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April 24, 2021, marks 1 year since the formation of the Access to COVID-19 Tools Accelerator (ACT-A) partnership. Its mission is to accelerate the development, production, and equitable access to COVID-19 tests, treatments, and vaccines, which is central to ending the acute phase of the COVID-19 pandemic. With the pandemic still raging, has ACT-A been successful so far? And what does the future hold?…

Since the beginning of the COVID-19 pandemic, many scientists and public health officials assumed that infection with SARS-CoV-2 would protect from reinfection and that neutralising antibodies would correlate with protection or would be at least one of the protective immune mechanisms.1 Early on, these assumptions were supported by non-human primate data showing protection from reinfection, a correlation between neutralising antibodies protection, and protection afforded by passive transfer of neutralising antibodies.

The use of rapid lateral flow antigen testing (LFT) for SARS-CoV-2 has been questioned1–3 with uncorroborated4 reports of poor LFT sensitivity. The debate surrounding the use of the Innova Lateral Flow SARS-CoV-2 Antigen Test in the UK risks confusing policy makers internationally and potentially stalling deployment of LFTs in other countries.5 As scientists and health professionals evaluating some of the world's largest pilots of LFT, we wish to challenge those interpretations and clarify the evidence on how such testing might be used to detect SARS-CoV-2 in minutes and improve COVID-19 control measures.

The COVID-19 pandemic and response are having profound impacts on India's people, leading to myriad health-care challenges, a looming economic recession, and humanitarian crises.1 The long-standing need for universal health coverage (UHC) in India has been brought into sharp focus by the pandemic. The mission of the Lancet Citizens’ Commission on reimagining India's health system is to lay out the path to achieving UHC in India in the coming decade.

Doctors are reporting shortages of critical drugs and the need to ration care, pointing to public health failures. Lise Alves reports from São Paulo.

By mid March, 2021, vaccination against COVID-19 using the ChAdOx1 nCoV-19 (AZD1222) vaccine from Oxford–AstraZeneca1,2 was paused in a number of European countries due to reports of thromboembolic events in vaccinated individuals.3 According to the European Medicines Agency (EMA), 30 cases of thromboembolic events (predominantly venous) had been reported by March 10, 2021, among the approximately 5 million recipients of the Oxford–AstraZeneca COVID-19 vaccine in the European Economic Area.3 The EMA subsequently stated that “The number of thromboembolic events in vaccinated people is no higher than the number seen in the general population”.

The Islamic month of fasting, Ramadan, begins around April 12, 2021. In 2020, Ramadan coincided with the beginning of the COVID-19 pandemic, moving what is a month of communal prayers and social gatherings into the era of virtual prayers. 2021 brings further challenges with ongoing virtual prayers and a global vaccination programme. For 1·9 billion Muslims worldwide, Ramadan coinciding with the vaccination programmes crucially means that their vaccinations might be offered during this time. With ongoing concerns of vaccine hesitancy among minority ethnic populations,1 could Ramadan impede successful vaccination roll-out?…

Soham Bandyopadhyay1 claimed that the UK Government's national lockdown, announced in November, 2020, to control COVID-19, was an institutionally racist policy. Claims of institutional racism are serious allegations and thus warrant critical appraisal. I therefore raise three points.

Bojorquez I, Cabieses B, Arósquipa C, et al. Migration and health in Latin America during the COVID-19 pandemic and beyond. Lancet 2021; 397: 1243–45—In this Comment, the date of the Ibero-American Summit has been corrected to April 21, 2021. This correction has been made to the online version as of April 15, 2021.

by Lauren E. Parmley, Kieran Hartsough, Oliver Eleeza, Akopon Bertin, Bockarie Sesay, Amon Njenga, Mame Toure, Ginika Egesimba, Haja Bah, Alex Bayoh, Abdulraheem Yakubu, Ellen A. B. Morrison, Susan Michaels-Strasser After a decade of civil war and the 2014–2016 West African Ebola outbreak, Sierra Leone now faces the COVID-19 pandemic with a fragile health system. As was demonstrated during Ebola, preparedness is key to limiting a health crisis’ spread and impact on health systems and ensuring continued care for vulnerable populations including people living with HIV (PLHIV). To assess COVID-19 preparedness and inform interventions to ensure continuity of HIV services at health facilities (HFs) and community service points (CSPs), we conducted site readiness assessments in Freetown, the epicenter of COVID-19 in Sierra Leone. Data were collected at nine high-volume HIV HFs and seven CSPs in April 2020, a month after COVID-19 was declared a pandemic. CSPs comprised three community drop-in centers providing HIV counseling and testing services as well as HIV prevention services (e.g., condoms and lubricants) for key and priority populations and four community-based support groups serving PLHIV. At the time of assessment, CSPs did not provide antiretroviral therapy (ART) but were considered potential sites for expansion of differentiated service delivery (DSD)—a client-centered approach to HIV care—in the context of COVID-19. Overall, 5/9 HFs had trained staff on use of personal protective equipment (PPE) and prevention of COVID-19 transmission. Most had access to masks (5/9) and gloves (7/9) for management of suspected/confirmed COVID-19 cases, and 4/9 HFs had triage procedures for isolation of suspected cases. Conversely, few CSPs had access to masks (2/7) or gloves (2/7) and no staff were trained on PPE use or COVID-19 transmission. 7/9 HFs had adequate ART stock for multi-month dispensing though few had procedures for (3/9) or had trained staff in providing DSD (2/9). Among CSPs where measures were applicable, 2/4 had procedures for DSD, 1/3 had staff trained on DSD and none had adequate ART stock. Identification of gaps in COVID-19 preparedness is a critical step in providing support for infection control and modified service delivery. Findings from this assessment highlight gaps in COVID-19 preparedness measures at sites supporting PLHIV in Sierra Leone and indicate CSPs may require intensive supervision and training to ensure HIV services are uninterrupted while minimizing COVID-19 risk, especially if used as sites to scale up DSD.

by Rachael Phadnis, Champika Wickramasinghe, Juan Carlos Zevallos, Stacy Davlin, Vindya Kumarapeli, Veronica Lea, Juliette Lee, Udara Perera, Francisco Xavier Solórzano, Juan Francisco Vásconez Effective and rapid decision making during a pandemic requires data not only about infections, but also about human behavior. Mobile phone surveys (MPS) offer the opportunity to collect real-time data on behavior, exposure, knowledge, and perception, as well as care and treatment to inform decision making. The surveys aimed to collect coronavirus disease 2019 (COVID-19) related information in Ecuador and Sri Lanka using mobile phones. In Ecuador, a Knowledge, Attitudes and Practices (KAP) survey was conducted. In Sri Lanka, an evaluation of a novel medicine delivery system was conducted. Using the established mobile network operator channels and technical assistance provided through The Bloomberg Philanthropies Data for Health Initiative (D4H), Ministries of Health fielded a population-based COVID-19-specific MPS using Surveda, the open source data collection tool developed as part of the initiative. A total of 1,185 adults in Ecuador completed the MPS in 14 days. A total of 5,001 adults over the age of 35 in Sri Lanka completed the MPS in 44 days. Both samples were adjusted to the 2019 United Nations Population Estimates to produce population-based estimates by age and sex. The Ecuador COVID-19 MPS found that there was compliance with the mitigation strategies implemented in that country. Overall, 96.5% of Ecuadorians reported wearing a face mask or face covering when leaving home. Overall, 3.8% of Sri Lankans used the service to receive medicines from a government clinic. Among those who used the medicine delivery service in Sri Lanka, 95.8% of those who used a private pharmacy received their medications within one week, and 69.9% of those using a government clinic reported the same. These studies demonstrate that MPS can be conducted quickly and gather essential data. MPS can help monitor the impact of interventions and programs, and rapidly identify what works in mitigating the impact of COVID-19.

by Dani Zoorob, Shivam Shah, Danielle La Saevig, Courtney Murphy, Shaza Aouthmany, Kris Brickman Background Acute augmentation of stress and disruption of training, such as during the COVID-19 pandemic, may impact resident wellbeing. Objectives We investigated how residents in various specialties in the United States were impacted by COVID-19 on mental wellbeing and resilience levels, and the methodology for coping with the stress incurred. Methods In April 2020, the authors electronically surveyed 200 residency programs of all specialties nationally. The survey utilized two validated questionnaires to assess wellbeing and resilience, while investigating demographics and coping mechanisms. The authors used student t-test and ANOVA to quantitatively analyze the data. Results The sample consisted of 1115 respondents (with an 18% response rate). Male gender & Age >39 years were associated with more favorable average well-being indices (both p<0.01). Regarding resources, institutional support (IS) appeared favorable for resident well-being (IS 2.74, SD1.96 vs NoIS 3.71, SD2.29, p<0.01) & resilience (IS 3.72, SD0.70 vs NoIS 3.53, SD0.73, p = 0.05). The effects of mindfulness practices (MP) were not statistically significant for improvement of wellness (MP 2.87, SD 1.99 vs No MP 2.76, SD 2.15, p = 0.85) or resilience (MP 3.71, SD 0.70 vs No MP 3.72, SD 0.68, p = 0.87). Conclusions Findings highlight the critical importance of resident mental status in cases of augmented stress situations. Institutional support may contribute to promotion of resident wellbeing.

by Xiu-Fen Yang, Meng-qi Li, Lu-lu Liao, Hui Feng, Si Zhao, Shuang Wu, Ping Yin Background The pandemic of coronavirus disease 2019 (COVID-19) has global impact, Wuhan in Hubei province is a high-risk area. And the older people in nursing homes are the most susceptible group to COVID-19. The aim of this study was to describe the practice and experience of the first-line medical team, to provide insights of coping with COVID-19 in China. Method This qualitative study used a descriptive phenomenological design to describe the experience of medical staff supported the nursing homes in Wuhan fighting against COVID-19. Unstructured interviews via online video were conducted with seven medical staffs who supported the nursing homes in Wuhan. Data were analyzed using content analysis in five main themes: for nursing homes, we interviewed the difficulties faced at the most difficult time, services for the older people, and prevention and management strategies, for the medical staff, the psychological experience were interviewed, and the implications for public health emergencies were also reported. Conclusions It is imperative that effective preventive and response measures be implemented to face the outbreak of COVID-19 and meet the care needs of older people in the context of COVID-19. Implications Findings will inform managers of some reasonable instructional strategies for implementing effective infection management. Nursing homes need to provide targeted services to help alleviating their bad psychology for residents.

Objective To provide evidence on the effect of the COVID-19 pandemic on the mental health of young people who grew up in poverty in low/middle-income countries (LMICs). Design A phone survey administered between August and October 2020 to participants of a population-based longitudinal cohort study established in 2002 comprising two cohorts born in 1994–1995 and 2001–2002 in Ethiopia, India (Andhra Pradesh and Telangana), Peru and Vietnam. We use logistic regressions to examine associations between mental health and pandemic-related stressors, structural factors (gender, age), and lifelong protective/risk factors (parent and peer relationship, wealth, long-term health problems, past emotional problems, subjective well-being) measured at younger ages. Setting A geographically diverse, poverty-focused sample, also reaching those without mobile phones or internet access. Participants 10 496 individuals were approached; 9730 participated. Overall, 8988 individuals were included in this study; 4610 (51%) men and 4378 (49%) women. Non-inclusion was due to non-location or missing data. Main outcome measures Symptoms consistent with at least mild anxiety or depression were measured by Generalized Anxiety Disorder-7 (≥5) or Patient Health Questionnaire-8 (≥5). Results Rates of symptoms of at least mild anxiety (depression) were highest in Peru at 41% (32%) (95% CI 38.63% to 43.12%; (29.49–33.74)), and lowest in Vietnam at 9% (9%) (95% CI 8.16% to 10.58%; (8.33–10.77)), mirroring COVID-19 mortality rates. Women were most affected in all countries except Ethiopia. Pandemic-related stressors such as health risks/expenses, economic adversity, food insecurity, and educational or employment disruption were risk factors for anxiety and depression, though showed varying levels of importance across countries. Prior parent/peer relationships were protective factors, while long-term health or emotional problems were risk factors. Conclusion Pandemic-related health, economic and social stress present significant risks to the mental health of young people in LMICs where mental health support is limited, but urgently needed to prevent long-term consequences.

Nature Medicine, Published online: 15 April 2021; doi:10.1038/s41591-021-01308-7 Comprehensive large-scale nucleic acid–testing strategies support China’s sustained containment of COVID-19…

Examining unmanipulated SARS-CoV-2-specific T cells is important for understanding primary and recall responses during COVID-19. Nguyen et al. analyze ex vivo CD8+ T cells specific for SARS-CoV-2 epitopes and find that immunodominant B7/N105-specific CD8+ T cells are present at high frequencies in blood samples from unexposed, acute COVID-19, and convalescence individuals, which is underpinned by diverse TCR repertoires.

by Shadnaz Asgari, Jelena Trajkovic, Mehran Rahmani, Wenlu Zhang, Roger C. Lo, Antonella Sciortino The COVID-19 pandemic compelled the global and abrupt conversion of conventional face-to-face instruction to the online format in many educational institutions. Urgent and careful planning is needed to mitigate negative effects of pandemic on engineering education that has been traditionally content-centered, hands-on and design-oriented. To enhance engineering online education during the pandemic, we conducted an observational study at California State University, Long Beach (one of the largest and most diverse four-year university in the U.S.). A total of 110 faculty members and 627 students from six engineering departments participated in surveys and answered quantitative and qualitative questions to highlight the challenges they experienced during the online instruction in Spring 2020. Our results identified various issues that negatively influenced the online engineering education including logistical/technical problems, learning/teaching challenges, privacy and security concerns and lack of sufficient hands-on training. For example, more than half of the students indicated lack of engagement in class, difficulty in maintaining their focus and Zoom fatigue after attending multiple online sessions. A correlation analysis showed that while semi-online asynchronous exams were associated with an increase in the perceived cheating by the instructors, a fully online or open-book/open-note exams had an association with a decrease in instructor’s perception of cheating. To address various identified challenges, we recommended strategies for educational stakeholders (students, faculty and administration) to fill the tools and technology gap and improve online engineering education. These recommendations are practical approaches for many similar institutions around the world and would help improve the learning outcomes of online educations in various engineering subfields. As the pandemic continues, sharing the results of this study with other educators can help with more effective planning and choice of best practices to enhance the efficacy of online engineering education during COVID-19 and post-pandemic.

by Avishek Chatterjee, Guangyao Wu, Sergey Primakov, Cary Oberije, Henry Woodruff, Pieter Kubben, Ronald Henry, Marcel J. H. Aries, Martijn Beudel, Peter G. Noordzij, Tom Dormans, Niels C. Gritters van den Oever, Joop P. van den Bergh, Caroline E. Wyers, Suat Simsek, Renée Douma, Auke C. Reidinga, Martijn D. de Kruif, Julien Guiot, Anne-Noelle Frix, Renaud Louis, Michel Moutschen, Pierre Lovinfosse, Philippe Lambin Objective To establish whether one can build a mortality prediction model for COVID-19 patients based solely on demographics and comorbidity data that outperforms age alone. Such a model could be a precursor to implementing smart lockdowns and vaccine distribution strategies. Methods The training cohort comprised 2337 COVID-19 inpatients from nine hospitals in The Netherlands. The clinical outcome was death within 21 days of being discharged. The features were derived from electronic health records collected during admission. Three feature selection methods were used: LASSO, univariate using a novel metric, and pairwise (age being half of each pair). 478 patients from Belgium were used to test the model. All modeling attempts were compared against an age-only model. Results In the training cohort, the mortality group’s median age was 77 years (interquartile range = 70–83), higher than the non-mortality group (median = 65, IQR = 55–75). The incidence of former/active smokers, male gender, hypertension, diabetes, dementia, cancer, chronic obstructive pulmonary disease, chronic cardiac disease, chronic neurological disease, and chronic kidney disease was higher in the mortality group. All stated differences were statistically significant after Bonferroni correction. LASSO selected eight features, novel univariate chose five, and pairwise chose none. No model was able to surpass an age-only model in the external validation set, where age had an AUC of 0.85 and a balanced accuracy of 0.77. Conclusion When applied to an external validation set, we found that an age-only mortality model outperformed all modeling attempts (curated on www.covid19risk.ai) using three feature selection methods on 22 demographic and comorbid features.

by Olivia L. McGovern, Mark Stenger, Sara E. Oliver, Tara C. Anderson, Cheryl Isenhour, Matthew R. Mauldin, Nia Williams, Eric Griggs, Tonny Bogere, Chris Edens, Aaron T. Curns, Joana Y. Lively, Yingtao Zhou, Songli Xu, Maureen H. Diaz, Jessica L. Waller, Kevin R. Clarke, Mary E. Evans, Elisabeth M. Hesse, Sapna Bamrah Morris, Robert P. McClung, Laura A. Cooley, Naeemah Logan, Andrew T. Boyd, Allan W. Taylor, Kristina L. Bajema, Stephen Lindstrom, Christopher A. Elkins, Christopher Jones, Aron J. Hall, Samuel Graitcer, Alexandra M. Oster, Alicia M. Fry, Marc Fischer, Laura Conklin, Runa H. Gokhale Background The Coronavirus Disease 2019 (COVID-19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), evolved rapidly in the United States. This report describes the demographic, clinical, and epidemiologic characteristics of 544 U.S. persons under investigation (PUI) for COVID-19 with complete SARS-CoV-2 testing in the beginning stages of the pandemic from January 17 through February 29, 2020. Methods In this surveillance cohort, the U.S. Centers for Disease Control and Prevention (CDC) provided consultation to public health and healthcare professionals to identify PUI for SARS-CoV-2 testing by quantitative real-time reverse-transcription PCR. Demographic, clinical, and epidemiologic characteristics of PUI were reported by public health and healthcare professionals during consultation with on-call CDC clinicians and subsequent submission of a CDC PUI Report Form. Characteristics of laboratory-negative and laboratory-positive persons were summarized as proportions for the period of January 17−February 29, and characteristics of all PUI were compared before and after February 12 using prevalence ratios. Results A total of 36 PUI tested positive for SARS-CoV-2 and were classified as confirmed cases. Confirmed cases and PUI testing negative for SARS-CoV-2 had similar demographic, clinical, and epidemiologic characteristics. Consistent with changes in PUI evaluation criteria, 88% (13/15) of confirmed cases detected before February 12, 2020, reported travel from China. After February 12, 57% (12/21) of confirmed cases reported no known travel- or contact-related exposures. Conclusions These findings can inform preparedness for future pandemics, including capacity for rapid expansion of novel diagnostic tests to accommodate broad surveillance strategies to assess community transmission, including potential contributions from asymptomatic and presymptomatic infections.

by Kevin Guedj, Mathieu Uzzan, Damien Soudan, Catherine Trichet, Antonino Nicoletti, Emmanuel Weiss, Hana Manceau, Alexandre Nuzzo, Olivier Corcos, Xavier Treton, Katell Peoc’h Background Severe acute respiratory syndrome caused by the novel coronavirus (SARS-CoV-2) is frequently associated with gastrointestinal manifestations. Herein we evaluated the interest in measuring the intestinal fatty acid-binding protein (I-FABP), a biomarker of intestinal injury, in COVID-19 patients. Methods Serum I-FABP was analyzed in 28 consecutive patients hospitalized for a PCR-confirmed COVID-19, in 24 hospitalized patients with non-COVID-19 pulmonary diseases, and 79 patients admitted to the emergency room for abdominal pain. Results I-FABP serum concentrations were significantly lower in patients with COVID-19, as compared to patients with non-COVID-19 pulmonary diseases [70.3 pg/mL (47–167.9) vs. 161.1 pg/mL (88.98–305.2), respectively, p = 0.008]. I-FABP concentrations in these two populations were significantly lower than in patients with abdominal pain without COVID-19 [344.8 pg/mL (268.9–579.6)]. I-FABP was neither associated with severity nor the duration of symptoms. I-FABP was correlated with polymorphonuclear cell counts. Conclusions In this pilot study, we observed a low I-FABP concentration in COVID-19 patients either with or without gastrointestinal symptoms, of which the pathophysiological mechanisms and clinical impact remain to be established. Further explorations on a larger cohort of patients will be needed to unravel the molecular mechanism of such observation, including the effects of malabsorption and/or abnormal lipid metabolism.

by Katherine Klise, Walt Beyeler, Patrick Finley, Monear Makvandi As social distancing policies and recommendations went into effect in response to COVID-19, people made rapid changes to the places they visit. These changes are clearly seen in mobility data, which records foot traffic using location trackers in cell phones. While mobility data is often used to extract the number of customers that visit a particular business or business type, it is the frequency and duration of concurrent occupancy at those sites that governs transmission. Understanding the way people interact at different locations can help target policies and inform contact tracing and prevention strategies. This paper outlines methods to extract interactions from mobility data and build networks that can be used in epidemiological models. Several measures of interaction are extracted: interactions between people, the cumulative interactions for a single person, and cumulative interactions that occur at particular businesses. Network metrics are computed to identify structural trends which show clear changes based on the timing of stay-at-home orders. Measures of interaction and structural trends in the resulting networks can be used to better understand potential spreading events, the percent of interactions that can be classified as close contacts, and the impact of policy choices to control transmission.

by Benjamin R. Bates, Adriana Tami, Ana Carvajal, Mario J. Grijalva Background COVID-19 threatens health systems worldwide, but Venezuela’s system is particularly vulnerable. To prevent the spread of COVID-19, individuals must adopt preventive behaviors. However, to encourage behavior change, we must first understand current knowledge, attitudes, and practices (KAPs) that inform response to this health threat. Methods We explored KAPs among Venezuelans using a cross-sectional, internet-based questionnaire. The questionnaire explored individuals’ knowledge about COVID-19; their attitudes toward the world’s and the Venezuelan authorities’ abilities to control it; and their self-reported practices. We also collected demographic data. Binomial logistic regression analyses were used to predict the adoption of preventive behaviors based on demographic variables, individual knowledge level, and individual attitudes. Results 3122 individuals completed the questionnaire. Participants had a high level of knowledge about COVID-19. They expressed high levels of optimism that the world would eventually control COVID-19, but they were very pessimistic about the public authorities in Venezuela. Most participants adopted preventive practices. Binomial regression suggests younger people, less educated people, and manual laborers hold lower levels of knowledge, and these groups, as well as men, were less likely to adopt preventive practices. Knowledge, by itself, had no association with optimism and little association with self-reported practices. Conclusions As other KAP studies in Latin America found, knowledge is not sufficient to prompt behavior change. Venezuelans’ pessimism about their own country’s ability should be explored in greater depth. Health promotion in Venezuela may wish to target the most at risk groups: men, younger people, less educated people, and manual laborers.

American Journal of Respiratory and Critical Care Medicine, Volume 203, Issue 8, Page 1025-1027, April 15, 2021.

American Journal of Respiratory and Critical Care Medicine, Volume 203, Issue 8, Page 1041-1042, April 15, 2021.

American Journal of Respiratory and Critical Care Medicine, Volume 203, Issue 8, Page 1042-1043, April 15, 2021.

Abstract Background The primary objective of the study is to describe the cellular characteristics of bronchoalveolar lavage fluid (BALF) of COVID-19 patients requiring invasive mechanical ventilation; the secondary outcome is to describe BALF findings between survivors vs non-survivors. Materials and methods Patients positive for SARS-CoV-2 RT PCR, admitted to ICU between March and April 2020 were enrolled. At ICU admission, BALF were analyzed by flow cytometry. Univariate, multivariate and Spearman correlation analyses were performed. Results Sixty-four patients were enrolled, median age of 64 years (IQR 58–69). The majority cells in the BALF were neutrophils (70%, IQR 37.5–90.5) and macrophages (27%, IQR 7–49) while a minority were lymphocytes, 1%, TCD3+ 92% (IQR 82–95). The ICU mortality was 32.8%. Non-survivors had a significantly older age (p = 0.033) and peripheral lymphocytes (p = 0.012) were lower compared to the survivors. At multivariate analysis the percentage of macrophages in the BALF correlated with poor outcome (OR 1.336, CI95% 1.014–1.759, p = 0.039). Conclusions In critically ill patients, BALF cellularity is mainly composed of neutrophils and macrophages. The macrophages percentage in the BALF at ICU admittance correlated with higher ICU mortality. The lack of lymphocytes in BALF could partly explain a reduced anti-viral response.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has presented as a mysterious infection causing global pandemic in a short time, gaining world-wide attention, imposing challenges to medical field, researchers, epidemiologists, and policy makers about the nature of the virus, and posing challenges for a successful vaccine outcome (Umakanthan et al., 2020). SARS-CoV-2 is transmitted via respiratory droplets from face-to-face contact or contaminated surfaces. Although the role of aerosol spread in humans remains unclear, this mode of transmission is still a major concern (Ganyani et al., 2020).

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

We thank Mattia Trunfio and colleagues for their interest in our Personal View regarding the impact of non-pharmaceutical interventions (NPIs) on the viral inoculum of SARS-CoV-2.1 We agree that increasing evidence supports that NPIs are expected to lower the viral inoculum, potentially contributing to lower transmission. We acknowledge Trunfio and colleagues' point that the evidence supporting the impact of reduced inoculum on COVID-19 severity is less strong than that on infection; we had, therefore, presented this idea as a hypothesis and suggested potential experimental approaches.

We read with interest the Personal View by Matthew A Spinelli and colleagues.1 We agree with the authors on the evident advantage provided by non-pharmaceutical interventions (facial masking, social distancing, and improved ventilation) in lowering SARS-CoV-2 inoculum, thereby reducing viral transmission. Nevertheless, we call for caution before asserting that such measures could make a substantial difference in reducing COVID-19 severity.

Brazil has been severely hit by COVID-19, with rapid spatial spread of both cases and deaths. We use daily data on reported cases and deaths to understand, measure, and compare the spatiotemporal pattern of the spread across municipalities. Indicators of clustering, trajectories, speed, and intensity of the movement of COVID-19 to interior areas, combined with indices of policy measures show that while no single narrative explains the diversity in the spread, an overall failure of implementing prompt, coordinated, and equitable responses in a context of stark local inequalities fueled disease spread. This resulted in high and unequal infection and mortality burdens. With a current surge in cases and deaths and several variants of concern in circulation, failure to mitigate the spread could further aggravate the burden.

Abstract Background The SARS-CoV-2 infection has emerged as a rapidly spreading infection. Today it is relatively easy to isolate Covid-19 symptomatic cases, while remains problematic to control the disease spread by infected but symptom-free individuals. The control of this possible path of contagion requires drastic measures of social distancing, which imply the suspension of most activities and generate economic and social issues. This study is aimed at estimating the percentage of asymptomatic SARS-CoV-2 infection in a geographic area with relatively low incidence of Covid-19. Methods Blood serum samples from 388 healthy volunteers were analyzed for the presence of anti-SARS-CoV-2 IgG by using an ELISA assay based on recombinant viral nucleocapsid protein. Results We found that 7 out of 388 healthy volunteers, who declared no symptoms of Covid-19, like fever, cough, fatigue etc., in the preceding 5 months, have bona fide serum anti-SARS-CoV-2 IgG, that is 1.8% of the asymptomatic population (95% confidence interval: 0.69–2.91%). Conclusions The estimated range of asymptomatic individuals with anti-SARS-CoV-2 IgG should be between 26,565 and 112, 350. In the same geographic area, there are 4665 symptomatic diagnosed cases.

by Jennifer L. Essler, Sarah A. Kane, Pat Nolan, Elikplim H. Akaho, Amalia Z. Berna, Annemarie DeAngelo, Richard A. Berk, Patricia Kaynaroglu, Victoria L. Plymouth, Ian D. Frank, Susan R. Weiss, Audrey R. Odom John, Cynthia M. Otto While the world awaits a widely available COVID-19 vaccine, availability of testing is limited in many regions and can be further compounded by shortages of reagents, prolonged processing time and delayed results. One approach to rapid testing is to leverage the volatile organic compound (VOC) signature of SARS-CoV-2 infection. Detection dogs, a biological sensor of VOCs, were utilized to investigate whether SARS-CoV-2 positive urine and saliva patient samples had a unique odor signature. The virus was inactivated in all training samples with either detergent or heat treatment. Using detergent-inactivated urine samples, dogs were initially trained to find samples collected from hospitalized patients confirmed with SARS-CoV-2 infection, while ignoring samples collected from controls. Dogs were then tested on their ability to spontaneously recognize heat-treated urine samples as well as heat-treated saliva from hospitalized SARS-CoV-2 positive patients. Dogs successfully discriminated between infected and uninfected urine samples, regardless of the inactivation protocol, as well as heat-treated saliva samples. Generalization to novel samples was limited, particularly after intensive training with a restricted sample set. A unique odor associated with SARS-CoV-2 infection present in human urine as well as saliva, provides impetus for the development of odor-based screening, either by electronic, chemical, or biological sensing methods. The use of dogs for screening in an operational setting will require training with a large number of novel SARS-CoV-2 positive and confirmed negative samples.

by Hongwei Zhao, Naveed N. Merchant, Alyssa McNulty, Tiffany A. Radcliff, Murray J. Cote, Rebecca S. B. Fischer, Huiyan Sang, Marcia G. Ory Background Prediction of the dynamics of new SARS-CoV-2 infections during the current COVID-19 pandemic is critical for public health planning of efficient health care allocation and monitoring the effects of policy interventions. We describe a new approach that forecasts the number of incident cases in the near future given past occurrences using only a small number of assumptions. Methods Our approach to forecasting future COVID-19 cases involves 1) modeling the observed incidence cases using a Poisson distribution for the daily incidence number, and a gamma distribution for the series interval; 2) estimating the effective reproduction number assuming its value stays constant during a short time interval; and 3) drawing future incidence cases from their posterior distributions, assuming that the current transmission rate will stay the same, or change by a certain degree. Results We apply our method to predicting the number of new COVID-19 cases in a single state in the U.S. and for a subset of counties within the state to demonstrate the utility of this method at varying scales of prediction. Our method produces reasonably accurate results when the effective reproduction number is distributed similarly in the future as in the past. Large deviations from the predicted results can imply that a change in policy or some other factors have occurred that have dramatically altered the disease transmission over time. Conclusion We presented a modelling approach that we believe can be easily adopted by others, and immediately useful for local or state planning.

by Abdulelah A. Alghamdi The COVID-19 pandemic led to surprising and unexpected experiences for Saudi university students. Precautionary and preventive measures taken to contain this pandemic impacted the social and educational aspects of these students’ lives. All Umm Al-Qura University (UQU) students were invited to participate in an online survey on 30 impacts, both positive and negative, of the COVID-19 pandemic on their lives. Social impact theory (SIT) was applied to illustrate these impacts. The survey yielded 1,360 responses. The results showed high to moderate levels of agreement regarding students’ perceptions of the positive and negative impact of the COVID-19 pandemic on their lives, with social aspects impacted more than educational ones; and no statistically significant gender differences. Weak correlations were found between the social aspects and the educational aspects of students’ lives in relation to the impact of the pandemic, although all aspects were correlated positively. The SIT framework provided insights into how the COVID-19 pandemic impacted students’ lives.

by Charlie B. Fischer, Nedghie Adrien, Jeremiah J. Silguero, Julianne J. Hopper, Abir I. Chowdhury, Martha M. Werler Mask wearing has been advocated by public health officials as a way to reduce the spread of COVID-19. In the United States, policies on mask wearing have varied from state to state over the course of the pandemic. Even as more and more states encourage or even mandate mask wearing, many citizens still resist the notion. Our research examines mask wearing policy and adherence in association with COVID-19 case rates. We used state-level data on mask wearing policy for the general public and on proportion of residents who stated they always wear masks in public. For all 50 states and the District of Columbia (DC), these data were abstracted by month for April ─ September 2020 to measure their impact on COVID-19 rates in the subsequent month (May ─ October 2020). Monthly COVID-19 case rates (number of cases per capita over two weeks) >200 per 100,000 residents were considered high. Fourteen of the 15 states with no mask wearing policy for the general public through September reported a high COVID-19 rate. Of the 8 states with at least 75% mask adherence, none reported a high COVID-19 rate. States with the lowest levels of mask adherence were most likely to have high COVID-19 rates in the subsequent month, independent of mask policy or demographic factors. Mean COVID-19 rates for states with at least 75% mask adherence in the preceding month was 109.26 per 100,000 compared to 249.99 per 100,000 for those with less adherence. Our analysis suggests high adherence to mask wearing could be a key factor in reducing the spread of COVID-19. This association between high mask adherence and reduced COVID-19 rates should influence policy makers and public health officials to focus on ways to improve mask adherence across the population in order to mitigate the spread of COVID-19.

by Brydon Eastman, Cameron Meaney, Michelle Przedborski, Mohammad Kohandel The outbreak of SARS-CoV-2 is thought to have originated in Wuhan, China in late 2019 and has since spread quickly around the world. To date, the virus has infected tens of millions of people worldwide, compelling governments to implement strict policies to counteract community spread. Federal, provincial, and municipal governments have employed various public health policies, including social distancing, mandatory mask wearing, and the closure of schools and businesses. However, the implementation of these policies can be difficult and costly, making it imperative that both policy makers and the citizenry understand their potential benefits and the risks of non-compliance. In this work, a mathematical model is developed to study the impact of social behaviour on the course of the pandemic in the province of Ontario. The approach is based upon a standard SEIRD model with a variable transmission rate that depends on the behaviour of the population. The model parameters, which characterize the disease dynamics, are estimated from Ontario COVID-19 epidemiological data using machine learning techniques. A key result of the model, following from the variable transmission rate, is the prediction of the occurrence of a second wave using the most current infection data and disease-specific traits. The qualitative behaviour of different future transmission-reduction strategies is examined, and the time-varying reproduction number is analyzed using existing epidemiological data and future projections. Importantly, the effective reproduction number, and thus the course of the pandemic, is found to be sensitive to the adherence to public health policies, illustrating the need for vigilance as the economy continues to reopen.

by Kim Sui Wan, Peter Seah Keng Tok, Kishwen Kanna Yoga Ratnam, Nuraini Aziz, Marzuki Isahak, Rafdzah Ahmad Zaki, Nik Daliana Nik Farid, Noran Naqiah Hairi, Sanjay Rampal, Chiu-Wan Ng, Mohd Fauzy Samsudin, Vinura Venugopal, Mohammad Asyraf, Narisa Hatun Damanhuri, Sanpagavalli Doraimuthu, Catherine Thamarai Arumugam, Thaneswaran Marthammuthu, Fathhullah Azmie Nawawi, Faiz Baharudin, Diane Woei Quan Chong, Vivek Jason Jayaraj, Venna Magarita, Sasheela Ponnampalavanar, Nazirah Hasnan, Adeeba Kamarulzaman, Mas Ayu Said Introduction The reporting of Coronavirus Disease 19 (COVID-19) mortality among healthcare workers highlights their vulnerability in managing the COVID-19 pandemic. Some low- and middle-income countries have highlighted the challenges with COVID-19 testing, such as inadequate capacity, untrained laboratory personnel, and inadequate funding. This article describes the components and implementation of a healthcare worker surveillance programme in a designated COVID-19 teaching hospital in Malaysia. In addition, the distribution and characteristics of healthcare workers placed under surveillance are described. Material and methods A COVID-19 healthcare worker surveillance programme was implemented in University Malaya Medical Centre. The programme involved four teams: contact tracing, risk assessment, surveillance and outbreak investigation. Daily symptom surveillance was conducted over fourteen days for healthcare workers who were assessed to have low-, moderate- and high-risk of contracting COVID-19. A cross-sectional analysis was conducted for data collected over 24 weeks, from the 6th of March 2020 to the 20th of August 2020. Results A total of 1,174 healthcare workers were placed under surveillance. The majority were females (71.6%), aged between 25 and 34 years old (64.7%), were nursing staff (46.9%) and had no comorbidities (88.8%). A total of 70.9% were categorised as low-risk, 25.7% were moderate-risk, and 3.4% were at high risk of contracting COVID-19. One-third (35.2%) were symptomatic, with the sore throat (23.6%), cough (19.8%) and fever (5.0%) being the most commonly reported symptoms. A total of 17 healthcare workers tested positive for COVID-19, with a prevalence of 0.3% among all the healthcare workers. Risk category and presence of symptoms were associated with a positive COVID-19 test (p<0.001). Fever (p<0.001), cough (p = 0.003), shortness of breath (p = 0.015) and sore throat (p = 0.002) were associated with case positivity. Conclusion COVID-19 symptom surveillance and risk-based assessment have merits to be included in a healthcare worker surveillance programme to safeguard the health of the workforce.

Introduction A novel coronavirus, designated SARS-CoV-2, caused an international outbreak of a respiratory illness, termed COVID-19 in December 2019. There is a lack of specific therapeutic agents based on evidence for this novel coronavirus infection; however, several medications have been evaluated as a potential therapy. Therapy is required to treat symptomatic patients and decrease the virus carriage duration to limit the communitytransmission. Methods and analysis We hypothesise that patients with mild COVID-19 treated with favipiravir will have a shorter duration of time to virus clearance than the control group. The primary outcome is to evaluate the effect of favipiravir on the timing of the PCR test conversion from positive to negative within 15 days after starting the medicine. Adults (>18 years, men or nonpregnant women, diagnosed with mild COVID-19 within 5 days of disease onset) are being recruited by physicians participating from the Ministry of National Guard Health Affairs and the Ministry of Health ethics committee approved primary healthcare centres. This double-blind, randomised trial comprises three significant parts: screening, treatment and a follow-up period. The treating physician and patients are blinded. Eligible participants are randomised in a 1:1 ratio to either the therapy group (favipiravir) or a control group (placebo) with 1800 mg by mouth two times per day for the first day, followed by 800 mg two times per day for 4–7 days. Serial nasopharyngeal/oropharyngeal swab samples are obtained on day 1 (5 days before therapy). On day5±1 day, 10±1 day, 15±2 days, extra nasopharyngeal/oropharyngeal PCR COVID-19 samples are requested. The primary analysis population for evaluating both the efficacy and safety outcomes will be a modified intention to treat population. Anticipating a 10% dropout rate, we expect to recruit 288 subjects per arm. The results assume that the hazard ratio is constant throughout the study and that the Cox proportional hazard regression is used to analyse the data. Ethics and dissemination The study was approved by the King Abdullah International Medical Research Centre Institutional Review Board (28 April 2020) and the Ministry of Health Institutional Review Board (1 July 2020). Protocol details and any amendments will be reported to https://clinicaltrials.gov/ct2/show/NCT04464408. The results will be published in peer-reviewed journals. Trial registration number National Clinical Trial Registry (NCT04464408).

Introduction The NHS Health Check aims to identify individuals at increased risk of cardiovascular diseases (CVDs) among the adult population in England. The Health Check includes calculation of CVD risk and discussion of pharmacological and lifestyle approaches to manage risk, including referral to lifestyle support services. The programme is commissioned by Local Authorities (LAs) and is delivered by a range of different providers in different settings. There is significant variation in activity, with uptake ranging from 25% to 85% in different areas, and clear evidence of variation in implementation and delivery practice. Methods and analysis We aim to understand how the NHS Health Check programme works in different settings, for different groups, so that we can recommend improvements to maximise intended outcomes. To do so, we will undertake a realist review and a survey of LA public health teams. Our review will follow Pawson’s five iterative stages: (1) locate existing theories, (2) search for evidence, (3) article selection, (4) extract and organise data and (5) synthesise evidence and draw conclusions. Our review will include documents describing local implementation alongside published research studies. We will recruit a stakeholder group (including Public Health England, commissioners and providers of Health Checks, plus members of the public and patients) to advise us throughout. Our survey will be sent to all 152 LAs in England to gather detailed information on programme delivery (including COVID-19-related changes) and available referral services. This will enable us to map delivery across England and relate these data to programme outcomes. Ethics and dissemination Ethical approval is not required for this review. For the survey, we have received approval from the University of Kent Research Ethics Committee. Our findings will be used to develop recommendations on tailoring, implementation and design strategies to improve delivery of the NHS Health Check in different settings, for different groups. PROSPERO registration number CRD42020163822.

The COVID-19 pandemic caused by Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) has recently emerged as a new human-to-human transmissible disease, with a serious global health impact (Braun et al., 2020). SARS-CoV-2 is an enveloped virus with a positive stranded RNA genome and four structural proteins including spike glycoprotein (S), envelope protein (E), membrane protein (M), and nucleocapsid protein (N) (Koblischke et al., 2020; Le Bert et al., 2020).

An Editorial1 earlier this year described the potential for the evolution of SARS-CoV-2 variants that render vaccines less effective (vaccine escape), assisted by waning immunity following vaccination. This raises a crucial question: how can COVID-19 exit strategies be planned while limiting the vaccine escape risk?…

D. Chu et al.

M. Zhang et al.

by Michael Owusu, Augustina Angelina Sylverken, Philip El-Duah, Nana Kwame Ayisi-Boateng, Richmond Yeboah, Eric Adu, Jesse Asamoah, Michael Frimpong, Japhet Senyo, Godfred Acheampong, Mohamed Mutocheluh, John Amuasi, Ellis Owusu-Dabo, Yaw Adu-Sarkodie, Richard Odame Phillips Background The novel coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), continues to remain a global challenge. There is emerging evidence of SARS-CoV-2 virus found in the blood of patients from China and some developed countries. However, there is inadequate data reported in Ghana and other parts of Africa, where blood transfusion service heavily relies on voluntary and replacement blood donors. This study aimed to investigate whether plasma of infected individuals could pose significant transfusion transmitted risk of COVID-19 in Ghanaian populations. Methods This cross-sectional retrospective study was conducted at the Kumasi Centre for Collaborative Research into Tropical Medicine (KCCR), KNUST, Ghana. Study subjects comprised contacts of COVID-19 individuals, those with classical symptoms of COVID-19 and individuals who had recovered based on the new Ghana discharge criteria. Whole blood, sputum or deep coughed saliva samples were collected and transported to KCCR for SARS-CoV-2 testing. Viral nucleic acid was extracted from sputum/nasopharyngeal samples using Da An Gene column based kit and from plasma using LBP nucleic acid extraction kit. Real-Time PCR was performed specifically targeting the ORF1ab and Nucleocapsid (N) genomic regions of the virus. Results A total of 97 individuals were recruited into the study, with more than half being males (58; 59.7%). The mean age of all subjects was 33 years (SD = 7.7) with minimum being 22 years and maximum 56 years. Majority (76; 78.4%) of all the subjects were asymptomatic, and among the few symptomatic subjects, cough (10; 10.3%) was the most predominant symptom. Of the 97 sputum samples tested, 79 (81.4%) were positive for SARS-CoV-2. We identified SARS-CoV-2 viral RNA in the plasma of 1 (1.03%) subject who had clinically recovered. Conclusion This study reports the identification of SARS-CoV-2 viral RNA in a convalescent individual in Ghana. Due to the low prevalence observed and the marginal cycling thresholds associated, the risk of transfusion transmission of SARS-CoV-2 is negligible. Well-powered studies and advanced diagnostics to determine infectious viremia is recommended to further evaluate the potential risk of hematogenous transmission among recovered patients.