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1.
Medicine (Baltimore) ; 100(21): e26143, 2021 May 28.
Article in English | MEDLINE | ID: covidwho-2191018

ABSTRACT

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is a rapidly emerging infectious respiratory disease caused by severe acute respiratory syndrome coronavirus 2. Currently, more than 100 million cases of COVID-19 have been confirmed worldwide, with over 2.4 million mortalities. The pandemic affects people of all ages but older individuals and those with severe chronic illnesses, including cancer patients, are at higher risk. PATIENT CONCERNS: The impact of cancer treatment on the progression of COVID-19 is unclear. Therefore, we assessed the effects of chemotherapy on COVID-19 outcomes for 2 cancer patients. On January 24, 2020, a level I response to a major public health emergency was initiated in Hubei Province, China, which includes Enshi Autonomous Prefecture that has a population of 4.026 million people. As of April 30, 2020, 252 confirmed cases of COVID-19 and 11 asymptomatic carriers were identified in Enshi. DIAGNOSIS: Among the confirmed cases and asymptomatic carriers, 2 patients were identified who were previously diagnosed with malignant tumors, including one with hepatocellular carcinoma and the other with cardia carcinoma. INTERVENTIONS: These 2 patients were receiving or just completed chemotherapy at the time of their COVID-19 diagnosis. OUTCOMES: Both patients were followed and presented favorable outcomes. The positive outcomes for these 2 patients could be partially explained by their recent chemotherapy that impacted their immune status. Also, their relatively younger ages and lack of comorbidities were likely factors in their successful recovery from COVID-19. CONCLUSIONS: Anticancer treatment might enhance a patient's ability to respond favorably to COVID-19 infection. However, anticancer treatment is likely to impact immune function differently in different individuals, which can influence disease outcomes.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , COVID-19/immunology , Liver Neoplasms/drug therapy , SARS-CoV-2/immunology , Stomach Neoplasms/drug therapy , Adult , COVID-19/complications , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19 Nucleic Acid Testing , Cyclobutanes/therapeutic use , Docetaxel/therapeutic use , Drug Therapy, Combination/methods , Humans , Liver Neoplasms/complications , Liver Neoplasms/immunology , Lung/diagnostic imaging , Male , Middle Aged , Organoplatinum Compounds/therapeutic use , RNA, Viral/isolation & purification , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Sorafenib/therapeutic use , Stomach Neoplasms/complications , Stomach Neoplasms/immunology , Tomography, X-Ray Computed , Treatment Outcome
2.
Medicine (Baltimore) ; 100(21): e26034, 2021 May 28.
Article in English | MEDLINE | ID: covidwho-2191014

ABSTRACT

ABSTRACT: To determine the role of ultra-low dose chest computed tomography (uld CT) compared to chest radiographs in patients with laboratory-confirmed early stage SARS-CoV-2 pneumonia.Chest radiographs and uld CT of 12 consecutive suspected SARS-CoV-2 patients performed up to 48 hours from hospital admission were reviewed by 2 radiologists. Dosimetry and descriptive statistics of both modalities were analyzed.On uld CT, parenchymal abnormalities compatible with SARS-CoV-2 pneumonia were detected in 10/12 (83%) patients whereas on chest X-ray in, respectively, 8/12 (66%) and 5/12 (41%) patients for reader 1 and 2. The average increment of diagnostic performance of uld CT compared to chest X-ray was 29%. The average effective dose was, respectively, of 0.219 and 0.073 mSv.Uld CT detects substantially more lung injuries in symptomatic patients with suspected early stage SARS-CoV-2 pneumonia compared to chest radiographs, with a significantly better inter-reader agreement, at the cost of a slightly higher equivalent radiation dose.


Subject(s)
COVID-19/diagnosis , Lung/diagnostic imaging , Radiography, Thoracic/statistics & numerical data , SARS-CoV-2/isolation & purification , Tomography, X-Ray Computed/statistics & numerical data , Adult , Aged , Aged, 80 and over , COVID-19/virology , COVID-19 Nucleic Acid Testing , Female , Humans , Male , Middle Aged , Observer Variation , Predictive Value of Tests , RNA, Viral/isolation & purification , Radiation Dosage , Radiography, Thoracic/adverse effects , Radiography, Thoracic/methods , Radiometry/statistics & numerical data , Retrospective Studies , SARS-CoV-2/genetics , Tomography, X-Ray Computed/adverse effects , Tomography, X-Ray Computed/methods
3.
Medicine (Baltimore) ; 100(21): e25645, 2021 May 28.
Article in English | MEDLINE | ID: covidwho-2190994

ABSTRACT

ABSTRACT: Since December 2019, pneumonia caused by a novel coronavirus (SARS-CoV-2), namely 2019 novel coronavirus disease (COVID-19), has rapidly spread from Wuhan city to other cities across China. The present study was designed to describe the epidemiology, clinical characteristics, treatment, and prognosis of 74 hospitalized patients with COVID-19.Clinical data of 74 COVID-19 patients were collected to analyze the epidemiological, demographic, laboratory, radiological, and treatment data. Thirty-two patients were followed up and tested for the presence of the viral nucleic acid and by pulmonary computed tomography (CT) scan at 7 and 14 days after they were discharged.Among all COVID-19 patients, the median incubation period for patients and the median period from symptom onset to admission was all 6 days; the median length of hospitalization was 13 days. Fever symptoms were presented in 83.78% of the patients, and the second most common symptom was cough (74.32%), followed by fatigue and expectoration (27.03%). Inflammatory indicators, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) of the intensive care unit (ICU) patients were significantly higher than that of the non-ICU patients (P < .05). However, 50.00% of the ICU patients had their the ratio of T helper cells to cytotoxic T cells (CD4/CD8) ratio lower than 1.1, whose proportion is much higher than that in non-ICU patients (P < .01).Compared with patients in Wuhan, COVID-19 patients in Anhui Province seemed to have milder symptoms of infection, suggesting that there may be some regional differences in the transmission of SARS-CoV-2 between different cities.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/diagnosis , Cough/epidemiology , Fever/epidemiology , Hyperbaric Oxygenation/statistics & numerical data , Adolescent , Adult , Aged , Antibiotic Prophylaxis/statistics & numerical data , Blood Sedimentation , C-Reactive Protein/analysis , COVID-19/complications , COVID-19/epidemiology , COVID-19/therapy , COVID-19 Nucleic Acid Testing , Child , Child, Preschool , China/epidemiology , Cities/epidemiology , Cough/blood , Cough/therapy , Cough/virology , Female , Fever/blood , Fever/therapy , Fever/virology , Follow-Up Studies , Geography , Humans , Length of Stay/statistics & numerical data , Lung/diagnostic imaging , Male , Middle Aged , RNA, Viral/isolation & purification , Retrospective Studies , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Severity of Illness Index , Tomography, X-Ray Computed , Young Adult
4.
Elife ; 112022 Nov 15.
Article in English | MEDLINE | ID: covidwho-2203162

ABSTRACT

The COVID-19 pandemic has resulted in a step change in the scale of sequencing data, with more genomes of SARS-CoV-2 having been sequenced than any other organism on earth. These sequences reveal key insights when represented as a phylogenetic tree, which captures the evolutionary history of the virus, and allows the identification of transmission events and the emergence of new variants. However, existing web-based tools for exploring phylogenies do not scale to the size of datasets now available for SARS-CoV-2. We have developed Taxonium, a new tool that uses WebGL to allow the exploration of trees with tens of millions of nodes in the browser for the first time. Taxonium links each node to associated metadata and supports mutation-annotated trees, which are able to capture all known genetic variation in a dataset. It can either be run entirely locally in the browser, from a server-based backend, or as a desktop application. We describe insights that analysing a tree of five million sequences can provide into SARS-CoV-2 evolution, and provide a tool at cov2tree.org for exploring a public tree of more than five million SARS-CoV-2 sequences. Taxonium can be applied to any tree, and is available at taxonium.org, with source code at github.com/theosanderson/taxonium.


Since 2020, the SARS-CoV-2 virus has infected billions of people and spread to 185 countries. The virus spreads by making new copies of its genome inside human cells and exploits the cells' machinery to synthesise viral proteins it needs to infect further cells. Each time the virus copies its genetic material there's a chance that the replication process introduces an error to the genetic sequence. Over time, these mutations accumulate which can give rise to new variants with different properties. These new variants, originating from a common ancestor, may spread faster or be able to evade immune systems that have learnt to recognise previous variants. To understand where new variants of SARS-CoV-2 come from and how related they are to each other, scientists build family trees called 'phylogenetic trees' based on similarities in the genetic sequences of different variants of the virus. Looking at these trees researchers can track how a variant spreads geographically, and also attempt to identify new worrying variants that might lead to a new wave of infections. The scale of the COVID-19 pandemic together with the global effort by clinicians and researchers to sequence SARS-CoV-2 genetic material means a library of over 13 million SARS-CoV-2 genomes now exists, making it the largest such collection for any organism. Although phylogenetic trees of viruses have been studied for a long time, exploring the SARS-CoV-2 library presents technical and practical challenges due to its sheer size. Sanderson has developed an open-source web tool called Taxonium that allows users to explore phylogenetic trees with millions of sequences. With help from collaborators at the University of California, Santa Cruz, Sanderson built a website called Cov2Tree, that uses the Taxonium platform to allow immediate access to an expansive tree of all publicly available SARS-CoV-2 sequences. Cov2Tree enables users to visualise all SARS-CoV-2 genomes in a birds-eye view akin to a 'Google Earth for virus sequences' where anyone can zoom in on a related family of viruses down to the level of individual sequences. This can be used to compare variants and follow geographic spread. Using Taxonium, scientists can explore how virus sequences are related to each other. They can also see the individual mutations that have occurred at each branch of the tree, and can search for sequences based on mutation, geographical location, or other factors. Interestingly, a trend appearing in the SARS-CoV-2 phylogenetic tree is the emergence of identical mutations at different branches of the tree without a common origin. These mutations may be a result of convergent evolution, a phenomenon that occurs when a mutation appears independently in different variants as it confers an advantage to the virus making such mutations more likely to persist. This means that scientists may be able to expect certain mutations to appear in more distantly related variants if they have appeared independently in several different variants already. Overall, Taxonium is an important tool for monitoring SARS-CoV-2 genomes, but it also has broader applications. The tool can be used to browse phylogenetic trees of other viruses and organisms. Furthermore, the Taxonium website offers a way to browse a tree of life, with images and links to Wikipedia. The SARS-CoV-2 library might be the largest now, but in the future even bigger datasets will likely be available, highlighting the importance of tools like Taxonium.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Phylogeny , SARS-CoV-2/genetics , Pandemics , COVID-19/epidemiology , Internet
5.
Theranostics ; 12(10): 4779-4790, 2022.
Article in English | MEDLINE | ID: covidwho-2203050

ABSTRACT

New variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are continuing to spread globally, contributing to the persistence of the COVID-19 pandemic. Increasing resources have been focused on developing vaccines and therapeutics that target the Spike glycoprotein of SARS-CoV-2. Recent advances in microfluidics have the potential to recapitulate viral infection in the organ-specific platforms, known as organ-on-a-chip (OoC), in which binding of SARS-CoV-2 Spike protein to the angiotensin-converting enzyme 2 (ACE2) of the host cells occurs. As the COVID-19 pandemic lingers, there remains an unmet need to screen emerging mutations, to predict viral transmissibility and pathogenicity, and to assess the strength of neutralizing antibodies following vaccination or reinfection. Conventional detection of SARS-CoV-2 variants relies on two-dimensional (2-D) cell culture methods, whereas simulating the micro-environment requires three-dimensional (3-D) systems. To this end, analyzing SARS-CoV-2-mediated pathogenicity via microfluidic platforms minimizes the experimental cost, duration, and optimization needed for animal studies, and obviates the ethical concerns associated with the use of primates. In this context, this review highlights the state-of-the-art strategy to engineer the nano-liposomes that can be conjugated with SARS-CoV-2 Spike mutations or genomic sequences in the microfluidic platforms; thereby, allowing for screening the rising SARS-CoV-2 variants and predicting COVID-19-associated coagulation. Furthermore, introducing viral genomics to the patient-specific blood accelerates the discovery of therapeutic targets in the face of evolving viral variants, including B1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta), c.37 (Lambda), and B.1.1.529 (Omicron). Thus, engineering nano-liposomes to encapsulate SARS-CoV-2 viral genomic sequences enables rapid detection of SARS-CoV-2 variants in the long COVID-19 era.


Subject(s)
COVID-19 , Coronavirus Infections , Pneumonia, Viral , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/complications , COVID-19/diagnosis , Coronavirus Infections/prevention & control , Genomics , Humans , Liposomes , Microfluidics , Mutation , Pandemics/prevention & control , Peptidyl-Dipeptidase A/metabolism , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus
6.
Swiss Med Wkly ; 152: w30202, 2022 06 20.
Article in English | MEDLINE | ID: covidwho-2202460

ABSTRACT

AIMS OF THE STUDY: Wastewater-based epidemiology has contributed significantly to the comprehension of the dynamics of the current COVID-19 pandemic. Its additional value in monitoring SARS-CoV-2 circulation in the population and identifying newly arising variants independently of diagnostic testing is now undisputed. As a proof of concept, we report here correlations between SARS-CoV-2 detection in wastewater and the officially recorded COVID-19 case numbers, as well as the validity of such surveillance to detect emerging variants, exemplified by the detection of the B.1.1.529 variant Omicron in Basel, Switzerland. METHODS: From July 1 to December 31, 2021, wastewater samples were collected six times a week from the inflow of the local wastewater treatment plant that receives wastewater from the catchment area of the city of Basel, Switzerland, comprising 273,075 inhabitants. The number of SARS-CoV-2 RNA copies was determined by reverse transcriptase-quantitative PCR. Spearman's rank correlation coefficients were calculated to determine correlations with the median seven-day incidence of genome copies per litre of wastewater and official case data. To explore delayed correlation effects between the seven-day median number of genome copies/litre wastewater and the median seven-day incidence of SARS-CoV-2 cases, time-lagged Spearman's rank correlation coefficients were calculated for up to 14 days. RNA extracts from daily wastewater samples were used to genotype circulating SARS-CoV-2 variants by next-generation sequencing. RESULTS: The number of daily cases and the median seven-day incidence of SARS-CoV-2 infections in the catchment area showed a high correlation with SARS-CoV-2 measurements in wastewater samples. All correlations between the seven-day median number of genome copies/litre wastewater and the time-lagged median seven-day incidence of SARS-CoV-2 cases were significant (p<0.001) for the investigated lag of up to 14 days. Correlation coefficients declined constantly from the maximum of 0.9395 on day 1 to the minimum of 0.8016 on day 14. The B.1.1.529 variant Omicron was detected in wastewater samples collected on November 21, 2021, before its official acknowledgement in a clinical sample by health authorities. CONCLUSIONS: In this proof-of-concept study, wastewater-based epidemiology proved a reliable and sensitive surveillance approach, complementing routine clinical testing for mapping COVID-19 pandemic dynamics and observing newly circulating SARS-CoV-2 variants.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/diagnosis , COVID-19/epidemiology , Humans , Pandemics , RNA, Viral/genetics , SARS-CoV-2/genetics , Switzerland/epidemiology , Waste Water/analysis
7.
Indian J Med Res ; 155(1): 86-90, 2022 01.
Article in English | MEDLINE | ID: covidwho-2201765

ABSTRACT

To implement the strategy of test, track and treat to tackle the ongoing COVID-19 pandemic, the number of real-time RT-PCR-based testing laboratories was increased for diagnosis of SARS-CoV-2 in the country. To ensure reliability of the laboratory results, the Indian Council of Medical Research initiated external quality assessment (EQA) by deploying inter-laboratory quality control (ILQC) activity for these laboratories by nominating 34 quality control (QC) laboratories. This report presents the results of this activity for a period of September 2020 till November 2020. A total of 597 laboratories participated in this activity and 86 per cent of these scored ≥90 per cent concordance with QC laboratories. This ILQC activity showcased India's preparedness in quality diagnosis of SARS-CoV-2.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/diagnosis , COVID-19 Testing , Clinical Laboratory Techniques/methods , Humans , Pandemics , Reproducibility of Results , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/genetics
9.
Indian J Med Res ; 155(1): 165-170, 2022 01.
Article in English | MEDLINE | ID: covidwho-2201739

ABSTRACT

Background & objectives: COVID-19 cases have been rising rapidly in countries where the SARS-CoV-2 variant of concern (VOC), Omicron (B.1.1.529) has been reported. We conducted a study to describe the epidemiological and clinical characteristics and outcomes of COVID-19 patients with 'S' gene target failure (SGTF, suspected Omicron). Furthermore, their clinical outcomes with COVID-19 patients with non-SGTF (non-Omicron) were also compared. Methods: This study was conducted in Tamil Nadu, India, between December 14, 2021 and January 7, 2022 among patients who underwent reverse transcription-PCR testing for SARS-CoV-2 in four laboratories with facilities for S gene screening. Consecutively selected COVID-19 patients with SGTF were telephonically contacted, seven and 14 days respectively after their date of positive result to collect information on the socio-demographic characteristics, previous history of COVID-19, vaccination status and clinical course of illness along with treatment details. To compare their outcomes with non-SGTF patients, one randomly suspected non-Omicron case for every two suspected Omicron cases from the line-list were selected, matching for the date of sample collection and the testing laboratory. Results: A total of 1175 SGTF COVID-19 patients were enrolled for this study. Almost 6 per cent (n=72) reported a history of previous infection. 141 (13.5%) suspected Omicron cases were non-vaccinated, while 148 (14.2%) and 703 (67.4%) had received valid one and two doses of COVID-19 vaccines, respectively. Predominant symptoms reported included fever (n=508, 43.2%), body pain (n=275, 23.4%), running nose (n=261, 22.2%) and cough (n=249, 21.2%). Five (0.4%) of the 1175 suspected Omicron cases required oxygen supplementation as compared to ten (1.6%) of the 634 suspected non-Omicron cases. No deaths were reported among omicron suspects, whereas there were four deaths among suspected non-Omicron cases. Interpretation & conclusions: Majority of the suspected Omicron cases had a mild course of illness. The overall severity of these cases was less compared to the suspected non-Omicron cases.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , COVID-19 Vaccines , Humans , India/epidemiology , SARS-CoV-2/genetics
10.
Int J Mol Sci ; 23(16)2022 Aug 20.
Article in English | MEDLINE | ID: covidwho-2200284

ABSTRACT

Rapid identification of SARS-CoV-2 variants is essential for epidemiological surveillance. RT-qPCR-based variant differentiation tests can be used to quickly screen large sets of samples for relevant variants of concern/interest; this study was conducted on specimens collected at 11 centers located in Poland during routine SARS-CoV-2 diagnostics between August 2020 and December 2021. A total of 1096 samples (with CT < 30) were screened for Alpha, Beta, Delta, Kappa and Omicron variants using commercial assays targeting repeat mutation sites. Variants were assigned to 434 (39.6%) specimens; the remaining 662 (60.4%) samples were not classified (no tested mutations detected). Alpha (n = 289; 66.59%), Delta (n = 115; 26.5%), Kappa (n = 30; 6.91%) and Omicron (n = 2; 0.46%) variants were identified and their distribution changed over time. The first Alpha variant appeared in October 2020, and it began to gradually increase its proportion of the virus population by June 2021. In July 2021, it was replaced by the Delta variant, which already dominated by the end of the year. The first Kappa was detected in October 2021, while Omicron was found in December 2021. The screening of samples allowed the determination of epidemiological trends over a time interval reflecting the national COVID-19 waves.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19 Testing , Humans , Mutation , Poland/epidemiology , Real-Time Polymerase Chain Reaction , SARS-CoV-2/genetics
11.
Front Cell Infect Microbiol ; 12: 1009328, 2022.
Article in English | MEDLINE | ID: covidwho-2198710

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China in December 2019 and caused a global pandemic resulting in millions of deaths and tens of millions of patients positive tests. While studies have shown a D614G mutation in the viral spike protein are more transmissible, the effects of this and other mutations on the host response, especially at the cellular level, are yet to be fully elucidated. In this experiment we infected normal human bronchial epithelial (NHBE) cells with the Washington (D614) strain or the New York (G614) strains of SARS-CoV-2. We generated RNA sequencing data at 6, 12, and 24 hours post-infection (hpi) to improve our understanding of how the intracellular host response differs between infections with these two strains. We analyzed these data with a bioinformatics pipeline that identifies differentially expressed genes (DEGs), enriched Gene Ontology (GO) terms and dysregulated signaling pathways. We detected over 2,000 DEGs, over 600 GO terms, and 29 affected pathways between the two infections. Many of these entities play a role in immune signaling and response. A comparison between strains and time points showed a higher similarity between matched time points than across different time points with the same strain in DEGs and affected pathways, but found more similarity between strains across different time points when looking at GO terms. A comparison of the affected pathways showed that the 24hpi samples of the New York strain were more similar to the 12hpi samples of the Washington strain, with a large number of pathways related to translation being inhibited in both strains. These results suggest that the various mutations contained in the genome of these two viral isolates may cause distinct effects on the host transcriptional response in infected host cells, especially relating to how quickly translation is dysregulated after infection. This comparison of the intracellular host response to infection with these two SARS-CoV-2 isolates suggest that some of the mechanisms associated with more severe disease from these viruses could include virus replication, metal ion usage, host translation shutoff, host transcript stability, and immune inhibition.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , New York , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Viral Proteins , Washington
12.
PLoS One ; 17(8): e0271359, 2022.
Article in English | MEDLINE | ID: covidwho-2196940

ABSTRACT

The viral genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), particularly its cell-binding spike protein gene, has undergone rapid evolution during the coronavirus disease 2019 (COVID-19) pandemic. Variants including Omicron BA.1 and Omicron BA.2 now seriously threaten the efficacy of therapeutic monoclonal antibodies and vaccines that target the spike protein. Viral evolution over a much longer timescale has generated a wide range of genetically distinct sarbecoviruses in animal populations, including the pandemic viruses SARS-CoV-2 and SARS-CoV-1. The genetic diversity and widespread zoonotic potential of this group complicates current attempts to develop drugs in preparation for the next sarbecovirus pandemic. Receptor-based decoy inhibitors can target a wide range of viral strains with a common receptor and may have intrinsic resistance to escape mutant generation and antigenic drift. We previously generated an affinity-matured decoy inhibitor based on the receptor target of the SARS-CoV-2 spike protein, angiotensin-converting enzyme 2 (ACE2), and deployed it in a recombinant adeno-associated virus vector (rAAV) for intranasal delivery and passive prophylaxis against COVID-19. Here, we demonstrate the exceptional binding and neutralizing potency of this ACE2 decoy against SARS-CoV-2 variants including Omicron BA.1 and Omicron BA.2. Tight decoy binding tracks with human ACE2 binding of viral spike receptor-binding domains across diverse clades of coronaviruses. Furthermore, in a coronavirus that cannot bind human ACE2, a variant that acquired human ACE2 binding was bound by the decoy with nanomolar affinity. Considering these results, we discuss a strategy of decoy-based treatment and passive protection to mitigate the ongoing COVID-19 pandemic and future airway virus threats.


Subject(s)
Angiotensin-Converting Enzyme 2 , COVID-19 , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Angiotensin-Converting Enzyme 2/chemistry , Animals , COVID-19/drug therapy , Humans , Pandemics/prevention & control , Peptidyl-Dipeptidase A/metabolism , Protein Binding , Receptors, Virus/metabolism , SARS-CoV-2/genetics
13.
Ann Clin Microbiol Antimicrob ; 21(1): 32, 2022 Jul 03.
Article in English | MEDLINE | ID: covidwho-2196304

ABSTRACT

BACKGROUND: New vaccines are being developed to fight the ongoing COVID-19 pandemic. In our study we compared the efficacy of COVID-19 vaccines to prevent COVID-19-related infections and mortality. METHODS: 17 randomized clinical trials of COVID-19 vaccines were included after search in databases. We compared COVID-19 vaccines based on symptomatic and severe infections, number of deaths and hospitalizations related to COVID-19. Also, we analyzed the efficacy of COVID-19 against different variants of SARS-CoV-2 as well as according to different age groups. Random effects model using Mantel-Haenzeal method was used to pool relative risk (RR). RESULTS: Our meta-analysis shows that full vaccination could decrease not only the risk of symptomatic or severe COVID-19, the risk of hospitalization and death caused by COVID-19. COVID-19 vaccines were also effective against variants of SARS-CoV-2 (RR = 0.36; 95% CI [0.25; 0.53], p < 0.0001). However, efficacy of vaccination varied in COVID-19 variant-dependent manner. Moreover, the analysis in different age groups showed that COVID-19 vaccines had the similar results: the risk was slightly lower in adults compared to elderly cohort [Formula: see text] 65 years): (RR = 0.16, 95% CI [0.11; 0.23]) and (RR = 0.19, 95% CI [0.12; 0.30]), respectively. CONCLUSIONS: Data obtained from clinical trials of COVID-19 vaccines looks promising, in order to fully investigate efficacy of the vaccines further clinical examination is required especially considering new SARS-CoV-2 variants.


Subject(s)
COVID-19 , Viral Vaccines , Adult , Aged , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Pandemics , Randomized Controlled Trials as Topic , SARS-CoV-2/genetics , Vaccination
14.
Microbiol Spectr ; 10(1): e0245521, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-2193554

ABSTRACT

Containment measures employed during the COVID-19 pandemic included prompt recognition of cases, isolation, and contact tracing. Bilateral nasal (NA) swabs applied to a commercial antigen-based rapid diagnostic test (Ag-RDT) offer a simpler and more comfortable alternative to nasopharyngeal (NP) collection; however, little is known about the sensitivity of this method in an asymptomatic population. Participants in community-based asymptomatic testing sites were screened for SARS-CoV-2 using an Ag-RDT with NP sampling. Positive individuals returned for confirmatory molecular testing and consented to repeating the Ag-RDT using a bilateral NA swab for comparison. Residual test buffer (RTB) from Ag-RDTs was subjected to real-time reverse transcription-PCR (RT-PCR). Of 123,617 asymptomatic individuals, 197 NP Ag-RDT-positive participants were included, with 175 confirmed positive by RT-PCR. Of these cases, 154 were identified from the NA swab collection with Ag-RDT, with a sensitivity of 88.0% compared to the NP swab collection. Stratifying results by RT-PCR cycle threshold demonstrated that sensitivity of the nasal collection method varied based on the cycle threshold (CT) value of the paired RT-PCR sample. RT-PCR testing on the RTB from the Ag-RDT using NP and NA swab collections resulted in 100.0% and 98.7% sensitivity, respectively. NA swabs provide an adequate alternative to NP swab collection for use with Ag-RDT, with the recognition that the test is most sensitive in specimens with high viral loads. With the high sensitivity of RT-PCR testing on RTB from Ag-RDT, a more streamlined approach to confirmatory testing is possible without recollection or use of paired collections strategies. IMPORTANCE Nasal swabbing for SARS-CoV-2 (COVID-19) comes with many benefits but is slightly less sensitive than traditional nasopharyngeal swabbing; however, confirmatory lab-based testing could be performed directly from the residual buffer from either sample type.


Subject(s)
Antigens, Viral/analysis , COVID-19/virology , Carrier State/virology , Nasopharynx/virology , Nose/virology , SARS-CoV-2/isolation & purification , Specimen Handling/methods , Antigens, Viral/genetics , Antigens, Viral/immunology , Asymptomatic Diseases , COVID-19/diagnosis , COVID-19 Serological Testing , Humans , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/classification , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Sensitivity and Specificity
15.
Epidemiology ; 33(6): 797-807, 2022 Nov 01.
Article in English | MEDLINE | ID: covidwho-2190880

ABSTRACT

BACKGROUND: Marine recruits training at Parris Island experienced an unexpectedly high rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, despite preventive measures including a supervised, 2-week, pre-entry quarantine. We characterize SARS-CoV-2 transmission in this cohort. METHODS: Between May and November 2020, we monitored 2,469 unvaccinated, mostly male, Marine recruits prospectively during basic training. If participants tested negative for SARS-CoV-2 by quantitative polymerase chain reaction (qPCR) at the end of quarantine, they were transferred to the training site in segregated companies and underwent biweekly testing for 6 weeks. We assessed the effects of coronavirus disease 2019 (COVID-19) prevention measures on other respiratory infections with passive surveillance data, performed phylogenetic analysis, and modeled transmission dynamics and testing regimens. RESULTS: Preventive measures were associated with drastically lower rates of other respiratory illnesses. However, among the trainees, 1,107 (44.8%) tested SARS-CoV-2-positive, with either mild or no symptoms. Phylogenetic analysis of viral genomes from 580 participants revealed that all cases but one were linked to five independent introductions, each characterized by accumulation of mutations across and within companies, and similar viral isolates in individuals from the same company. Variation in company transmission rates (mean reproduction number R 0 ; 5.5 [95% confidence interval [CI], 5.0, 6.1]) could be accounted for by multiple initial cases within a company and superspreader events. Simulations indicate that frequent rapid-report testing with case isolation may minimize outbreaks. CONCLUSIONS: Transmission of wild-type SARS-CoV-2 among Marine recruits was approximately twice that seen in the community. Insights from SARS-CoV-2 outbreak dynamics and mutations spread in a remote, congregate setting may inform effective mitigation strategies.


Subject(s)
COVID-19 , Disease Outbreaks , Military Personnel , COVID-19/epidemiology , COVID-19/prevention & control , Disease Outbreaks/prevention & control , Female , Humans , Male , Military Personnel/statistics & numerical data , Phylogeny , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , United States/epidemiology
16.
Chin Med J (Engl) ; 135(10): 1213-1222, 2022 May 20.
Article in English | MEDLINE | ID: covidwho-2190861

ABSTRACT

ABSTRACT: The pandemic of coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to major public health challenges globally. The increasing viral lineages identified indicate that the SARS-CoV-2 genome is evolving at a rapid rate. Viral genomic mutations may cause antigenic drift or shift, which are important ways by which SARS-CoV-2 escapes the human immune system and changes its transmissibility and virulence. Herein, we summarize the functional mutations in SARS-CoV-2 genomes to characterize its adaptive evolution to inform the development of vaccination, treatment as well as control and intervention measures.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Mutation/genetics , Pandemics , SARS-CoV-2/genetics , Virulence
17.
Front Cell Infect Microbiol ; 12: 960938, 2022.
Article in English | MEDLINE | ID: covidwho-2154694

ABSTRACT

Coronavirus disease 2019 (COVID-19) is an extremely contagious illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Early disease recognition of COVID-19 is crucial not only for prompt diagnosis and treatment of the patients, but also for effective public health surveillance and response. The reverse transcription-polymerase chain reaction (RT-PCR) is the most common method for the detection of SARS-CoV-2 viral mRNA and is regarded as the gold standard test for COVID-19. However, this test and those for antibodies (IgM and IgG) and antigens have certain limitations (e.g., by yielding false-negative and false-positive results). We have developed an RNA fluorescence in situ hybridization (FISH) method for high-sensitivity detection of SARS-CoV-2 mRNAs in HEK 293T cell cultures as a model. After transfection of HEK 293T cells with plasmids, Spike (S)/envelope (E) proteins and their mRNAs were clearly detected inside the cells. In addition, hybridization time could be reduced to 2 hours for faster detection when probe concentration was increased. Our approach might thus significantly improve the sensitivity and specificity of SARS-CoV-2 detection and be widely applied for the high-sensitivity single-molecular detection of other RNA viruses (e.g., Middle East respiratory syndrome coronavirus (MERS-CoV), Hepatitis A virus, all influenza viruses, and human immunodeficiency virus (HIV)) in various types of samples including tissue, body fluid, blood, and water. RNA FISH can also be utilized for the detection of DNA viruses (e.g., Monkeypox virus, human papillomavirus (HPV), and cytomegalovirus (CMV)) by detection of their mRNAs inside cells or body fluid.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , COVID-19 Testing , Clinical Laboratory Techniques/methods , RNA, Messenger/genetics , In Situ Hybridization, Fluorescence , HEK293 Cells , Immunoglobulin M , Immunoglobulin G , Water
18.
Front Cell Infect Microbiol ; 12: 902914, 2022.
Article in English | MEDLINE | ID: covidwho-2154670

ABSTRACT

Identification of the main SARS-CoV-2 variants in real time is of interest to control the virus and to rapidly devise appropriate public health responses. The RT-qPCR is currently considered to be the reference method to screen SARS-CoV-2 mutations, but it has some limitations. The multiplexing capability is limited when the number of markers to detect increases. Moreover, the performance of this allele-specific method may be impacted in the presence of new mutations. Herein, we present a proof-of-concept study of a simple molecular assay to detect key SARS-CoV-2 mutations. The innovative features of the assay are the multiplex asymmetric one-step RT-PCR amplification covering different regions of SARS-CoV-2 S gene and the visual detection of mutations on a lateral flow DNA microarray. Three kits (Kit 1: N501Y, E484K; Kit 2: L452R, E484K/Q; Kit 3: K417N, L452R, E484K/Q/A) were developed to match recommendations for surveillance of SARS-CoV-2 variants between January and December 2021. The clinical performance was assessed using RNA extracts from 113 SARS-CoV-2-positive samples with cycle thresholds <30, and results demonstrated that our assay allows specific and sensitive detection of mutations, with a performance comparable to that of RT-qPCR. The VAR-CoV assay detected four SARS-CoV-2 targets and achieved specific and sensitive screening of spike mutations associated with the main variants of concern, with a performance comparable to that of RT-qPCR. With well-defined virus sequences, this assay can be rapidly adapted to other emerging mutations; it is a promising tool for variant surveillance.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/diagnosis , Humans , Mutation , SARS-CoV-2/genetics
19.
Front Cell Infect Microbiol ; 12: 887754, 2022.
Article in English | MEDLINE | ID: covidwho-2154665

ABSTRACT

Candida auris continues to be a global threat for infection and transmission in hospitals and long-term care facilities. The emergence of SARS-CoV-2 has rerouted attention and resources away from this silent pandemic to the frontlines of the ongoing COVID-19 disease. Cases of C. auris continue to rise, and clinical laboratories need a contingency plan to prevent a possible outbreak amid the COVID-19 pandemic. Here, we introduce a two-tier Candida auris surveillance program that includes, first, a rapid qualitative rt-PCR for the identification of high-risk patients and, second, a method to analyze the isolated C. auris for strain typing using the Fourier-Transform Infrared spectroscopy. We have performed this two-tier surveillance for over 700 at-risk patients being admitted into our hospital and have identified 28 positive specimens (4%) over a 1-year period. Strain typing analysis by the IR spectrum acquisition typing method, supplemented by whole genome sequencing, has shown grouping of two significant clusters. The majority of our isolates belong to circulating African lineage associated with C. auris Clade III and an isolated strain grouping differently belonging to South Asian lineage C. auris Clade I. Low numbers of genomic variation point to local and ongoing transmission within the Los Angeles area not specifically within the hospital setting. Collectively, clinical laboratories having the ability to rapidly screen high-risk patients for C. auris and to participate in outbreak investigations by offering strain typing will greatly assist in the control of C. auris transmission within the hospital setting.


Subject(s)
COVID-19 , Candidiasis , Algorithms , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19 Testing , Candida , Humans , Pandemics , Real-Time Polymerase Chain Reaction , SARS-CoV-2/genetics
20.
Euro Surveill ; 27(43)2022 10.
Article in English | MEDLINE | ID: covidwho-2154580

ABSTRACT

BackgroundTracking person-to-person SARS-CoV-2 transmission in the population is important to understand the epidemiology of community transmission and may contribute to the containment of SARS-CoV-2. Neither contact tracing nor genomic surveillance alone, however, are typically sufficient to achieve this objective.AimWe demonstrate the successful application of the integrated genomic surveillance (IGS) system of the German city of Düsseldorf for tracing SARS-CoV-2 transmission chains in the population as well as detecting and investigating travel-associated SARS-CoV-2 infection clusters.MethodsGenomic surveillance, phylogenetic analysis, and structured case interviews were integrated to elucidate two genetically defined clusters of SARS-CoV-2 isolates detected by IGS in Düsseldorf in July 2021.ResultsCluster 1 (n = 67 Düsseldorf cases) and Cluster 2 (n = 36) were detected in a surveillance dataset of 518 high-quality SARS-CoV-2 genomes from Düsseldorf (53% of total cases, sampled mid-June to July 2021). Cluster 1 could be traced back to a complex pattern of transmission in nightlife venues following a putative importation by a SARS-CoV-2-infected return traveller (IP) in late June; 28 SARS-CoV-2 cases could be epidemiologically directly linked to IP. Supported by viral genome data from Spain, Cluster 2 was shown to represent multiple independent introduction events of a viral strain circulating in Catalonia and other European countries, followed by diffuse community transmission in Düsseldorf.ConclusionIGS enabled high-resolution tracing of SARS-CoV-2 transmission in an internationally connected city during community transmission and provided infection chain-level evidence of the downstream propagation of travel-imported SARS-CoV-2 cases.


Subject(s)
COVID-19 , Communicable Diseases, Imported , Humans , SARS-CoV-2/genetics , Travel , Communicable Diseases, Imported/epidemiology , COVID-19/epidemiology , Phylogeny , Contact Tracing , Germany/epidemiology , Genomics
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