Secondary Contacts Research Articles

Analysis on infectivity of COVID-19 patients before and after last negative nucleic acid test

Objective: To investigate the infection rate in close contacts of COVID-19 patients before and after the last negative nucleic acid test, evaluate the effect of dynamic nucleic acid test in determining the infectivity of COVID-19 patients. Methods: Dynamic nucleic acid test results of COVID-19 cases were collected in a retrospective cohort study. COVID-19 cases with negative nucleic acid test results before their first positive nucleic acid tests were selected as study subjects. Close contacts of the index cases and the secondary close contacts were kept isolation for medical observation to assess their risk of infection. Results: This study included 89 confirmed cases from two local COVID-19 epidemics in Ningbo. A total of 5 609 close contacts were surveyed, the overall infection rate was 0.20%. No close contacts of the COVID-19 cases before the last negative nucleic acid test were infected, and the infection rate in the close contacts of the COVID-19 cases after the last negative nucleic acid test was 1.33%, all of these close contacts lived together with the index cases. No secondary close contacts were infected. Conclusion: COVID-19 patient becomes infectious after the last nucleic acid is negative, and has no infectivity before the last nucleic acid negative.

Epidemiological characteristics of COVID-19 caused by 2019-nCoV Delta variant in Shangyu district, Shaoxing of Zhejiang province

Objective: To investigate the epidemiological characteristics of COVID-19 caused by 2019-nCoV Delta variant in Shangyu district, Shaoxing of Zhejiang province in 2021, and provide evidence for the improvement of COVID-19 control and prevention measures. Methods: The incidence data of COVID-19 in Shangyu from December 7 to 21, 2021 was obtained from Shangyu District Center for Disease Control and Prevention. The epidemiological characteristics of the cases, i.e. the population, time and space distributions, were analyzed, and the incubation period and time-varying reproduction numbers (Rt) were calculated. Results: From December 7 to 21, 2021, a total of 380 COVID-19 cases caused by 2019-nCoV Delta variant were detected in Shangyu, the median age of the cases was 52 years, M (Q1，Q3: 38, 61). The male to female ratio of the cases was 1∶1.25, and the cases were mainly workers (36.58%) and farmers (27.63%). The epidemic affected 9 townships (or community) of Shangyu, especially Caoe and Baiguan communities with the cases accounting for 57.10% and 31.53% respectively. The median incubation period of cases was 4.00 days, M (Q1，Q3: 3.00, 5.75). The basic reproduction number (R0) was 4.06, and the Rt was 5.62 in early phase of the outbreak (the highest) and continuously decreased to less than 1.00 within 10 days after the detection of the outbreak. The number of COVID-19 cases decreased to 0 within 14 days after the outbreak (December 7-21), and the main detection methods were screening in centralized isolation (55.53%) and home isolation (40.00%). The infection rates of close contacts and secondary close contacts were 2.06% and 0.46% respectively. Conclusion: The epidemic of COVID-19 in Shangyu characterized by short incubation period, large number of infected people, and case clustering, suggesting the strong transmission of Delta variant (B.1.617.2). Comprehensive prevention and control measures, such as management of close contacts and secondary close contacts, and high-risk area, are essential for the rapid control of the epidemic.

Multivalent protein–protein interactions are pivotal regulators of eukaryotic Hsp70 complexes

Heat shock protein 70 (Hsp70) is a molecular chaperone and central regulator of protein homeostasis (proteostasis). Paramount to this role is Hsp70’s binding to client proteins and co-chaperones to produce distinct complexes, such that understanding the protein–protein interactions (PPIs) of Hsp70 is foundational to describing its function and dysfunction in disease. Mounting evidence suggests that these PPIs include both “canonical” interactions, which are universally conserved, and “non-canonical” (or “secondary”) contacts that seem to have emerged in eukaryotes. These two categories of interactions involve discrete binding surfaces, such that some clients and co-chaperones engage Hsp70 with at least two points of contact. While the contributions of canonical interactions to chaperone function are becoming increasingly clear, it can be challenging to deconvolute the roles of secondary interactions. Here, we review what is known about non-canonical contacts and highlight examples where their contributions have been parsed, giving rise to a model in which Hsp70’s secondary contacts are not simply sites of additional avidity but are necessary and sufficient to impart unique functions. From this perspective, we propose that further exploration of non-canonical contacts will generate important insights into the evolution of Hsp70 systems and inspire new approaches for developing small molecules that tune Hsp70-mediated proteostasis.

Inter-Specific Genetic Exchange Despite Strong Divergence in Deep-Sea Hydrothermal Vent Gastropods of the Genus Alviniconcha.

Deep hydrothermal vents are highly fragmented and unstable habitats at all temporal and spatial scales. Such environmental dynamics likely play a non-negligible role in speciation. Little is, however, known about the evolutionary processes that drive population-level differentiation and vent species isolation and, more specifically, how geography and habitat specialisation interplay in the species history of divergence. In this study, the species range and divergence of Alviniconcha snails that occupy active Western Pacific vent fields was assessed by using sequence variation data of the mitochondrial Cox1 gene, RNAseq, and ddRAD-seq. Combining morphological description and sequence datasets of the three species across five basins, we confirmed that A. kojimai, A. boucheti, and A. strummeri, while partially overlapping over their range, display high levels of divergence in the three genomic compartments analysed that usually encompass values retrieved for reproductively isolated species with divergences rang from 9% to 12.5% (mtDNA) and from 2% to 3.1% (nuDNA). Moreover, the three species can be distinguished on the basis of their external morphology by observing the distribution of bristles and the shape of the columella. According to this sampling, A. boucheti and A. kojimai form an east-to-west species abundance gradient, whereas A. strummeri is restricted to the Futuna Arc/Lau and North Fiji Basins. Surprisingly, population models with both gene flow and population size heterogeneities among genomes indicated that these three species are still able to exchange genes due to secondary contacts at some localities after a long period of isolation.

Healthcare contacts with self-harm during COVID-19: An e-cohort whole-population-based study using individual-level linked routine electronic health records in Wales, UK, 2016-March 2021.

IntroductionReduced rates of help seeking by those who self-harmed during the COVID-19 pandemic have been reported.ObjectivesTo understand changes in healthcare service contacts for self-harm during the COVID-19 pandemic across primary, emergency and secondary care.MethodsThis retrospective cohort study used routine electronic healthcare data for Wales, United Kingdom, from 2016 to March 14, 2021. Population-based data from primary care, emergency departments and hospital admissions were linked at individual-level. All Welsh residents aged ≥10 years over the study period were included in the study. Primary, emergency and secondary care contacts with self-harm at any time between 2016 and March 14, 2021 were identified. Outcomes were counts, incidence, prevalence and proportion of self-harm contacts relative to all contacts in each and all settings, as well as the proportion of people contacting one or more settings with self-harm. Weekly trends were modelled using generalised estimated equations, with differences between 2020 (to March 2021) and comparison years 2016–2018 (to March 2017–2019) quantified using difference in differences, from which mean rate of odds ratios (μROR) across years was reported.ResultsThe study included 3,552,210 individuals over the study period. Self-harm contacts reduced across services in March and December 2020 compared to previous years. Primary care contacts with self-harm reduced disproportionately compared to non-self-harm contacts (μROR = 0.7, p<0.05), while their proportion increased in emergency departments during April 2020 (μROR = 1.3, p<0.05 in 2/3 comparison years) and hospital admissions during April-May 2020 (μROR = 1.2, p<0.05 in 2/3 comparison years). Despite this, those who self-harmed in April 2020 were more likely to be seen in primary care than other settings compared to previous years (μROR = 1.2, p<0.05). A lower proportion of those with self-harm contacts in emergency departments were subsequently admitted to hospital in December 2020 compared to previous years (μROR = 0.5, p<0.05).ConclusionsThese findings suggest that those who self-harmed during the COVID-19 pandemic may have been less likely to seek help, and those who did so faced more stringent criteria for admission. Communications encouraging those who self-harm to seek help during pandemics may be beneficial. However, this needs to be supported by maintained provision of mental health services.

Landscape and Climatic Variations Shaped Secondary Contacts amid Barn Owls of the Western Palearctic.

The combined actions of climatic variations and landscape barriers shape the history of natural populations. When organisms follow their shifting niches, obstacles in the landscape can lead to the splitting of populations, on which evolution will then act independently. When two such populations are reunited, secondary contact occurs in a broad range of admixture patterns, from narrow hybrid zones to the complete dissolution of lineages. A previous study suggested that barn owls colonized the Western Palearctic after the last glaciation in a ring-like fashion around the Mediterranean Sea, and conjectured an admixture zone in the Balkans. Here, we take advantage of whole-genome sequences of 94 individuals across the Western Palearctic to reveal the complex history of the species in the region using observational and modeling approaches. Even though our results confirm that two distinct lineages colonized the region, one in Europe and one in the Levant, they suggest that it predates the last glaciation and identify a secondary contact zone between the two in Anatolia. We also show that barn owls recolonized Europe after the glaciation from two distinct glacial refugia: a previously identified western one in Iberia and a new eastern one in Italy. Both glacial lineages now communicate via eastern Europe, in a wide and permeable contact zone. This complex history of populations enlightens the taxonomy of Tyto alba in the region, highlights the key role played by mountain ranges and large water bodies as barriers and illustrates the power of population genomics in uncovering intricate demographic patterns.

392. 3D-DOSS – Using Digital Twins and Spatiotemporal Data Mapping for Infectious Disease Surveillance and Outbreak Investigations

BackgroundThe COVID-19 pandemic has brought to light the importance of contact tracing in outbreak management. Digital technologies have been leveraged to enhance contact tracing in community settings. However, within complex hospital environments, where patient and staff movement and interpersonal interactions are central to care delivery, tools for contact tracing and cluster detection remain limited. We aimed to develop a system to promptly, identify contacts in infectious disease exposures and detect infectious disease clusters. MethodsWe prototyped a 3D mapping tool 3-Dimensional Disease Outbreak Surveillance System (3D-DOSS), to have a spatial representation of patients in the hospital inpatient locations. Based on the AutoCAD drawings, the hospital physical spaces are built within a game-development software to obtain accurate digital replicas. This concept borrows from the way gamers interact with the virtual world/space, to mimic the interactions in physical space, like the SIMS franchise. Clinical, laboratory and patient movement data is then integrated into the virtual map to develop syndromic and disease surveillance systems. Risk assignment to individuals exposed is through mathematical modeling based on distance coordinates, room type and ventilation parameters and whether the disease is transmitted via contact, droplet or airborne route. ResultsWe have mapped acute respiratory illness (ARI) data for the period September to December 2018. We identified an influenza cluster of 10 patients in November 2018. In a COVID-19 exposure involving a healthcare worker (HCW), we identified 44 primary and 162 secondary contacts who were then managed as per our standard exposure management protocols. MDRO outbreaks could also be mapped.ConclusionThrough early identification of at-risk contacts and detection of infectious disease clusters, the system can potentially facilitate interventions to prevent onward transmission. The system can also support security, environmental cleaning, bed assignment and other operational processes. Simulations of novel diseases outbreaks can enhance preparedness planning as health systems that had been better prepared have been more resilient in this current pandemic. Disclosures All Authors: No reported disclosures

Efficacy and Safety of Lianhuaqingwen Capsules for the Prevention of Coronavirus Disease 2019: A Prospective Open-Label Controlled Trial.

Coronavirus disease 2019 (COVID-19) has become a global pandemic. Community and close contact exposures continue to drive the COVID-19 pandemic. There is no confirmed effective treatment for suspected cases and close contacts. Lianhuaqingwen (LH) capsules, a repurposed Chinese herbal product that is currently on the market, have proven effective for influenza and COVID-19. To determine the safety and efficacy of LH capsules for the prevention of COVID-19, we conducted a prospective open-label controlled trial of LH capsules on subjects who had close contact with people infected with COVID-19. Subjects received LH capsules (4 capsules, three times daily) or the usual medical observation for 14 days. The primary endpoint was the rate of positive nucleic acid tests of nasal and pharyngeal swabs during the quarantine medical observation period. We included 1976 patients, including 1101 in the treatment group and 875 in the control group. The rate of positive nucleic acid tests in the treatment group was significantly lower than that in the control group (0.27% vs. 1.14%, respectively; mean difference: −0.87%; 95% CI: −1.83 to −0.13; p=0.0174) during the quarantine medical observation period (14 days). Among subjects with different close contact states, there was no significant difference in the rate of positive nucleic acid test results among close contacts in the treatment group and the control group (6.45% vs. 11.43%, respectively; p=0.6762). Among secondary close contacts, the rate of positive nucleic acid tests in the treatment group was significantly lower than that in the control group (0.09% vs. 0.71%, respectively; p=0.0485). No serious adverse events were reported. Taken together, and in light of the safety and effectiveness profiles, these results show that LH capsules can be considered to prevent the progression of COVID-19 after close contact with an infected person. This trial is registered with ChiCTR2100043012.

Lessons learnt from the first large outbreak of COVID-19 in health-care settings in Tasmania, Australia.

ProblemOne month after the initial case of coronavirus disease 2019 (COVID-19) in Tasmania, an island state of Australia, two health-care workers (HCWs) from a single regional hospital were notified to public health authorities following positive tests for SARS-CoV-2 nucleic acid. These were the first recognized cases in an outbreak that overwhelmed the hospital’s ability to function.ContextThe outbreak originated from two index cases. Both had returned to Tasmania following travel on a cruise ship and required hospital admission for management of COVID-19. A total of 138 cases were subsequently linked to this outbreak: 81 HCWs (most being nurses) and 23 patients across three hospitals, one resident of an aged-care facility and 33 close contacts.ActionThe outbreak was controlled through the identification and isolation of cases, identification and quarantining of close contacts and their household members, closure of the affected facilities and community-level restrictions to reduce social mixing in the affected region.Lessons learntFactors that were likely to have contributed to ongoing transmission in this setting included workplace practices that prevented adequate physical distancing, attending work while symptomatic, challenges in rapidly identifying contacts, mobility of staff and patients between facilities, and challenges in the implementation of infection control practices.DiscussionMany commonly accepted hospital practices before the COVID-19 pandemic amplified the outbreak. The lessons learnt from this investigation changed work practices for HCWs and led to wider public health interventions in the management of potential primary and secondary contacts.

Strategies to maximise study retention and limit attrition bias in a prospective cohort study of men reporting a history of injecting drug use released from prison: the prison and transition health study

BackgroundThere are significant challenges associated with studies of people released from custodial settings, including loss to follow-up in the community. Interpretation of findings with consideration of differences between those followed up and those not followed up is critical in the development of evidence-informed policies and practices. We describe attrition bias in the Prison and Transition Health (PATH) prospective cohort study, and strategies employed to minimise attrition.MethodsPATH involves 400 men with a history of injecting drug use recruited from three prisons in Victoria, Australia. Four interviews were conducted: one pre-release (‘baseline’) and three interviews at approximately 3, 12, and 24 months post-release (‘follow-up’). We assessed differences in baseline characteristics between those retained and not retained in the study, reporting mean differences and 95% confidence intervals (95% CIs). ResultsMost participants (85%) completed at least one follow-up interview and 162 (42%) completed all three follow-up interviews. Retained participants were younger than those lost to follow-up (mean diff − 3.1 years, 95% CI -5.3, − 0.9). There were no other statistically significant differences observed in baseline characteristics.ConclusionThe high proportion of participants retained in the PATH cohort study via comprehensive follow-up procedures, coupled with extensive record linkage to a range of administrative datasets, is a considerable strength of the study. Our findings highlight how strategic and comprehensive follow-up procedures, frequent contact with participants and secondary contacts, and established working relationships with the relevant government departments can improve study retention and potentially minimise attrition bias.

Adaptive Introgression Facilitates Adaptation to High Latitudes in European Aspen (Populus tremula L.).

Understanding local adaptation has become a key research area given the ongoing climate challenge and the concomitant requirement to conserve genetic resources. Perennial plants, such as forest trees, are good models to study local adaptation given their wide geographic distribution, largely outcrossing mating systems, and demographic histories. We evaluated signatures of local adaptation in European aspen (Populus tremula) across Europe by means of whole-genome resequencing of a collection of 411 individual trees. We dissected admixture patterns between aspen lineages and observed a strong genomic mosaicism in Scandinavian trees, evidencing different colonization trajectories into the peninsula from Russia, Central and Western Europe. As a consequence of the secondary contacts between populations after the last glacial maximum, we detected an adaptive introgression event in a genome region of ∼500 kb in chromosome 10, harboring a large-effect locus that has previously been shown to contribute to adaptation to the short growing seasons characteristic of Northern Scandinavia. Demographic simulations and ancestry inference suggest an Eastern origin—probably Russian—of the adaptive Nordic allele which nowadays is present in a homozygous state at the north of Scandinavia. The strength of introgression and positive selection signatures in this region is a unique feature in the genome. Furthermore, we detected signals of balancing selection, shared across regional populations, that highlight the importance of standing variation as a primary source of alleles that facilitate local adaptation. Our results, therefore, emphasize the importance of migration–selection balance underlying the genetic architecture of key adaptive quantitative traits.

Symptom and Age Homophilies in SARS-CoV-2 Transmission Networks during the Early Phase of the Pandemic in Japan.

Simple SummaryIn the early stages of the COVID-19 pandemic, Japan conducted contact tracing extensively and published detailed records of thousands of anonymized patients. We leveraged the registry data to perform an exponential random graph model (ERGM) network analysis to examine demographic and symptomological homophilies of SARS-CoV-2 transmission networks in Hokkaido and Kanagawa. Our analysis showed: (1) Age, symptom, and asymptomatic status homophilies in both prefectures; (2) Asymptomatic infections increased as the virus was passed from primary cases to secondary and tertiary ones; (3) Transmission was mostly seen at the primary and secondary levels, with none occurring beyond quaternary; (4) Transmission occurred primarily in healthcare settings, as well as in families.Kanagawa and Hokkaido were affected by COVID-19 in the early stage of the pandemic. Japan’s initial response included contact tracing and PCR analysis on anyone who was suspected of having been exposed to SARS-CoV-2. In this retrospective study, we analyzed publicly available COVID-19 registry data from Kanagawa and Hokkaido (n = 4392). Exponential random graph model (ERGM) network analysis was performed to examine demographic and symptomological homophilies. Age, symptomatic, and asymptomatic status homophilies were seen in both prefectures. Symptom homophilies suggest that nuanced genetic differences in the virus may affect its epithelial cell type range and can result in the diversity of symptoms seen in individuals infected by SARS-CoV-2. Environmental variables such as temperature and humidity may also play a role in the overall pathogenesis of the virus. A higher level of asymptomatic transmission was observed in Kanagawa. Moreover, patients who contracted the virus through secondary or tertiary contacts were shown to be asymptomatic more frequently than those who contracted it from primary cases. Additionally, most of the transmissions stopped at the primary and secondary levels. As expected, significant viral transmission was seen in healthcare settings.

The healthcare resource impact of maternal mental illness on children and adolescents: UK retrospective cohort study.

The general health of children of parents with mental illness is overlooked. To quantify the difference in healthcare use of children exposed and unexposed to maternal mental illness (MMI). This was a retrospective cohort study of children aged 0-17 years, from 1 April 2007 to 31 July 2017, using a primary care register (Clinical Practice Research Datalink) linked to Hospital Episodes Statistics. MMI included non-affective/affective psychosis and mood, anxiety, addiction, eating and personality disorders. Healthcare use included prescriptions, primary care and secondary care contacts; inflation adjusted costs were applied. The rate and cost was calculated and compared for children exposed and unexposed to MMI using negative binomial regression models. The total annual cost to NHS England of children with MMI was estimated. The study included 489 255 children: 238 106 (48.7%) girls, 112 741 children (23.0%) exposed to MMI. Compared to unexposed children, exposed children had a higher rate of healthcare use (rate ratio 1.27, 95% CI 1.26-1.28), averaging 2.21 extra contacts per exposed child per year (95% CI 2.14-2.29). Increased healthcare use among exposed children occurred in inpatients (rate ratio 1.37, 95% CI 1.32-1.42), emergency care visits (rate ratio 1.34, 95% CI 1.33-1.36), outpatients (rate ratio 1.30, 95% CI 1.28-1.32), prescriptions (rate ratio 1.28, 95% CI 1.26-1.30) and primary care consultations (rate ratio 1.24, 95% CI 1.23-1.25). This costs NHS England an additional £656 million (95% CI £619-£692 million), annually. Children of mentally ill mothers are a health vulnerable group for whom targeted intervention may create benefit for individuals, families, as well as limited NHS resources.

Deep genetic structure at a small spatial scale in the endangered land snail Xerocrassa montserratensis

Species with small geographic ranges do not tend to have a high genetic structure, but some land snail species seem to be an exception. Xerocrassa montserratensis, an endangered land snail endemic to Catalonia (northeastern Iberian Peninsula), is an excellent model to study the processes affecting the phylogeography of specialized species of conservation concern. This species is restricted to xerophilous stony slopes and occurs within a small and fragmented area of ca. 500 km2. We sequenced the COI barcode region of 152 individuals from eight sites covering the entire range of the species. We found four genetic groups mostly coincident with their geographic distribution: a central ancestral group containing shared haplotypes among five localities and three groups restricted to a single locality each. Two of these derived groups were geographically and genetically isolated, while the third and most differentiated group was not geographically isolated. Geomorphologic and paleoclimatic processes during the Pleistocene can explain the divergence found between populations of this low dispersal species with historical fragmentation and secondary contacts. Nonetheless, recent passive large dispersal through streams was also detected in the central group. Overall, our study uncovered four evolutionary units, partially matching morphologically described subspecies, which should be considered in future conservation actions.

Amphiphilic core–shell magnetic adsorbents for efficient removal and detection of phthalate esters

A new class of amphiphilic magnetic adsorbents (denoted as Fe3O4-GPS-A) is fabricated by functionalization of the Fe3O4 surface with six different amphiphilic silanizing agents that are specifically tailor-made to the chemical structure of PAEs. The resulting Fe3O4-GPS-A exhibit different contact angles due to the significant changes in functional groups, as revealed by 1H NMR and FTIR spectroscopy. Among six Fe3O4-GPS-A, Fe3O4-DOA and Fe3O4-OAN exhibit a fast adsorption process (within 60 min) and high adsorption capacity for dibutyl phthalate (DBP) and dioctyl phthalate (DOP), two commonly used phthalate esters (173.7 mg g−1 for DOP and 104.4 mg g−1 for DBP), in conjunction with fast magnetic responsiveness and good thermal stability. The adsorption performance of Fe3O4-DOA and Fe3O4-OAN were well-maintained even after ten cycles. Besides, the adsorption mechanism was investigated through adsorption fitting models and theoretical calculations, which inferred that the interactions between adsorbent and adsorbate are mainly based on hydrophobic interactions along with secondary non-covalent contacts. Finally, the adsorbents combined with GC–MS analyses were applied to monitor DBP and DOP in the lake water samples. This work not only opens up a strategy for amphiphilic modification of magnetic adsorbents, but also provides a new avenue in their application for phthalate esters detection.

Pressure and Chemical Unfolding of an α-Helical Bundle Protein: The GH2 Domain of the Protein Adaptor GIPC1.

When combined with NMR spectroscopy, high hydrostatic pressure is an alternative perturbation method used to destabilize globular proteins that has proven to be particularly well suited for exploring the unfolding energy landscape of small single-domain proteins. To date, investigations of the unfolding landscape of all-β or mixed-α/β protein scaffolds are well documented, whereas such data are lacking for all-α protein domains. Here we report the NMR study of the unfolding pathways of GIPC1-GH2, a small α-helical bundle domain made of four antiparallel α-helices. High-pressure perturbation was combined with NMR spectroscopy to unravel the unfolding landscape at three different temperatures. The results were compared to those obtained from classical chemical denaturation. Whatever the perturbation used, the loss of secondary and tertiary contacts within the protein scaffold is almost simultaneous. The unfolding transition appeared very cooperative when using high pressure at high temperature, as was the case for chemical denaturation, whereas it was found more progressive at low temperature, suggesting the existence of a complex folding pathway.

COVID-19 (SARS-CoV-2) Outbreaks in Rural United Kingdom: Patterns of Spread and Empirical Evidence for the 'Rule of Six'

Background: Multiple countries across the world are facing the second wave of severe acute respiratory syndrome coronavirus. Understanding the early transmission dynamics is crucial for outbreak control measures and evaluating public health policy. Methods: We used detailed contact tracing data for the rural county of Lincolnshire to quantify risk factors of infection and model disease spread. We used subcritical branching processes ( Findings: 158,390 individuals were contact traced between the periods of May 11, 2020 to September 14, 2020 during the early phase of the second wave with 1143 confirmed positives in Lincolnshire. We found empirical evidence in support of the “rule of 6” for secondary contacts and largest gathering component size of 60 people. There is highly-over dispersed offspring distribution k=0·35 95% CI [0·41-0·29] indicative of super spreading events. We found through multivariable analysis, evidence of young adult population driving the outbreak and protection increasing with age for those in isolation. There is an increased risk of 66% (IRR 1·66, 95% CI [1·02 - 2·20]), 50% (IRR 1·50, 95% CI [1·16 - 2·37]) associated with eating out and shopping followed by social events respectively when compared to house hold acquired covid-19 infections. Interpretation: Generating functions and random graph theory help model the local transmission heterogeneities from the very onset of the outbreak. Focusing on the secondary contacts and case cluster size distribution is a better method for detecting the stochastic beginnings of a pandemic, rather than decision-making being based on exceeding particular threshold. Contact tracing and viral testing is essential to provide the reliable data and help with the public health policy for effective interventions. Funding: NoneDeclaration of Interests: None.Ethics Approval Statement: Ethics permission has been granted by University of Lincoln Ethics Committee (Protocol ID: 4188).

Weak yet Decisive: Molecular Halogen Bond and Competing Weak Interactions of Iodobenzene and Quinuclidine.

The halogen bonded adduct between the commonly used constituents quinuclidine and iodobenzene is based on a single weak nitrogen-iodine contact, and the isolation of this adduct was initially unexpected. Iodobenzene does not contain any electron-withdrawing group and therefore represents an unconventional halogen bond donor. Based on excellent diffraction data of high resolution, an electron density study was successfully accomplished and confirmed one of the longest N···I molecular halogen bonds with a distance of 2.9301(4) Å. The topological analysis identified the XB as a directional but weak σ hole interaction and revealed secondary contacts between peripheral regions of opposite charge. These additional contacts and their competition with a nitrogen-based interaction were confirmed by NOESY experiments in solution. Integration enabled us to determine the relative NOE ratios and provided insight regarding the existing interactions.

Dynamic network connectivity influences the spread of a sub-lineage of porcine reproductive and respiratory syndrome virus.

Swine production in the United States is characterized by dynamic farm contacts through animal movements; such movements shape the risk of disease occurrence on farms. Pig movements have been linked to the spread of a virulent porcine reproductive and respiratory syndrome virus (PRRSV), RFLP type 1-7-4, herein denoted as phylogenetic sub-lineage 1A [L1A]. This study aimed to quantify the contribution of pig movements to the risk of L1A occurrence on farms in the United States. Farms were defined as L1A-positive in a given 6-month period if at least one L1A sequence was recovered from the farm. Temporal network autocorrelation modelling was performed using data on animal movements and 1,761 PRRSV ORF5 sequences linked to 494 farms from a dense pig production area in the United States between 2014 and 2017. A farm's current and past exposure to L1A and other PRRSV variants was assessed through its primary and secondary contacts in the animal movement network. Primary and secondary contacts with an L1A-positive farm increased the likelihood of L1A occurrence on a farm by 19% (p=.04) and 23% (p=.03), respectively. While the risk posed by primary contacts with PRRS-positive farms is unsurprising, the observation that secondary contacts also increase the likelihood of infection is novel. Risk of L1A occurrence on a farm also increased by 3.0% (p=.01) for every additional outgoing shipment, possibly due to biosecurity breaches during loading and transporting pigs from the farm. Finally, use of vaccines or field virus inoculation on sow farms one year prior reduced the risk of L1A occurrence in downstream farms by 36% (p=.04), suggesting that control measures that reduce viral circulation and enhance immunological protection in sow farms have a carry-over effect on L1A occurrence in downstream farms. Therefore, coordinated disease management interventions between farms connected via animal movements may be more effective than individual farm-based interventions.

SARS-CoV-2 infection prevalence and characteristics in domestic contacts: Study of 39 families and 132 people in a general medicine clinic in Toledo (Spain). implications for the general practitioner

BackgroundMost people with COVID-19 receive care at home, increasing the likelihood of exposure for household members.ObjectiveTo study the prevalence and characteristics of secondary cases in families after the appearance of a primary caseMethodologyAn observational and retrospective study of families with at least one polymerase chain reaction (PCR) confirmed COVID-19 primary case was conducted from March 15 to December 25, 2020, in a general medicine office in Toledo, Spain. Socio-demographic and clinical variables were compared between primary and secondary cases in the families. The outcome of interest was secondary attack rate of SARS-CoV-2 within the family.Results39 families with a primary case (average size 3.4 members) with a total of 132 cohabitants were included. There were 22 cohabitants with negative PCR (22/92 = 24%), 70 secondary cases with positive PCR (Secondary attack rate 76%), of which 25 were asymptomatic (25/70 = 36%), and a cohabiting new-born. A high frequency of people from ethnic minorities, low household income and complex families was found, both in primary and secondary cases. The secondary cases with respect to the primary ones were more women, younger, students and with a lower socio-occupational level, with more asymptomatic cases, and milder symptomatic cases.ConclusionsIn this context, the prevalence of secondary domestic contacts is very high, and it occur in young women, being asymptomatic or mild. The high secondary attack rate suggests the importance of the pre-symptomatic or early symptomatic period of COVID-19, as well as the possible failure to comply with isolation measures.