bioRxiv, medRxiv, F1000, ChemRxiv, PeerJ Preprints, Preprints.org, Beilstein Archive, and Research Square. Relevant government documents and grey literature will be sought on the FDA's Emergency Use Authorizations website, the ECDC's website, and the website of the Foundation for Innovative New Diagnostics. Finally, papers categorized as diagnosis papers by the EPPI Centre's COVID-19 living systematic map will be added to our screening process;those papers are tagged with the diagnosis topic based on human review, rather than database searches, and thus this set of papers might include ones that have not been captured by our search strategy.

11.
PLoS Biol ; 19(7): e3001333, 2021 07.
Article in English | MEDLINE | ID: covidwho-1305572

ABSTRACT

SARS-CoV-2 infections are characterized by viral proliferation and clearance phases and can be followed by low-level persistent viral RNA shedding. The dynamics of viral RNA concentration, particularly in the early stages of infection, can inform clinical measures and interventions such as test-based screening. We used prospective longitudinal quantitative reverse transcription PCR testing to measure the viral RNA trajectories for 68 individuals during the resumption of the 2019-2020 National Basketball Association season. For 46 individuals with acute infections, we inferred the peak viral concentration and the duration of the viral proliferation and clearance phases. According to our mathematical model, we found that viral RNA concentrations peaked an average of 3.3 days (95% credible interval [CI] 2.5, 4.2) after first possible detectability at a cycle threshold value of 22.3 (95% CI 20.5, 23.9). The viral clearance phase lasted longer for symptomatic individuals (10.9 days [95% CI 7.9, 14.4]) than for asymptomatic individuals (7.8 days [95% CI 6.1, 9.7]). A second test within 2 days after an initial positive PCR test substantially improves certainty about a patient's infection stage. The effective sensitivity of a test intended to identify infectious individuals declines substantially with test turnaround time. These findings indicate that SARS-CoV-2 viral concentrations peak rapidly regardless of symptoms. Sequential tests can help reveal a patient's progress through infection stages. Frequent, rapid-turnaround testing is needed to effectively screen individuals before they become infectious.


Subject(s)
COVID-19 Nucleic Acid Testing/statistics & numerical data , COVID-19/diagnosis , RNA, Viral/genetics , SARS-CoV-2/genetics , Virus Replication/genetics , Virus Shedding/genetics , Adult , Athletes , Basketball , COVID-19/epidemiology , COVID-19/pathology , COVID-19/virology , Convalescence , Humans , Male , Prospective Studies , Public Health/methods , SARS-CoV-2/growth & development , Severity of Illness Index , United States/epidemiology
12.
Med (N Y) ; 2(3): 263-280.e6, 2021 03 12.
Article in English | MEDLINE | ID: covidwho-1284368

ABSTRACT

BACKGROUND: Scaling SARS-CoV-2 testing to meet demands of safe reopenings continues to be plagued by assay costs and supply chain shortages. In response, we developed SalivaDirect, which received Emergency Use Authorization (EUA) from the U.S. Food and Drug Administration (FDA). METHODS: We simplified our saliva-based diagnostic test by (1) not requiring collection tubes with preservatives, (2) replacing nucleic acid extraction with a simple enzymatic and heating step, and (3) testing specimens with a dualplex qRT-PCR assay. Moreover, we validated SalivaDirect with reagents and instruments from multiple vendors to minimize supply chain issues. FINDINGS: From our hospital cohort, we show a high positive agreement (94%) between saliva tested with SalivaDirect and nasopharyngeal swabs tested with a commercial qRT-PCR kit. In partnership with the National Basketball Association (NBA) and National Basketball Players Association (NBPA), we tested 3,779 saliva specimens from healthy individuals and detected low rates of invalid (0.3%) and false-positive (<0.05%) results. CONCLUSIONS: We demonstrate that saliva is a valid alternative to swabs for SARS-CoV-2 screening and that SalivaDirect can make large-scale testing more accessible and affordable. Uniquely, we can designate other laboratories to use our sensitive, flexible, and simplified platform under our EUA (https://publichealth.yale.edu/salivadirect/). FUNDING: This study was funded by the NBA and NBPA (N.D.G.), the Huffman Family Donor Advised Fund (N.D.G.), a Fast Grant from Emergent Ventures at the Mercatus Center at George Mason University (N.D.G.), the Yale Institute for Global Health (N.D.G.), and the Beatrice Kleinberg Neuwirth Fund (A.I.K.). C.B.F.V. is supported by NWO Rubicon 019.181EN.004.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/diagnosis , COVID-19 Testing , Humans , Laboratories , SARS-CoV-2/genetics , Saliva
13.
Nature ; 595(7866): 283-288, 2021 07.
Article in English | MEDLINE | ID: covidwho-1233713

ABSTRACT

COVID-19 manifests with a wide spectrum of clinical phenotypes that are characterized by exaggerated and misdirected host immune responses1-6. Although pathological innate immune activation is well-documented in severe disease1, the effect of autoantibodies on disease progression is less well-defined. Here we use a high-throughput autoantibody discovery technique known as rapid extracellular antigen profiling7 to screen a cohort of 194 individuals infected with SARS-CoV-2, comprising 172 patients with COVID-19 and 22 healthcare workers with mild disease or asymptomatic infection, for autoantibodies against 2,770 extracellular and secreted proteins (members of the exoproteome). We found that patients with COVID-19 exhibit marked increases in autoantibody reactivities as compared to uninfected individuals, and show a high prevalence of autoantibodies against immunomodulatory proteins (including cytokines, chemokines, complement components and cell-surface proteins). We established that these autoantibodies perturb immune function and impair virological control by inhibiting immunoreceptor signalling and by altering peripheral immune cell composition, and found that mouse surrogates of these autoantibodies increase disease severity in a mouse model of SARS-CoV-2 infection. Our analysis of autoantibodies against tissue-associated antigens revealed associations with specific clinical characteristics. Our findings suggest a pathological role for exoproteome-directed autoantibodies in COVID-19, with diverse effects on immune functionality and associations with clinical outcomes.


Subject(s)
Autoantibodies/analysis , Autoantibodies/immunology , COVID-19/immunology , COVID-19/metabolism , Proteome/immunology , Proteome/metabolism , Animals , Antigens, Surface/immunology , COVID-19/pathology , COVID-19/physiopathology , Case-Control Studies , Complement System Proteins/immunology , Cytokines/immunology , Disease Models, Animal , Disease Progression , Female , Humans , Male , Mice , Organ Specificity/immunology
14.
PLoS Biol ; 19(5): e3001236, 2021 05.
Article in English | MEDLINE | ID: covidwho-1220158

ABSTRACT

With the emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants that may increase transmissibility and/or cause escape from immune responses, there is an urgent need for the targeted surveillance of circulating lineages. It was found that the B.1.1.7 (also 501Y.V1) variant, first detected in the United Kingdom, could be serendipitously detected by the Thermo Fisher TaqPath COVID-19 PCR assay because a key deletion in these viruses, spike Δ69-70, would cause a "spike gene target failure" (SGTF) result. However, a SGTF result is not definitive for B.1.1.7, and this assay cannot detect other variants of concern (VOC) that lack spike Δ69-70, such as B.1.351 (also 501Y.V2), detected in South Africa, and P.1 (also 501Y.V3), recently detected in Brazil. We identified a deletion in the ORF1a gene (ORF1a Δ3675-3677) in all 3 variants, which has not yet been widely detected in other SARS-CoV-2 lineages. Using ORF1a Δ3675-3677 as the primary target and spike Δ69-70 to differentiate, we designed and validated an open-source PCR assay to detect SARS-CoV-2 VOC. Our assay can be rapidly deployed in laboratories around the world to enhance surveillance for the local emergence and spread of B.1.1.7, B.1.351, and P.1.


Subject(s)
COVID-19/virology , SARS-CoV-2/genetics , COVID-19/diagnosis , COVID-19/genetics , DNA Primers , Humans , Multiplex Polymerase Chain Reaction/methods , Mutation , Polyproteins/genetics , Viral Proteins/genetics
15.
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
16.
Emerg Infect Dis ; 27(4): 1146-1150, 2021 04.
Article in English | MEDLINE | ID: covidwho-1147295

ABSTRACT

The expense of saliva collection devices designed to stabilize severe acute respiratory syndrome coronavirus 2 RNA is prohibitive to mass testing. However, virus RNA in nonsupplemented saliva is stable for extended periods and at elevated temperatures. Simple plastic tubes for saliva collection will make large-scale testing and continued surveillance easier.


Subject(s)
COVID-19 Nucleic Acid Testing/methods , COVID-19 , RNA, Viral , SARS-CoV-2 , Saliva/virology , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/virology , Capacity Building/methods , Humans , RNA Stability , RNA, Viral/isolation & purification , RNA, Viral/physiology , Reproducibility of Results , Resource Allocation , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Specimen Handling/economics , Specimen Handling/instrumentation , Specimen Handling/methods
18.
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
19.
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
20.
medRxiv ; 2020 Jul 04.
Article in English | MEDLINE | ID: covidwho-637873

ABSTRACT

BACKGROUND: Highly sensitive, non-invasive, and easily accessible diagnostics for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are essential for the control of the Coronavirus Disease 2019 (COVID-19) pandemic. There is a clear need to establish a gold standard diagnostic for SARS-CoV-2 infection in humans using respiratory tract specimens. METHODS: Searches will be conducted in the bibliographic databases Medline, Embase, bioRxiv, medRxiv, F1000, ChemRxiv, PeerJ Preprints, Preprints.org, Beilstein Archive, and Research Square. Relevant government documents and grey literature will be sought on the FDA's Emergency Use Authorizations website, the ECDC's website, and the website of the Foundation for Innovative New Diagnostics. Finally, papers categorized as diagnosis papers by the EPPI Centre's COVID-19 living systematic map will be added to our screening process; those papers are tagged with the diagnosis topic based on human review, rather than database searches, and thus this set of papers might include ones that have not been captured by our search strategy.

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