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2.
Transfusion ; JOUR:112A-113A, 62(Supplement 2).
Article in English | EMBASE | ID: covidwho-2088348

ABSTRACT

Background/Case Studies: An immunohematology reference laboratory (IRL) at a regional blood center provides education for medical laboratory science (MLS) students, covering methods infrequently performed in hospitals (elution, adsorption, etc.). Rotations include wet lab benchwork, background instruction, a handbook of educational material, and conclude with a post-test. Students provide feedback by evaluation form. In response to the COVID-19 pandemic, and to cover required material while minimizing in-person time with students, online modules were created and incorporated into the rotation. In this hybrid model, the interactive modules provided background instruction, while inperson learning focused on performing methods. This study compared length of in-person experience, post-test scores, and student evaluation data before and after incorporating online modules into MLS rotations. Study Design/Methods: Online modules, created with Articulate 360 eLearning software, and incorporating voiceover instruction, interactive quizzes, and how-to videos, were uploaded onto the blood center website. Students completed online modules, ranging from 24- 34 min in length, along with accompanying worksheets, prior to in-person IRL learning. The study period prior to online module implementation (in-person only) was September 2017- October 2020. The post-implementation study period (online modules and abbreviated in-person experience) was November 2020- January 2022. Average length of in-person learning and post-test scores were compared for the two study periods. Average evaluation scores were also compared, calculated from student evaluations containing 5-6 questions utilizing a 5-point Likert scale. The IRL hosted 80 MLS students during the study periods, 61 prior to online module implementation and 19 after. The IRL rotation is a routine part of MLS programs, and only the hybrid model was offered postimplementation. Results/Findings: Average length of in-person experience prior to implementation was 8.48 h compared to 5.28 h for the hybrid model (p < 0.001, two-tailed t test). Average post-test score prior to implementation was 81% compared to 87% after, while student evaluation feedback scores averaged 4.70 out of 5 prior to use of the online modules and 4.76 out of 5 with the hybrid model. Conclusion(s): The incorporation of online modules into an IRL rotation for MLS students resulted in students spending significantly less time in the IRL, while attaining similar post-test scores. There was no significant difference in student evaluations. Based on these results, this hybrid strategy will continue to be used and applied to other educational programs.

3.
Sci Total Environ ; 858(Pt 2): 159161, 2022 Oct 01.
Article in English | MEDLINE | ID: covidwho-2049911

ABSTRACT

The presence of SARS-CoV-2 in untreated sewage has been confirmed in many countries but its incidence and infection risk in contaminated waters is poorly understood. The River Thames in the UK receives untreated sewage from 57 Combined Sewer Overflows (CSOs), with many discharging dozens of times per year. This study investigated if such discharges provide a pathway for environmental transmission of SARS-CoV-2. Samples of wastewater, surface water, and sediment collected close to six CSOs on the River Thames were assayed over eight months for SARS-CoV-2 RNA and infectious virus. Bivalves were also sampled as an indicator species of viral bioaccumulation. Sediment and water samples from the Danube and Sava rivers in Serbia, where raw sewage is also discharged in high volumes, were assayed as a positive control. No evidence of SARS-CoV-2 RNA or infectious virus was found in UK samples, in contrast to RNA positive samples from Serbia. Furthermore, this study shows that infectious SARS-CoV-2 inoculum is stable in Thames water and sediment for <3 days, while SARS-CoV-2 RNA is detectable for at least seven days. This indicates that dilution of wastewater likely limits environmental transmission, and that detection of viral RNA alone is not an indication of pathogen spillover.

4.
HemaSphere ; 6:1985-1987, 2022.
Article in English | EMBASE | ID: covidwho-2032163

ABSTRACT

Background: Ibrutinib (IBR) is an oral covalent Bruton tyrosine kinase inhibitor (BTKi), licensed for treatment of relapsed or refractory mantle cell lymphoma (MCL). Under NHS interim Covid-19 agreements in England, IBR with or without rituximab (R) was approved for the frontline treatment for MCL patients (pts) as a safer alternative to conventional immunochemotherapy. Although recent phase 2 studies have reported high response rates in low-risk patients for this combination in the frontline setting, randomised phase 3 and real-world data are currently lacking. Aims: To describe the real-world response rates (overall response rate (ORR), complete response (CR) rate) and toxicity profile of IBR +/-R in adult patients with previously untreated MCL. Methods: Following institutional approval, adults commencing IBR +/-R for untreated MCL under interim Covid-19 arrangements were prospectively identified by contributing centres. Hospital records were interrogated for demographic, pathology, response, toxicity and survival data. ORR/CR were assessed per local investigator according to the Lugano criteria using CT and/or PET-CT. Results: Data were available for 66 pts (72.7% male, median age 71 years, range 41-89). Baseline demographic and clinical features are summarised in Table 1. 23/66 pts (34.8%) had high-risk disease (defined as presence of TP53 mutation/deletion, blastoid or pleomorphic variant MCL, or Ki67%/MiB-1 ≥30%). IBR starting dose was 560mg in 56/62 pts (90%) and was given with R in 22/64 pts (34%). At a median follow up of 8.7 months (m) (range 0-18.6), pts had received a median of 7 cycles of IBR. 19/60 pts (32%) required a dose reduction or delay in IBR treatment. New atrial fibrillation and grade ≥3 any-cause toxicity occurred in 3/59 pts (5.8%) and 8/57 (14.0%) respectively. For the whole population and high-risk pts only, ORR was 74.4% and 64.7% respectively (p=0.2379), with a median time to response of 3.8m, coinciding with the first response assessment scan. Seven pts (16.7%), of whom 2 had highrisk disease, attained CR at a median of 6.0m. ORR for pts receiving vs not receiving R were 84.2% and 66.7% respectively (p=0.1904). IBR was discontinued in 20/61 pts (32.8%) at a median time to discontinuation of 4.1m, due to progressive disease (PD, 19.7%), toxicity (4.9%), death (3.3%;1 pt each of Covid-19 and E. coli infection), pt choice (3.3%) and other unspecified reasons (1.6%). 15/66 pts (22.7%) overall and 7/23 (30.4%) with high-risk disease progressed on IBR at a median time to PD of 4.0m. No pts underwent autologous stem cell transplantation consolidation during the study period. 12/57 pts (21.1%) received second line treatment (R-chemotherapy n=7, Nordic MCL protocol n=2, VR-CAP n=2, pirtobrutinib n=1). Response to second line treatment was CR in 4/11 pts, PD in 7/11. Of the 2 Nordic-treated patients, 1 had CR after cycle 2 and 1 PD. Fourteen pts (21.2%) died during the follow up period, due to MCL (n=11), Covid-19 (n=2) and congestive cardiac failure (n=1). Overall survival was lower for patients with high-risk disease (HR 0.55, p=0.038). Image: Summary/Conclusion: In this real-world UK cohort of pts receiving first-line IBR +/-R for MCL, including older and high-risk pts, we report high ORR rates in a similar range to the phase II Geltamo IMCL-2015 study of combination IBR-R in an exclusively low-risk population. Documented CR rates were lower, possibly reflecting a low usage of rituximab in the Covid-19 pandemic as well as CT assessment of response. Treatment was generally well tolerated, with low rates of toxicityrelated treatment discontinuation. The study is ongoing.

5.
Innovation in Aging ; 5:491-491, 2021.
Article in English | Web of Science | ID: covidwho-2012439
6.
Journal of Clinical Oncology ; 40(16), 2022.
Article in English | EMBASE | ID: covidwho-2009576

ABSTRACT

Background: We provide care for the rural, low-income, and underserved population of Oroville. The community has a vaccination rate of 50% and booster rate of over 20% in the 3rd year of the ongoing global SARS-CoV-2 pandemic in 2022. During this period, a subset of our cancer patients benefited from the use of immune checkpoint inhibitors. Methods: This is a cross-sectional observational study of the effectiveness of a mRNA-based vaccine in medical care workers compared to patients with systemic malignancies treated with immunomodulation of PD-1 and CTLA-4 inhibitors. The study was approved by the hospital IRB. We evaluated the total anti-Spike protein antibody titer using a commercial semi-quantitative assay, Labcorp Test #164090. All subjects received 3 doses of the mRNA vaccine. We excluded anyone who was administered therapeutic monoclonal antibodies (mAb) or had a recent infection within 120 days. Results: Subjects with systemic malignancies were significantly older, p = 0.0001 by t-test: median age: 76, range: 64-82, compared to health care workers: median age: 52, range: 21-75. Accrual had to be prematurely stopped upon the arrival of Omicron wave in the community. Out of the seven subjects treated with immunomodulation, six received nivolumab, including two in combination with ipilimumab. One subject received pembrolizumab. Six of the subjects had metastatic disease: one was treated adjuvantly for locally advanced esophageal adenocarcinoma. The rest had NSCLC and one case of urothelioma. We divided the groups to those who had the highest titer of antibody versus everybody else and found a similar distribution in both groups using the Chi2 test. The vast majority of the healthcare workers, 24/27 or 89%, had above the upper limit antibody titer. Patients with systemic malignancy, 5/7 or 71%, had above the upper limit antibody titer p = N.S. Conclusions: Three doses of the mRNA vaccine provided high titers irrespective of frailty or age. We hypothesize that immunomodulation could favorably affect vaccination response.

7.
WIDER Working Papers 2021. (93):38 pp. many ref. ; 2021.
Article in English | CAB Abstracts | ID: covidwho-1965130

ABSTRACT

This study aims to assess the economic costs of COVID-19 and the state of emergency implemented by the Government of Mozambique, relying on a social accounting matrix. It produces numerical results that represent the direct effect on (or 'shocks' to) the economy associated with the pandemic. We distinguish four channels-supply, demand, investment, and export-by which the state of emergency and other efforts influence economic activity. Our simulation suggests that the Mozambican economy lost a total of 3.6 per cent growth in 2020 and that total employment was 1.9 per cent down compared to a scenario without COVID-19. The main part of this loss is foreign-instigated, resulting from a demand reduction for Mozambican products by the rest of the world. The most heavily affected economic sectors are trade and accommodation and mining. Furthermore, our simulation implies that the production factors of capital and urban labour are more affected than rural labour. Moreover, the multisector multiplier analysis brings out the high dependence of Mozambique on a small number of export items (including tourism). Accordingly, Mozambique should promote economic diversification and explore the potential of reducing Mozambique's vulnerability to foreign shocks.

8.
Neuro-Oncology ; 24:i149-i150, 2022.
Article in English | EMBASE | ID: covidwho-1956578

ABSTRACT

BACKGROUND: The SARS-COV2 pandemic had huge impact on how clinical research is conducted when clinical research coordinators (CRC) transitioned to working remotely. An urgent transition of paper documentation into electronic formats had to occur without compromising participant safety or data integrity. Adverse event (AE) reporting had previously been captured in various paper formats with wet signature. AEs, attribution, severity, and clinical significance had to be changed into being electronically captured and incorporated into the medical record that captures the events in real time. METHOD: We assessed the satisfaction of the new method of AE recording amongst pediatric hematology oncology physicians and staff in a large academic institution during the COVID pandemic through a REDCap survey. The survey assessed the time, effort, perceived efficacy and overall acceptability of the paper-based and electronic methods of AE documentation. RESULTS: Seventy-one staff members were surveyed. Fifty (65%) responded, including 6 participants who were not involved in the AE reporting process and did not complete the survey. Of the remaining 44 participants, 43 (98%) preferred an electronic documentation method. Secondary results and further analysis will be presented at the meeting. CONCLUSIONS: The COVID pandemic has changed how CRC report AEs and electronic documentation seems to be the preferred method of documentation.

10.
Transportation Research Part a-Policy and Practice ; 161:48-67, 2022.
Article in English | Web of Science | ID: covidwho-1886103

ABSTRACT

Paratransit plays an important role in offering mobility and accessibility in local communities, especially for mobility disadvantaged group such as seniors, persons with disabilities, and persons with medical conditions. This study comprehensively evaluates the impacts of COVID-19 on paratransit services from paratransit operator and individual rider perspectives. In particular, we mine a paratransit dataset that covers trip logs of more than 800 unique riders over a seven month period in order to understand how the pandemic impacted service and influenced trip purposes of individual riders. For service providers, our analyses show that a significant loss in paratransit ridership was accompanied by drastic changes in travel behavior among paratransit riders. Results indicate that the operator was able to deliver safe and efficient mobility services during COVID-19, but at a 60% higher cost per rider than under pre-pandemic conditions. The results also reveal a varying level of impacts for individual riders given heterogeneity among trip purposes and demographic profiles. Moreover, similarities are identified across a range of individual riders, depending on specific trip purposes and the availability of alternative travel options. This study is among the first to investigate paratransit operations during COVID-19 in terms of impacts to both operators and individual riders. The lessons learned and policy insights should be useful to other paratransit operators and policymakers in preparing for current and future pandemics.

11.
Neuropathology and Applied Neurobiology ; 48(SUPPL 1), 2022.
Article in English | EMBASE | ID: covidwho-1868681

ABSTRACT

Aims: Activation of microglial cells represents the most common neu-ropathological change in fatal cases of COVID-19 with particular prominence in the brainstem. However, detailed assessments are lacking. Here, we assessed reactive microglia in COVID-19 tissue and tested for disease-specific activation patterns. Methods: We used an early-(Iba1) and a late-stage (CD68) immuno-histochemistry marker for microglial activation in human post-mortem brainstem and frontal lobe tissues in eight fatal COVID-19 cases, seven septic controls and six non-septic controls. We quantified the level of microglial activation employing a Qu-Path-based automated approach. Using a mixed three-way ANOVA, we tested for effects and interactions of brain region, microglial marker and group. Results: Reactive microglia were detected in all cases across brain regions and antibodies. However, COVID-19 brains exhibited significantly higher levels of microglial activation than septic and control brains, especially of late-stage microglia (CD68+). Irrespective of disease, microglia activation was significantly more pronounced and further progressed (CD68+) in brainstem tissues, particularly the medulla, than in the frontal lobe. Whilst survival time from admission marginally significantly correlated with the level of reactive microglia in COVID-19, no associations were found between neuroinflammation and either gender or age at death. Conclusions: Whilst the brainstem demonstrates a disease-independent high susceptibility to inflammation, microglial activation in COVID-19 (COVID-19 microglia encephalopathy) is specific and of importance for understanding the involvement of the CNS in this disease.

12.
Rheumatology (United Kingdom) ; 61(SUPPL 1):i157, 2022.
Article in English | EMBASE | ID: covidwho-1868426

ABSTRACT

Background/Aims For some time, there has been an importance placed in rheumatology on promoting and supporting patient self-management. Self-management aims to improve patients' independence and quality of life by empowering individuals to be proactive decision makers while managing their illness. Self-management support (SMS) as detailed in the Practical RevIews in Self-Management Support (PRISMS) taxonomy can include education, monitoring, adherence, training, and support with healthcare practitioner (HCP) interaction. In rheumatic and musculoskeletal diseases (RMDs), interventions for SMS are complex, and have been described by the European League Against Rheumatism (EULAR) as a current unmet need. In response to the COVID-19 pandemic, telerehabilitation has been successfully used at the Royal National Hospital for Rheumatic Diseases in Bath to provide continued SMS to axial spondyloarthritis (axial SpA) patients. Although some research into SMS of inflammatory arthritis has been conducted, there appears to be a scarcity of research on SMS interventions provided through telerehabilitation for axial SpA. The present scoping review aims to systematically identify and describe existing SMS interventions delivered via telehealth for RMDs, and how effectiveness is evaluated within these interventions. Methods The method for a scoping review protocol will be outlined using the JBI manual for evidence synthesis guidance. It is anticipated that there will be a lack of interventions for axial SpA, therefore the broader population of RMDs will be included. Three electronic databases will be searched (Embase, Scopus and Web of Science Core Collection), as well as the reference lists of included full-text studies. A study team of three researchers will apply a priori eligibility criteria, based on the Population (RMDs), Concept (rehabilitation) and Context (telehealth) components of the research focus, to the screening and fulltext screening. Results Data will be extracted into a charting table for relevant full-text articles to allow a narrative synthesis of identified SMS telerehabilitation interventions. We will explore SMS definitions used, aspects of rehabilitation targeted (e.g. education, disease management, psychological support, physical activity, physiotherapy, occupational health input, behaviour change techniques), details on the SMS intervention (e.g. autonomous/group-based, mode of telerehabilitation delivery, length of intervention, synchronous/asynchronous interaction), components of SMS included (PRISMS taxonomy), HCP interaction details, and measures of effectiveness. Conclusion Telehealth, and specifically telerehabilitation, have become a critical feature of healthcare over the last 18 months and may provide an effective long-term solution to broaden provision of SMS for RMDs and improve symptoms, while relieving pressure on healthcare systems. Through this scoping review, existing telehealth delivered SMS interventions for RMDs will be identified, which will help to understand how interventions are currently delivered and effectiveness evaluated in rheumatology. A greater understanding of existing interventions will be critical as we move into the new post-COVID-19 age of blended in-person/ virtual service provision.

13.
Wellcome Open Research ; 6:220, 2021.
Article in English | MEDLINE | ID: covidwho-1863328

ABSTRACT

Background: We aimed to measure SARS-CoV-2 seroprevalence in a cohort of healthcare workers (HCWs) during the first UK wave of the COVID-19 pandemic, explore risk factors associated with infection, and investigate the impact of antibody titres on assay sensitivity.

14.
WHO Drug Information ; 35(3):638-661, 2021.
Article in English | EMBASE | ID: covidwho-1857076

ABSTRACT

Background In view of the need for the development of health products, including the research and development for the treatment of COVID-19 therapies, the World Health Organization (WHO) Prequalification Inspection Services Team (PQT INS) raised the urgency for the development of life cycle appropriate good practices text to address the manufacturing of developmental  batches, pilot batches and the sequential stability data that are submitted in product applications (dossiers) for marketing authorization and the prequalification of medical products.

15.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-336833

ABSTRACT

ABSTRACT HostSeq was launched in April 2020 as a national initiative to integrate whole genome sequencing data from 10,000 Canadians infected with SARS-CoV-2 with clinical information related to their disease experience. The mandate of HostSeq is to support the Canadian and international research communities in their efforts to understand the risk factors for disease and associated health outcomes and support the development of interventions such as vaccines and therapeutics. HostSeq is a collaboration among 13 independent epidemiological studies of SARS-CoV-2 across five provinces in Canada. Aggregated data collected by HostSeq are made available to the public through two data portals: a phenotype portal showing summaries of major variables and their distributions, and a variant search portal enabling queries in a genomic region. Individual-level data is available to the global research community through a Data Access Agreement and Data Access Compliance Office approval. Here we provide an overview of the collective project design along with summary level information for HostSeq. We highlight several statistical considerations for researchers using the HostSeq platform regarding data aggregation, sampling mechanism, covariate adjustment, and X chromosome analysis. In addition to serving as a rich data source, the diversity of study designs, sample sizes, and research objectives among the participating studies provides unique opportunities for the research community.

16.
Embase; 2022.
Preprint in English | EMBASE | ID: ppcovidwho-336645

ABSTRACT

Viruses are microscopic pathogens capable of causing disease and are responsible for a range of human mortality and morbidity worldwide. They can be rendered harmless or destroyed with a range of antiviral chemical compounds. Cucurbit[n]urils (CB[n]s) are a macrocycle chemical compound existing as a range of homologues;due to their structure they can bind to biological materials, acting as supramolecular “hosts” to “guests”, such as amino acids. Due to the increasing need for a non-toxic antiviral compound, we investigated whether cucurbit[n]urils could act in an antiviral manner. We have found that certain cucurbit[n]uril homologues do indeed have an antiviral effect against a range of viruses, including RSV and SARS-CoV-2. In particular, we demonstrate that CB[7] is the active homologue of CB[n] mixtures, having an antiviral effect against enveloped and non-enveloped species. High levels of efficacy were observed with five-minute contact times across different viruses. We also demonstrate that CB[7] acts with an extracellular virucidal mode of action via host-guest supramolecular interactions between viral surface proteins and the CB[n] cavity, rather than via cell internalisation or a virustatic mechanism. This finding demonstrates that CB[7] acts as a supramolecular virucidal antiviral (a mechanism distinct from other current extracellular antivirals) demonstrating the potential of supramolecular interactions for future antiviral disinfectants.

17.
Embase; 2022.
Preprint in English | EMBASE | ID: ppcovidwho-335852

ABSTRACT

Viruses are microscopic pathogens capable of causing disease and are responsible for a range of human mortality and morbidity worldwide. They can be rendered harmless or destroyed with a range of antiviral chemical compounds. Cucurbit[n]urils (CB[n]s) are a macrocycle chemical compound existing as a range of homologues;due to their structure they can bind to biological materials, acting as supramolecular “hosts” to “guests”, such as amino acids. Due to the increasing need for a non-toxic antiviral compound, we investigated whether cucurbit[n]urils could act in an antiviral manner. We have found that certain cucurbit[n]uril homologues do indeed have an antiviral effect against a range of viruses, including RSV and SARS-CoV-2. In particular, we demonstrate that CB[7] is the active homologue of CB[n] mixtures, having an antiviral effect against enveloped and non-enveloped species. High levels of efficacy were observed with five-minute contact times across different viruses. We also demonstrate that CB[7] acts with an extracellular virucidal mode of action via host-guest supramolecular interactions between viral surface proteins and the CB[n] cavity, rather than via cell internalisation or a virustatic mechanism. This finding demonstrates that CB[7] acts as a supramolecular virucidal antiviral (a mechanism distinct from other current extracellular antivirals) demonstrating the potential of supramolecular interactions for future antiviral disinfectants.

18.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-333830

ABSTRACT

BACKGROUND: We aimed to measure SARS-CoV-2 seroprevalence in a cohort of healthcare workers (HCWs) during the first UK wave of the COVID-19 pandemic, explore risk factors associated with infection, and investigate the impact of antibody titres on assay sensitivity. METHODS: HCWs at Sheffield Teaching Hospitals NHS Foundation Trust (STH) were prospectively enrolled and sampled at two time points. SARS-CoV-2 antibodies were tested using an in-house assay for IgG and IgA reactivity against Spike and Nucleoprotein (sensitivity 99.47%, specificity 99.56%). Data were analysed using three statistical models: a seroprevalence model, an antibody kinetics model, and a heterogeneous sensitivity model. FINDINGS: As of 12th June 2020, 24.4% (n=311/1275) HCWs were seropositive. Of these, 39.2% (n=122/311) were asymptomatic. The highest adjusted seroprevalence was measured in HCWs on the Acute Medical Unit (41.1%, 95% CrI 30.0-52.9) and in Physiotherapists and Occupational Therapists (39.2%, 95% CrI 24.4-56.5). Older age groups showed overall higher median antibody titres. Further modelling suggests that, for a serological assay with an overall sensitivity of 80%, antibody titres may be markedly affected by differences in age, with sensitivity estimates of 89% in those over 60 years but 61% in those <=30 years. INTERPRETATION: HCWs in acute medical units working closely with COVID-19 patients were at highest risk of infection, though whether these are infections acquired from patients or other staff is unknown. Current serological assays may underestimate seroprevalence in younger age groups if validated using sera from older and/or more symptomatic individuals. RESEARCH IN CONTEXT: Evidence before this study: We searched PubMed for studies published up to March 6th 2021, using the terms "COVID", "SARS-CoV-2", "seroprevalence", and "healthcare workers", and in addition for articles of antibody titres in different age groups against coronaviruses using "coronavirus", "SARS-CoV-2, "antibody", "antibody tires", "COVID" and "age". We included studies that used serology to estimate prevalence in healthcare workers. SARS-CoV-2 seroprevalence has been shown to be greater in healthcare workers working on acute medical units or within domestic services. Antibody levels against seasonal coronaviruses, SARS-CoV and SARS-CoV-2 were found to be higher in older adults, and patients who were hospitalised. Added value of this study: In this healthcare worker seroprevalence modelling study at a large NHS foundation trust, we confirm that those working on acute medical units, COVID-19 "Red Zones" and within domestic services are most likely to be seropositive. Furthermore, we show that physiotherapists and occupational therapists have an increased risk of COVID-19 infection. We also confirm that antibody titres are greater in older individuals, even in the context of non-hospitalised cases. Importantly, we demonstrate that this can result in age-specific sensitivity in serological assays, where lower antibody titres in younger individuals results in lower assay sensitivity. Implications of all the available evidence: There are distinct occupational roles and locations in hospitals where the risk of COVID-19 infection to healthcare workers is greatest, and this knowledge should be used to prioritise infection prevention control and other measures to protect healthcare workers. Serological assays may have different sensitivity profiles across different age groups, especially if assay validation was undertaken using samples from older and/or hospitalised patients, who tend to have higher antibody titres. Future seroprevalence studies should consider adjusting for age-specific assay sensitivities to estimate true seroprevalence rates. Author contributions:

19.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-333738

ABSTRACT

Close contact between people is the primary route for transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). We sought to quantify interpersonal contact at the population-level by using anonymized mobile device geolocation data. We computed the frequency of contact (within six feet) between people in Connecticut during February 2020 - January 2021. Then we aggregated counts of contact events by area of residence to obtain an estimate of the total intensity of interpersonal contact experienced by residents of each town for each day. When incorporated into a susceptible-exposed-infective-removed (SEIR) model of COVID-19 transmission, the contact rate accurately predicted COVID-19 cases in Connecticut towns during the timespan. The pattern of contact rate in Connecticut explains the large initial wave of infections during March-April, the subsequent drop in cases during June-August, local outbreaks during August-September, broad statewide resurgence during September-December, and decline in January 2021. Contact rate data can help guide public health messaging campaigns to encourage social distancing and in the allocation of testing resources to detect or prevent emerging local outbreaks more quickly than traditional case investigation. ONE SENTENCE SUMMARY: Close interpersonal contact measured using mobile device location data explains dynamics of COVID-19 transmission in Connecticut during the first year of the pandemic.

20.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-333691

ABSTRACT

There is an urgent need to understand the nature of immune responses generated against SARS-CoV-2, to better inform risk-mitigation strategies for people living with HIV (PLWH). Although not all PLWH are considered immunosuppressed, residual cellular immune deficiency and ongoing inflammation could influence COVID-19 disease severity, the evolution and durability of protective memory responses. Here, we performed an integrated analysis, characterizing the nature, breadth and magnitude of SARS-CoV-2-specific immune responses in PLWH, controlled on ART, and HIV negative subjects. Both groups were in the convalescent phase of predominately mild COVID-19 disease. The majority of PLWH mounted SARS-CoV-2 Spike- and Nucleoprotein-specific antibodies with neutralizing activity and SARS-CoV-2-specific T cell responses, as measured by ELISpot, at levels comparable to HIV negative subjects. T cell responses against Spike, Membrane and Nucleocapsid were the most prominent, with SARS-CoV-2-specific CD4 T cells outnumbering CD8 T cells. Notably, the overall magnitude of SARS-CoV-2-specific T cell responses related to the size of the naive CD4 T cell pool and the CD4:CD8 ratio in PLWH, in whom disparate antibody and T cell responses were observed. Both humoral and cellular responses to SARS-CoV-2 were detected at 5-7 months post-infection, providing evidence of medium-term durability of responses irrespective of HIV serostatus. Incomplete immune reconstitution on ART and a low CD4:CD8 ratio could, however, hamper the development of immunity to SARS-CoV-2 and serve as a useful tool for risk stratification of PLWH. These findings have implications for the individual management and potential effectiveness of vaccination against SARS-CoV-2 in PLWH. ONE SENTENCE SUMMARY: Adaptive immune responses to SARS-CoV-2 in the setting of HIV infection.

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