Phoresy and Mites: More Than Just a Free Ride.

Mites are masters at attaching to larger animals, often insects, in a temporary symbiosis called phoresy that allows these tiny animals to exploit patchy resources. In this article, we examine phoresy in the Acari, including those that feed on their carriers in transit, from a broad perspective. From a phylogenetic perspective, phoresy has evolved several times from free-living ancestors but also has been lost frequently. Rotting logs appear to be the first patchy resource exploited by phoretic mites, but the evolution of rapid life cycles later permitted exploitation of short-lived resources. As phoresy is a temporary symbiosis, most species have off-host interactions with their carrier. These relationships can be highly complex and context dependent but often are exploitative of the carrier's resources or progeny. Transitions from phoresy to parasitism seem widespread, but evidence for transitions from obligate phoretic parasitism to permanent parasitism is weak.

The Importance of Habitat in the Ecology of Decomposition on Rabbit Carcasses in Malaysia: Implications in Forensic Entomology.

The stages of decomposition and the faunal succession on rabbit carcasses in three different habitats, namely jungle, rural, and highland areas, were studied. Three New Zealand White rabbit (Oryctolagus cuniculus) carcasses weighing ∼2 kg were sampled daily until the decomposition process was completed. Representative specimens of adult flies, larvae, pupa, and mites were collected from the carcasses and processed in the laboratory. There were differences in decomposition rate and faunal succession between the carcasses. The fastest rate of decomposition was recorded in rural area, and the slowest rate of decomposition was recorded in highland area. The carcasses exhibited the same pattern of colonization by adult flies, but the dominant species of larvae and adult flies on each carcass in specific habitats were different. The primary species of flies recorded in jungle were Chrysomya megacephala F., Chrysomya rufifacies (Macquart), Chrysomya chani Kurahashi, Chrysomya villenuevi Patton, Chrysomya nigripes Aubertin, Chrysomya pinguis (Walker), Hemipyrellia ligurriens (Wiedemann), Hemipyrellia tagaliana (Bigot), Hypopyiopsis fumipennis (Walker), Hypopygiopsis violacea (Macquart), and Hydrotaea spinigera Stein represented by both adults and larvae. Musca domestica L., Atherigona sp., Lioproctia pattoni (Senior-White), Lioproctia saprianovae Pape & Bänziger, and Seniorwhitea princeps (Wiedemann) were represented by adults only. The biodiversity of flies in the rural area were C. megacephala, C. rufifacies, H. ligurriens, Fannia canicularis L., Hydrotaea chalcogaster (Wiedemann), and Hyd. spinigera represented by both adults and larvae, meanwhile M. domestica, Atherigona sp., Boettcherisca peregrina (Robineau-Desvoidy), Parasarcophaga taenionota Wiedemann, Parasarcophaga scopariiformis Senior-White, and S. princeps were represented by adults only. The species of flies collected in the highland area were Lucilia porphyrina (Walker), C. megacephala, C. rufifacies, C. villenuevi, C. pinguis, H. ligurriens, Hyd. spinigera, Hyd. chalcogaster, F. canicularis, and Boettcherisca highlandica Kurahashi & Tan represented by both adults and larvae, whereas C. nigripes, Chrysomya thanomthini Kurahashi & Tumrasvin, M. domestica, Atherigona sp., Parasarcophaga albiceps Meigen, P. taenionota, Sepsidae, Phoridae, and Millichidae were represented by adults only. Faunal succession followed the sequence of dominant flies, i.e., Calliphoridae, Sarcophagidae, Muscidae, Sepsidae, and lastly Stratiomyidae for jungle, or Sepsidae for rural and highland studies. Mites, from suborders Mesostigmata, Prostigmata, Astigmatina, and Oribatida, were also recovered throughout decomposition, which could be used for future implementation in forensic investigations. The data obtained from this study could provide more accurate indicators for local forensic scientists in solving criminal cases especially on the determination of time and primary location of death.

Separating soil CO2 efflux into C-pool-specific decay rates via inverse analysis of soil incubation data.

Soil organic matter (SOM) is heterogeneous in structure and has been considered to consist of various pools with different intrinsic turnover rates. Although those pools have been conceptually expressed in models and analyzed according to soil physical and chemical properties, separation of SOM into component pools is still challenging. In this study, we conducted inverse analyses with data from a long-term (385 days) incubation experiment with two types of soil (from plant interspace and from underneath plants) to deconvolute soil carbon (C) efflux into different source pools. We analyzed the two datasets with one-, two- and three-pool models and used probability density functions as a criterion to judge the best model to fit the datasets. Our results indicated that soil C release trajectories over the 385 days of the incubation study were best modeled with a two-pool C model. For both soil types, released C within the first 10 days of the incubation study originated from the labile pool. Decomposition of C in the recalcitrant pool was modeled to contribute to the total CO2 efflux by 9-11 % at the beginning of the incubation. At the end of the experiment, 75-85 % of the initial soil organic carbon (SOC) was modeled to be released over the incubation period. Our modeling analysis also indicated that the labile C-pool in the soil underneath plants was larger than that in soil from interspace. This deconvolution analysis was based on information contained in incubation data to separate carbon pools and can facilitate integration of results from incubation experiments into ecosystem models with improved parameterization.

A new genus and family of sejine mites (Acari, Parasitiformes, Mesostigmata, Sejoidea) based on new species from Lord Howe Island and Brazil, and a redescription of Sejus americanus (Banks, 1902).

The Sejoidea currently contains three families (Sejidae, Ichthyostomatogasteridae, Uropodellidae) of enigmatic mesostigmatic mites with a mixture of characters of general distribution in the Parasitiformes (e.g., hypertrichy, tarsus IV with an intercalary sclerite bearing a pair of ventral setae, archispermous mating system) and derived character states both unique (e.g., distinctive female sterno-gential region; first hypostomal setae adjacent and more or less membranous) and apparently convergent with other Mesostigmata (e.g., 2-tined palpal apotele, reduced dorsal sclerotisation in the adult, phoretic deutonymph). In this paper, I review the characters defining the Sejoidea; propose a new genus, Reginacharlottia gen. nov. based on two new species: one from Lord Howe Island, New South Wales, Australia (R. lordhowensis sp. nov.) and one from Bahia State, Brazil (R. braziliensis sp. nov.) and erect a new family, Reginacharlottiidae fam. nov. to accommodate them. These new species share a number of unusual characters not otherwise known in the Sejida, including a plumose interdigital cheliceral excrescence, a highly reduced female genital shield, and a highly modified anal region covered by a pair of hypertrophied preanal setae; the postanal seta is absent. Adult female R. lordhowensis carry up to a dozen eggs that enclose fully developed larvae; the larvae also lack the postanal seta, but have a unique pygidial tubercle that may act as an egg burster. In addition, the female of Sejus americanus (Banks, 1902) is redescribed and the male described for the first time. Sejus species tend to be more typical of the warmer parts of the world, but S. americanus extends well into the boreal forest of Alberta, Canada (56 degrees N). A key to separate the families of Sejoidea is provided.

A review of the ecology and distribution of Protoribates (Oribatida, Oripodoidea, Haplozetidae) in Alberta, Canada, with the description of a new species.

The oribatid mite genus Protoribates Berlese (Haplozetidae) is reviewed for North America and the genus diagnosis is revised to account for the North American species, Protoribates robustior (Jacot, 1937) is redescribed and newly reported from western North America and a new species from Alberta is described. Protoribates haughlandae sp. n. is bisexual, heterotridactylous, and lives primarily in the peat soils of fens and bogs. Protoribates robustior is all-female, monodactylous, and occurs primarily in dry forests or in dry, treeless sites dominated by grasses, sedges, and shrubs. Both species feed on fungal hyphae and spores, but P. haughlandae also is an opportunistic predator and/or necrophage of small arthropods and P. robustior gut contents often include material that resembles plant cell walls. Examination of type specimens confirms that Protoribates prionotus (Woolley, 1968) is a junior synonym of the widespread Protoribates lophotrichus (Berlese, 1904). A key to differentiate Lagenobates from Protoribates and to identify the 7 species of the latter that are known or reported from North America is provided.

A revision of the Heatherellidae (Parasitiformes: Mesostigmata) with a new genus and two new species from Australasia.

The discovery of a new genus of Heatherellidae in New Zealand has led us to revise this enigmatic family and its constituent genera. Aheatherella n. gen., based on A. mira n. sp. from the North Island of New Zealand, lacks some of the derived character states that link the Australian Heatherella, most notably the lack of sexual dimorphism in the dorsal shields and in the presence of peritremes in adult Aheatherella. Heatherella osleri n. sp. is described from New South Wales, extending the distribution of this genus beyond Queensland. New collection records of H. callimaulos and a key to the genera and species of the family are provided. We propose that the Heatherellidae-previously placed in its own cohort outside the Gamasina-are best considered a superfamily of gamasine mites within the subcohort Epicriiae.

Impact of Intravenous Aspirin Administration on Ventriculostomy-Associated Hemorrhage in Coiled Acute Subarachnoid Hemorrhage Patients / 신경중재치료의학

Purpose@#Aspirin has beneficial effects on coiling, even in acute subarachnoid hemorrhage, but there is also a perceived risk of increased bleeding and, importantly, a concern regarding ventriculostomy-associated hemorrhage (VAH) in those with complicating hydrocephalus. We aimed to assess the rate and extent of VAH in patients specifically treated with procedural intravenous aspirin during endovascular coiling of ruptured intracranial aneurysms. @*Materials and Methods@#This was a single neurovascular center retrospective observational study of consecutive patients treated over a three-year period. The rate of VAH assessed using computed tomography and clinical outcomes were compared in patients receiving intraprocedural intravenous aspirin loading (n=90) versus those that did not receive the drug (n=40). @*Results@#There was a significantly elevated rate of VAH in patients receiving intravenous aspirin (30% vs. 2.5%, odds ratio 16.7 [95% confidence interval: 2.2–128.0], P<0.0001). The majority of VAH was <10 mm in size (70%) with the largest bleed measuring 20 mm. No hematoma required surgical evacuation. No difference in favorable outcome at discharge was demonstrated. There was no difference in mortality between the 2 groups. @*Conclusion@#Loading with intravenous aspirin during endovascular treatment of ruptured intracranial aneurysms significantly increases the risk of VAH, but most are small with minimal impact on clinical outcome at discharge. Intravenous aspirin should probably be reserved for selected cases but should not be withheld based on risk of VAH.

Impact of Intravenous Aspirin Administration on Ventriculostomy-Associated Hemorrhage in Coiled Acute Subarachnoid Hemorrhage Patients / 신경중재치료의학

Purpose@#Aspirin has beneficial effects on coiling, even in acute subarachnoid hemorrhage, but there is also a perceived risk of increased bleeding and, importantly, a concern regarding ventriculostomy-associated hemorrhage (VAH) in those with complicating hydrocephalus. We aimed to assess the rate and extent of VAH in patients specifically treated with procedural intravenous aspirin during endovascular coiling of ruptured intracranial aneurysms. @*Materials and Methods@#This was a single neurovascular center retrospective observational study of consecutive patients treated over a three-year period. The rate of VAH assessed using computed tomography and clinical outcomes were compared in patients receiving intraprocedural intravenous aspirin loading (n=90) versus those that did not receive the drug (n=40). @*Results@#There was a significantly elevated rate of VAH in patients receiving intravenous aspirin (30% vs. 2.5%, odds ratio 16.7 [95% confidence interval: 2.2–128.0], P<0.0001). The majority of VAH was <10 mm in size (70%) with the largest bleed measuring 20 mm. No hematoma required surgical evacuation. No difference in favorable outcome at discharge was demonstrated. There was no difference in mortality between the 2 groups. @*Conclusion@#Loading with intravenous aspirin during endovascular treatment of ruptured intracranial aneurysms significantly increases the risk of VAH, but most are small with minimal impact on clinical outcome at discharge. Intravenous aspirin should probably be reserved for selected cases but should not be withheld based on risk of VAH.

Kleptoparasites or commensals? Effects of Argyrodes antipodianus (Araneae: Theridiidae) on Nephila plumipes (Araneae: Tetragnathidae).

Argyrodes antipodianus is a small kleptobiotic spider that steals prey from webs of the large orb-weaving spider Nephila plumipes, and sometimes removes the web itself. We used experiments in a greenhouse to test how the presence of the kleptobiont, differences in food availability, and web damage affected fitness of the web owner. After 49 days, N. plumipes with four A. antipodianus on their webs gained 55% less weight and relocated their webs 4.5 times as often as spiders with no kleptobionts. Increased web relocation and decreased weight gain may have resulted from reduced prey levels or from web damage by A. antipodianus. A second experiment demonstrated that hosts gained weight at the feeding rate used in the first experiment, but not at lower rates. Web relocation rate also varied with feeding rate, but in a non-linear manner. Web loss was evaluated in a separate experiment, by manually removing one-quarter of the web every 5 days for 30 days; however, neither weight gain nor rate of web relocation were affected. We conclude that A. antipodianus is a true kleptoparasite that can reduce the growth rate of its host N. plumipes, but that neither food theft nor web damage alone explain increased web relocation rates.

Failure of a traffic control "fatality" sign to affect pedestrians' and motorists' behavior.

The behavior of 643 pedestrians and 1749 motorists at two signal-controlled intersections was observed over a 2-mo. period of observation in March and November. One intersection had a coffin-shaped traffic sign with the wording "Fatality" erected during the first month of observation (March). The second intersection was identical in traffic and pedestrian volume but lacked a "Fatality" sign in either March or November. "Fatality" signs are erected and maintained by the City of Edmonton for 6 mo. whenever a pedestrian death has occurred, and they are intended to raise the awareness of both pedestrians and motorists concerning the risks at dangerous intersections. This sign had been removed for nearly 3 mo. when a follow-up observation was made in November. While female pedestrians and pedestrians over the age of 50 years showed greater caution at both intersections, the presence or absence of the "Fatality" sign had no statistically significant influence on safety. Similarly, the presence or absence of a sign did not significantly influence motorists' behavior. Of motorists 7.6% ran either amber or red traffic control lights at the two intersections. The "Fatality" sign did not affect the rates of these violations.

Keys and the crisis in taxonomy: extinction or reinvention?

Dichotomous keys that follow a single pathway of character state choices to an end point have been the primary tools for the identification of unknown organisms for more than two centuries. However, a revolution in computer diagnostics is now under way that may result in the replacement of traditional keys by matrix-based computer interactive keys that have many paths to a correct identification and make extensive use of hypertext to link to images, glossaries, and other support material. Progress is also being made on replacing keys entirely by optical matching of specimens to digital databases and DNA sequences. These new tools may go some way toward alleviating the taxonomic impediment to biodiversity studies and other ecological and evolutionary research, especially with better coordination between those who produce keys and those who use them and by integrating interactive keys into larger biological Web sites.

Research for universal health coverage: World health report 2013

 

Universal health coverage ensures everyone has access to the health services they need without suffering financial hardship as a result. In December 2012, a UN resolution was passed encouraging governments to move towards providing universal access to affordable and quality health care services. As countries move towards it, common challenges are emerging - challenges to which research can help provide answers.

The World health report: research for universal health coverage focuses on the importance of research in advancing progress towards universal health coverage. In addition, it identifies the benefits of increased investment in health research by low- and middle-income countries using case studies from around the world, and proposes ways to further strengthen this type of research.

CORONAVIRUS IN PREGNANCY AND DELIVERY: RAPID REVIEW AND EXPERT CONSENSUS

BACKGROUNDPerson to person spread of COIVD-19 in the UK has now been confirmed. There are limited case series reporting the impact on women affected by coronaviruses (CoV) during pregnancy. In women affected by SARS and MERS, the case fatality rate appeared higher in women affected in pregnancy compared with non-pregnant women. We conducted a rapid, review to guide management of women affected by COVID -19 during pregnancy and developed interim practice guidance with the RCOG and RCPCH to inform maternity and neonatal service planning METHODSSearches were conducted in PubMed and MedRxiv to identify primary case reports, case series, observational studies or randomised-controlled trial describing women affected by coronavirus in pregnancy and on neonates. Data was extracted from relevant papers and the review was drafted with representatives of the RCPCH and RCOG who also provided expert consensus on areas where data were lacking RESULTSFrom 9964 results on PubMed and 600 on MedRxiv, 18 relevant studies (case reports and case series) were identified. There was inconsistent reporting of maternal, perinatal and neonatal outcomes across case reports and series concerning COVID-19, SARS, MERS and other coronaviruses. From reports of 19 women to date affected by COVID-19 in pregnancy, delivering 20 babies, 3 (16%) were asymptomatic, 1 (5%) was admitted to ICU and no maternal deaths have been reported. Deliveries were 17 by caesarean section, 2 by vaginal delivery, 8 (42%) delivered pre-term. There was one neonatal death, in 15 babies who were tested there was no evidence of vertical transmission. CONCLUSIONSMorbidity and mortality from COVID-19 appears less marked than for SARS and MERS, acknowledging the limited number of cases reported to date. Pre-term delivery affected 42% of women hospitalised with COVID-19, which may put considerable pressure on neonatal services if the UK reasonable worse-case scenario of 80% of the population affected is realised. There has been no evidence of vertical transmission to date. The RCOG and RCPCH have provided interim guidance to help maternity and neonatal services plan their response to COVID-19.

The role of sub-genomic RNA in discordant results from RT-PCR tests for COVID-19.

Reverse transcription-PCR (RT-PCR) is the standard method of diagnosing COVID-19. An inconclusive test result occurs when one RT-PCR target is positive for SARS-CoV-2 and one RT-PCR target is negative within the same sample. An inconclusive result generally requires retesting. One reason why a sample may yield an inconclusive result is that one target is at a higher concentration than another target. It was hypothesized that concentration differences across targets may be due to the transcription of sub-genomic RNA, as this would result in an increase in the concentration of gene targets near the 3 end of the SARS-CoV-2 genome. A panel of six digital droplet (dd)PCR assays was designed to quantitate the ORF1, E-gene, and N-gene of SARS-CoV-2. This panel was used to quantify viral cultures of SARS-CoV-2 that were harvested during the eclipse phase and at peak infectivity in such a way as to maximize gene-to-gene copy ratios. Eleven clinical nasopharyngeal swabs were also tested with this panel. In culture, infected cells showed higher N-gene/ORF1 copy ratios than culture supernatants. Both the highest specific infectivity (copies/pfu) and the highest differences between gene targets were observed at 6 hours post-infection (eclipse phase) in infected cells. The same trends in the relative abundance of copies across different targets observed in infected cells was observed in clinical samples, though trends were more pronounced in infected cells. This study showed that a greater copy number of N-gene relative to E-gene and ORF1 transcripts could potentially explain inconclusive results for some RT-PCR tests on low viral load samples. The use of N-gene RT-PCR target(s) as opposed to ORF1 targets for routine testing is supported by this data. Author SummaryThis paper provides insight into a drawback of the standard method of testing for COVID-19 (RT-PCR). The results presented here propose an explanation for why inconclusive results sometimes occur with this method. These results can aid microbiologists in the interpretation of inconclusive test results. These results can also aid in decisions about which COVID-19 test a laboratory should use, as there are a plethora of options available. This is important because this standard testing method will remain a critical tool - globally - for managing the COVID-19 pandemic and any future viral pandemics and epidemics. Thus, it is important to investigate every facet of the testing method. The findings presented here are applicable to any virus which makes sub-genomic transcripts as part of its life cycle. Trends observed in viral cultures are presented alongside the same trends observed in clinical samples. Unlike similar papers in the field, this paper did not strive to develop a new methodology or tool.

Transmission of SARS-CoV-2 from pre and asymptomatic infected individuals. A systematic review

BackgroundThe transmission role of SARS-Cov-2 infected persons who develop symptoms post testing (pre symptomatics) or not at all throughout the course of positivity (asymptomatics) is unknown. We carried out a systematic review of available evidence to determine whether they were infectious or not and if so for how long and their probable contribution to the pandemic spread of SARS-CoV-2. MethodsWe searched LitCovid, medRxiv, Google Scholar and the WHO Covid-19 databases and reference lists of included studies. Search terms were COVID-19, SARS-CoV-2, transmission, asymptomatic, presymptomatic and appropriate synonyms. Searches were carried out to 31 March 2021. We included studies on people exposed to SARS CoV-2 within 2-14 days (incubation time) of close contact or suspected community or institutional exposure to index asymptomatic (at the time of observation) infected individuals, as defined in the study. We included studies with a proven or hypothesised chain of transmission with secondary case infected based on fulfilling a confirmed or probable case definition and confirmation of infectiousness and transmission outcome based either on serial PCR cycle threshold readings or viral culture or gene sequencing or any combination thereof and adequate follow up. We assessed the reliability of eliciting symptom and signs compatible with contemporary knowledge and extracted documentation of the likelihood of transmission, presence of replicating virus and/or documentation of phylodynamics (genetic sequence lineage) and/or adequate follow-up and reporting of symptoms and signs. We wrote to all included studies corresponding authors to request further details and assessed likelihood of transmission using adapted causality criteria. ResultsWe included 18 studies from a variety of settings. Because of the current lack of standardized methodology and clear reporting criteria there was substantial methodological variation in transmission studies. Asymptomatic prevalence at the time of initial testing varied from 12.5% to 100% and of these 6% to 100% were pre-symptomatic cases, depending on the setting and the methods of case ascertainment and the population. Nursing/care home facilities reported high rates of presymptomatic: 50% - 100% (n=3 studies). Fifteen studies were classified as high risk and three studies at moderate risk of symptom ascertainment bias. In practice, this assessment means that high-risk studies may be less likely to distinguish between pre-symptomatic and asymptomatic cases. Six of the asymptomatic studies and four presymptomatic studies reported growing infectious virus although the data was too sparse to determine duration of infectiousness. Three studies were judged as providing possible and three of probable/likely evidence of asymptomatic transmission of SARs-CoV-2. Five studies provided evidence of possible and two of probable/likely presymptomatic transmission of SARs-CoV-2. Author response rate was 100%. ConclusionsReliable studies included here provide probable evidence of transmission of SARS-CoV-2 from presymptomatic and asymptomatic individuals. Single point in time estimates and binary PCR testing alone cannot provide reliable information on symptom status and information on infectivity. The number of studies and asymptomatic and presymptomatic cases eligible for inclusion was low, with more data and international standardisation of methods needed to further reduce uncertainty.

The evidence on transmission dynamics of COVID-19 from pre and asymptomatic cases: protocol for a systematic review

BackgroundThe role of forward transmission of infection from cases of SARS-CoV-2 who remain without symptoms and signs throughout the active phase of the disease (asymptomatic) and those who have not developed symptoms or signs when surveyed (presymptomatic) is at present unclear, despite the important role that they may play in transmission dynamics. MethodsWe will search LitCovid, medRxiv, Google Scholar and the WHO Covid-19 database using Covid-19, SARS-CoV-2, transmission, and appropriate synonyms as search terms. We will also search the reference lists of included studies for additional relevant studies. We will include studies of people exposed to SARS-CoV-2 within 2-14 days of close contact or suspected community or institutional exposure to index asymptomatic or pre-symptomatic infected individuals, as defined in each study along with secondary case(s) infected. We will include only studies that provide proof of transmission outcome using culturable virus and /or genetic sequencing. The inclusion of this higher-quality evidence aims to overcome the methodological shortcomings of lower quality studies. We will assess the microbiologic or genetic sequencing evidence in an effort to inform the quality of the chain of transmission evidence and adequacy of follow up of sign and symptom monitoring. Expected resultsWe intend to present the evidence in three distinct packages: study description, methodological quality assessment and data extracted. We intend on summarising the evidence and drawing conclusions as to the quality of the evidence.

Viral cultures, PCR Cycle threshold values and viral load estimation for COVID-19 infectious potential assessment in transplant patients: systematic review - Protocol Version 29 December 2021

This is the protocol for a systematic review focussing on people receiving solid organ or hematopoietic stem cell transplants. Our research questions are as follows: What is the relationship between serial PCR Ct value or other measures of viral burden, and the likelihood and duration of the presence of infectious virus from viral culture, among transplant recipients with SARS-CoV-2 infection? What is the influence of age, sex, underlying pathologies, degree of immunosuppression, vaccination status, COVID-19 symptoms and COVID-19 disease course on viral burden and the likelihood of presence of infectious SARS-CoV-2? We will include single studies reporting serial Cts from sequential rt-PCR testing or other measures of viral burden such as RNA gene copies of respiratory samples (from nasopharyngeal specimens) along with viral culture data on the same samples, from patients about to receive a transplant or who are post transplant with SARS-CoV-2 infection.

Donor Anti-Spike Immunity is Related to Recipient Recovery and Can Predict the Efficacy of Convalescent Plasma Units.

BackgroundThe novel coronavirus, SARS-CoV2 that causes COVID-19 has resulted in the death of more than 2.31 million people within the last year and yet no cure exists. Whereas passive immunization with COVID-19 convalescent plasma (CCP) provides a safe and viable option, selection of optimal units for therapy and lack of clear therapeutic benefit from transfusion remain as barriers to the use of CCP. Study design and methodsTo identify plasma that is expected to benefit recipients, we measured anti-SARS-CoV2 antibody levels using clinically available serological assays and correlated with the neutralizing activity of CCP from donors. Neutralizing titer of plasma samples was measured by assaying infectivity of SARS-CoV-2 spike protein pseudotyped retrovirus particles in the presence of dilutions of plasma samples. We also used this assay to identify evidence of passive transfusion of neutralizing activity in CCP recipients. ResultsViral neutralization and anti-spike protein antibodies in 109 samples from 87 plasma donors were highly varied but modestly correlated with each other. Recipients who died of COVID-19 were found to have been transfused with units with lower anti-spike antibody levels and neutralizing activity. Passive transfer of neutralization activity was documented in 62% of antibody naive plasma recipients. ConclusionsSince viral neutralization is the goal of CCP transfusion, our observations not only support the use of anti-spike SARS-CoV2 serology tests to identify beneficial CCP units, but also support the therapeutic value of convalescent plasma with high titers of anti-spike antibodies.

HIV infection and COVID-19 death: population-based cohort analysis of UK primary care data and linked national death registrations within the OpenSAFELY platform

BackgroundIt is unclear whether HIV infection is associated with risk of COVID-19 death. We aimed to investigate this in a large-scale population-based study in England. MethodsWorking on behalf of NHS England, we used the OpenSAFELY platform to analyse routinely collected electronic primary care data linked to national death registrations. People with a primary care record for HIV infection were compared to people without HIV. COVID-19 death was defined by ICD-10 codes U07.1 or U07.2 anywhere on the death certificate. Cox regression models were used to estimate the association between HIV infection and COVID-19 death, initially adjusted for age and sex, then adding adjustment for index of multiple deprivation and ethnicity, and finally for a broad range of comorbidities. Interaction terms were added to assess effect modification by age, sex, ethnicity, comorbidities and calendar time. Results17.3 million adults were included, of whom 27,480 (0.16%) had HIV recorded. People living with HIV were more likely to be male, of black ethnicity, and from a more deprived geographical area than the general population. There were 14,882 COVID-19 deaths during the study period, with 25 among people with HIV. People living with HIV had nearly three-fold higher risk of COVID-19 death than those without HIV after adjusting for age and sex (HR=2.90, 95% CI 1.96-4.30). The association was attenuated but risk remained substantially raised, after adjustment for deprivation and ethnicity (adjusted HR=2.52, 1.70-3.73) and further adjustment for comorbidities (HR=2.30, 1.55-3.41). There was some evidence that the association was larger among people of black ethnicity (HR = 3.80, 2.15-6.74, compared to 1.64, 0.92-2.90 in non-black individuals, p-interaction=0.045) InterpretationHIV infection was associated with a markedly raised risk of COVID-19 death in a country with high levels of antiretroviral therapy coverage and viral suppression; the association was larger in people of black ethnicity.

OpenSAFELY: Representativeness of Electronic Health Record platform OpenSAFELY-TPP data compared to the population of England.

BackgroundSince its inception in March 2020, data from the OpenSAFELY-TPP electronic health record platform has been used for more than 50 studies relating to the global COVID-19 emergency. OpenSAFELY-TPP data is derived from practices in England using SystmOne software, and has been used for the majority of these studies. We set out to investigate the representativeness of OpenSAFELY-TPP data by comparing it to national population estimates. MethodsWith the approval of NHS England, we describe the age, sex, Index of Multiple Deprivation and ethnicity of the OpenSAFELY-TPP population compared to national estimates from the Office for National Statistics. The five leading causes of death occurring between the 1st January 2020 and the 31st December 2020 were also compared to deaths registered in England during the same period. ResultsDespite regional variations, TPP is largely representative of the general population of England in terms of IMD (all within 1.1 percentage points), age, sex (within 0.1 percentage points), ethnicity and causes of death. The proportion of the five leading causes of death is broadly similar to those reported by ONS (all within 1 percentage point). ConclusionsData made available via OpenSAFELY-TPP is broadly representative of the English population. SummaryUsers of OpenSAFELY must consider the issues of representativeness, generalisability and external validity associated with using TPP data for health research. Although the coverage of TPP practices varies regionally across England, TPP registered patients are generally representative of the English population as a whole in terms of key demographic characteristics. Key messagesO_LIThere is regional variability across England in terms of key population characteristics C_LIO_LIUsers of OpenSAFELY should carefully consider the issues of representativeness, generalisability and external validity associated with using TPP data for health research. C_LIO_LITPP registered patients are a representative sub-sample of the English population as a whole in terms of age, sex, IMD and ethnicity. C_LIO_LIThe proportions of the five leading causes of death in TPP in 2020 are broadly similar to those reported by ONS. C_LI