Detection of SARS-CoV-2 RNA in wastewater and comparison to COVID-19 cases in two sewersheds, North Carolina, USA

Wastewater surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be useful for monitoring population-wide coronavirus disease 2019 (COVID-19) infections, especially given asymptomatic infections and limitations in diagnostic testing. We aimed to detect SARS-CoV-2 RNA in wastewater and compare viral concentrations to COVID-19 case numbers in the respective counties and sewersheds. Influent 24-hour composite wastewater samples were collected from July to December 2020 from two municipal wastewater treatment plants serving different population sizes in Orange and Chatham Counties in North Carolina. After a concentration step via HA filtration, SARS-CoV-2 RNA was detected and quantified by reverse transcription droplet digital polymerise chain reaction (RT-ddPCR) and quantitative PCR (RT-qPCR), targeting the N1 and N2 nucleocapsid genes. SARS-CoV-2 RNA was detected by RT-ddPCR in 100 % (24/24) and 79 % (19/24) of influent wastewater samples from the larger and smaller plants, respectively. In comparison, viral RNA was detected by RT-qPCR in 41.7 % (10/24) and 8.3 % (2/24) of samples from the larger and smaller plants, respectively. Positivity rates and method agreement further increased for the RT-qPCR assay when samples with positive signals below the limit of detection were counted as positive. The wastewater data from the larger plant generally correlated (square similar to 0.5, p < 0.05) with, and even anticipated, the trends in reported COVID-19 cases, with a notable spike in measured viral RNA preceding a spike in cases when students returned to a college campus in the Orange County sewershed. Correlations were generally higher when using estimates of sewershed-level case data rather than county-level data. This work supports use of wastewater surveillance for tracking COVID-19 disease trends, especially in identifying spikes in cases. Wastewater-based epidemiology can be a valuable resource for tracking disease trends, allocating resources, and evaluating policy in the fight against current and future pandemics.

Evaluating the transmission risk of SARS-CoV-2 from sewage pollution.

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.

Low-dose radiotherapy for COVID-19 pneumonia and cancer: summary of a recent symposium and future perspectives.

The lessons learned from the Coronavirus Disease 2019 (COVID-19) pandemic are numerous. Low dose radiotherapy (LDRT) was used in the pre-antibiotic era as treatment for bacterially/virally associated pneumonia. Motivated in part by these historic clinical and radiobiological data, LDRT for treatment of COVID-19-associated pneumonia was proposed in early 2020. Although there is a large body of epidemiological and experimental data pointing to effects such as cancer at low doses, there is some evidence of beneficial health effects at low doses. It has been hypothesized that low dose radiation could be combined with immune checkpoint therapy to treat cancer. We shall review here some of these old radiobiological and epidemiological data, as well as the newer data on low dose radiation and stimulated immune response and other relevant emerging data. The paper includes a summary of several oral presentations given in a Symposium on "Low dose RT for COVID and other inflammatory diseases" as part of the 67th Annual Meeting of the Radiation Research Society, held virtually 3-6 October 2021.

GRIEF AND BEREAVEMENT SUPPORT FOR THOSE THAT DIE WITHIN 72 HOURS OF ADMISSION

Background: Supporting a patient's loved ones is an important component of end-of-life care, and health services have a responsibility to provide families and carers access to bereavement services. However, structured supports can be lacking despite established bereavement standards. Loved ones of patients who die within a short time from admission to hospital are potentially at risk of missing out on formal grief and bereavement assessment and support. This is particularly important because unexpected death can be a risk factor for poor adjustment in bereavement (1). Aim: The objective of this study is to identify for patients who die within 72 hours of admission to Alfred Health, what grief supports take place during the admission while the patient is still alive, and in bereavement. A secondary outcome is to identify differences in grief and bereavement support before and during the COVID-19 pandemic. Methods: A retrospective audit of the electronic medical record was conducted to identify records of patients who died within 72 hours of admission to Alfred Health, from October to December 2019 (prior to the COVID-19 pandemic) and June to August 2020 (during the COVID-19 pandemic). Results (preliminary): There were 159 patients included in this study, consisting of 74 patients who died prior to the COVID-19 pandemic and 85 patients who died during the pandemic. Patients ranged from 18 to 100 years old, with a median age of 81 years. Death occurred in the emergency department for 21.4% (n=34), in ICU for 33.3% (n=53), on the ward for 42.8% (n=68), and 2.6% (n=4) died in other locations. Unexpected deaths made up 64.0% (n=102), and 19.5% (n=31) were traumatic deaths or suicides. Of all cases, 52.0% (n=83) of loved ones had any input from either social work (specifically for end-of-life support), pastoral care, or a grief counsellor. There was no difference in this regard between the pre-pandemic and during pandemic groups. Social work provided end-of-life support to 37.7% (n=60) of patients;24.5% (n=39) received support before death, and 30.8% (n=49) after death. Pastoral care saw 11.3% (n=18) of cases, and 10.7% (n=17) had grief counsellor input, of which fourteen were in the form of a condolence letter. Palliative care reviewed 22.6% (n=36) of patients, consisting of 27.0% of patients before the pandemic, and 18.8% of patients during the pandemic. These patients were more likely to be referred to a grief counsellor (69.4%, n=25), and just over half of those referred were contacted by a grief counsellor (38.9%, n=14). Conclusion: Based on preliminary results, almost half of cases did not receive any formal grief or bereavement supports despite a significant proportion of deaths being unexpected or traumatic. We anticipate formal findings will identify areas for further improvement in provision of such supports, and encourage positive change to processes to improve the end-of-life experience for patients and families, as well as clinicians providing their care.

Experimental Investigation of a MopFan-Based Photocatalytic Air Purification Device

Photocatalytic oxidation (PCO) is a potential approach for air cleaning, especially when utilising titanium dioxide (TiO2). A MopFan is similar to a roller brush but is made of flexible fibres coated with TiO2. Unlike conventional filter/mesh UV systems, a MopFan provides a wide UV-TiO2 interaction surface area and airflow passage. This revolutionary technique can be low cost, efficient, and potentially effective against viruses, making it suitable for cleaning indoor air. It is easy to use but technically advanced. The system may be mounted on walls, floors, or placed on desktops. A photocatalytic air purification based on MopFan prototype was designed, constructed and tested. This study utilised copper wires (0.1 mm, 0.3 mm, 0.4 mm, and 0.5 mm), plastic fibres (0.5 mm and 1.1 mm), brass wire (0.4 mm), steel wire (0.38 mm), and organic “coco” fibres (0.4 mm). Copper wire (0.5 mm) and organic fibre (0.4 mm) were found to be effective against SARS-CoV-2, but brass (0.4 mm) and plastic (0.5 mm) fibres were found only partially effective. The purification performance was compared using MopFan with plastic (0.5 mm), brass (0.4 mm) and organic “coco” (0.4 mm) fibres but the other materials were rejected due to their poor qualities or difficulties in manufacturing. It was found that the system has a better effectiveness with organic fibres, around 21% of reduction consistently throughout the test. It was also found that by using the photocatalytic MopFan air cleaning system, the final concentration of pollutants in a room is determined by the rate and concentration of pollutant generation. Highlights 1. Organic fibres do not require sanding prior to being coated with TiO2 solution. 2. Copper and organic fibres are effective SARS-CoV-2 inhibitors. 3. Organic fibres are the most efficient for air purification. 4. The performance of purification is related to the concentration of pollutants. © 2022 The Author(s).

Preparedness for a 'no-notice' mass-casualty incident: a nuclear detonation scenario.

PURPOSE: An effective response for a mass-casualty incident requires understanding the relevant basic science and physical impact; detailed preparedness among jurisdictions; and clear, sequential response planning, including formal operational exercises, logistics, interagency, and public-private coordination, rapid activation of resilience, and continual improvement from lessons learned and new knowledge. This ConRad 2021 meeting report describes steps for civilian medical and public health response planning for a nuclear detonation; the utility of this type of planning for broader application; and extension of this planning to the international community. CONCLUSION: A nuclear detonation requires a response within minutes to what will be a large-scale disaster complicated by radiation, including some elements that are similar to a broad range of incidents. The response could be further complicated if multiple incidents occur simultaneously. Required are detailed planning, preparedness and scripting for an immediate operational response, addressing clinical manifestations of evolving radiation illness, and flexibility to adapt to a rapidly changing situation. This need translates into the use of just-in-time information; effective, credible communication; situational awareness on a global scale; and a template upon which to apply capabilities in a multi-sector response. This effort is greatly facilitated using a 'playbook' approach, the basics of which are presented.

United States medical preparedness for nuclear and radiological emergencies.

With the end of the Cold War in 1991, U.S. Government (USG) investments in radiation science and medical preparedness were phased out; however, the events of 11 September, which involved a terroristic attack on American soil, led to the re-establishment of funding for both radiation preparedness and development of approaches to address injuries. Similar activities have also been instituted worldwide, as the global threat of a radiological or nuclear incident continues to be a concern. Much of the USG's efforts to plan for the unthinkable have centred on establishing clear lines of communication between agencies with responsibility for triage and medical response, and external stakeholders. There have also been strong connections made between those parts of the government that establish policies, fund research, oversee regulatory approval, and purchase and stockpile necessary medical supplies. Progress made in advancing preparedness has involved a number of subject matter meetings and tabletop exercises, publication of guidance documents, assessment of available resources, clear establishment of anticipated concepts of operation for multiple radiation and nuclear scenarios, and identification/mobilization of resources. From a scientific perspective, there were clear research gaps that needed to be addressed, which included the need to identify accurate biomarkers and design biodosimetry devices to triage large numbers of civilians, develop decorporation agents that are more amenable for mass casualty use, and advance candidate products to address injuries caused by radiation exposure and thereby improve survival. Central to all these activities was the development of several different animal constructs, since efficacy testing of these approaches requires extensive work in research models that accurately simulate what would be expected in humans. Recent experiences with COVID-19 have provided an opportunity to revisit aspects of radiation preparedness, and leverage those lessons learned to enhance readiness for a possible future radiation public health emergency.

Prevalence of anti-sars-cov-2 antibodies in south african blood donors

Background: Given the inevitable, likely substantial, under-ascertainment of SARS-CoV-2 infection at the population level, using routine laboratory testing, the prevalence of SARS-CoV-2 antibodies ('seroprevalence') is an important marker of Covid-19 epidemiology. As nationally representative household surveys are a major undertaking, it will be important to find efficient ways to reliably estimate antibody prevalence from much simpler, less expensive protocols. Methods: Subject to meeting standard blood donor eligibility criteria, and a standing opt-out arrangement for research use of specimens primarily obtained for blood safety screening, unsolicited blood donations, obtained on particular 'collection days' at 219 donation sites in South Africa, during January 2021, were tested for SARS-CoV-2 antibodies using the Roche Cobas e411 platform. Donors are currently requested to defer donation if they were diagnosed with Covid-19, or experienced Covid-19-like symptoms, in the preceding 14 days. Estimates were stratified by age, sex and race. The study will have additional testing days. Phone interviews with both antibody positive and negative donors are being conducted to probe PCR diagnosis and symptoms. Results: Tested donations numbered 4547, from donors aged 16-81. Seroprevalence did not vary significantly between sexes or age groups. Headline results for the main race groups (in South African nomenclature) are: Black 58.3% (95% CI 55.8 - 60.7% ), White 13.8% (95% CI 12.3 -15.4%), Asian 23.4% (95% CI 19.4 - 27.7%) and Coloured 36.2%(95% CI 31.4 - 41.1%). The population group weighted overall national estimate is then 51.4% (95% CI 49.4 - 53.4%). This is almost 25 times as high as the official prevalence, on 10 January, of having been diagnosed with Covid-19, namely 2.1%. See Figure. Conclusion: These are the first relatively widely representative SARSCoV- 2 antibody prevalence estimates from South Africa. Population level representativeness of this methodology warrants further exploration - but it is worth noting that 1) as elsewhere, the obtained antibody prevalence estimates imply SARS-CoV-2 attack rates that are easily an order of magnitude higher than the apparently relatively uninformative official case counts;and 2) the marginal cost of performing this study, over the cost of routine blood bank operations, was almost entirely comprised of the cost of reagents. South African case fatality rate estimates will need significant revision.

Equitably sharing the benefits and burdens of research: COVID-19 raises the stakes. (Special Issue: Participants with autism. Big data and pragmatic trials. Covid-19 research.)

The question of where Covid-19 clinical trials will be conducted is relevant to both the burdens and benefits of research. On the burdens side, there have long been concerns about the "off-shoring" of studies to low and middle-income countries (LMICs) to take advantage of looser regulation and of populations eager to participate in research because they have no other good options for accessing health care. At the same time, excluding LMICs from Covid-19 research is clearly not the solution, as doing so would reduce the potential benefits of research for persons in those regions. This is because the results of clinical trials conducted in one part of the world are not necessarily applicable to persons living elsewhere, due to differences in genetic makeups, the prevalence of comorbidities, and local health care infrastructures. The manner in which participants are recruited into studies also raises equity considerations. For example, in the United States, there is substantial evidence that African American and Hispanic and Latinx patients are underrepresented among clinical trial participants. This is a problem because, just like people from different parts of the world, people from different racial and ethnic backgrounds may respond differently to medical interventions. Also important is support for research specifically focused on the unique needs of certain subpopulations. For example, residents of nursing homes and group homes for the developmentally disabled have been especially hard hit by the Covid-19 outbreak. Because these populations have suffered a disproportionate share of the burdens of the pandemic, equity requires support for research specifically designed to reduce risk and improve outcomes in these institutional settings. Similarly, studies should focus on the unique needs of other populations that may be excluded from large-scale clinical trials, such as patients who are pregnant.

Intraoperative radiation therapy (IORT)for1200 early breast tumors

Introduction: Two prospective randomized trials, TARGIT-A and ELIOT, have shown intraoperative radiationtherapy (IORT) to be a safe alternative with a low-risk of local recurrence compared to whole breast radiationtherapy following breast conserving surgery for selected low-risk patients. We report the first 1200 tumors treatedwith this modality at our facility. Methods: 1200 distinct breast cancers in 1169 patients (31 bilateral) were treatedwith breast conserving surgery and X-ray IORT, using the Xoft Accent System from June 2010 to November 2018.Patients were enrolled in an IORT registry trial and data were collected at 1 week, 1 month, 6 months, 1 year, andyearly thereafter. The primary endpoint was local recurrence. Results: To date, there have been 61 events in 54patients: 50 ipsilateral local recurrences (14 DCIS and 36 invasive), 7 regional nodal recurrences and 4 distantrecurrences. Of local recurrences, 9 were within the IORT field, 21 outside of the IORT field but within the samequadrant as the index cancer, and 20 were new cancers in different quadrants. There has been no breast cancerrelated deaths and 27 non-breast cancer deaths. Currently, with a median follow-up of 52 months, Kaplan Meieranalysis projects 5.2 % local recurrence rate at 5 years. In the table below, the five-year probability of localrecurrence is analyzed by quadrant and/or type of recurrence (all recurrences or just invasive). Using the 2017,ASTRO Categories, 520 patients (43%) were suitable for IORT, 415 (35%) were cautionary, and 265 (22%) wereunsuitable for IORT after final histopathology was evaluated. Conclusion: IORT is profoundly convenient. Whenused as the only adjuvant breast irradiation, it eliminates approximately 15-35 outpatient visits. This has become increasingly important during the current COVID-19 pandemic. In the group of patients described here, more that100,000 patient-hours were saved. The local, regional, and distant recurrence rates observed in this trial wereslightly higher than those of the prospective randomized TARGIT-A and ELIOT Trials. This may be explained by22% of our patients being considered unsuitable for IORT by ASTRO Criteria. The low complication rates previouslyreported by our group as well as the low recurrence rates reported in this study support the cautious use andcontinued study of X-ray IORT in women with low-risk breast cancer.

#Educationinthetimeofcovid: Using twitter to disseminate evidence- based medicine during a pandemic

Background. The medical community has used Twitter as a learning tool during the COVID-19 pandemic to digest the high volume of rapidly evolving literature. However, Twitter contains educational content of varying quality and accuracy. To address this issue, we created and disseminated visual abstracts of COVID-19 literature on Twitter to educate health professionals. Methods. Fellows and faculty members from multiple institutions collaborated with Emory University medical students to create visual abstracts of published COVID-19 literature (Figure 1). ID fellows and faculty identified and summarized 10-15 high-impact COVID-19 articles each week. Medical students created visual abstracts for each article, which fellows or faculty reviewed for accuracy. We disseminated them on Twitter (@JenniferSpicer4, 4,373 followers) and our website (Figure 2). We measured engagement with tweets using Twitter Analytics. Results. Since March 2020, we have created, reviewed, and disseminated 139 graphics with 116 student authors and 33 fellow/faculty reviewers across three academic institutions (Table 1). Topics included public health & prevention, virology & basic science, epidemiology, transmission & infection control, clinical syndrome, diagnostics, therapeutics, vaccinology, and ethics & policy. Tweets had a median of 9,300 impressions (interquartile range [IQR] 5,432-13,233) with 766 engagements (IQR 432-1,288) and an engagement rate of 8.6% (IQR 7.1%-10.0%) (Table 2). Each tweet had a median of 25 retweets (IQR 17-38) and 55 likes (IQR 34-81). A few tweets had significantly higher metrics;maximum values were 84,257 impressions, 9,758 engagements, 19.0% engagement rate, 239 retweets, and 381 likes. In addition to disseminating graphics on Twitter, we received requests to use them as teaching aids from multiple health professionals worldwide, and the visual abstracts have been translated into Spanish and disseminated on Twitter and Instagram via @MEdSinFrontera. Conclusion. Engagement rates with our visual abstracts were high, demonstrating the power of Twitter. ID educators can use visual abstracts to summarize and disseminate accurate information to a large audience on social media, which is especially important in the setting of an emerging infection.

Achieving flexible competence: bridging the investment dichotomy between infectious diseases and cancer.

Today's global health challenges in underserved communities include the growing burden of cancer and other non-communicable diseases (NCDs); infectious diseases (IDs) with epidemic and pandemic potential such as COVID-19; and health effects from catastrophic 'all hazards' disasters including natural, industrial or terrorist incidents. Healthcare disparities in low-income and middle-income countries and in some rural areas in developed countries make it a challenge to mitigate these health, socioeconomic and political consequences on our globalised society. As with IDs, cancer requires rapid intervention and its effective medical management and prevention encompasses the other major NCDs. Furthermore, the technology and clinical capability for cancer care enables management of NCDs and IDs. Global health initiatives that call for action to address IDs and cancer often focus on each problem separately, or consider cancer care only a downstream investment to primary care, missing opportunities to leverage investments that could support broader capacity-building. From our experience in health disparities, disaster preparedness, government policy and healthcare systems we have initiated an approach we call flex-competence which emphasises a systems approach from the outset of program building that integrates investment among IDs, cancer, NCDs and disaster preparedness to improve overall healthcare for the local community. This approach builds on trusted partnerships, multi-level strategies and a healthcare infrastructure providing surge capacities to more rapidly respond to and manage a wide range of changing public health threats.

Comorbid diabetes results in immune dysregulation and enhanced disease severity following MERS-CoV infection

Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 in Saudi Arabia and has caused over 2400 cases and more than 800 deaths. Epidemiological studies identified diabetes as the primary comorbidity associated with severe or lethal MERS-CoV infection. Understanding how diabetes affects MERS is important because of the global burden of diabetes and pandemic potential of MERS-CoV. We used a model in which mice were made susceptible to MERS-CoV by expressing human DPP4, and type 2 diabetes was induced by administering a high-fat diet. Upon infection with MERS-CoV, diabetic mice had a prolonged phase of severe disease and delayed recovery that was independent of virus titers. Histological analysis revealed that diabetic mice had delayed inflammation, which was then prolonged through 21 days after infection. Diabetic mice had fewer inflammatory monocyte/macrophages and CD4+ T cells, which correlated with lower levels of Ccl2 and Cxcl10 expression. Diabetic mice also had lower levels of Tnfa, Il6, Il12b, and Arg1 expression and higher levels of Il17a expression. These data suggest that the increased disease severity observed in individuals with MERS and comorbid type 2 diabetes is likely due to a dysregulated immune response, which results in more severe and prolonged lung pathology.

Low-Dose Radiation Therapy (LDRT) for COVID-19: Benefits or Risks?

The limited impact of treatments for COVID-19 has stimulated several phase 1 clinical trials of whole-lung low-dose radiation therapy (LDRT; 0.3-1.5 Gy) that are now progressing to phase 2 randomized trials worldwide. This novel but unconventional use of radiation to treat COVID-19 prompted the National Cancer Institute, National Council on Radiation Protection and Measurements and National Institute of Allergy and Infectious Diseases to convene a workshop involving a diverse group of experts in radiation oncology, radiobiology, virology, immunology, radiation protection and public health policy. The workshop was held to discuss the mechanistic underpinnings, rationale, and preclinical and emerging clinical studies, and to develop a general framework for use in clinical studies. Without refuting or endorsing LDRT as a treatment for COVID-19, the purpose of the workshop and this review is to provide guidance to clinicians and researchers who plan to conduct preclinical and clinical studies, given the limited available evidence on its safety and efficacy.