COVID 19 Special Collection
COVID-19 (SARS-CoV-2) Special Collection
Latest COVID-19 Articles
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Minireview
Preserve a Voucher Specimen! The Critical Need for Integrating Natural History Collections in Infectious Disease Studies
Despite being nearly 10 months into the COVID-19 (coronavirus disease 2019) pandemic, the definitive animal host for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the causal agent of COVID-19, remains unknown. Unfortunately, similar problems exist for other betacoronaviruses, and no vouchered specimens exist to corroborate host species identification for most of these pathogens. This most basic information is critical to the full understanding and mitigation of emerging zoonotic diseases. To overcome this hurdle, we recommend that host-pathogen researchers adopt vouchering practices and collaborate with natural history collections to permanently archive microbiological samples and host specimens. Vouchered specimens and associated samples provide both repeatability and extension to host-pathogen studies, and using them mobilizes a large workforce (i.e., biodiversity scientists) to assist in pandemic preparedness. We review several well-known examples that successfully integrate host-pathogen research with natural history collections (e.g., yellow fever, hantaviruses, helminths). However, vouchering remains an underutilized practice in such studies. Using an online survey, we assessed vouchering practices used by microbiologists (e.g., bacteriologists, parasitologists, virologists) in host-pathogen research. A much greater number of respondents permanently archive microbiological samples than archive host specimens, and less than half of respondents voucher host specimens from which microbiological samples were lethally collected. To foster collaborations between microbiologists and natural history collections, we provide recommendations for integrating vouchering techniques and archiving of microbiological samples into host-pathogen studies. This integrative approach exemplifies the premise underlying One Health initiatives, providing critical infrastructure for addressing related issues ranging from public health to global climate change and the biodiversity crisis.
12 January 2021, mBio
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Research Article
Generation and Characterization of recombinant SARS-CoV-2 expressing reporter genes
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen that causes coronavirus disease 2019 (COVID-19), has significantly impacted the human health and economic status worldwide. There is an urgent need to identify effective prophylactics and therapeutics for the treatment of SARS-CoV-2 infection and associated COVID-19 disease. The use of fluorescent- or luciferase-expressing reporter expressing viruses has significantly advanced viral research. Here, we generated recombinant (r)SARS-CoV-2 expressing fluorescent (Venus and mCherry) or luciferase (Nluc) reporter genes and demonstrate that they represent an excellent option to track viral infections in vitro. Importantly, reporter-expressing rSARS-CoV-2 display similar growth kinetics and plaque phenotype that their wild-type counterpart (rSARS-CoV-2/WT), demonstrating their feasibility to identify drugs and/or neutralizing antibodies (NAbs) for the therapeutic treatment of SARS-CoV-2. Henceforth, these reporter-expressing rSARS-CoV-2 can be used to interrogate large libraries of compounds and/or monoclonal antibodies (MAb), in high-throughput screening settings, to identify those with therapeutic potential against SARS-CoV-2.
Accepted Manuscript Posted 11 January 2021, JVI; Final Article Posted 10 March 2021
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Research Article
Performance characteristics of the VIDAS® SARS-COV-2 IgM and IgG serological assays
The COVID-19 pandemic, caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to spread worldwide. Serological testing for SARS-CoV-2-specific antibodies plays an important role in understanding and controlling the pandemics, notably through epidemiological surveillance. Well validated and highly specific SARS-CoV-2 serological assays are urgently needed. We describe here the analytical and clinical performance of VIDAS® SARS-CoV-2 IgM and VIDAS® SARS-CoV-2 IgG, two CE-marked, EUA-authorized, automated, qualitative assays for the detection of SARS-CoV-2-specific IgM and IgG, respectively. Both assays showed high within-run and within-laboratory precision (coefficients of variation < 11.0%) and very low cross-reactivity towards sera of patients with a past common coronavirus or respiratory virus infection. Clinical specificity determined on up to 989 pre-pandemic healthy donors was ≥ 99% with a narrow 95% confidence interval for both IgM and IgG assays. Clinical sensitivity was determined on up to 232 samples from 130 RT-PCR-confirmed SARS-CoV-2 patients. The positive percent agreement (PPA) with SARS-CoV-2 PCR reached 100% at ≥ 16 days (VIDAS® SARS-CoV-2 IgM) and ≥ 32 days (VIDAS® SARS-CoV-2 IgG) of symptom onset. Combined IgM/IgG test results improved the PPA compared to each test alone. SARS-CoV-2 IgG seroconversion followed closely that of SARS-CoV-2 IgM and remained stable over time, while SARS-CoV-2 IgM levels rapidly declined. Interestingly, SARS-CoV-2-specific IgM and IgG responses were significantly higher in COVID-19 hospitalized vs. non-hospitalized patients. Altogether, the VIDAS® SARS-CoV-2 IgM and IgG assays are highly specific and sensitive serological tests suitable for the reliable detection of past acute SARS-CoV-2 infections.
Accepted Manuscript Posted 8 January 2021, JCM; Final Article Posted 19 March 2021
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Research Article
Performance of saliva specimens for the molecular detection of SARS-CoV-2 in the community setting: does sample collection method matter?
Data on the performance of saliva specimens for diagnosing COVID-19 in ambulatory patients are scarce and inconsistent. We assessed saliva-based specimens for detecting SARS-CoV-2 by RT-PCR in the community setting and compared three different collection methods. Prospective study conducted in three primary care centres. RT-PCR was performed in paired nasopharyngeal swabs (NPS) and saliva samples collected from outpatients with a broad clinical spectrum of illness. To assess differences in collection methods, saliva specimens were obtained in a different way in each of the participating centres: supervised collection (SVC), oropharyngeal washing (OPW) and self-collection (SC). NPS and saliva pairs of samples from 577 patients (median age 39 years, 44% men, 42% asymptomatic) were collected and tested, and 120 (20.8%) gave positive results. The overall agreement with NPS and kappa coefficients (Ƙ) for SVC, OPW and SC were 95% (Ƙ=0.85), 93.4% (Ƙ=0.76), and 93.3% (Ƙ=0.76), respectively. The sensitivity (95% CI) of the saliva specimens varied from 86% (72.6-93.7) for SVC to 66.7% (50.4-80) for SC samples. The sensitivity was higher in samples with lower cycle threshold (Ct) values. The best performance of RT-PCR was observed for SVC, with sensitivity (95% CI) for Ct values ≤30 of 100% (85.9-100) in symptomatic, and 88.9% (50.7-99.4) in asymptomatic individuals. Saliva is an acceptable specimen for the detection of SARS-CoV-2 in the community setting. Specimens collected under supervision perform comparably to NPS and can effectively identify individuals with higher risk of transmission in real life conditions.
Accepted Manuscript Posted 8 January 2021, JCM; Final Article Posted 19 March 2021
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Research Article
Pneumococcal Conjugate Vaccine Protection against Coronavirus-Associated Pneumonia Hospitalization in Children Living with and without HIV
SARS-CoV-2 may cause severe hospitalization, but little is known about the role of secondary bacterial infection in these severe cases, beyond the observation of high levels of reported inflammatory markers, associated with bacterial infection, such as procalcitonin. We did a secondary analysis of a double-blind randomized trial of PCV to examine its impact on human CoV infections before the pandemic. We found that both children living with and without HIV randomized to receive PCV had evidence of less hospitalization due to seasonal CoV, suggesting that pneumococcal coinfection may play a role in severe hospitalized CoV infections.
8 January 2021, mBio
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Research Article
COVID-19 vaccine candidates based on modified vaccinia virus Ankara expressing the SARS-CoV-2 spike induce robust T- and B-cell immune responses and full efficacy in mice
The continuous dissemination of the novel emerging SARS-CoV-2 virus, with more than 78 million infected cases worldwide and higher than 1,700,000 deaths as of December 23, 2020, highlights the urgent need for the development of novel vaccines against COVID-19. With this aim, we have developed novel vaccine candidates based on the poxvirus modified vaccinia virus Ankara (MVA) strain expressing the full-length SARS-CoV-2 spike (S) protein, and we have evaluated their immunogenicity in mice using DNA/MVA or MVA/MVA prime/boost immunization protocols. The results showed the induction of a potent S-specific T-cell response and high titers of neutralizing antibodies. Remarkably, humanized K18-hACE2 mice immunized with one or two doses of the MVA-based vaccine were 100% protected from SARS-CoV-2 lethality. Moreover, two doses of the vaccine prevented virus replication in lungs. Our findings prove the robust immunogenicity and efficacy of MVA-based COVID-19 vaccines in animal models and support its translation to the clinic.
Accepted Manuscript Posted 7 January 2021, JVI; Final Article Posted 10 March 2021
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Research Article
Insight into vaccine development for Alpha-coronaviruses based on structural and immunological analyses of spike proteins
Outbreak of coronaviruses, especially SARS-CoV-2, poses a serious threat to global public health. Development of vaccines to prevent the coronaviruses that can infect humans has always been a top priority. Coronavirus spike (S) protein is considered as a major target for vaccine development. Currently, structural studies have shown that Alpha-coronavirus (HCoV-229E) and Beta-coronavirus (SARS-CoV and SARS-CoV-2) RBDs are in “lying” and “standing” states in the prefusion S-trimer structure. Here, we evaluated the ability of S-trimer and RBD to induce neutralizing antibodies among these coronaviruses. Our results showed that the S-trimer and RBD are both candidates for subunit vaccines in Beta-coronavirus (SARS-CoV and SARS-CoV-2) with a RBD “standing” state. However, for Alpha-coronavirus (HCoV-229E) with a RBD “lying” state, the S-trimer may be more suitable for subunit vaccines than the RBD. Our results will provide novel ideas for the development of vaccines targeting S protein in the future.
Accepted Manuscript Posted 7 January 2021, JVI; Final Article Posted 10 March 2021
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Genome Sequences
Genomic Sequences and Analysis of Five SARS-CoV-2 Variants Obtained from Patients in Lambayeque, Peru
Here, we report the genomic sequences of five severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains obtained from nasopharyngeal samples from five tested coronavirus disease 2019 (COVID-19)-infected patients from the Lambayeque region in Peru during early April 2020.
7 January 2021, MRA
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Genome Sequences
Genome Sequences of Two GH Clade SARS-CoV-2 Strains Isolated from Patients with COVID-19 in South Korea
We report the genome sequences of two GH clade severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains isolated from nasopharyngeal swabs from patients with coronavirus disease 2019 (COVID-19) in South Korea. These strains had two mutations in the untranslated regions and seven nonsynonymous substitutions in open reading frames, compared with Wuhan/Hu-1/2019, showing 99.96% sequence identity.
7 January 2021, MRA
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Genome Sequences
Mutation Profile of SARS-CoV-2 Genome Sequences Originating from Eight Israeli Patient Isolates
We report the genome sequences and the identification of genetic variations in eight clinical samples of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Samples were collected from nasopharyngeal swabs of symptomatic and asymptomatic individuals from five care homes for elderly and infirm persons in Israel. The sequences obtained are valuable, as they carry a newly reported nonsynonymous substitution located within the nucleoprotein open reading frame.
7 January 2021, MRA
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Research Article
Monitoring COVID-19 Transmission Risks by Quantitative Real-Time PCR Tracing of Droplets in Hospital and Living Environments
Several studies have evaluated the presence of SARS-CoV-2 in the environment. Saliva and nasopharyngeal droplets can land on objects and surfaces, creating fomites. A suitable indicator would allow the detection of droplets or biofluids carrying the virus. Therefore, we searched for viral RNA and droplets and fomites on at risk surfaces. We monitored by qPCR or next generation sequencing (NGS) droplets through their microbiota. Although the study was performed during the pandemic, SARS-CoV-2 was not significantly found on surfaces, with the only exception of environmental areas near infectious patients. Conversely, anthropic contamination was frequent, suggesting a role for biofluids as putative markers of indirect transmission and risk assessment. Moreover, all SARS-CoV-2-contaminated surfaces showed droplets’ microbiota. Fomite monitoring by qPCR may have an impact on public health strategies, supporting prevention of indirect transmission similarly to what is done for other communicable diseases (e.g., influenza and influenza-like infections).
6 January 2021, mSphere
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Minireview
The Importance and Challenges of Identifying SARS-CoV-2 Reinfections
Reports of SARS-CoV-2 reinfection have raised important questions about the strength and durability of the immune response to primary infection, which are key factors in predicting the course of the pandemic. Identifying reinfection requires detecting the virus at two different time points and using viral genomic data to distinguish reinfection from persistent viral carriage. This process is hindered by challenges of logistics and capacity, such as banking samples from primary infection and performing viral genome sequencing. These challenges may help to explain why very few cases have been described to date. In addition, reinfection may be a rare phenomenon, but detailed prospective studies are needed to rigorously assess its frequency. To provide context for future investigations of SARS-CoV-2 reinfection, we review 16 cases that have been published to date or are available in pre-print. Reinfection occurred across demographic spectra and in patients whose initial infections were both asymptomatic/mild and moderate/severe. For cases in which severity could be compared between episodes, half of reinfections were less severe, raising the possibility of partial immune protection. Although many patients had a positive total immunoglobulin or IgG result at the time of reinfection, very little examination of their immune response was performed. Further work is needed to elucidate the frequency, determinants, and consequences of SARS-CoV-2 reinfection. Establishing the necessary frameworks for surveillance and investigation will rely heavily on clinical laboratories and clinical investigators, and we propose several considerations to guide the medical community in identifying and characterizing SARS-CoV-2 reinfections.
Accepted Manuscript Posted 23 December 2020, JCM; Final Article Posted 19 March 2021
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Minireview
Designing the Next Generation of Vaccines: Relevance for Future Pandemics
The development of vaccines is one of the greatest medical interventions in the history of global infectious diseases and has contributed to the annual saving of at least 2 to 3 million lives worldwide. However, many diseases are not preventable through currently available vaccines, and the potential of modulating the immune response during vaccination has not been fully exploited. The first golden age of vaccines was based on the germ theory and the use of live, attenuated, inactivated pathogens or toxins. New strategies and formulations (e.g., adjuvants) with an immunomodulatory capacity to enhance the protective qualities and duration of vaccines have been incompletely exploited. These strategies can prevent disease and improve protection against infectious diseases, modulate the course of some noncommunicable diseases, and increase the immune responses of patients at a high risk of infection, such as the elderly or immunocompromised patients. In this minireview, we focus on how metabolic and epigenetic modulators can amplify and enhance the function of immunity in a given vaccine. We propose the term “amplifier” for such additives, and we pose that future vaccines will have three components: antigen, adjuvant, and amplifier.
22 December 2020, mBio
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Research Article
Identification of SARS-CoV-2 Nucleocapsid and Spike T-cell Epitopes for Assessing T-cell Immunity
The development of specific and validated immunologic tools is critical for understanding the level and duration of the cellular response induced by SARS-CoV-2 infection and/or vaccines against this novel coronavirus disease. To contribute to this effort, we employed an immunoinformatics analysis pipeline to define 57 SARS-CoV-2 immunogenic peptides within topologically important regions of the nucleocapsid (NC) and spike (S) proteins that will be effective for detecting cellular immune responses in 80-100% of the global population. Our immunoinformatics analysis revealed that 18 of these peptides had limited homology to circulating seasonal human coronaviruses, and therefore are promising candidates for distinguishing SARS-CoV-2 specific immune responses from pre-existing coronavirus immunity. Importantly, CD8+ T-cells derived from SARS-CoV-2 survivors exhibited polyfunctional effector responses to two novel NC-derived peptides identified as HLA-binders. These studies provide a proof of concept that our immunoinformatics analysis pipeline identifies novel immunogens which can elicit polyfunctional SARS-CoV-2 specific T-cell responses.
Accepted Manuscript Posted 21 December 2020, JVI; Final Article Posted 24 February 2021
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Genome Sequences
Two SARS-CoV-2 Genome Sequences of Isolates from Rural U.S. Patients Harboring the D614G Mutation, Obtained Using Nanopore Sequencing
Two coding-complete sequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were obtained from samples from two patients in Arkansas, in the southeastern corner of the United States. The viral genome was obtained using the ARTIC Network protocol and Oxford Nanopore Technologies sequencing.
17 December 2020, MRA