ABSTRACT
The highly mutated SARS-CoV-2 variant, BA.2.86, and its descendants are now the most frequently sequenced variants of SARS-CoV-2. We analyze antibody neutralization data from eight laboratories from the UK, USA, Denmark, and China, including two datasets assessing the effect of XBB.1.5 vaccines, to determine the effect of infection and vaccination history on neutralization of variants up to and including BA.2.86, and produce antibody landscapes to describe these neutralization profiles. We find evidence for lower levels of immune imprinting on pre-Omicron variants in sera collected from Denmark and China, which may be explained by lower levels of circulation of the ancestral variant in these countries, and the use of an inactivated virus vaccine in China.
ABSTRACT
Background: Socio-economic disparities were associated with disproportionate viral incidence between neighborhoods of New York City (NYC) during the first wave of SARS-CoV-2. We investigated how these disparities affected the co-circulation SARS-CoV-2 variants during the second wave in NYC. Methods: We tested for correlation between the prevalence, in late 2020/early 2021, of Alpha, Iota, Iota with E484K mutation (Iota-E484K), and B.1-like genomes and pre-existing immunity (seropositivity) in NYC neighborhoods. In the context of varying seroprevalence we described socio-economic profiles of neighborhoods and performed migration and lineage persistence analyses using a Bayesian phylogeographical framework. Findings: Seropositivity was greater in areas with high poverty and a larger proportion of Black and Hispanic or Latino residents. Seropositivity was positively correlated with the proportion of Iota-E484K and Iota genomes, and negatively correlated with the proportion of Alpha and B.1-like genomes. The proportion of persisting Alpha lineages declined over time in locations with high seroprevalence, whereas the proportion of persisting Iota-E484K lineages remained the same in high seroprevalence areas. Interpretation: During the second wave, the geographic variation of standing immunity, due to disproportionate disease burden during the first wave of SARS-CoV-2 in NYC, allowed for the immune evasive Iota-E484K variant, but not the more transmissible Alpha variant, to circulate in locations with high pre-existing immunity. Funding: We acknowledge funding from the National Institutes of Health and the Centers for Disease Control and Prevention.
ABSTRACT
Rapid identification of new SARS-CoV-2 variants is a critical component of the public health response to the COVID-19 pandemic. However, we lack a quantitative framework to assess the expected performance of sampling strategies in varying epidemic contexts. To address this gap, we used a multi-patch stochastic model of SARS-CoV-2 spread in New York City to evaluate the impact of the volume of testing and sequencing, geographic representativeness of sampling, location and timing of variant emergence, and relative variant transmissibility on the time to first detection of a new variant. The strategy of targeted sampling of likely emergence locations offered the most improvement in detection speed. Increasing sequencing capacity reduced detection time more than increasing testing volumes. The relative transmissibility of the new variant and the epidemic context of variant emergence also influenced detection times, showing that individual surveillance strategies can result in a wide range of detection outcomes, depending on the underlying dynamics of the circulating variants. These findings help contextualize the design, interpretation, and trade-offs of genomic surveillance strategies.
Subject(s)
COVID-19ABSTRACT
COVID-19 impacted multiple facets of life, with implications on physical, mental, and societal health. Specifically, long COVID and related losses have exacerbated complex and prolonged grief responses and mental disorders including depression and anxiety. These mental health concerns are in turn associated with increased detrimental coping strategies including substance use disorders (SUD). The social and interpersonal implications of SUD are varied. Secondary data analyses from the National Survey on Drug Use and Health (NSDUH) collected during the COVID-19 pandemic revealed an increase in substance use behaviors and mental health problems. Self-reported religious activities had a positive meditating effect on reducing substance use behaviors. Accordingly, we explored the importance of one's religion and faith in coping with stress, grief, and mental health challenges during the COVID-19 pandemic, highlighting the impact of religion and faith in bringing hope and purpose during periods of loss, grief, mental health challenges, and SUD.
Subject(s)
Anxiety Disorders , Substance-Related Disorders , Depressive Disorder , Mental Disorders , COVID-19ABSTRACT
Background. Monitoring the emergence and spread of SARS-CoV-2 variants is an important public health objective. Travel restrictions, aimed to prevent viral spread, have major economic consequences and unclear effectiveness despite considerable research. We investigated the introduction and establishment of the Gamma variant in New York City (NYC) in 2021. Methods. We performed phylogeographic analysis on 15,967 Gamma sequences available on GISAID and sampled between March 10th through May 1st, 2021, to identify geographic sources of Gamma lineages introduced into NYC. We identified locally circulating Gamma transmission clusters and inferred the timing of their establishment in NYC. Findings. We identified 16 phylogenetically-distinct Gamma clusters established in NYC (cluster sizes ranged 2-108 genomes). Most of the NYC clusters were introduced from Florida and Illinois; only one was introduced from outside the United States (US). By the time the first Gamma case was reported by genomic surveillance in NYC on March 10th, the majority (57%) of circulating Gamma lineages had already been established in the city for at least two weeks. Interpretation. Despite the expansion of SARS-CoV-2 genomic surveillance in NYC, there was a substantial gap between Gamma variant introduction and establishment in January/February 2021, and its identification by genomic surveillance in March 2021. Although travel from Brazil to the US was restricted from May 2020 through the end of the study period, this restriction did not prevent Gamma from becoming established in NYC as most introductions occurred from domestic locations.
ABSTRACT
Recombination is an evolutionary process by which many pathogens generate diversity and acquire novel functions. Although a common occurrence during coronavirus replication, recombination can only be detected when two genetically distinct viruses contemporaneously infect the same host. Here, we identify an instance of SARS-CoV-2 superinfection, whereby an individual was simultaneously infected with two distinct viral variants: Alpha (B.1.1.7) and Epsilon (B.1.429). This superinfection was first noted when an Alpha genome sequence failed to exhibit the classic S gene target failure behavior used to track this variant. Full genome sequencing from four independent extracts revealed that Alpha variant alleles comprised between 70-80% of the genomes, whereas the Epsilon variant alleles comprised between 20-30% of the sample. Further investigation revealed the presence of numerous recombinant haplotypes spanning the genome, specifically in the spike, nucleocapsid, and ORF 8 coding regions. These findings support the potential for recombination to reshape SARS-CoV-2 genetic diversity.
Subject(s)
InfectionsABSTRACT
BACKGROUNDReports on medium and long-term sequelae of SARS-CoV-2 infections largely lack quantification of incidence and relative risk. We describe the rationale and methods of the Innovative Support for Patients with SARS-CoV-2 Registry (INSPIRE) that combines patient-reported outcomes with data from digital health records to understand predictors and impacts of SARS-CoV-2 infection. METHODSINSPIRE is a prospective, multicenter, longitudinal study of individuals with symptoms of SARS-CoV-2 infection in eight regions across the US. Included are adults fluent in English or Spanish, with self-reported symptoms suggestive of acute SARS-CoV-2 infection, enrolled within 42 days of having a US Food and Drug Administration approved SARS-CoV-2 viral test (i.e., nucleic acid amplification test or antigen test). Recruitment occurs in-person, by phone or email, and through online advertisement. A secure online platform is used to facilitate the collation of consent-related materials, digital health records, and responses to self-administered surveys. Participants will be followed for up to 18 months, with patient-reported outcomes collected every three months via survey and linked to concurrent digital health data; follow-up includes no in-person involvement. Our maximum expected enrollment is 4,800 participants, including 3,600 SARS-CoV-2 positive and 1,200 SARS-CoV-2 negative participants (as a concurrent comparison group). These data will allow assessment of longitudinal outcomes from SARS-CoV-2 infection and comparison of the relative risk of outcomes in individuals with and without infection. Patient-reported outcomes include self-reported health function and status, as well as clinical outcomes including health system encounters and new diagnoses. RESULTSParticipating sites obtained institutional review board approval. Enrollment and follow-up are ongoing. CONCLUSIONSThis study will characterize medium and long-term sequelae of SARS-CoV-2 infection among a diverse population, predictors of sequelae, and their relative risk compared to persons with similar symptomatology but without SARS-CoV-2 infection. These data may inform clinical interventions for individuals with sequelae of SARS-CoV-2 infection.
Subject(s)
COVID-19 , Severe Acute Respiratory SyndromeABSTRACT
COVID-19 is currently spreading widely around the world, causing huge threats on public safety and global society. This study analyzes the spatiotemporal spread pattern of the COVID-19 in China, reveals China’s epicenters of the epidemic through spatial clustering, and delineates the substantial effect of distance to Wuhan on the COVID-19 spread. The results show that the daily new COVID-19 cases mostly occurred in and around Wuhan before March 6, and then moved to the Grand Bay Area (Shenzhen, Hong Kong and Macau). The total COVID-19 cases in China were mainly distributed in the east of the Huhuanyong Line, where the epicenters account for more than 60% of the country’s total on 24 January and 7 February, half on 31 January, and more than 70% from 14 February. The total cases finally stabilized around 84,000, and the inflection point for Wuhan was on 14 February, one week later than those of Hubei (outside Wuhan) and China (outside Hubei). The generalized additive model-based analysis shows that population density and distance to provincial cities significantly associated with the total number of the cases, while distances to prefecture cities and inter-city traffic stations, and population inflow from Wuhan after 24 January, had no strong relationships with the total number of cases. The results and findings should provide valuable insights for understanding the changes in the COVID-19 transmission and controlling the global COVID-19 spread.
Subject(s)
COVID-19ABSTRACT
Background and Aims: No medications are proven to improve clinical outcomes in COVID-19. Famotidine is commonly used for gastric acid suppression but has recently gained attention as an antiviral that may inhibit SARS-CoV-2 replication. This study tested whether famotidine use is associated with improved clinical outcomes in patients with COVID-19 initially hospitalized to a non-intensive care setting. Methods: This was retrospective cohort study conducted among consecutive hospitalized patients with COVID-19 infection from February 25 to April 13, 2020 at a single medical center. The primary exposure was famotidine, received within 24 hours of hospital admission. The primary outcome was intubation or death. Propensity score matching was used to balance the baseline characteristics of patients who did and did not use famotidine. Results: 1,620 hospitalized patients with COVID-19 were identified including 84 (5.1%) who received famotidine within 24 hours of hospital admission. 340 (21%) patients met the study composite outcome of death or intubation. Use of famotidine was associated with reduced risk for death or intubation (adjusted hazard ratio (aHR) 0.42, 95% CI 0.21-0.85) and also with reduced risk for death alone (aHR 0.30, 95% CI 0.11-0.80). After balancing baseline patient characteristics using propensity score matching, these relationships were unchanged (HR for famotidine and death or intubation 0.43, 95% CI 0.21-0.88). Proton pump inhibitors, which also suppress gastric acid, were not associated with reduced risk for death or intubation. Conclusion: Famotidine use is associated with reduced risk of intubation or death in hospitalized COVID-19 patients. Randomized controlled trials are warranted to determine whether famotidine therapy improves outcomes in hospitalized COVID-19 patients.
Subject(s)
COVID-19 , DeathABSTRACT
Background: In this study, we preliminarily investigated the mechanism of Yin-Chai-Xiao-Du decoction for the treatment of COVID-19 by the method of network pharmacology. Methods: The potential targets and pathways of Yin-Chai-Xiao-Du decoction for the treatment of COVID-19 were examined using network pharmacology;the ingredient and active targets of Yin-Chai-Xiao-Du decoction were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and PharmMapper databases;the COVID-19-related targets were obtained from the online Mendelian inheritance in man, GeneCards, and GeneMANIA databases;the STRING database and Cytoscape were used to build a protein-protein interaction network, and a Network Analyzer tool was used to perform topology analysis to screen for the key ingredients and targets;the ClueGO and KOBAS 3.0 databases were for the enrichment analysis of gene function (Gene Oncology) and gene pathway (Kyoto Encyclopedia of Genes and Genomes);the herb-ingredient-target-pathway network diagram was constructed by Cytoscape. Results: The core herbs screened by the network pharmacological analysis were Jinyinhua (Lonicerae japonicae flos), Lianqiao (Forsythia suspensa), Chaihu (Bupleuri radix), Huangqin (Scutellariae radix), Yinchen (Herba Artemisiae Scopariae), Guanghuoxiang (Pogostemonis herba), Roudoukou (Semen myristicae) and Qinghao (Artemisiae annuae herba). A total of 293 active ingredients were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and the key ingredients were quercetin, kaempferol, isorhamnetin, stigmasterol, beta-sitosterol, and luteolin. Yin-Chai-Xiao-Du decoction has 138 COVID-19-related targets, and the key targets were mitogen-activated protein kinase 3, interleukin-6, tumor necrosis factor, vascular endothelial growth factor A, and CC motif ligand 2. Kyoto Encyclopedia of Genes and Genomes analysis revealed 120 enriched gene pathways, and the key pathways were signaling by interleukins, immune system, cytokine signaling in the immune system, and the signaling pathways of interleukin-17, tumor necrosis factor, and relaxin. Conclusion: The core herbs of Yin-Chai-Xiao-Du decoction are Jinyinhua (Lonicerae japonicae flos), Lianqiao (Forsythia suspensa), Chaihu (Bupleuri radix), Huangqin (Scutellariae radix), Yinchen (Herba Artemisiae Scopariae), Guanghuoxiang (Pogostemonis herba), Roudoukou (Semen myristicae) and Qinghao (Artemisiae annuae herba). The key ingredients are quercetin, kaempferol, isorhamnetin, stigmasterol, and beta-sitosterol;the critical targets are luteolin, interleukin-6, mitogen-activated protein kinase 3, tumor necrosis factor, and CC motif ligand 2;and the core signaling pathways are those mediated by interleukin-17, tumor necrosis factor, and relaxin.