Background and Purpose: COVID-19 patients treated with RAAS blockers are among the patients at highest risk of poor outcome. ACE2 is the functional receptor for SARS-CoV-2. Animal studies suggest that RAAS blockers might increase the expression of ACE2 and potentially increase the risk of SARS-Cov-2 infection. Experimental Approach and Key Results: The effect of ACE inhibitor treatment on the incidence of pneumonia in non-COVID-19 patients was analyzed in 25 studies (330,780 patients). ACE inhibitor use was associated with a 27% reduction of pneumonia risk (OR: 0.73, p<0.001). Pneumonia related death cases in ACE inhibitor treated non-COVID-19 patients were reduced by 27% (OR: 0.73, p=0.004). ARB treatment was analyzed in 10 studies (275,621 non-COVID-19 patients). The risk of pneumonia was not different between patients who did or did not use ARBs. Pooled results from 16 studies in 22,333 COVID-19 patients showed that COVID-19 related server adverse clinical outcomes (admission to ICU, need for assisted ventilation or death) were reduced by 26% when using RAAS blocking agents (OR=0.74, p=0.04). Pooled results from 10 studies in 11,514 COVID-19 patients showed that RAAS blockede reduces all-cause mortality by 41% (OR=0.59, p=0.01). Conclusion and Implications: Given the weak evidence coming from animal studies and the clear beneficial data of ACE inhibition in non-COVID-19 patients and the promising data in COVID-19 patients, the use of RAAS blocking agents in patients with SARS-CoV-2 infection is justified and should be maintained. Further clinical studies analysing ARBs and ACE inhibitors separately in COVID-19 patients are needed.

Background Currently, the coronavirus disease 2019 (COVID-19) has become pandemic globally. 10-20% of the cases are severe and more than 397,000 deaths have occurred. The risk factors for the mortality of critically ill COVID-19 patients remain to be elucidated. Conclusions Survived severe and non-survived COVID-19 patients had distinct clinical and laboratory characteristics, which were separated by principle component analysis. Logistic regression revealed several risk factors such as elder age, greater affected lobe numbers and higher level of serum CRP for the mortality of severe COVID-19 patients. Longitudinal changes of laboratory findings indicate the advancement of the disease and may be helpful in predicting the progression of severe patients.

Asthma control, self-management and healthcare access during the COVID-19 Epidemic in BeijingChun Chang a* M.D., Linlin Zhanga*B.S., Fawu Dong a* B.S., Ying Liang a M.D., Yahong Chen a M.D., Ying Shang a B.S., Mairipaiti Abulikemua B.S., Yongchang Suna# M.D.aDepartment of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing, China.#, Corresponding to Yongchang Sun:Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing, China.North Garden Rd. 49.Haidian District, Beijing, 100191, ChinaTel: +86 010 139 1097 9132Fax +86 108 226 6989E-mail: suny@bjmu.edu.cn* Chun Chang, Linlin Zhang and Fawu Dong contributed equally to this work;To the Editor:The pandemic of COVID-19, caused by the pathogen SARS-CoV-2, has now spread around the globe. Social distancing and restriction measures during COVID-19 pandemic may have impacts on asthma control and management in terms of medication availability and healthcare access. International societies responded quickly by releasing guidance on the management of asthma during the COVID-19 pandemic1-4. However, these temporary guidelines were based largely on previous asthma guidelines and expert consensus, because evidence from related studies was lacking. Therefore, we investigated the status of asthma control, self-management, medications and healthcare utilization of asthma patients during the COVID-19 epidemic in Beijing, aiming to provide data for guideline recommendations on asthma managements during the emergency.Patients with asthma, selected randomly from our hospital database, were interviewed by phone call. Detailed description of items in the questionnaire is available in this article’s online supplementary material.We contacted 286 patients, of whom 178 (62.2%) responded with valid results. Sociodemographic data and clinical characteristics of the patients before the COVID-19 pandemic are provided as online supplements. During the COVID-19 epidemic in Beijing (January 25, 2020 to April 25, 2020), the majority (74.2%, 132/178) of the patients felt that their symptoms had not changed as compared with usual times, while 18.0% (32/178) felt better, and 7.9% (14/178) felt worse. The mean ACT score of the 178 patients was 22.76 ± 3.06 (ranging from 8 to 25) in the last 4 weeks before the survey. According to the criteria of ACT scoring from GINA, asthma was classified as well-controlled in 89.3%, not well-controlled in 6.2%, and very poorly controlled in 4.5% of the patients. During this period, only 24.7% (44/178) of the patients had ever visited a hospital or clinic for asthma, of whom 11 patients had 2 visits, and 6 had ≥3 visits, totaling 74 visits. 14.9% (11/74) of all medical visits were due to exacerbation of asthma, while the remaining visits (63/74, 85.1%) were for regular prescription of asthma medications. Only 6 patients (3.4%) sought consultation online. (Table 1)Notably, 25.6% (45/176) of the patients experienced aggravation of asthma symptoms during the COVID-19 epidemic, but 75.6% (34/45) of them did not see a doctor, because 67.6% (23/34) of the patients thought that they did not need to go to the hospital and took more medications by themselves, and the remaining 32.4% (11/34) worried about cross-infection of COVID-19 in the hospital. No patient said that they did not see a doctor because they could not arrange an appointment. Eleven patients went to the hospital due to aggravation, 81.8% (9/11) to the outpatient, while only 18.2% (2/11) to the Emergency Department (ED).Table 1 Asthma control and management during the COVID-19 epidemic in Beijing

Infection with the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) induces the coronavirus infectious disease 19 (COVID-19). Its pandemic form in human population and its probable animal origin, along with recent case reports in pets, make drivers of emergence crucial in carnivore domestic pets, especially cats, dogs and ferrets. Few data are available in these species; we first listed forty-six possible drivers of emergence of COVID-19 in pets, regrouped in eight domains (i.e. pathogen/disease characteristics, spatial-temporal distance of outbreaks, ability to monitor, disease treatment and control, characteristics of pets, changes in climate conditions, wildlife interface, human activity, and economic and trade activities). Secondly, we developed a scoring system per driver, then elicited experts (N = 33) to: (i) allocate a score to each driver, (ii) weight the drivers scores within each domain and (iii) weight the different domains between them. Thirdly, an overall weighted score per driver was calculated; drivers were ranked in decreasing order. Fourthly, a regression tree analysis was used to group drivers with comparable likelihood to play a role in the emergence of COVID-19 in pets. Finally, the robustness of the expert elicitation was verified. Five drivers were ranked with the highest probability to play a key role in the emergence of COVID-19 in pets: availability and quality of diagnostic tools, human density close to pets, ability of preventive/control measures to avoid the disease introduction or spread in a country (except treatment, vaccination and reservoir(s) control), current species specificity of the disease causing agent and current knowledge on the pathogen. As scientific knowledge on the topic is scarce and still uncertain, expert elicitation of knowledge, in addition with clustering and sensitivity analyses, is of prime importance to prioritize future studies, starting from the top five drivers. The present methodology is applicable to other emerging pet diseases.

We present a late presentation of saddle pulmonary embolism and thrombus-in-transit straddle the patent foramen on patient who successfully recovered from severe acute respiratory syndrome coronavirus-2 (COVID-19) pneumonia. Seven days post-discharge (i.e. 28 days after initial COVID-19 symptom onset), she was readmitted to hospital for severe dyspnea. Computer tomography angiogram and echocardiography confirmed the diagnosis. Severe pro-inflammatory and pro-thrombotic states with endothelial involvement have been reported associated with severe COVID-19 infection. However the duration of hypercoagulable state has not yet known. This case highlights the risk of thromboembolic phenomena for prolonged periods of times after recovering from COVID-19 pneumonia.

Point-of-care tests (POCTs) offer considerable potential for improving clinical and public health management of COVID-19 by providing timely information to guide decision-making, but data on real-world performance are in short supply. Besides SARS-CoV2-specific tests, there is growing interest in the role of surrogate (non-specific) tests such as FebriDx, a biochemical POCT which can be used to distinguish viral from bacterial infection in patients with influenza-like illnesses. This short communication assesses what is currently known about FebriDx performance across settings and populations by comparison with some of the more intensively evaluated SARS-CoV2-specific POCTs. While FebriDx shows some potential in supporting triage for early-stage infection in acute care settings, this is dependent on SARS-CoV2 being the most likely cause for influenza-like illnesses, with reduction in discriminatory power when COVID-19 case numbers are low, and when co-circulating viral respiratory infections become more prevalent during the autumn and winter. Too little is currently known about its performance in primary care and the community to support use in these contexts and further evaluation is needed. Reliable SARS CoV2-specific POCTs – when they become available – are likely to rapidly overtake surrogates as the preferred option given the greater specificity they provide.

Coronavirus disease 2019 (COVID-19) may present with different symptoms and complications. Acrocyanosis and digital necrosis may be associated with COVID-19. We describe two patients with COVID-19 who died with acrocyanosis and digital necrosis at the terminal stage of their illness.

An increasing number of COVID-19 cases worldwide has overwhelmed the healthcare system. Physicians are struggling to allocate resources and to focus their attention on high-risk patients, partly because early identification of high-risk individuals is difficult. This can be attributed to the fact that COVID-19 is a novel disease and its pathogenesis is still partially understood. However, machine learning algorithms have the capability to correlate a large number of parameters within a short period of time to identify the predictors of disease outcome. Implementing such an algorithm to predict high-risk individuals during the early stages of infection, would be helpful in decision making for clinicians. Here, we propose recommendations to integrate machine learning model with electronic health records so that a real-time risk score can be developed for COVID-19.

Most common clinical manifestations of COVID-19 are fever, dry cough, dyspnea, fatigue, myalgia, sore throat, expectoration, hemoptysis, nausea, diarrhoea, abdominal pain and headache. But pleuritic chest pain as lone presenting symptom with COVID-19 is not reported till date.

Background and Purpose: SARS-coV-2 pandemic continues to cause an unprecedented global destabilization. There is an urgent need to develop vaccines or identify molecules to treat severe cases and repurposing of drugs is the best approach at this hour. Thalidomide, despite having an infamous history has been successfully repurposed and tested for various disease conditions including inflammatory diseases and tumor. Few reports emphasize the use of thalidomide with a SARS-coV-2 pneumonia patient being successfully treated with thalidomide. Experimental Approach: A meta-analysis comparing the transcriptomes of SARS-coV-2 infected tissues with thalidomide and lenalidomide-induced transcriptomic changes in transformed lung, endothelial and hematopoietic models was performed. Key Results: Thalidomide and lenalidomide exhibited pleiotropic effects affecting a range of biological processes including inflammation, immune response, angiogenesis, MAPK signaling, NOD-like receptor signaling, TLR signaling, leukocyte differentiation and innate immunity, the processes which are aberrantly regulated in severe COVID-19 patients. In addition, we show the similarities between the expression profiles of SARS-coV-2 infected lung and systemic lupus erythematous. Conclusion and Implications: The present study recommends thalidomide analogs as a “better fit” to treat severe cases of novel viral infections, healing the damaged network by compensating the impairment caused by the Coronavirus disease-2019 (COVID-19).

The covid-19 pandemic has forced citizens worldwide to rely on social distancing measures as the main tools to prevent the rapid spreading of the virus (1). In pediatric oncology, there were important initial concerns for immunocompromised patients who were considered to be at higher risk of developing severe form of the disease (2,3). Consequently, potential challenges (2) have been identified and advice given by the principal child cancer organizations (3). Although more experience from countries that have been facing the pandemic are being published, results are inconsistent so far ranging from reassuring in Milano (4), Madrid (5) or New York (6) to worrying in France where 4 out of 33 Covid-19 positive patients required intensive care and 1 death at last follow up (7).Over the last weeks, despite the pandemic we were able to maintain “normal“ care for pediatric cancer patients in our institution, including high-dose chemotherapy followed by peripheral stem cells transplantations, or recruitment in early phase clinical trials. Only follow-up visits have been re-scheduled or switched to remote consultations. After almost 2 months of lock-down and still ongoing social distancing measures, an unexpected challenge has emerged. Inddeed, during that period, as usual we had to break bad news: for diagnosis, for relapse or palliative care. Initially, when breaking bad news, I had the feeling something was going wrong, or at least was not going as usual. Was I doing something wrong? Was stress induced by a high level of anxiety due to the lack of specific information on the real risk for adolescents/children with cancer both among the medical team and or parents affecting the “breaking bad news” process?Why didn’t I take that teenagers in my arms after disclosing her a metastatic relapse and she looked in such a distress?Social distancing!Masks to start with. They are of course a barrier to saliva droplets potentially containing covid-19, but most importantly they are also a barrier to adequately transmit and discriminate emotions just relying on eyes expression, looks…beyond tears. Silent communication with long looks without words can sometimes be enough and better that long talks but do parents and children feel the same when half of the face is covered. I asked about it to one of my patients and he answered“I think can read your eyes” . By increasing the physical space between people to avoid virus spreading, but here again, for physicians and some parents/patients, holding hands, holding shoulders, hugging are important non-verbal elements of communications and help showing compassion.We might break social distancing to break bad news, but if not pre-agreed by the patient or its parents, is it acceptable? Couldn’t it be perceived as an additional threat, contribute to alter intuitive communication which is characterized by broad, shared goals and mutual respect?Breaking bad news while trying to maintain social distancing is an unexpected new challenge associated with Covid-19. We will very likely learn to better communicate, read & share our respective emotions even with masks and physical distancing and sometimes allow ourselves exceptions to social distancing. Meanwhile, this impact shall be further evaluated among all stakeholders: patients, their parents, and physicians and adapted strategies to better cope with it developed.

The pandemic of the novel coronavirus disease, COVID-19 is having a serious impact on pediatric patients with cancer. Social distancing, self-quarantining and nationwide lockdown have resulted in restricted movements of patients and families across the country. This has made the optimum management of children with cancer difficult. In this clinical perspective, we discuss the issues related to COVID-19 and pediatric cancer and how we have attempted to optimize the treatment for our patients using telemedicine, reorganizing the day care services, triaging our patients and modifying their treatment plans, partnered with the NGOs and local medical centres to provide care to our patients.

With the pandemic emergence of SARS-CoV-2, the exposure of cell substrates used for manufacturing of medicines has become a possibility. Cell lines used in biomanufacturing were thus evaluated for their SARS-CoV-2 susceptibility, and the detection of SARS-CoV-2 in culture supernatants was tested by routine adventitious virus testing of fermenter harvest.

Flying fox (Pteropus hypomelanus) belongs to the frugivorous bats, which play a crucial role in maintaining proper functioning of an ecosystem and conservation of environment. Bats are well known carriers of pathogenic viruses such as BatCov RaTG13 from the coronavirus family that share 90.55% with SARS-CoV-2, the pathogen causing recent global pandemic coronavirus disease 19 (COVID-19). However, bats’ possible role as a carrier of pathogenic bacteria is less explored. Here, using metagenomic analysis through high-throughput sequencing, we explored the gut microbiome composition of different island populations on the east and west coasts of Peninsula Malaysia. The 16S rRNA gene in samples from Redang Island, Langkawi Island, Pangkor Island and Tinggi Island was amplified. Bacterial community composition and structure were analyzed with α and β diversity metrics. In contrast to recent studies of host-microbe associations in other mammals, we found no correlation between host phylogeny and bacterial community dissimilarity across four island populations. Our analyses suggest that the significant linear relationship between Redang Island and Langkawi Island implies high bacteria diversity which supporting latitudinal correlation. We found geographic locality is a strong predictor of microbial community composition and observed a positive correlation between ecological features and bacterial richness.

Tracing and isolation of close contacts is used to control outbreaks of coronavirus disease 2019 (COVID-19) in China. However, risk factors associated with occurrence of COVID-19 among close contacts have not been well described. 106 household contacts were included in this study, of whom 19 were developed into COVID-19 cases and the secondary attack rate was 17.9%. Multivariable analysis showed increasing risk of occurrence of COVID-19 among household contacts associated with female of index patients (Adjusted Hazard Ratio [aHR] = 5.61, 95%CI = 1.51-20.83), critical disease of index patients ([aHR] = 7.58, 95%CI = 1.66-34.66), effective contact duration with index patients >2 days ([aHR] = 4.21, 95%CI = 1.29-13.73), and effective contact duration >11 days ([aHR] = 17.88, 95%CI = 3.26-98.01).The sex and disease severity of index COVID-19 patients, and longer effective contact duration with COVID-19 confirmed cases could help epidemiologists to identify potential COVID-19 case among household contacts at an early stage.

The SARS-CoV-2 strain of the coronavirus is responsible for the current COVID-19 pandemic, with an ongoing toll of over 5 million infections and 333 thousand deaths worldwide within the first 5 months. Insight into the phylodynamics and mutation variants of this strain is vital to understanding the nature of its spread in different climate conditions. The incidence rate of COVID-19 is increasing at an alarming pace within subtropical Southeast Asian nations with high temperatures and humidity. To understand this spread, we analyzed 60 genome sequences of SARS-CoV-2 available in GISAID platform from 6 Southeast Asian countries. Multiple sequence alignments and maximum likelihood phylogenetic analyses were performed to analyze and characterize the non-synonymous mutant variants circulating in this region. Global mutation distribution analysis showed that the majority of the mutations found in this region are also prevalent in Europe and North America, and the concurrent presence of these mutations at a high frequency in Australia and Saudi Arabia indicate possible transmission routes. Unique spike protein and non-structural protein mutations were observed circulating within a localized area. We divided the circulating viral strains into 4 major groups and 2 sub-groups on the basis of the most frequent non-synonymous mutations. Strains with a unique set of 4 co-evolving mutations were found to be circulating at a high frequency within India, specifically, group 2 strains characterized by two co-evolving NS mutants which alter in RdRp (P323L) and spike protein (D614G) common in Europe and North America. These European and North American variants (Nextstrain clade A2) have rapidly emerged as dominant strains within Southeast Asia, increasing from a 0% presence in January to an 85% presence by May 2020. These variants may have an evolutionary advantage over their ancestral types and could present the largest threat to Southeast Asia for the coming winter.

Title: Age-related risk of household transmission of COVID-19 in SingaporeRachael Pung1, Minah Park2,3, Alex R Cook2,3, Vernon J Lee1,21 Ministry of Health, Singapore2 Saw Swee Hock School of Public Health, National University of Singapore3 National University Health System

The Coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is overwhelming healthcare resources and infrastructure worldwide. Cardiac surgical operating capacity during the COVID-19 pandemic is dramatically lower due to postponement or cancellation of elective or semi-urgent procedures. Earlier reports have demonstrated complicated post-operative courses and high fatality rates in patients undergoing emergent cardiothoracic surgery who were diagnosed post-operatively with COVID-19. These reports raise the possibility that active COVID-19 might precipitate a catastrophic pathophysiogical response to infection in the post-operative period and lead to unfavorable surgical outcomes. Hence, it is imperative to screen patients with SARS-CoV-2 infection prior to surgery and to carefully monitor them in the post-operative period to identify any early signs of active COVID-19. In this report, we present the successful outcome of coronary artery bypass grafting (CABG) operation in a patient with asymptomatic SARS-CoV-2 infection presenting with an acute coronary syndrome and requiring urgent surgical intervention. We employed a meticulous strategy to identify subclinical COVID-19 disease, and after confirming the absence of active disease, proceeded with the CABG operation. The patient outcome was successful with the absence of any overt COVID-19 manifestations in the post-operative period.

The authors share their experience of managing the cardiac surgery services across London during the challenging Covid-19 pandemic. The Pan London Emergency Cardiac Surgery Service model could serve as a blueprint to design policies applicable to other surgical specialities and parts of the UK and worldwide.

COVID-19 PANDEMIC: A CHALLENGE TO A CHILD WITH CANCER Dear Editor,People of all ages can be infected by the new coronavirus (2019-nCoV). Older people, and people with pre-existing medical conditions (such as asthma, diabetes, heart disease) are more vulnerable to becoming severely ill with the virus. There is a widespread anxiety among families of children with cancer due to risk of exposure to SARS-CoV-2, either in the hospital or community setting. [1]Recently Ogimi et al [2] reported that infants and younger children (i.e., ≤5 years) are more likely to develop severe clinical manifestations than older children, maybe due to immaturity of the immune system. Sullivan et al [3] reported that the COVID-19 pandemic was one of the most serious global challenge to delivering affordable and equitable treatment to children with cancer. They have provided some practical advice for adapting diagnostic and treatment protocols for children with cancer during the pandemic, the measures to be taken to contain it (e.g. extreme social distancing) and how to prepare for the anticipated recovery period.The Government and administrative measures such as lockdown has further compounded these challenges. Lack of state transport, closure of district borders, non-availability of medications has put these children at risk of rapid growth of disease, delay in treatment and poor outcome. A four and half year-old child, a known case of synchronous bilateral Wilms tumour, having undergone bilateral nephron sparing surgery was on adjuvant chemotherapy. The COVID-19 pandemic brought about an interruption in his chemotherapy schedule in January 2020. When he presented in early May, he had a small swelling of 1.5 cm diameter below the left subcostal margin (Figure 1a). Ultra sonography revealed a hypoechoic lesion below the skin measuring 1.5 cm in diameter (Figure 1b). Fine needle aspiration cytology was done which revealed sheets of cells with high nuclear/cytoplasm ratio (Figure 1c). The features were highly suspicious of a malignant lesion. The lesion was excised and histo-pathological examination revealed a metastasis from WILMS tumour (Figure 1d). The child has been resumed on further chemotherapy.Most childhood cancers behave aggressively and need immediate treatment, often requiring prolonged periods of intensive multiagent chemotherapy. Postponement of treatment such as surgery, radiation and chemotherapy is not a safe option in children. There is an urgent need amongst health professionals and families for informed guidance on the range of reasonable and safe adaptations to their services and cancer treatment during the pandemic.Conflict of Interest: None.Compliance with Ethical Standards.

In December 2019, China reported the first cases of the coronavirus disease 2019 (COVID-19). This disease, caused by the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), has developed into a pandemic. To date it has resulted in ~5.6 million confirmed cases and caused 353,334 related deaths worldwide. Unequivocally, the COVID-19 pandemic is the gravest health and socio-economic crisis of our time. In this context, numerous questions have emerged in demand of basic scientific information and evidence-based medical advice on SARS-CoV-2 and COVID-19. Although the majority of the patients show a very mild, self-limiting viral respiratory disease, many clinical manifestations in severe patients are unique to COVID-19, such as severe lymphopenia and eosinopenia, extensive pneumonia, a “cytokine storm” leading to acute respiratory distress syndrome, endothelitis, thrombo-embolic complications and multiorgan failure. The epidemiologic features of COVID-19 are distinctive and have changed throughout the pandemic. Vaccine and drug development studies and clinical trials are rapidly growing at an unprecedented speed. However, basic and clinical research on COVID-19-related topics should be based on more coordinated high-quality studies. This paper answers pressing questions, formulated by young clinicians and scientists, on SARS-CoV-2, COVID-19 and allergy, focusing on the following topics: virology, immunology, diagnosis, management of patients with allergic disease and asthma, treatment, clinical trials, drug discovery, vaccine development and epidemiology. Over 140 questions were answered by experts in the field providing a comprehensive and practical overview of COVID-19 and allergic disease.

Aims: Accumulating evidence links COVID-19 incidence and outcomes with vitamin D status. We investigated if an interaction existed between vitamin D levels and social deprivation in those with and without COVID-19 infection. Methods: Upper- or lower-respiratory tract samples from 104 patients were tested for SARS-CoV-2 RNA in accordance with Public Health England criteria (January–May 2020) using RT-PCR. The latest serum total 25-hydroxyvitamin D(25-OHD) levels, quantified by LC-MS/MS, was obtained for each patient (September 2019–April 2020). Index of Multiple Deprivation (IMD) was generated for each patient. Univariate and logistic regression analyses examined associations between age, gender, 25-OHD, IMD score and SARS-CoV-2 result in the total cohort and subgroups. Results: In the total cohort, a positive SARS-CoV-2 test was significantly associated with lower 25-OHD levels and higher IMD. A positive test was associated with higher IMD in the male subgroup and with lower 25-OHD levels in those aged >72 years. Low 25-OHD and IMD quintile 5 were separately associated with positive COVID-19 outcome in the cohort. Patients in IMD quintile 5 with vitamin D levels ≤34.4 nmol/L were most likely to have a positive COVID-19 outcome, even more so if aged >72 years (OR: 19.07, 95%CI: 1.71–212.25; p=0.016). Conclusions: In this cohort, combined low vitamin D levels and higher social deprivation were most associated with COVID-19 infection. In older age, this combination was even more significant. Our data supports the recommendations for normalising vitamin D levels in those with deficient / insufficient levels and in groups at high-risk for deficiency.

Our purpose is to assess epidemiological agent-based models– or ABMs - of the SARS-CoV-2 pandemic methodologically. The rapid spread of the outbreak requires fast-paced decision-making regarding mitigation measures. However, the evidence for the efficacy of non-pharmaceutical interventions such as imposed social distancing and school or workplace closures is scarce: few observational studies use quasi-experimental research designs, and conducting randomized controlled trials seems infeasible. Additionally, evidence from the previous coronavirus outbreaks of SARS and MERS lacks external validity, given the significant differences in contagiousness of those pathogens relative to SARS-CoV-2. To address the pressing policy questions that have emerged as a result of COVID-19, epidemiologists have produced numerous models that range from simple compartmental models to highly advanced agent-based models. These models have been criticized for involving simplifications and lacking empirical support for their assumptions. In order to address these voices and methodologically appraise epidemiological ABMs, we consider AceMod (the model of the COVID-19 epidemic in Australia) as an example of the modeling practice. Our case study shows that, although epidemiological ABMs involve simplifications of various sorts, the key characteristics of social interactions and the spread of SARS-CoV-2 are represented sufficiently accurately. This is the case because these modelers treat empirical results as inputs for constructing modeling assumptions and rules that the agents follow; and they use calibration to assert the adequacy to benchmark variables. Given this, we claim that the best epidemiological ABMs are models of actual mechanisms and deliver both mechanistic and difference-making evidence. Furthermore, the efficacy claims are not only internally valid but also adequately describe the effects of interventions in the targets of the models. We also discuss the limitations of ABMs and put forward policy recommendations.

Objectives To investigate the ability of a physical barrier to reduce aerosol particle spread during a simulated aerosol generating procedure. Design A simulated aerosol generating procedure. Setting Standard hospital ward, St George’s Hospital, London. Participant One volunteer participant - they were healthy, asymptomatic, and a non-smoker. Main Outcome Measures 1. To compare the effect of the shield on particle frequency (according to particle size) at different locations. 2. To evaluate the length of time that particles remained within the shield, both with and without an aspiration unit. Results Clinical investigations using the shield demonstrated a twelve-fold decrease in the number of particles detected at the position of the operating surgeon when the shield was used (particle size 0.3μm; with shield 8662 versus 103800 without shield). Over a 7-minute period, there was a reduction in the number of particles. At 7 minutes, the total number of particles (size 0.3μm) measured within the shield was comparable to the particle frequency at ambient levels (8752 within the shield compared with 8592 within the ambient environment). The aspiration unit reduced the number of particles detected within the shield over time. An average of 9649 particles (similar to ambient level) sized 0.3μm were measured under the shield after 2 minutes when the aspiration unit was used. Conclusion The clinical simulation illustrates a significant decrease in the number of particles detected at varying locations when the shield is used. The shield, used with appropriate PPE, could help to minimise exposure to aerosol-generated particles such as during tracheostomies on patients with COVID-19.