Broadly neutralizing antibodies against emerging delta-coronaviruses (preprint)

Porcine deltacoronavirus (PDCoV) spillovers were recently detected in children with acute undifferentiated febrile illness, underscoring recurrent zoonoses of divergent coronaviruses. To date, no vaccines or specific therapeutics are approved for use in humans against PDCoV. To prepare for possible future PDCoV epidemics, we isolated human spike (S)-directed monoclonal antibodies from transgenic mice and found that two of them, designated PD33 and PD41, broadly neutralized a panel of PDCoV variants. Cryo-electron microscopy structures of PD33 and PD41 in complex with the PDCoV receptor-binding domain and S ectodomain trimer provide a blueprint of the epitopes recognized by these mAbs, rationalizing their broad inhibitory activity. We show that both mAbs inhibit PDCoV by competitively interfering with host APN binding to the PDCoV receptor-binding loops, explaining the mechanism of viral neutralization. PD33 and PD41 are candidates for clinical advancement, which could be stockpiled to prepare for possible future PDCoV outbreaks.

Linitis plastica of the rectum secondary to prostate carcinoma.

Linitis plastica is an intramural carcinoma that may occur in any hollow organ. Rectal linitis plastica (RLP) is a morphological variant cancer that may occur as a primary form of cancer or secondary as a metastasis of a primary malignancy. We report the case of a man in his 70s with RLP secondary to prostate carcinoma who was initially suspected to have an obstructing rectal adenocarcinoma. During colonoscopy a segment of cobblestone mucosa was seen in the distal rectum. Subsequent imaging showed enhancement of all wall-layers of the rectum and diffuse retroperitoneal fat infiltration with traction on both ureters. A prostate-specific membrane antigen scan confirmed RLP secondary to a prostate carcinoma mimicking the clinical and radiological signs of an obstructing rectal carcinoma with retroperitoneal fibrosis.This case emphasises the possible pitfalls in the diagnosis of RLP and the importance of advanced imaging techniques, such as MRI, as well as appropriate histological samples. The patient underwent androgen deprivation therapy to which RLP responded well and neither systemic chemotherapy or surgery was necessary.

Radical abdomino-pelvic surgery in the management of uterine carcinosarcoma with concomitant para-aortic lymphadenopathy metastasising from anal carcinoma.

Uterine carcinosarcomas are aggressive gynaecological cancers comprising less than 5% of uterine malignancies. We present the case of a woman in her 70s with a complicated history of advanced anal carcinoma treated with pelvic radiotherapy and multiple laparotomies, who was referred to gynae-oncology following MRI surveillance imaging showing evidence of endometrial carcinoma and para-aortic lymphadenopathy. Successful surgical excision required multidisciplinary teamwork between gynae-oncology, colorectal and urology surgeons. The patient underwent midline laparotomy, with adhesiolysis, ileum resection and side to side anastomosis, posterior exenteration, left kidney mobilisation and suspension, para-aortic lymph node debulking and left ureteric stent insertion. Significant challenge was posed by the extensive adhesions from previous laparotomies and the debulking of the para-aortic lymph nodes around the renal vessels. This case demonstrates the importance of a multidisciplinary approach in complex pelvic surgery and the vitality of good communication between colleagues in achieving effective patient care.

Targeting Underlying Inflammation in Carcinoma Is Essential for the Resolution of Depressiveness.

In modern clinical practice and research on behavioral changes in patients with oncological problems, there are several one-sided approaches to these problems. Strategies for early detection of behavioral changes are considered, but they must take into account the specifics of the localization and phase in the course and treatment of somatic oncological disease. Behavioral changes, in particular, may correlate with systemic proinflammatory changes. In the up-to-date literature, there are a lot of useful pointers on the relationship between carcinoma and inflammation and between depression and inflammation. This review is intended to provide an overview of these similar underlying inflammatory disturbances in both oncological disease and depression. The specificities of acute and chronic inflammation are considered as a basis for causal current and future therapies. Modern therapeutic oncology protocols may also cause transient behavioral changes, so assessment of the quality, quantity, and duration of behavioral symptoms is necessary to prescribe adequate therapy. Conversely, antidepressant properties could be used to ameliorate inflammation. We will attempt to provide some impetus and present some unconventional potential treatment targets related to inflammation. It is certain that only an integrative oncology approach is justifiable in modern patient treatment.

Impact of the SARS-CoV-2 pandemic on the diagnostic delay of oral carcinoma: a retrospective analysis.

BACKGROUND: The aim of the present study was to investigate how the organisation of healthcare activity during the first wave of the SARS-CoV-2 pandemic affected the timing of diagnosis of oral carcinoma in the Functional Head and Neck Department of Padua (Italy). This study gives an effective temporal dimension of the diagnostic delay that occurred during the pandemic, compared with data from the literature. METHODS: A retrospective analysis of the diagnostic path of a patient affected by oral cancer during COVID-19 pandemic was performed. The time elapsed from the patient's awareness of the problem to the first curative surgical intervention was considered both during the blockage of elective care activities and in the period immediately following. The results were compared to a group of patients treated in the same period of the year 2019. RESULTS: The territorial time was 53.9% longer in the post-lockdown period than in the lockdown period (39.6 days) while the hospital time was 56.6% shorter than in the post-lockdown period (56 days). CONCLUSIONS: The response time of territorial medicine has been longer during the pandemic peak. The unintentional creation of exclusive pathways for oncological patients speeded up the diagnostic process. The organization and accessibility of operating theatres can become particularly problematic during the acute phases of a pandemic.

The intersection of biological sex and gender in adverse events following seasonal influenza vaccination in older adults (preprint)

Background Women/females report more adverse events (AE) following immunization than men/males for many vaccines, including the influenza and COVID-19 vaccines. This discrepancy is often dismissed as a reporting bias, yet the relative contributions of biological sex and gender are poorly understood. We investigated the roles of sex and gender in the rate of AE following administration of the high-dose seasonal influenza vaccine to older adults (≥ 75 years) using an AE questionnaire administered 5–8 days post-vaccination. Participant sex (male or female) was determined by self-report and a gender score questionnaire was used to assign participants to one of four gender categories (feminine, masculine, androgynous, or undifferentiated). Sex steroid hormones and inflammatory cytokines were measured in plasma samples collected prior to vaccination to elucidate a possible biological mechanism for the AE reported.Results A total of 423 vaccines were administered to 173 participants over four influenza seasons (2019-22) and gender data were available for 339 of these vaccinations (2020-22). At least one AE was reported following 105 vaccinations (25%), by 23 males and 82 females. The majority of AE occurred at the site of injection, were mild, and transient. The odds of experiencing an AE were 3-fold greater in females than males and decreased with age to a greater extent in females than males. The effects of gender, however, were not statistically significant, supporting a central role of biological sex in the occurrence of AE. In males, estradiol was significantly associated with IL-6 and with the probability of experiencing an AE. Both associations were absent in females, suggesting a sex-specific effect of estradiol on the occurrence of AE that supports the finding of a biological sex difference.Conclusions These data support a larger role for biological sex than for gender in the occurrence of AE following influenza vaccination in older adults and provide an initial investigation of hormonal mechanisms that may mediate this sex difference. This study highlights the complexities of measuring gender and the importance of assessing AE separately for males and females to better understand how vaccination strategies can be tailored to different subsets of the population.

Bone metastatic carcinoma coexisting with plasma cell myeloma: a case report.

OBJECTIVE: Multiple myeloma is a clonal plasma cell proliferation often causing bone lytic lesions. It is sometimes challenging to differentiate these lytic lesions associated with multiple myeloma from bone destruction due to a metastasis. Although coexistence of solid tumors and plasma cell myeloma in one patient has been described, synchronous skeletal metastases from both neoplasms occurring in the same bone lesion is exceptional. Indeed, only one case has been reported in the literature. CASE PRESENTATION: Herein, we report a case involving a 68-year-old Caucasian male patient admitted to our department for coronavirus disease 2019 infection with incidental finding of multiple lytic bone lesions during hospitalization. Laboratory tests revealed an increased immunoglobulin G kappa M protein and high levels of carbohydrate antigen 19-9. Bone marrow aspiration showed increased atypical plasma cells consistent with multiple myeloma. Percutaneous image-guided biopsy of one of the osteolytic lesions was performed. Pathological examination identified both plasma cell neoplasm and poorly differentiated metastatic carcinoma within the same bone lytic lesions. CONCLUSION: The present case raises awareness among clinicians and pathologists that clinical and radiologic suspicion of multiple myeloma may be within the spectrum of second primary malignancies.

Integrated SARS-CoV-2 serological and virological screening across an acute fever surveillance platform to monitor temporal changes in anti-spike antibody levels and risk of infection during sequential waves of variant transmission - Dominican Republic, March 2021 to August 2022 (preprint)

We monitored SARS-CoV-2 antibody changes following implementation of a national COVID-19 vaccination campaign and assessed implications for immunological protection against variants of concern. Between March 2021 and August 2022, we prospectively enrolled 2,300 patients seeking care for undifferentiated febrile illnesses across two study sites in the Dominican Republic. Sera was tested for total anti-spike antibodies (anti-S) and simultaneously collected nasopharyngeal samples by RT-PCR for acute SARS-CoV-2 infection. Geometric mean anti-S titers increased from 6.6 BAU/ml (95% CI 5.1-8.7) to 1,332 BAU/ml (CI 1055-1,682) during the study period. Multivariable binomial odds ratios for acute SARS-CoV-2 infection were 0.55 (0.40-0.74), 0.38 (0.27-0.55), and 0.27 (0.18-0.40) for the second, third, and fourth versus the first anti-S quartile, with similar findings by viral strain. Integrated serological and virological screening present an opportunity to rethink existing surveillance platforms by simultaneously monitoring population-level immunological markers and implications for emerging variant transmission.

In vitro evidence against productive SARS-CoV-2 infection of human testicular cells: Bystander effects of infection mediate testicular injury. (preprint)

The hallmark of severe COVID-19 involves systemic cytokine storm and multi-organ failure including testicular injury and germ cell depletion. The ACE2 receptor is also expressed in the resident testicular cells however, SARS-CoV-2 infection and mechanisms of testicular injury are not fully understood. The testicular injury can likely result either from direct virus infection of resident cells or by exposure to systemic inflammatory mediators or virus antigens. We here characterized SARS-CoV-2 infection in different human testicular 2D and 3D models including primary Sertoli cells, Leydig cells, mixed seminiferous tubule cells (STC), and 3D human testicular organoids (HTO). Data shows that SARS-CoV-2 does not establish a productive infection in any testicular cell types. However, exposure of STC and HTO to inflammatory supernatant from infected airway epithelial cells and COVID-19 plasma depicted a significant decrease in cell viability and death of undifferentiated spermatogonia. Further, exposure to only SARS-CoV-2 envelope protein, but not Spike or nucleocapsid proteins led to cytopathic effects on testicular cells that was dependent on the TLR2 receptor. A similar trend was observed in the K18h-ACE2 mouse model which revealed gross pathology in the absence of virus replication in the testis. Collectively, data strongly indicates that the testicular injury is not due to direct infection of SARS-CoV-2 but more likely an indirect effect of exposure to systemic inflammation or SARS-CoV-2 antigens. Data also provide novel insights into the mechanism of testicular injury and could explain the clinical manifestation of testicular symptoms associated with severe COVID-19.

Application of meso-CF3-Fluorophore BODIPY with Phenyl and Pyrazolyl Substituents for Lifetime Visualization of Lysosomes.

A bright far-red emitting unsymmetrical meso-CF3-BODIPY fluorescent dye with phenyl and pyrazolyl substituents was synthesized by condensation of trifluoropyrrolylethanol with pyrazolyl-pyrrole, with subsequent oxidation and complexation of the formed dipyrromethane. This BODIPY dye exhibits optical absorption at λab ≈ 610-620 nm and emission at λem ≈ 640-650 nm. The BODIPY was studied on Ehrlich carcinoma cells as a lysosome-specific fluorescent dye that allows intravital staining of cell structures with subsequent real-time monitoring of changes occurring in the cells. It was also shown that the rate of uptake by cells, the rate of intracellular transport into lysosomes, and the rate of saturation of cells with the dye depend on its concentration in the culture medium. A concentration of 5 µM was chosen as the most suitable BODIPY concentration for fluorescent staining of living cell lysosomes, while a concentration of 100 µM was found to be toxic to Ehrlich carcinoma cells.

Incidence and management of inflammatory arthritis in England before and during the COVID-19 pandemic: a population-level cohort study using OpenSAFELY (preprint)

ObjectiveTo use the OpenSAFELY platform to replicate key metrics from a national clinical audit, and assess the impact of COVID-19 on disease incidence and care delivery for inflammatory arthritis (IA) in England. DesignPopulation-based cohort study, with the approval of NHS England. SettingPrimary care and linked hospital outpatient data for more than 17 million people registered with general practices in England that use TPP electronic health record software. ParticipantsAdults (18-110 years) with new diagnoses of IA (rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, undifferentiated IA) between 1 April 2019 and 31 March 2022. Main outcome measuresThe following outcomes were explored before and after April 2020: 1) incidence of IA diagnoses; 2) time from primary care referral to first rheumatology assessment; 3) time to first prescription of a disease-modifying anti-rheumatic drug (DMARD) in primary care. ResultsFrom a reference population of 17,683,500 adults, there were 31,280 incident IA diagnoses between April 2019 and March 2022. The incidence of IA decreased by 20.3% in the year commencing April 2020, relative to the preceding year (5.1 vs. 6.4 diagnoses per 10,000 adults, respectively). For those who presented with IA, the time to first rheumatology assessment was shorter during the pandemic (median 18 days; interquartile range 8 to 35 days) than before (21 days; 9 to 41 days). Overall, the proportion of patients prescribed DMARDs in primary care was comparable during the pandemic to before; however, the choice of medication changed, with fewer people prescribed methotrexate or leflunomide during the pandemic, and more people prescribed sulfasalazine or hydroxychloroquine. ConclusionsThe incidence of IA diagnoses in England decreased markedly during the early COVID-19 pandemic. However, for people who sought medical attention, the impact of the pandemic on service delivery was less marked than might have been anticipated. This study demonstrates that it is feasible to use routinely captured, near real-time data in the secure OpenSAFELY platform to benchmark care quality for long-term conditions on a national scale, without the need for manual data collection.

Colonoscopic-Assisted Laparoscopic Wedge Resection for Colonic Lesions: A Prospective Multicenter Cohort Study (LIMERIC-Study).

OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of a modified CAL-WR. SUMMARY BACKGROUND DATA: The use of segmental colectomy in patients with endoscopically unresectable colonic lesions results in significant morbidity and mortality. CAL-WR is an alternative procedure that may reduce morbidity. METHODS: This prospective multicenter study was performed in 13 Dutch hospitals between January 2017 and December 2019. Inclusion criteria were (1) colonic lesions inaccessible using current endoscopic resection techniques (judged by an expert panel), (2) non-lifting residual/recurrent adenomatous tissue after previous polypectomy or (3) an undetermined resection margin after endoscopic removal of a low-risk pathological T1 (pT1) colon carcinoma. Thirty-day morbidity, technical success rate and radicality were evaluated. RESULTS: Of the 118 patients included (56% male, mean age 66 years, standard deviation ± 8 years), 66 (56%) had complex lesions unsuitable for endoscopic removal, 34 (29%) had non-lifting residual/recurrent adenoma after previous polypectomy and 18 (15%) had uncertain resection margins after polypectomy of a pT1 colon carcinoma. CAL-WR was technically successful in 93% and R0 resection was achieved in 91% of patients. Minor complications (Clavien-Dindo i-ii) were noted in 7 patients (6%) and an additional oncologic segmental resection was performed in 12 cases (11%). Residual tissue at the scar was observed in 5% of patients during endoscopic follow-up. CONCLUSIONS: CAL-WR is an effective, organ-preserving approach that results in minor complications and circumvents the need for major surgery. CAL-WR, therefore, deserves consideration when endoscopic excision of circumscribed lesions is impossible or incomplete.

Uterine cervix metastasis from primary colon adenocarcinoma: a case report and review of the literature.

INTRODUCTION: Metastases to the female genital tract from extragenital primary tumors are unusual. We report a rare case of uterine cervix metastasis from colon adenocarcinoma and discuss diagnostic and therapeutic issues. CASE REPORT: We report a case of a 38-year-old North African Caucasian woman treated for a non-metastatic colon adenocarcinoma. She had a sigmoidectomy and incomplete adjuvant chemotherapy. Six months later, she consulted with vaginal bleeding caused by a cervical tumor, which was confirmed to be metastatic disease, and the patient underwent decompressive and hemostatic radiotherapy. CONCLUSION: Uterine cervix metastasis from primary colon adenocarcinoma is rare. The resection remains the standard protocol for the local treatment of resectable metastatic disease. Otherwise, systemic therapy is the preferable option.

Replication kinetics and infectivity of SARS-CoV-2 variants of concern in common cell culture models.

BACKGROUND: During the ongoing Covid-19 pandemic caused by the emerging virus SARS-CoV-2, research in the field of coronaviruses has expanded tremendously. The genome of SARS-CoV-2 has rapidly acquired numerous mutations, giving rise to several Variants of Concern (VOCs) with altered epidemiological, immunological, and pathogenic properties. METHODS: As cell culture models are important tools to study viruses, we investigated replication kinetics and infectivity of SARS-CoV-2 in the African Green Monkey-derived Vero E6 kidney cell line and the two human cell lines Caco-2, a colon epithelial carcinoma cell line, and the airway epithelial carcinoma cell line Calu-3. We assessed viral RNA copy numbers and infectivity of viral particles in cell culture supernatants at different time points ranging from 2 to 96 h post-infection. RESULTS: We here describe a systematic comparison of growth kinetics of the five SARS-CoV-2 VOCs Alpha/B.1.1.7, Beta/B.1.351, Gamma/P.1, Delta/B.1.617.2, and Omicron/B.1.1.529 and a non-VOC/B.1.1 strain on three different cell lines to provide profound information on the differential behaviour of VOCs in different cell lines for researchers worldwide. We show distinct differences in viral replication kinetics of the SARS-CoV-2 non-VOC and five VOCs on the three cell culture models Vero E6, Caco-2, and Calu-3. CONCLUSION: This is the first systematic comparison of all SARS-CoV-2 VOCs on three different cell culture models. This data provides support for researchers worldwide in their experimental design for work on SARS-CoV-2. It is recommended to perform virus isolation and propagation on Vero E6 while infection studies or drug screening and antibody-based assays should rather be conducted on the human cell lines Caco-2 and Calu-3.

Technical aspects of the use of cytopathological specimens for diagnosis and predictive testing in malignant epithelial neoplasms of the lung.

Lung cancer is a leading cause of cancer mortality worldwide but recent years have seen a rapidly rising proportion of cases of advanced non-small cell carcinoma amenable to increasingly targeted therapy, initially based on the differential response to systemic treatment of tumours of squamous or glandular differentiation. In two-thirds of the cases, where patients present with advanced disease, both primary pathological diagnosis and biomarker testing is based on small biopsies and cytopathological specimens. The framework of this article is an overview of the technical aspect of each stage of the specimen pathway with emphasis on maximising potential for success when using small cytology samples. It brings together the current literature addressing pre-analytical and analytical aspects of specimen acquisition, performing rapid onsite evaluation, and undertaking diagnostic and predictive testing using immunocytochemistry and molecular platforms. The advantages and drawbacks of performing analysis on cell block and non-cell block specimen preparations is discussed.

Frequency and outcomes of MRI-detected axillary adenopathy following COVID-19 vaccination.

OBJECTIVES: To assess the frequency of ipsilateral axillary adenopathy on breast MRI after COVID-19 vaccination. To investigate the duration, outcomes, and associated variables of vaccine-related adenopathy. METHODS: In this retrospective cohort study, our database was queried for patients who underwent breast MRI following COVID-19 vaccination from January 22, 2021, to March 21, 2021. The frequency of ipsilateral axillary adenopathy and possible associated variables were evaluated, including age, personal history of ipsilateral breast cancer, clinical indication for breast MRI, type of vaccine, side of vaccination, number of doses, and number of days between the vaccine and the MRI exam. The outcomes of the adenopathy were investigated, including the duration of adenopathy and biopsy results. RESULTS: A total of 357 patients were included. The frequency of adenopathy on breast MRI was 29% (104/357 patients). Younger patients and shorter time intervals from the second dose of the vaccine were significantly associated with the development of adenopathy (p = 0.002 for both). Most adenopathy resolved or decreased on follow-up, with 11% of patients presenting persistence of adenopathy up to 64 days after the second dose of the vaccine. Metastatic axillary carcinoma was diagnosed in three patients; all three had a current ipsilateral breast cancer diagnosis. CONCLUSIONS: Vaccine-related adenopathy is a frequent event after COVID-19 vaccination; short-term follow-up is an appropriate clinical approach, except in patients with current ipsilateral breast cancer. Adenopathy may often persist 4-8 weeks after the second dose of the vaccine, thus favoring longer follow-up periods. KEY POINTS: • MRI-detected ipsilateral axillary adenopathy is a frequent benign finding after mRNA COVID-19 vaccination. • Axillary adenopathy following COVID-19 vaccination often persists > 4 weeks after vaccination, favoring longer follow-up periods. • In patients with concurrent ipsilateral breast cancer, axillary adenopathy can represent metastatic carcinoma and follow-up is not appropriate.

COVID-19 outcomes of patients with gynecologic cancer in New York City: An updated analysis from the initial surge of the pandemic.

BACKGROUND: Despite significant increase in COVID-19 publications, characterization of COVID-19 infection in patients with gynecologic cancer remains limited. Here we present an update of COVID-19 outcomes among people with gynecologic cancer in New York City (NYC) during the initial surge of severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]). METHODS: Data were abstracted from gynecologic oncology patients with COVID-19 infection among 8 NYC area hospital systems between March and June 2020. Multivariable logistic regression was utilized to estimate associations between factors and COVID-19 related hospitalization and mortality. RESULTS: Of 193 patients with gynecologic cancer and COVID-19, the median age at diagnosis was 65.0 years (interquartile range (IQR), 53.0-73.0 years). One hundred six of the 193 patients (54.9%) required hospitalization; among the hospitalized patients, 13 (12.3%) required invasive mechanical ventilation, 39 (36.8%) required ICU admission. Half of the cohort (49.2%) had not received anti-cancer treatment prior to COVID-19 diagnosis. No patients requiring mechanical ventilation survived. Thirty-four of 193 (17.6%) patients died of COVID-19 complications. In multivariable analysis, hospitalization was associated with an age ≥ 65 years (odds ratio [OR] 2.12, 95% confidence interval [CI] 1.11, 4.07), Black race (OR 2.53, CI 1.24, 5.32), performance status ≥2 (OR 3.67, CI 1.25, 13.55) and ≥ 3 comorbidities (OR 2.00, CI 1.05, 3.84). Only former or current history of smoking (OR 2.75, CI 1.21, 6.22) was associated with death due to COVID-19 in multivariable analysis. Administration of cytotoxic chemotherapy within 90 days of COVID-19 diagnosis was not predictive of COVID-19 hospitalization (OR 0.83, CI 0.41, 1.68) or mortality (OR 1.56, CI 0.67, 3.53). CONCLUSIONS: The case fatality rate among patients with gynecologic malignancy with COVID-19 infection was 17.6%. Cancer-directed therapy was not associated with an increased risk of mortality related to COVID-19 infection.

Interlobular Septal Thickening in a Young Man With Dyspnea.

CASE PRESENTATION: A 30-year-old man with a history of childhood asthma, a 15-pack-year smoking history, and methamphetamine abuse was intubated and started on mechanical ventilation because of acute hypoxic respiratory failure after experiencing progressive dyspnea and a nonproductive cough over the previous year. During the previous 3 months, he had multiple clinic visits, with chest radiographs showing diffuse, bilateral, reticulonodular opacities and small bilateral pleural effusions and was treated for community-acquired pneumonia. Testing for COVID pneumonia was negative, and he failed to respond to antimicrobial therapy. Physical examination on admission showed diffuse fine crackles bilaterally on lung auscultation. Admission laboratory test results were unremarkable.

A prospective diagnostic evaluation of accuracy of self-taken and healthcare worker-taken swabs for rapid COVID-19 testing (preprint)

ObjectivesTo compare self-taken and healthcare worker (HCW)-taken throat/nasal swabs to perform rapid diagnostic tests (RDT) for SARS-CoV-2, and how these compare to RT-PCR. We hypothesised that self-taken samples are non-inferior for use with RDTs and in clinical and research settings could have substantial individual and public health benefit. DesignA prospective diagnostic accuracy evaluation as part of the Facilitating Accelerated Clinical Evaluation of Novel Diagnostic Tests for COVID -19 (FALCON C-19), workstream C (undifferentiated community testing). SettingNHS Test and Trace drive-through community PCR testing site (Liverpool, UK). Participants Eligible participants 18 years or older with symptoms of COVID-19. 250 participants recruited; one withdrew before analysis. SamplingSelf-administered throat/nasal swab for the Covios(R) RDT, a trained HCW taken throat/nasal sample for PCR and HCW comparison throat/nasal swab for RDT. Main outcome measuresSensitivity, specificity, and positive and negative predictive values (PPV, NPV) were calculated; comparisons between self-taken and HCW-taken samples used McNemars test. ResultsSeventy-five participants (75/249, 30.1%) were positive by RT-PCR. RDTs with self-taken swabs had a sensitivity of 90.5% (67/74, 95% CI: 83.9-97.2), compared to 78.4% (58/74, 95% CI: 69.0-87.8) for HCW-taken swabs (absolute difference 12.2%, 95% CI: 4.7-19.6, p=0.003). Specificity for self-taken swabs was 99.4% (173/174, 95% CI: 98.3-100.0), versus 98.9% (172/174, 95% CI: 97.3-100.0) for HCW-taken swabs (absolute difference 0.6%, 95% CI: 0.5-1.7, p=0.317). The PPV of self-taken RDTs (98.5%, 67/68, 95% CI: 95.7-100.0) and HCW-taken RDTs (96.7%, 58/60, 95% CI 92.1-100.0) were not significantly different (p=0.262). However, the NPV of self-taken swab RDTs was significantly higher (96.1%, 173/180, 95% CI: 93.2-98.9) than HCW-taken RDTs (91.5%, 172/188, 95% CI 87.5-95.5, p=0.003). ConclusionSelf-taken swabs for COVID-19 testing offer substantial individual benefits in terms of convenience, accuracy, and reduced risk of transmitting infection. Our results demonstrate that self-taken throat/nasal samples can be used by lay individuals as part of rapid testing programmes for symptomatic adults. Trial RegistrationIRAS ID:28422, clinical trial ID: NCT04408170 SummaryO_ST_ABSWhat is already known on this topic?C_ST_ABSO_LIRapid diagnostic tests (RDTs)for SARS-CoV-2 Ag are a cheaper point-of-care alternative to RT-PCR for diagnosing COVID-19 disease. C_LIO_LIThe accuracy of tests can vary dependent on sampling technique, test processing and reading of results. C_LI What this study adds?O_LISelf-taken throat-nasal swabs for RDTs can be used by symptomatic adults to give reliable results to diagnose SARS-CoV-2. C_LIO_LISelf-sampling can be implemented with little training and no assistance. C_LI