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A model anti-pandemic portal for scientists & public
Non-Pubmed Articles (BioRXiv, MedRXiv)
Last updated: 2021 Oct 08
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Angiotensin converting enzyme 2 (ACE2) is expressed in murine cutaneous under single-cell transcriptome resolution
Angiotensin converting enzyme 2 (Ace2) is widely distributed in human organs, which was identified as a functional receptor for severe acute respiratory syndrome (SARS) coronavirus in human beings. It was also confirmed that SARS-CoV-2 uses the same cell entry receptor, ACE2, as SARS-CoV. However, related research still not discover the expression data associated with murine skin under single cell RNA resolution. In this study, we performed single-cell RNA sequencing (scRNA-seq) on unsorted cells from mouse dorsal skin after 7 days post-wounding. 8312 sequenced cells from four skin samples met quality control metrics and were analyzed.
Inhibition of SARS-CoV-2 spike protein palmitoylation reduces virus infectivity
Spike glycoproteins of almost all enveloped viruses are known to undergo post-translational attachment of palmitic acid moieties. The precise role of such palmitoylation of the spike protein in membrane fusion and infection is not completely understood. Here, we report that palmitoylation of the first five cysteine residues of the c-terminal cysteine-rich domain of the SARS-CoV-2 spike are indispensable for infection, and palmitoylation deficient spike mutants are defective in trimerization and subsequent membrane fusion. The DHHC9 palmitoyltransferase interacts with and palmitoylates the spike protein in the ER and Golgi, and knockdown of DHHC9 results in reduced fusion and infection of SARS-CoV-2. Two bis-piperazine backbone-based DHHC9 inhibitors inhibit SARS-CoV-2 spike protein palmitoylation and the resulting progeny virion particles released are defective in fusion and infection. This establishes these palmitoyltransferase inhibitors as potential new intervention strategies against SARS-CoV-2.
Ahmed A. Ramadan
A bacteria-based assay to study SARS-CoV-2 protein-protein interactions
Methods for detecting and dissecting the interactions of virally encoded proteins are essential for probing basic viral biology and providing a foundation for therapeutic advances. The dearth of targeted therapeutics for the treatment of COVID-19, an ongoing global health crisis, underscores the importance of gaining a deeper understanding of the interactions of SARS-CoV-2-encoded proteins. Here we describe the use of a convenient bacteria-based two-hybrid (B2H) system to analyze the SARS-CoV-2 proteome. We identify sixteen distinct intraviral protein-protein interactions (PPIs), involving sixteen proteins. We find that many of the identified proteins interact with more than one partner. We further show how our system facilitates the genetic dissection of these interactions, enabling the identification of selectively disruptive mutations. We also describe a modified B2H system that permits the detection of disulfide bond-dependent PPIs in the normally reducing Escherichia coli cytoplasm and we use this system to detect the interaction of the SARS-CoV-2 spike protein receptor-binding domain (RBD) with its cognate cell surface receptor ACE2. We then examine how the RBD-ACE2 interaction is perturbed by several RBD amino acid substitutions found in currently circulating SARS-CoV-2 variants. Our findings illustrate the utility of a genetically tractable bacterial system for probing the interactions of viral proteins and investigating the effects of emerging mutations. In principle, the system could also facilitate the identification of potential therapeutics that disrupt specific interactions of virally encoded proteins. More generally, our findings establish the feasibility of using a B2H system to detect and dissect disulfide bond-dependent interactions of eukaryotic proteins.
Non-invasive Imaging of Sense of Smell by Tracking the Voltage-Gated Sodium Channel NaV1.7
Background: Anosmia/hyposmia affects 13.3 million people in the U.S. alone according to the recent U.S. National Health and Nutrition Examination Survey (NHANES). Hundreds of thousands more people with persistent olfactory dysfunction will be added to this number due to the COVID-19 pandemic. Patients with loss-of-function mutations in SCN9A, the gene encoding NaV1.7, experience anosmia in addition to congenital insensitivity to pain. Tsp1a is a recently discovered peptide that inhibits NaV1.7 with high potency and selectivity. In this study, we examined whether a fluorescently tagged version of Tsp1a could be used to visualize normal and damaged mouse olfactory nerves. Methods: Athymic nude mice were intravenously injected with Tsp1a-IR800. As a control, mice were injected with PBS only, and as a blocking control were injected with combination of Tsp1a and Tsp1a-IR800. All mice were imaged in-vivo and epifluorescence images were acquired using an IVIS Spectrum animal imaging system. Semiquantitative analysis of the Tsp1a-IR800 signal was conducted by measuring the average radiant efficiency in the region of the olfactory epithelium/bulb (ROEB). Methimazole was used to chemically ablate the olfactory epithelium. We performed a food buried test to correlate the level of anosmia with the level of radiance efficiency. Results: The area of olfactory epithelium/bulb was clearly visible in epifluorescence in-vivo images of mice receiving the imaging agent. The radiant efficiency was significantly less in both mice injected with PBS and in mice injected with the blocking formulation. The mice after olfactory ablation had a significantly reduced radiant efficiency compared with normal mice. Moreover, there was a statistically significant and inverse correlation between the time required for the mouse to find buried food and the radiant efficiency. We also performed immunohistochemistry using NaV1.7 antibody. Mice after olfactory ablation as well as COVID-19-infected mice had significantly lower expression of NaV1.7 on the level of olfactory epithelium/bulb. Conclusion: We show that the fluorescent imaging of mouse olfactory epithelium/bulb is possible, suggesting that labeled Tsp1a tracers may serve as the first objective diagnostic tool of smell disorders, including those caused by COVID-19.
Compositional analysis of Sindbis virus ribonucleoproteins reveals an extensive co-opting of key nuclear RNA-binding proteins
The expansion of tropical mosquito habitats and associated arboviruses is a risk for human health, and it thus becomes fundamental to identify new antiviral strategies. In this study we employ a new approach to elucidate the composition of the ribonucleoproteins (RNPs) of a prototypical arbovirus called Sindbis (SINV). SINV RNPs contain 453 cellular and 6 viral proteins, many of these proteins are nuclear in uninfected cells and redistribute to the cytoplasm upon infection. These findings suggest that SINV RNAs act as 'spiderwebs', capturing host factors required for viral replication and gene expression in the cytoplasm. Functional perturbation of several of these host proteins causes profound effects in virus infection, as illustrated here with the tRNA ligase complex. Moreover, inhibition of viral RNP components with available drugs hampers the infection of a wide range of viruses, opening new avenues for the development of broad-spectrum therapies.
Inactivated Poliovirus Vaccine Induces Antibodies that Inhibit RNA Synthesis of SARS-CoV-2: An open-label, pre-post vaccine clinical trial
Background: Poliovirus vaccination induces an adaptive humoral immune response; in vitro experiments show polio-immune sera contain antibodies against the poliovirus RNA transcriptase that cross-react with SARS-CoV-2. While structural similarities between poliovirus and SARS-CoV-2 could have major implications for the COVID-19 response worldwide, polio-induced immune responses against SARS-CoV-2 have not been confirmed in prospective clinical trials. Objective: To evaluate whether immune sera from adults who recently received inactivated poliovirus vaccination (IPV) can block SARS-CoV-2's ability to synthesize RNA. Intervention: IPV intramuscular injection. Measurements: Pre-inoculation and 4-weeks post-inoculation sera were tested for anti-3Dpol (RNA-dependent RNA polymerase, RdRp) antibodies using enzyme-linked immunosorbent assays (ELISA). To assess IPV's ability to induce antibodies that inhibit SARS-CoV-2 RNA synthesis, immune-based detection assays tested RdRp enzymatic activity in polio-immune sera. Results: 298 of the 300 enrolled participants completed both on-site visits. Comparing pre-inoculation to 4-week samples, 85.2% of participants demonstrated an increase in anti-3Dpol antibodies against RdRp proteins. Among tested post-inoculation samples, 94.4% demonstrated inhibition of SARS-CoV-2 RNA synthesis. Few inoculation-related side effects were reported (2.0%), all were minor. Limitations: Participants were not systematically tested for COVID-19, though known exposures were reported and positive results (1.7%) were documented. Conclusion: IPV can induce antibodies that inhibit SARS-CoV-2 RNA synthesis, minimizing the risk of viral replication in infected individuals. This finding has practical implications for resource-deficient areas that may have limited access to newly developed COVID-19 vaccines and/or areas with low COVID-19 vaccination rates due to hesitancy. Funding Source: Private donors. Registration: ClinicalTrials.gov: NCT04639375.
Brittany A. Comunale
public and global health
Detection and quantification of SARS-CoV-2 RNA in wastewater influent in relation to reported COVID-19 incidence in Finland
Wastewater-based surveillance is a cost-effective concept for monitoring COVID-19 pandemics at a population level. Here, SARS-CoV-2 RNA was monitored from a total of 693 wastewater (WW) influent samples from 28 wastewater treatment plants (WWTP, N = 21-42 samples per WWTP) in Finland from August 2020 to May 2021, covering WW of ca. 3.3 million inhabitants (~ 60% of the Finnish population). The relative quantity of SARS-CoV-2 RNA fragments in the 24h-composite samples was determined by using the ultrafiltration method followed by nucleic acid extraction and RT-qPCR assay targeted with N2-assay. SARS-CoV-2 RNA signals at each WWTP were compared over time to the numbers of new and confirmed COVID-19 cases in the sewer network area. Over the 10-month surveillance period, the detection rate of SARS-CoV-2 RNA in WW was 79% (including 6% uncertain results), while only 24% of all samples exhibited gene copy (GC) numbers above the quantification limit. The range of the SARS-CoV-2 detection rate in WW varied from 33% (including 10% uncertain results) in Pietarsaari to 100% in Espoo. Only six out of 693 WW samples were positive with SARS-COV-2 RNA when the reported COVID-19 case number from the preceding 14 days was zero. Overall, the 14-day COVID-19 incidence was 7.0, 18 and 36 cases within the sewer network area when the probability to detect SARS-CoV-2 RNA in wastewater samples was 50%, 75% and 95%, respectively. The quantification of SARS-CoV-2 GC required significantly more COVID-19 cases: the quantification rate was 50%, 75% and 95% when the 14-day incidence was 110, 152 and 223 COVID-19 cases, respectively, per 100 000 persons. Multiple linear regression confirmed the relationship between the COVID-19 incidence and the SARS-CoV-2 GC quantified in WW at 15 out of 28 WWTPs (overall R2 = 0.36, p < 0.001). At four of the 13 WWTPs where a significant relationship was not found, the GC of SARS-CoV-2 RNA remained below the quantification limit during the whole study period. In the five other WWTPs, the sewer coverage was less than 80% of the total population in the area and thus the COVID-19 cases may have been inhabitants from the areas not covered. Based on the results obtained, WW-based surveillance of SARS-CoV-2 could be used as an indicator for local and national COVID-19 incidence trends. Importantly, the determination of SARS-CoV-2 RNA fragments from WW is a powerful and non-invasive public health surveillance measure, independent of possible changes in the clinical testing strategies or in the willingness of individuals to be tested for COVID-19.
Minority and Rural Coronavirus Insights Study (MRCIS): The Need for Targeted COVID-19 Vaccination Efforts in Minority Populations
Abstract Importance: Racial and ethnic minority populations have been disproportionately affected in terms of hospitalizations and deaths during the COVID-19 pandemic. Vaccine uptake remains a barrier to full population inoculation against this highly infectious disease. Objective: The purpose of this report is to describe SARS-CoV-2 vaccine interest rates in a racially, geographically, and ethnically diverse study cohort and characterize vaccine interest across a racially, ethnically, and geographically diverse study population. Design: This report describes responses to a survey administered between November 2020 and May 2021 using a community convenience sample through a partnership between the National Minority Quality Forum (NMQF) and Federally Qualified Health Centers (FQHCs) as part of the Minority and Rural Coronavirus Insights Study (MRCIS). Analysis of survey responses from 3,624 participants are provided. Results: Early data from the MRCIS cohort suggest that [SARS-CoV-2 vaccine hesitancy] is more prevalent in Black versus Non-Hispanic Whites survey respondents, and the Hispanic community has positive interest in the vaccine, to a similar degree as Whites. The persistent presence of [vaccine undecided] across different sites and racial/ethnic groups uncovers the need for more public health efforts to influence positive views about vaccination. Conclusion: These findings highlights the urgent need for interventional educational campaigns targeted at populations at risk of low vaccine interest. Focused efforts are needed to combat misinformation and explain vaccine safety and effectiveness to promote its uptake and avoid low inoculation rates. Public health communication must consider differences in population groups, regions, and social determinants of health to fully address vaccine uptake disparities and overcome alleged hesitancy. Key Points -Willingness to receive the SARS CoV-2 varies among minority populations. -[SARS-CoV-2 vaccine hesitancy] is more prevalent in the non-Hispanic Black population than the non-Hispanic White and Hispanic populations. -Public health infrastructure is needed in underserved communities for efficient assessment and targeted communication of public health priorities such as the SARS CoV-2 vaccination.
public and global health
A joint hierarchical model for the number of cases and deaths due to COVID-19 across the boroughs of Montreal
Montreal has been the epicentre of the COVID-19 pandemic in Canada with the highest number of deaths in the country. The cumulative numbers of cases and deaths, as of July 25th, 2021, recorded in the 33 areas of Montreal are modelled through a bivariate hierarchical Bayesian model using Poisson distributions. The Poisson means are decomposed in the log scale as the sums of fixed effects and latent effects. The areal median age, the educational level, and the number of beds in long-term care homes are included in the fixed effects. To explore the correlation between cases and deaths inside each area and across areas, three bivariate models are considered for the latent effects, namely an independent one, a conditional autoregressive model, and one that allows for both spatially structured and unstructured sources of variability. As the inclusion of spatial effects change some of the fixed effects, we extend the Spatial+ approach to a Bayesian areal set up to investigate the presence of spatial confounding. Results show that the cumulative totals of cases and deaths are negatively correlated inside and across the boroughs of Montreal. The covariates are not associated in a similar manner for the cases and deaths due to COVID-19. The educational level and the median age seem spatially confounded for the cases and deaths across the boroughs of Montreal.
Detailed reconstruction of the Iranian COVID-19 epidemic reveals high attack rates of SARS-CoV-2 in several provinces
Since the first cases of COVID-19 were reported in Qom, Iran, almost 19 months ago, the transmission dynamics across the country and the health burden of COVID-19 has remained largely unknown due to the scarcity of epidemiological analyses and lack of provincial data on the number of COVID-19 cases and deaths. For the first time, we reconstruct the epidemic trajectory across the country and assess the level of under-reporting in infections and deaths using province-level age-stratified weekly all-cause mortality data. Our estimates suggest that as of 2021-09-17, only 48% (95% confidence interval 43-55%) of COVID-19 deaths in Iran have been reported. We find that in the most affected provinces such as Qazvin, Qom, and East Azerbaijan approximately 0.4% of the population have died of COVID-19 so far. We also find significant heterogeneity in the estimated attack rates across the country with 11 provinces reaching close to or higher than 100% attack rates. Despite a relatively young age structure in Iran, our analysis reveals that the infection fatality rate gradually increased over time in several provinces and reached levels that are comparable some of the high-income countries with a larger percentage of older adults, suggesting that limited access to medical services, coupled with undercounting of COVID-19-related deaths, can have a significant impact on COVID-19 fatalities. These results also show that despite several waves of infection and high attack rates in many provinces with largely unmitigated epidemics, herd immunity through natural infection has not been achieved.
Comparative transmissibility of SARS-CoV-2 variants Delta and Alpha in New England, USA
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant quickly rose to dominance in mid-2021, displacing other variants, including Alpha. Studies using data from the United Kingdom and India estimated that Delta was 40-80% more transmissible than Alpha, allowing Delta to become the globally dominant variant. However, it was unclear if the ostensible difference in relative transmissibility was due mostly to innate properties of Delta's infectiousness or differences in the study populations. To investigate, we formed a partnership with SARS-CoV-2 genomic surveillance programs from all six New England US states. By comparing logistic growth rates, we found that Delta emerged 37-163% faster than Alpha in early 2021 (37% Massachusetts, 75% New Hampshire, 95% Maine, 98% Rhode Island, 151% Connecticut, and 163% Vermont). We next computed variant-specific effective reproductive numbers and estimated that Delta was 58-120% more transmissible than Alpha across New England (58% New Hampshire, 68% Massachusetts, 76% Connecticut, 85% Rhode Island, 98% Maine, and 120% Vermont). Finally, using RT-PCR data, we estimated that Delta infections generate on average ~6 times more viral RNA copies per mL than Alpha infections. Overall, our evidence indicates that Delta's enhanced transmissibility could be attributed to its innate ability to increase infectiousness, but its epidemiological dynamics may vary depending on the underlying immunity and behavior of distinct populations.
Characterizing the effective reproduction number during the COVID-19 epidemic: Insights from Qatar experience
Background: The effective reproduction number, Rt, is a tool to track and understand epidemic dynamics. This investigation of Rt estimations was conducted to guide the national COVID-19 response in Qatar, from the onset of the epidemic until August 18, 2021. Methods: Real-time empirical RtEmpirical was estimated using five methods, including the Robert Koch Institute, Cislaghi, Systrom-Bettencourt and Ribeiro, Wallinga and Teunis, and Cori et al. methods. Rt was also estimated using a transmission dynamics model (RtModel-based). Uncertainty and sensitivity analyses were conducted. Agreements between different Rt estimates were assessed by calculating correlation coefficients. Results: RtEmpirical captured the evolution of the epidemic through three waves, public health response landmarks, effects of major social events, transient fluctuations coinciding with significant clusters of infection, and introduction and expansion of the B.1.1.7 variant. The various estimation methods produced consistent and overall comparable RtEmpirical estimates with generally large correlation coefficients. The Wallinga and Teunis method was the fastest at detecting changes in epidemic dynamics. RtEmpirical estimates were consistent whether using time series of symptomatic PCR-confirmed cases, all PCR-confirmed cases, acute-care hospital admissions, or ICU-care hospital admissions, to proxy trends in true infection incidence. RtModel-based correlated strongly with RtEmpirical and provided an average RtEmpirical. Conclusions: Rt estimations were robust and generated consistent results regardless of the data source or the method of estimation. Findings affirmed an influential role for Rt estimations in guiding national responses to the COVID-19 pandemic, even in resource-limited settings.
Comparison of MIS-C Related Myocarditis, Classic Viral Myocarditis, and COVID-19 Vaccine related Myocarditis in Children
Background: Although rare, myocarditis in the pediatric population is a disease process that carries significant morbidity and mortality. Prior to the SARS-CoV-2 related (COVID-19) pandemic, enteroviruses were the most common cause of classic myocarditis. However, since 2020, myocarditis linked to multisystem inflammatory syndrome in children (MIS-C) is now common. In recent months, myocarditis related to COVID-19 vaccines has also been described. This study aims to compare these three different types of myocarditis with regards to clinical presentation, course, and outcomes. Methods: In this retrospective cohort study, we included all patients <21 years of age hospitalized at our institution with classic viral myocarditis from 2015-2019, MIS-C myocarditis from 3/2020-2/2021 and COVID-19 vaccine-related myocarditis from 5/2021-6/2021. We compared demographics, initial symptomatology, treatment, laboratory data, and echocardiogram findings. Results: Of 201 total participants, 43 patients had classic myocarditis, 149 had MIS-C myocarditis, and 9 had COVID-19 vaccine-related myocarditis. Peak troponin was highest in the classic myocarditis group, whereas the MIS-C myocarditis group had the highest recorded brain natriuretic peptide (BNP). There were significant differences in time to recovery of normal left ventricular ejection fraction (LVEF) for the three groups: nearly all patients with MIS-C myocarditis (n=139, 93%) and all patients with COVID-19 vaccine-related myocarditis (n=9, 100%) had normal LVEF at the time of discharge, but a lower proportion of the classic myocarditis group (n=30, 70%) had a normal LVEF at discharge (p<0.001). Three months post-discharge, 18 of 40 children (45%) in the classic myocarditis group still required heart failure treatment, whereas only one of the MIS-C myocarditis patients and none of the COVID-19 vaccine-associated myocarditis patients did. Conclusions: Compared to those with classic myocarditis, those with MIS-C myocarditis had more significant hematologic derangements and worse inflammation at presentation, but had better clinical outcomes, including rapid recovery of cardiac function. Patients with COVID-19 vaccine-related myocarditis had similar clinical presentation to patients with classic myocarditis, but their pattern of recovery was similar to those with MIS-C, with prompt resolution of symptoms and improvement of cardiac function. Long-term follow-up should focus on cardiac and non-cardiac consequences of myocarditis associated with COVID-19 illness and vaccination. Key Words: MIS-C, myocarditis, COVID-19, mRNA vaccine
Serum but not mucosal antibody responses are predicted by pre-existing SARS-CoV-2 spike cross-reactive CD4+ T cells following BNT162b2 vaccination in the elderly
Advanced age is a main risk factor for severe COVID-19 and thus elderly were often prioritized for vaccination. However, low vaccination efficacy and accelerated waning immunity have been reported in this age group. To elucidate age-related differences in immunogenicity, we analysed cellular, serological and salivary SARS-CoV-2 spike glycoprotein-specific immune responses to BNT162b2 COVID-19 vaccine in old (69-92 years) and middle-aged (24-57 years) vaccinees compared to natural infection (COVID-19 convalescents of 21-55 years). Serological humoral responses to vaccination exceeded those of convalescents but salivary anti-spike subunit 1 (S1) IgA and neutralizing capacity were less durable in vaccinees. In old vaccinees, we observed that pre-existing spike-specific CD4+ T cells correlated with efficient induction of serological anti-S1 IgG and neutralizing capacity after vaccination. Our results highlight the role of pre-existing cross-reactive CD4+ T cells with respect to SARS-CoV-2 vaccination particularly in old individuals, in whom their presence predicted efficient COVID-19-vaccine-induced humoral immune responses.
allergy and immunology
Comparison of antibody immune responses between BNT162b2 and mRNA-1273 SARS-CoV-2 vaccines in naive and previously infected individuals
Two mRNA vaccines, Pfizer-BNT162b2 and Moderna-mRNA-1273, were granted the US Food and Drug Administration Emergency Use Authorization for preventing COVID-19. However, little is known about the difference in antibody responses induced by the two mRNA vaccines in naive and individuals with a previous history of infections (PI group). Therefore, we investigated the levels of anti-S-RBD total antibodies (IgM, IgA, and IgG), anti-S-RBD IgG, and anti-S-RBD IgA in these two groups 1-13 (median=6) weeks following administration of two doses of mRNA-1273 or BNT162b2 vaccines. Results showed that in naive-vaccinated group, the mRNA-1327 vaccine induces significantly higher levels of S-RBD total antibodies (3.5-fold; p<0.001), S-RBD IgG (2-fold-p<0.01), and S-IgA (2.1-fold, p<0.001) than the BNT162b2 vaccine. In the PI-vaccinated group, both vaccines produce significantly higher S-RBD total antibodies level than those of the naive-vaccinated group. The PI group produced a higher level of S-RBD IgG than the naive-BNT162b2 (p=0.05) but not more than the naive-mRNA-1273 (p=0.9) group. Interestingly, the PI-vaccinated group produced a comparable level of IgA ratio to the naive-mRNA-1273 group but significantly higher than the naive-BNT162b2 group (1.6-fold, p<0.001). Our results showed that the mRNA-1327 vaccine is more immunogenic and induces a greater antibody response than the BNT162b2 vaccine.
An assessment of a rapid SARS-CoV-2 antigen test in Bangladesh
Early detection of SARS-CoV-2 infection is crucial to prevent the spread of the virus. In this study, we evaluated the performance of a commercial rapid antigen detection test, BD Veritor, and compared this (and another rapid test, Standard Q) against a gold-standard of nasopharyngeal (NP) swab tested by reverse transcription-polymerase chain reaction (RT-PCR) in prospectively recruited adults in Dhaka, Bangladesh. We compared the sensitivity and specificity of the two rapid antigen tests against RT-PCR results in 130 symptomatic and 130 asymptomatic adults. In addition, we evaluated the suitability and ease-of-use of the BD Veritor test in a subsample of study participants (n=42) and implementers (n=5). The sensitivity of the BD Veritor rapid antigen 66 test was 70% in symptomatic (95% confidence interval [CI]: 51-85%) and 87% (95% CI: 69-96%) in asymptomatic individuals with positive SARSCoV-2 RT-PCR, for overall sensitivity of 78% (95% CI: 66-88%). The sensitivity of the Standard Q rapid antigen test was 63% (95% CI: 44-69 80%) in symptomatic and 73% (95% CI: 54-87%) in asymptomatic individuals. One false positive in BD Veritor test (specificity 99.5) and no false positive in Standard Q tests were observed (specificity 100%). The BD Veritor rapid antigen test was 78% sensitive when compared with RT-PCR irrespective of the cycle threshold (Ct) levels in this evaluation in Bangladesh. The implementation evaluation data showed good acceptability in the field settings. This warrants large field evaluation as well as use of the rapid antigen test for quick assessment of SARS-CoV-2 for containment of epidemics in the country.
Is the infection of the SARS-CoV-2 Delta variant associated with the outcomes of COVID-19 patients?
Background: SARS-CoV-2 Delta variant (B.1.617.2) has been responsible for the current increase in COVID-19 infectivity rate worldwide. We compared the impact of the Delta variant and non-Delta variant on the COVID-19 outcomes in patients from Yogyakarta and Central Java provinces, Indonesia. Methods: We ascertained 161 patients, 69 with the Delta variant and 92 with the non-Delta variant. The Illumina MiSeq next-generation sequencer was used to perform the whole genome sequences of SARS-CoV-2. Results: The mean age of patients with Delta and the non-Delta variant was 27.3 +/- 20.0 and 43.0 +/- 20.9 (p=3x10-6). The patients with Delta variant consisted of 23 males and 46 females, while the patients with the non-Delta variant involved 56 males and 36 females (p=0.001). The Ct value of the Delta variant (18.4 +/- 2.9) was significantly lower than the non-Delta variant (19.5 +/- 3.8) (p=0.043). There was no significant difference in the hospitalization and mortality of patients with Delta and non-Delta variants (p=0.80 and 0.29, respectively). None of the prognostic factors was associated with the hospitalization, except diabetes with an OR of 3.6 (95% CI=1.02-12.5; p=0.036). Moreover, the patients with the following factors have been associated with higher mortality rate than patients without the factors: age [≥]65 years, obesity, diabetes, hypertension, and cardiovascular disease with the OR of 11 (95% CI=3.4-36; p=8x10-5), 27 (95% CI=6.1-118; p=1x10-5), 15.6 (95% CI=5.3-46; p=6x10-7), 12 (95% CI=4-35.3; p=1.2x10-5), and 6.8 (95% CI=2.1-22.1; p=0.003), respectively. Multivariate analysis showed that age 65 years, obesity, diabetes, and hypertension were the strong prognostic factors for the mortality of COVID-19 patients with the OR of 3.6 (95% CI=0.58-21.9; p=0.028), 16.6 (95% CI=2.5-107.1; p=0.003), 5.5 (95% CI=1.3-23.7; p=0.021), and 5.8 (95% CI=1.02-32.8; p=0.047), respectively. Conclusions: We show that the patients infected by the SARS-CoV-2 Delta variant have a lower Ct value than the patients infected by the non-Delta variant, implying that the Delta variant has a higher viral load, which might cause a more transmissible virus among humans. However, the Delta variant does not affect the COVID-19 outcomes in our patients. Our study also confirms the older age and comorbidity increase the mortality rate of COVID-19 patients.
A twelve-month projection to September 2022 of the Covid-19 epidemic in the UK using a Dynamic Causal Model
Objectives Predicting the future UK Covid-19 epidemic allows other countries to compare their epidemic with one unfolding without public health measures except a vaccine programme. Methods A Dynamic Causal Model (DCM) is used to estimate the model parameters of the epidemic such as vaccine effectiveness and increased transmissibility of alpha and delta variants, the vaccine programme roll-out and changes in contact rates. The model predicts the future trends in infections, long-Covid, hospital admissions and deaths. Results Two dose vaccination given to 66% of the UK population prevents transmission following infection by 44%, serious illness by 86% and death by 93%. Despite this, with no other public health measures used, cases will increase from 37 million to 61 million, hospital admission from 536,000 to 684,000 and deaths from 136,000 to 142,000 over twelve months. Discussion Vaccination alone will not control the epidemic. Relaxation of mitigating public health measures carries several risks including overwhelming the health services, the creation of vaccine resistant variants and the economic cost of huge numbers of acute and chronic cases.
public and global health
Single-Molecule Detection of SARS-CoV-2 by Plasmonic Sensing of Isothermally Amplified Nucleic Acids
Single-molecule detection of pathogens such as SARS-CoV-2 is key to combat infectious diseases outbreak and pandemic. Currently colorimetric sensing with loop-mediated isothermal amplification (LAMP) provides simple readouts but suffers from intrinsic non-template amplification. Herein, we report that plasmonic sensing of LAMP amplicons via DNA hybridization allows highly specific and single-molecule detection of SARS-CoV-2 RNA. Our work has two important advances. First, we develop gold and silver alloy (Au-Ag) nanoshells as plasmonic sensors that have 4-times stronger extinction in the visible wavelengths and give 20-times lower detection limit for oligonucleotides than Au nanoparticles. Second, we demonstrate that the diagnostic method allows cutting the complex LAMP amplicons into short repeats that are amendable for hybridization with oligonucleotide-functionalized nanoshells. This additional sequence identification eliminates the contamination from non-template amplification. The detection method is a simple and single-molecule diagnostic platform for virus testing at its early representation.
Changes in ischemic stroke presentations and associated workflow during the first wave of the COVID-19 pandemic: A population study in Alberta, Canada
Background: Pandemics may promote hospital avoidance among patients with emergencies, and added precautions may exacerbate treatment delays. There is a paucity of population-based data on these phenomena for stroke. We examined the effect of the COVID-19 pandemic on the presentation and treatment of ischemic stroke in an entire population. Methods: We used linked provincial administrative data and data from the Quality Improvement and Clinical Research Alberta Stroke Program, a registry capturing stroke-related data on the entire population of Alberta(4.3 million), to identify all patients presenting with stroke in the pre-pandemic(1-January-2016 to 27-February-2020, n=19,531) and pandemic(28-February-2020 to 30-August-2020, n=2,255) periods. We examined changes in thrombolysis and endovascular therapy(EVT) rates, workflow, and in-hospital outcomes. Results: Hospitalizations/presentations for ischemic stroke dropped (weekly adjusted-incidence-rate-ratio[aIRR]:0.48, 95%CI:0.46-0.50, adjusted for age, sex, comorbidities, pre-admission care needs), as did population-level incidence of thrombolysis(aIRR:0.49,0.44-0.56) or EVT(aIRR:0.59,0.49-0.69). However, the proportions of presenting patients receiving acute therapies did not decline (e.g. thrombolysis:11.7% pre-pandemic vs 13.1% during-pandemic, aOR:1.02,0.75-1.38). Onset-to-door times were prolonged; EVT recipients experienced longer door-to-reperfusion times (median door-to-reperfusion:110-minutes, IQR:77-156 pre-pandemic vs 132.5-minutes, 99-179 during-pandemic; adjusted-coefficient:18.7-minutes, 95%CI:1.45-36.0). Hospitalizations were shorter but stroke severity and in-hospital mortality did not differ. Interpretation: The first COVID-19 wave was associated with a halving of presentations and acute therapy utilization for ischemic stroke at a population level, and greater pre-hospital and in-hospital treatment delays. Our data can inform public health messaging and stroke care in current and future waves. Messaging should encourage attendance for emergencies and stroke systems should re-examine code stroke protocols to mitigate inefficiencies.
Prenatal maternal distress during the COVID-19 pandemic and its effects on the infant brain
The COVID-19 pandemic has caused elevated distress in pregnant individuals, which has the potential to impact the developing infant. In this study, we examined anxiety and depression symptoms during the pandemic in a large sample of pregnant individuals (n=8602). For a sub-sample of participants, their infants underwent magnetic resonance imaging (MRI) at 3-months of age to examine whether this prenatal maternal distress was associated with infant brain changes. We found significantly elevated prenatal maternal distress compared to pre-pandemic rates, with 47% and 33% of participants reporting clinically significant symptoms of anxiety and depression, respectively. Importantly, we identified social support as a protective factor for clinically elevated prenatal maternal distress. We found significant relationships between prenatal maternal distress and infant amygdala-prefrontal microstructural and functional connectivity and demonstrate for the first time that social support moderates this relationship. Our findings suggest a potentially long-lasting impact of the COVID-19 pandemic on children and show that social support acts as a protective factor not just for pregnant individuals, but also for their developing infants. These findings provide timely evidence to inform clinical practice and policy surrounding the care of pregnant individuals and highlight the importance of social support.
Kathryn Y Manning
Covid-19 vaccine perceptions in Senegal and in Mali: a mixed approach
This paper presents the results of two qualitative surveys in Senegal and in Mali, which include questions about hesitancy to the COVID-19 vaccine between April and June 2021. It took place within a larger 2-year research project involving researchers in Senegal, Mali and Canada which examines the uses of artificial intelligence technologies in the fight against COVID-19. The study involved 1000 respondents in Senegal and 555 in Mali. The researchers found that overall, 55% of respondents in Senegal and 52% of respondents in Mali did not plan to be vaccinated. Hesitancy was much higher in youth aged 15-35 in both cases, with 70% of youth in Senegal and 57% of youth in Mali not planning to be vaccinated, compared to only 42% of elderly in Senegal and 37% of elderly in Mali. The researchers did not find disparities between male and female respondents in Senegal but found some in Mali. They also found that those who had a member of the family with chronic disease (diabetes or hypertension) were slightly more likely to want to be vaccinated. Reasons for vaccine hesitancy fell in several categories, including fear of vaccine side-effects, disbelief in vaccine efficacy or usefulness, and general distrust in the public health system.
Seropositivity to Nucleoprotein to detect SARS-CoV-2 infections: a tool to detect breakthrough infections after COVID-19 vaccination
Background With COVID-19 vaccine roll-out ongoing in many countries globally, monitoring of breakthrough infections is of great importance. Antibodies persist in the blood after a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Since COVID-19 vaccines induce immune response to the Spike protein of the virus, which is the main serosurveillance target to date, alternative targets should be explored to distinguish infection from vaccination. Methods Multiplex immunoassay data from 1,513 SARS-CoV-2 RT-qPCR-tested individuals (352 positive and 1,161 negative) with a primary infection and no vaccination history were used to determine the accuracy of Nucleoprotein-specific immunoglobulin G (IgG) in detecting past SARS-CoV-2 infection. We also described Spike S1 and Nucleoprotein-specific IgG responses in 230 COVID-19 vaccinated individuals (Pfizer/BioNTech). Results The sensitivity of Nucleoprotein seropositivity was 85% (95% confidence interval: 80-90%) for mild COVID-19 in the first two months following symptom onset. Sensitivity was lower in asymptomatic individuals (67%, 50-81%). Participants who had experienced a SARS-CoV-2 infection up to 11 months preceding vaccination, as assessed by Spike S1 seropositivity or RT-qPCR, produced 2.7-fold higher median levels of IgG to Spike S1 [≥]14 days after the first dose as compared to those unexposed to SARS-CoV-2 at [≥]7 days after the second dose (p=0.011). Nucleoprotein-specific IgG concentrations were not affected by vaccination in naive participants. Conclusions Serological responses to Nucleoprotein may prove helpful in identifying SARS-CoV-2 infections after vaccination. Furthermore, it can help interpret IgG to Spike S1 after COVID-19 vaccination as particularly high responses shortly after vaccination could be explained by prior exposure history.
Lotus Leonie van den Hoogen
Rotational worker vaccination provides indirect protection to vulnerable groups in regions with low COVID-19 prevalence
As COVID-19 vaccines become available, different model-based approach have been developed to evaluate strategic priorities for vaccine allocation to reduce severe illness. One strategy is to directly prioritize groups that are likely to experience medical complications due to COVID-19, such as older adults. A second strategy is to limit community spread by reducing importations, for example by vaccinating members of the mobile labour force, such as rotational workers. This second strategy may be appropriate for regions with low disease prevalence, where importations are a substantial fraction of all cases and reducing the importation rate reduces the risk of community outbreaks, which can provide significant indirect protection for vulnerable individuals. Current studies have focused on comparing vaccination strategies in the absence of importations, and have not considered allocating vaccines to reduce the importation rate. Here, we provide an analytical criteria to compare the reduction in the risk of hospitalization and intensive care unit (ICU) admission over four months when either older adults or rotational workers are prioritized for vaccination. Vaccinating rotational workers (assumed to be 6,000 individuals and about 1% of the Newfoundland and Labrador (NL) population) could reduce the average risk of hospitalization and ICU admission by 42%, if no community spread is observed at the time of vaccination, because epidemic spread is reduced and vulnerable individuals are indirectly protected. In contrast, vaccinating all individuals aged 75 and older (about 43,300 individuals, or 8% of the NL population) would lead to a 24% reduction in the average risk of hospitalization, and to a 45% reduction in the average risk of ICU admission, because a large number of individuals at high risk from COVID-19 are now vaccinated. Therefore, reducing the risk of hospitalization and ICU admission of the susceptible population by reducing case importations would require a significantly lower number of vaccines. Benefits of vaccinating rotational workers decrease with increasing infection prevalence in the community. Prioritizing members of the mobile labour force should be considered as an efficient strategy to indirectly protect vulnerable groups from COVID-19 exposure in regions with low disease prevalence.
Maria M Martignoni
Postvaccination SARS-CoV-2 infection among healthcare workers: A Systematic Review and meta-analysis
INTRODUCTION: Healthcare workers (HCWs) remain on the front line of the battle against SARS-CoV-2 and COVID-19 infection, and are among the highest groups at risk of infection during this raging pandemic. We conducted a systematic review and meta-analysis to assess incidence of postvaccination SARS-CoV-2 infection among vaccinated HCWs. METHODS: We searched multiple databases from inception through August 2021 to identify studies that reported on incidence of postvaccination SARS-CoV-2 infection among HCWs. Meta-analysis was performed to determine pooled proportions of COVID-19 infection in partially and fully vaccinated individuals. RESULTS: Eighteen studies with 228,873 HCWs were included in the final analysis. Total number of partially vaccinated, fully vaccinated, and unvaccinated HCWs were 132,922, 155,673 and 17505, respectively. Overall pooled proportion of COVID-19 infections among partially/fully vaccinated and unvaccinated HCWs was 2.1% (95% CI 1.2-3.5). Among partially vaccinated, fully vaccinated and unvaccinated HCWs, pooled proportion of COVID-19 infections was 3.7% (95% CI 1.8-7.3), 1.3% (95% CI 0.6-2.9), and 10.1% (95% CI 4.5-19.5), respectively. DISCUSSION: Our analysis shows the risk of COVID-19 infection in both partially and fully vaccinated HCWs remains exceedingly low when compared to unvaccinated individuals. There remains an urgent need for all frontline HCWs to be vaccinated against SARS-CoV-2 infection.