title: C-Reactive protein and SOFA score as early predictors of critical care requirement in patients with COVID-19 pneumonia in Spain.

text: Background: Some patients infected by SARS-CoV-2 in the recent pandemic have required critical care, becoming one of the main limitations of the health systems. Our objective has been to identify potential markers at admission predicting the need for critical care in patients with COVID-19 pneumonia Methods: We retrospectively collected and analyzed data from electronic medical records of patients with laboratory-confirmed SARS-CoV-19 infection by real-time RT-PCR. A comparison was made between patients staying in the hospitalization ward with those who required critical care. Univariable and multivariable logistic regression methods were used to identify risk factors predicting critical care need Findings: Between March 15 and April 15, 2020, 150 patients under the age of 75 were selected (all with laboratory confirmed SARS-CoV-19 infection), 75 patients requiring intensive care assistance and 75 remaining the regular hospitalization ward. Most patients requiring critical care were males, 76% compared with 60% in the non-critical care group (p<0,05). Multivariable regression showed increasing odds of in-hospital critical care associated with increased C-reactive protein (CRP) (odds ratio 1,052 (1,009-1,101); p=0,0043) and higher Sequential Organ Failure Assessment (SOFA) score (1,968 (1,389-2,590) p<0,0001) both at the time of hospital admission. The AUC-ROC for the combined model was 0,83 (0,76-0,90) (vs AUC-ROC SOFA p<0,05) Interpretation: Patients COVID-19 positive presenting at admission with high SOFA score [≥]2 combined with CRP [≥] 9,1 mg/mL could help clinicians to identify them as a group that will more likely require critical care so further actions might be implemented to improve their prognosis


title: A modified SEIR model to predict the COVID-19 outbreak in Spain and Italy: simulating control scenarios and multi-scale epidemics

text: After the spread of SARS-CoV-2 epidemic out of China, evolution in the pandemic worldwide shows dramatic differences among countries. In Europe, the situation of Italy first and later Spain has generated great concern, and despite other countries show better prospects, large uncertainties yet remain on the future evolution and the efficacy of containment, mitigation or attack strategies. Here we applied a modified SEIR compartmental model accounting for the spread of infection during the latent period, in which we also incorporate effects of varying proportions of containment. We fit data to quarantined populations in order to account for the uncertainties in case reporting and study the scenario projections for the 17 individual regions (CCAA). Results indicate that with data for March 23, the epidemics follow an evolution similar to the isolation of 1,5 percent of the population and if there were no effects of intervention actions it might reach a maximum of over 1.4M infected around April 27. The effect on the epidemics of the ongoing partial confinement measures is yet unknown (an update of results with data until March 31st is included), but increasing the isolation around ten times more could drastically reduce the peak to over 100k cases by early April, while each day of delay in taking this hard containment scenario represents a 90 percent increase of the infected population at the peak. Dynamics at the sub aggregated levels of CCAA show epidemics at the different levels of progression with the most worrying situation in Madrid an Catalonia. Increasing alpha values up to 10 times, in addition to a drastic reduction in clinical cases, would also more than halve the number of deaths. Updates for March 31st simulations indicate a substantial reduction in burden is underway. A similar approach conducted for Italy pre- and post-interventions also begins to suggest substantial reduction in both infected and deaths has been achieved, showing the efficacy of drastic social distancing interventions.


title: SUCCESSFUL MANUFACTURING OF CLINICAL-GRADE SARS-CoV-2 SPECIFIC T CELLS FOR ADOPTIVE CELL THERAPY

text: Background Adoptive therapy with SARS-CoV-2 specific T cells for COVID-19 has not been reported. The feasibility of rapid clinical-grade manufacturing of virus-specific T cells from convalescent donors has not been demonstrated for this or prior pandemics. Methods One unit of whole blood was collected from each convalescent donor following standard blood bank practices. After the plasma was separated and stored separately, the leukocytes were stimulated using overlapping peptides of SARS-CoV-2, covering the immunodominant sequence domains of the S protein and the complete sequence of the N and M proteins. Thereafter, functionally reactive cells were enriched overnight using an automated device capturing IFN{gamma}-secreting cells. Findings From 1x10[9] leukocytes, 0.56 to 1.16x10[6] IFN{gamma}+ T cells were produced from each of the first two donors. Most of the T cells (64% to 71%) were IFN{gamma}+, with preferential enrichment of CD56+ T cells, effector memory T cells, and effector memory RA+ T cells. TCRV{beta} spectratyping revealed oligoclonal distribution, with over-representation of subfamilies including V{beta}3, V{beta}16 and V{beta}17. With just two donors, the probability that a recipient in the same ethnic group would share at least one donor HLA allele or one haplotype could be as high as >90% and >30%, respectively. Interpretations This study is limited by small number of donors and absence of recipient data; however, crucial first proof-of-principle data are provided demonstrating the feasibility of clinical-grade production of SARS-CoV-2 specific T cells for urgent clinical use, conceivably with plasma therapy concurrently. Our data showing that virus-specific T cells can be detected easily after brief stimulation with SARS-CoV-2 specific peptides suggest that a parallel diagnostic assay can be developed alongside serology testing.


title: The true case fatality of COVID19: An analytical solution

text: The exact risk of dying from COVID-19 has remained elusive and a topic of debate. The observed case fatality rates of 46 different countries are hypothesized to be dependent on their testing rates. An analytical test to this hypothesis suggests that the case fatality rate of COVID-19 could be consistent to a certain degree across all countries and states. The current global fatality rate is estimated to be around 1% and expected to converge between 1-3% when the pandemic ends. This model can be helpful to estimate the true infection rate for individual countries.


title: Systemic analysis of putative SARS-CoV-2 entry and processing genes in cardiovascular tissues identifies a positive correlation of BSG with age in endothelial cells

text: COVID-19, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has rapidly spread throughout the world with unprecedented global healthcare and socio-economic consequences. There is now an established secondary syndrome of COVID-19 characterised by thrombosis, vascular dysfunction and hypertension, seen in those most severely affected. Advancing age in adults is the single most significant risk factor for hospitalisation and death with COVID-19. In light of the cardiovascular/thrombotic sequalae associated with severe COVID-19 disease and the overwhelming risk that increased age carries, in this study, our aim was to obtain mechanistic insight by interrogating gene expression profiles in cardiovascular tissues and cells. Our focus was on the two putative receptors for SARS-CoV-2, ACE2 and BSG along with a selected range of genes thought to be involved in virus binding/processing. In this study we have made four important observations: (i)Cardiovascular tissues and/or endothelial cells express the required genes for SARS-CoV-2 infection, (ii) SASR-CoV-2 receptor pathways, ACE2/TMPRSS2 and BSG/PPIB(A) polarise to lung/epithelium and vessel/endothelium respectively, (iii) expression of SARS-CoV-2 host genes are, on the whole, relatively stable with age and (iv) notable exceptions were ACE2 which decreases with age in some tissues and BSG which increases with age in endothelial cells. Our data support the idea that that BSG is the dominate pathway utilised by SARS-CoV-2 in endothelial cells and are the first to demonstrate a positive correlation with age. We suggest BSG expression in the vasculature is a critical driver which explains the heightened risk of severe disease and death observed in those >40 years of age. Since BSG is utilised by other pathogens our findings have implications beyond the current pandemic. Finally, because BSG is functions in a range of cardiovascular diseases and fibrosis, our observations may have relevance to our understanding of the diseases associated with aging.


title: Partial unlock model for COVID-19 or similar pandemic averts medical and economic disaster

text: Data as of March 29, 2020 show that the flattening strategy for COVID-19 in the U.S. is working so well that a clean removal of social distancing (aka unlock) at any time in 2020 will produce a renewed catastrophe, overloading the healthcare system. Leaving the economy locked down for a long time is its own catastrophe. An SIR-type model with clear parameters suitable for public information, and both tracking and predictive capabilities which learns disease spread characteristics rapidly as policy changes, suggests that a solution to the problem is a partial unlock. Case load can be managed so as not to exceed critical resources such as ventilators, yet allow enough people to get sick that herd immunity develops and a full unlock can be achieved in as little as five weeks from beginning of implementation. The partial unlock could be for example 3 full working days per week. Given that not all areas or individuals will respond, and travel and public gatherings are still unlikely, the partial unlock might be 5 full working days per week. The model can be regionalized easily, and by expediting the resolution of the pandemic in the U.S. medical equipment and volunteers, many of them with already acquired immunity, can be made available to other countries.


COVID-19 international outbreak and the need for a suitable estimation model: A second-order polynomial equation with constant coefficients based on imported infected cases seems inadequate


title: Traffic-derived particulate matter and angiotensin-converting enzyme 2 expression in human airway epithelial cells

text: Background The mechanism for the association between traffic-derived particulate matter less than 10 microns (PM10) and cases of COVID-19 disease reported in epidemiological studies is unknown. To infect cells, the spike protein of SARS-CoV-2 interacts with angiotensin-converting enzyme 2 (ACE2) on host airway cells. Increased ACE2 expression in lower airway cells in active smokers, suggests a potential mechanism whereby PM10 increases vulnerability to COVID-19 disease. Objective To assess the effect of traffic-derived PM10 on human airway epithelial cell ACE2 expression in vitro. Methods PM10 was collected from Marylebone Road (London) using a kerbside impactor. A549 and human primary nasal epithelial cells were cultured with PM10 for 2 h, and ACE2 expression (median fluorescent intensity; MFI) assessed by flow cytometry. We included cigarette smoke extract as a putative positive control. Data were analysed by either Mann-Whitney test, or Kruskal-Wallis with Dunn’s multiple comparisons test. Results PM10 at 10 μg/mL, and 20 μg/mL increased ACE2 expression in A549 cells (P<0.05, 0.01 vs. medium control, respectively). Experiments using a single PM10 concentration (10 μg/mL), found increased ACE2 expression in both A549 cells (control vs. PM10, median (IQR) MFI; 470 (0.1 to 1114) vs 6217 (5071 to 8506), P<0.01), and in human primary epithelial cells (0 (0 to 591) vs. 4000 (2610 to 7853), P<0.05). Culture of A549 cells with 5% cigarette smoke extract increased ACE2 expression (n=4, 0 (0 to 28) vs. 9088 (7557 to 15831, P<0.05). Conclusion Traffic-related PM10 increases the expression of the receptor for SARS-CoV-2 in human respiratory epithelial cells.


title: Platform philanthropy, ‘public value’, and the COVID-19 pandemic moment

text: This commentary examines the COVID-19 pandemic as a moment of strategic advancement for digital platforms. Focusing on the redeployment of Google Maps data for tracking adherence to mobility restrictions, I argue that demonstrating such ‘public value’ uses of Google’s vast geolocation and behavioral data forms part of a larger effort to strengthen their economic and political position in the face of two existential threats—declining advertising revenues and platform regulation.


title: Estimating the burden of United States workers exposed to infection or disease: a key factor in containing risk of COVID-19 infection

text: Introduction: With the global spread of COVID-19, there is a compelling public health interest in quantifying who is at increased risk of disease. Occupational characteristics, such as interfacing with the public and being in close quarters with other workers, not only put workers at high risk for disease, but also make them a nexus of disease transmission to the community. This can further be exacerbated through presenteeism, the term used to describe the act of coming to work despite being symptomatic for disease. Understanding which occupational groups are exposed to infection and disease in the workplace can help to inform public health risk response and management for COVID-19, and subsequent infectious disease outbreaks. Methods: To estimate the burden of United States workers exposed to infection and disease in the workplace, national employment data (by Standard Occupational Classification) maintained by the Bureau of Labor Statistics (BLS) was merged with BLS O*NET survey data, which ranks occupations with particular physical, ergonomic, and structural exposures. For this analysis, occupations reporting exposure to infection or disease more than once a month was the focus. Results: Based on our analyses, approximately 10% (14.4 M) of United States workers are employed in occupations where exposure to disease or infection occurs at least once per week. Approximately 18.4% (26.7 M) of all United States workers are employed in occupations where exposure to disease or infection occurs at least once per month. While the majority of exposed workers are employed in healthcare sectors, other occupational sectors also have high proportions of exposed workers. These include protective service occupations (e.g. police officers, correctional officers, firefighters), office and administrative support occupations (e.g. couriers and messengers, patient service representatives), education occupations (e.g. preschool and daycare teachers), community and social services occupations (community health workers, social workers, counselors), and even construction and extraction occupations (e.g. plumbers, septic tank installers, elevator repair). Conclusions: The large number of persons employed in a wide variety of occupations with frequent exposure to infection and disease underscore the importance of all workplaces developing risk response plans for COVID-19. This work also serves as an important reminder that the workplace is a key locus for public health interventions, which could protect both workers and the communities they serve.


title: Diagnosis of COVID-19 using CT scan images and deep learning techniques

text: Early diagnosis of the coronavirus disease in 2019 (COVID-19) is essential for controlling this pandemic. COVID-19 has been spreading rapidly all over the world. There is no vaccine available for this virus yet. Fast and accurate COVID-19 screening is possible using computed tomography (CT) scan images. The deep learning techniques used in the proposed method was based on a convolutional neural network (CNN). Our manuscript focuses on differentiating the CT scan images of COVID-19 and non-COVID 19 CT using different deep learning techniques. A self developed model named CTnet-10 was designed for the COVID-19 diagnosis, having an accuracy of 82.1 %. Also, other models that we tested are DenseNet-169, VGG-16, ResNet-50, InceptionV3, and VGG-19. The VGG-19 proved to be superior with an accuracy of 94.52 % as compared to all other deep learning models. Automated diagnosis of COVID-19 from the CT scan pictures can be used by the doctors as a quick and efficient method for COVID-19 screening.


title: Differences in antibody kinetics and functionality between severe and mild SARS-CoV-2 infections.

text: We determined and compared the humoral immune response in severe, hospitalized and mild, non-hospitalized COVID-19 patients. Severe patients (n=38) develop a robust antibody response to SARS-CoV-2, including IgG and IgA antibodies. The geometric mean 50% virus neutralization titer is 1:240. SARS-CoV-2 infected hospital personnel (n=24), who developed mild symptoms necessitating leave of absence, self-isolation, but not hospitalization, 75 % develop antibodies, but with low/absent virus neutralization (60% < 1:20). While severe COVID-19 patients develop a strong antibody response, mild SARS-CoV-2 infections induce a modest antibody response. Long term monitoring will show whether these responses predict protection against future infections.


title: Evaluating How Smartphone Contact Tracing Technology Can Reduce the Spread of Infectious Diseases: The Case of COVID-19

text: Detecting and controlling the diffusion of infectious diseases such as COVID-19 is crucial to managing epidemics One common measure taken to contain or reduce diffusion is to detect infected individuals and trace their prior contacts so as to then selectively isolate any individuals likely to have been infected These prior contacts can be traced using mobile devices such as smartphones or smartwatches, which can continuously collect the location and contacts of their owners by using their embedded localisation and communications technologies, such as GPS, Cellular networks, Wi-Fi, and Bluetooth This paper evaluates the effectiveness of these technologies and determines the impact of contact tracing precision on the spread and control of infectious diseases To this end, we have created an epidemic model that we used to evaluate the efficiency and cost (number of people quarantined) of the measures to be taken, depending on the smartphone contact tracing technologies used Our results show that in order to be effective for the COVID-19 disease, the contact tracing technology must be precise, contacts must be traced quickly, and a significant percentage of the population must use the smartphone contact tracing application These strict requirements make smartphone-based contact tracing rather ineffective at containing the spread of the infection during the first outbreak of the virus However, considering a second wave, where a portion of the population will have gained immunity, or in combination with some other more lenient measures, smartphone-based contact tracing could be extremely useful


title: Lactate dehydrogenase, a Risk Factor of Severe COVID-19 Patients

text: BACKGROUND The World Health Organization (WHO) has recently declared coronavirus disease 2019 (COVID-19) a public health emergency of global concern. Updated analysis of cases might help identify the characteristic and risk factors of the illness severity. METHODS We extracted data regarding 47 patients with confirmed COVID-19 from Renmin Hospital of Wuhan University between February 1 and February 18, 2020. The degree of severity of COVID-19 patients (severe vs. non-severe) was defined at the time of admission according to American Thoracic Society (ATS) guidelines for community-acquired pneumonia (CAP). RESULTS The median age was 64.91 years, 26 cases (55.31%) were male of which, and 70.83% were severe cases. Severe patients had higher APACHE II (9.92 vs 4.74) and SOFA (3.0 vs 1.0) scores on admission, as well as the higher PSI (86.13 vs 61.39), Curb-65 (1.14 vs 0.48) and CT semiquantitative scores (5.0 vs 2.0) when compared with non-severe patients. Among all univariable parameters, APACHE II, SOFA, lymphocytes, CRP, LDH, AST, cTnI, BNP, et al were significantly independent risk factors of COVID-19 severity. Among which, LDH was most positively related both with APACHE II (R = 0.682) and SOFA (R = 0.790) scores, as well as PSI (R = 0.465) and CT (R = 0.837) scores. To assess the diagnostic value of these selected parameters, LDH (0.9727) had maximum sensitivity (100.00%) and specificity (86.67%), with the cutoff value of 283. As a protective factor, lymphocyte counts less than 1.045 x 109 /L showed a good accuracy for identification of severe patients with AUC = 0.9845 (95%CI 0.959-1.01), the maximum specificity (91.30%) and sensitivity (95.24%). In addition, LDH was positively correlated with CRP, AST, BNP and cTnI, while negatively correlated with lymphocyte cells and its subsets, including CD3+, CD4+ and CD8+ T cells (P < 0.01). CONCLUSIONS This study showed that LDH coule be identified as a powerful predictive factor for early recognition of lung injury and severe COVID-19 cases. And importantly, lymphocyte counts, especially CD3+, CD4+, and CD8+ T cells in the peripheral blood of COVID-19 patients, which was relevant with serum LDH, were also dynamically correlated with the severity of the disease. FUNDING Key Project of Shanghai Municipal Health Bureau (2016ZB0202)


title: THE USE OF DENATURING SOLUTION AS COLLECTION AND TRANSPORT MEDIA TO IMPROVE SARS-COV-2 RNA DETECTION AND REDUCE INFECTION OF LABORATORY PERSONNEL

text: Background Since the emergence of the COVID-19, health officials have struggled to devise strategies to counteract the speed of the pandemic's spread across the globe. It became imperative to implement accurate diagnostic tests for the detection of SARS-CoV-2 RNA on respiratory samples. In many places, however, besides the limited availability of test reagents, laboratory personnel face the challenge of adapting their working routines to manipulate highly infective clinical samples. Here, we proposed the use of a virus-inactivating solution as part of a sample collection kit to decrease the infectious potential of the collected material without affecting the integrity of RNA samples used in diagnostic tests based on RT-qPCR. Methods Nasopharyngeal and oropharyngeal swab samples were collected from SARS-CoV-2-infected patients and from laboratory personnel using a commercially available viral transport solution (VTM) and the denaturing solution (DS) described here. RNA extracted from all samples was tested by RT-qPCR using probes for viral and human genes. Exposure of laboratory personnel to infective viruses was also accessed using ELISA tests. Findings The use of the DS did not interfere with the detection of viral genome or the endogenous human mRNA, since similar results were obtained from samples collected with VTM or DS. In addition, all tests of laboratory personnel for the presence of viral RNA and IgG antibodies against SARS-CoV-2 were negative. Interpretation The methodology described here provides a strategy that allow high diagnostic accuracy as well as safe manipulation of clinical samples by those involved with diagnostic procedures. Funding: CAPES, FAPEMIG, CNPq, MCTIC, FIOCRUZ and the UK Global Challenges Research Fund (GCRF).


title: Endemic human coronaviruses induce distinct antibody repertoires in adults and children

text: Four endemic human coronaviruses (HCoVs) are commonly associated with acute respiratory infection in humans but immune responses to these “common cold” viruses remain incompletely understood. Moreover, there is evidence emerging from independent studies which suggests that endemic HCoVs can induce broadly cross-reactive T cell responses and may thereby affect clinical outcomes of acute infections with the phylogenetically related epidemic viruses, namely MERS-CoV and SARS-CoV-2. Here we report a comprehensive retrospective analysis of CoV-specific antibody specificities in a large number of samples from children and adults using Phage-Immunoprecipitation Sequencing (PhIP-Seq). We estimate the seroprevalence for endemic HCoVs to range from ~4% to ~27% depending on species and cohort. Most importantly, we identified a large number of novel linear B cell epitopes of HCoV proteins and demonstrate that antibody repertoires against endemic HCoVs are qualitatively different in children in comparison to the general adult population and healthy adult blood bank donors. We show that anti-HCoV IgG specificities more frequently found among children target functionally important and structurally conserved regions of the HCoV spike and nucleocapsid proteins and some antibody specificities are broadly cross-reactive with peptides of epidemic human and non-human coronavirus isolates. Our findings shed light on the humoral immune responses to natural infection with endemic HCoVs and may have important implications for understanding of the highly variable clinical outcomes of human coronavirus infections, for the development of prophylactic or therapeutic monoclonal antibodies and vaccine design.


The COVID-19 outbreak: The latest challenge to psychological and psychiatric intervention


title: Health-care workers with COVID-19 living in Mexico City: clinical characterization and related outcomes

text: BACKGROUND: Health-care workers (HCWs) have increased risk for SARS-CoV-2 infection. Information about the prevalence and risk factors for adverse outcomes in HCWs is scarce in Mexico. Here, we aimed to explore prevalence of SARS-CoV-2, symptoms, and risk factors associated with adverse outcomes in HCWs in Mexico City. METHODS: We explored data collected by the National Epidemiological Surveillance System in Mexico City. All cases underwent real-time RT-PCR test. We explored outcomes related to severe COVID-19 in HCWs and the diagnostic performance of symptoms to detect SARS-CoV-2 infection in HCWs. RESULTS: As of July 2nd, 2020, 34,263 HCWs were tested for SARS-CoV-2, and 10,925 were confirmed (31.9%). Overall, 4,200 were nurses (38.4%), 3,244 physicians (29.7%), 126 dentists (1.15%) and 3,355 laboratory personnel and other HCWs (30.7%). After follow-up, 992 HCWs required hospitalization (9.08%), 206 developed severe outcomes (1.89%), and 90 required mechanical-ventilatory support (0.82%). Lethality was recorded in 224 (2.05%) cases. Symptoms associated with SARS-CoV-2 positivity were fever, cough, malaise, shivering, myalgias at evaluation but neither had significant predictive value. We also identified 333 asymptomatic SARS-CoV-2 infections (3.05%). Older HCWs with chronic non-communicable diseases, pregnancy, and severe respiratory symptoms were associated with higher risk for adverse outcomes. Physicians had higher risk for hospitalization and for severe outcomes compared with nurses and other HCWs. CONCLUSIONS: We report a high prevalence of SARS-CoV-2 in HCWs in Mexico City. No symptomatology can accurately discern HCWs with SARS-CoV-2 infection. Particular attention should focus on HCWs with risk factors to prevent adverse outcomes and reduce infection risk.


title: Quarantine decision due to coronavirus pandemic

text: These days the world is facing Coronavirus disease (COVID-19) pandemic. More or less, governments decide to quarantine some of the cities. However, it would be a hard decision to decide which cities should be on the list of quarantine due to the social, psychological and financial costs. This short letter is proposing a systematic methodology to solve this decision making challenge in public health administration.


title: Unreported cases for Age Dependent COVID-19 Outbreak in Japan

text: We investigate the age structured data for the COVID-19 outbreak in Japan. We consider epidemic mathematical model with unreported infectious patient with and without age structure. In particular, we build a new mathematical model which allows to take into account differences in the response of patients to the disease according to their age. This model also allows for a heterogeneous response of the population to the social distancing measures taken by the local government. We fit this model to the observed data and obtain a snapshot of the effective transmissions occurring inside the population at different times, which indicates where and among whom the disease propagates after the start of the public measures.


title: Supporting lives lived whilst protecting lives saved during COVID-19: The relational invariant in person-centred care

text: There has been an impressive development of nursing knowledge around the ethics, principles, frameworks, models and practices of person-centred care over the last 15 years, with colleagues from the Nordic countries making significant contributions to global knowledge across the discipline of nursing and beyond. A disciplinary challenge remains to map the variability in person-centred care with an aim to empirically clarify the invariant in person-centred care. Based on current research and practice, as well as the COVID-19 pandemic, this article argues that the relational aspect of person-centred care is such an invariant, building on the socially constructive notion of ‘personhood’ being a standing or status that is bestowed on one human being by another in the context of relationship and social being. During the current COVID-19 pandemic, several of the key determinants of person-centred care are under threat due to health service responses and/or infection control measures, such as keeping older adults safe, imposing relationship restrictions, social distancing and isolation (or the lack thereof). Clinical examples from an Australian health service are used to show how recognizing the relational invariant of person-centred aged care facilitated supporting lives lived whilst also protecting lives saved. The relational invariant to person-centred care is who we are, constructed or deconstructed by and with others; something that may have become more visible through the relational restrictions imposed due to COVID-19. Protecting relationality in life and care and advocating for both safe and person-centred care for those who need it most is now more important than ever.


Rationale for Prolonged Corticosteroid Treatment in the Acute Respiratory Distress Syndrome Caused by Coronavirus Disease 2019


Exploring the presence of animal origin in the causation of corona virus disease 2019 outbreak and strategies to prevent acquisition of the infection


title: Prevent the resurgence of infectious disease with asymptomatic carriers

text: As many countries reached the peak of the COVID-19 outbreak, there is debate on how to reopen the economy without causing a significant resurgence. Here we show, using a microsimulation model, that how to reopen safely depends on what percentage of COVID-19 cases can be detected by testing. The higher the detection rate, the less restrictive the reopen plan needs to be. If 70% of cases can be detected, schools and businesses can reopen if 2-layer quarantine is imposed on each confirmed case. Our results suggest that increasing the detection rate is essential to prevent the resurgence of COVID-19.


title: Evaluating growth pattern and assessing future scenario of COVID-19 epidemic of India

text: COVID-19 the modern pandemic has spread across the world at a rapid pace. SARS-CoV 2 is highly transmissible and the rate of infection is exponential for heavily infected countries. Asymptotic carriers and longer incubation period have been key towards such a large-scale distribution of disease. Data released by official authorities on COVID-19 cases is significantly affected by various factors such as size of sample, incubation period of disease and time taken to test the sample. These factors mask the useful pattern (signal) of disease spread. Thus, an ingenious method to group data into cycles of five and seven days, for studying pattern of disease spread is undertaken. Occurrence of recurrent peaks as indicated by Adjusted Rate of infection per day indicated the spread of disease has been non-uniform. Currently, India is yet to reach the critical point (peak of epidemic) with adjusted daily cases more than 1000. Increasing testing capacity along with random sampling and sample pooling can help in preventing formation of these peaks in future. The proposed method helps in assessing the current state and for predicting future scenarios epidemics.


Clinical characteristics and epidemiology survey of lung transplantation recipients accepting surgeries during the COVID-19 pandemic:from area near Hubei Province


title: Challenges posed by COVID-19 to the health of people with disabilities living in residential care facilities in Romania

text: In this contribution, I discuss potential risk to the health of people with disabilities in residential care institutions during the COVID-19 outbreak by looking at evidence from Romania. As an academic who has studied deinstitutionalization of services for people with disabilities in Romania, I argue that residential care institutions for people with disabilities are at risk of becoming sites for community contagion with COVID-19. These institutions are often located in remote and economically peripheral areas of the country that have been characterized by high rates of outmigration. Now, these are becoming areas of intense return migration. Community contagion in adjacent locations can easily spill over to residential institutions through care and health workers’ trajectories. Once spread to residential institutions, COVID-19 has a high chance of adversely affecting the health of residents with disabilities. It is vital to ensure disabled people’s health and wellbeing through adequate contagion prevention measures.


Public health preparedness towards COVID-19 outbreak in Nigeria


title: Antibiotic treatment for COVID-19 complications could fuel resistant bacteria

text: In her regular job, Priya Nori runs Montefiore Medical Center’s antibiotic stewardship program, and spends most of her time ensuring that the Bronx-based hospital doesn’t overuse the drugs and allow bacteria resistant to them to thrive But like many physicians, Nori is now spending all of her time helping treat COVID-19 patients at her New York City hospital, which like other medical centers in the pandemic hot spot, is crowded with 50% more patients than normal As part of that care, she and other doctors are administering many more antibiotics than normal, which is a recipe for the rapid rise or spread of resistant bacteria, especially given the crowded conditions


title: Comorbidity and its impact on 1,590 patients with COVID-19 in China: A Nationwide Analysis

text: Objective: To evaluate the spectrum of comorbidities and its impact on the clinical outcome in patients with coronavirus disease 2019 (COVID-19). Design: Retrospective case studies Setting: 575 hospitals in 31 province/autonomous regions/provincial municipalities across China Participants: 1,590 laboratory-confirmed hospitalized patients. Data were collected from November 21st, 2019 to January 31st, 2020. Main outcomes and measures: Epidemiological and clinical variables (in particular, comorbidities) were extracted from medical charts. The disease severity was categorized based on the American Thoracic Society guidelines for community-acquired pneumonia. The primary endpoint was the composite endpoints, which consisted of the admission to intensive care unit (ICU), or invasive ventilation, or death. The risk of reaching to the composite endpoints was compared among patients with COVID-19 according to the presence and number of comorbidities. Results: Of the 1,590 cases, the mean age was 48.9 years. 686 patients (42.7%) were females. 647 (40.7%) patients were managed inside Hubei province, and 1,334 (83.9%) patients had a contact history of Wuhan city. Severe cases accounted for 16.0% of the study population. 131 (8.2%) patients reached to the composite endpoints. 399 (25.1%) reported having at least one comorbidity. 269 (16.9%), 59 (3.7%), 30 (1.9%), 130 (8.2%), 28 (1.8%), 24 (1.5%), 21 (1.3%), 18 (1.1%) and 3 (0.2%) patients reported having hypertension, cardiovascular diseases, cerebrovascular diseases, diabetes, hepatitis B infections, chronic obstructive pulmonary disease, chronic kidney diseases, malignancy and immunodeficiency, respectively. 130 (8.2%) patients reported having two or more comorbidities. Patients with two or more comorbidities had significantly escalated risks of reaching to the composite endpoint compared with those who had a single comorbidity, and even more so as compared with those without (all P<0.05). After adjusting for age and smoking status, patients with COPD (HR 2.681, 95%CI 1.424-5.048), diabetes (HR 1.59, 95%CI 1.03-2.45), hypertension (HR 1.58, 95%CI 1.07-2.32) and malignancy (HR 3.50, 95%CI 1.60-7.64) were more likely to reach to the composite endpoints than those without. As compared with patients without comorbidity, the HR (95%CI) was 1.79 (95%CI 1.16-2.77) among patients with at least one comorbidity and 2.59 (95%CI 1.61-4.17) among patients with two or more comorbidities. Conclusion: Comorbidities are present in around one fourth of patients with COVID-19 in China, and predispose to poorer clinical outcomes.


title: Automatic Detection of COVID-19 Using X-ray Images with Deep Convolutional Neural Networks and Machine Learning

text: The COVID-19 pandemic continues to have a devastating effect on the health and well-being of the global population. A vital step in the combat towards COVID-19 is a successful screening of contaminated patients, with one of the key screening approaches being radiological imaging using chest radiography. This study aimed to automatically detect COVID-19 pneumonia patients using digital chest x-ray images while maximizing the accuracy in detection using deep convolutional neural networks (DCNN). The dataset consists of 864 COVID-19, 1345 viral pneumonia and 1341 normal chest x-ray images. In this study, DCNN based model Inception V3 with transfer learning have been proposed for the detection of coronavirus pneumonia infected patients using chest X-ray radiographs and achieved more than 96% accuracy. The results demonstrate that transfer learning proved to be effective, showed robust performance and easily deployable approach for COVID-19 detection.


title: Modelling strategies to predict hospital demand during the COVID-19 outbreak in Bogotá, Colombia

text: This paper presents a prediction of the total number of ICU and regular beds that will be needed during the pandemic COVID-19 for Bogotá-Colombia. We use a SEIR model that includes three different compartments of infection: those who can stay at home, those in regular hospital beds and those in need of ICU treatment. The model allows for a time varying transmission rate which we use to incorporate the measures introduced by the government over the period of one year. The model predicts that by mid July 2020, the city will reach the peak of the epidemic with a total of 22 526 prevalent ICUs needed and 84 816 regular hospital beds needed. By the end of May 2020, the number of patients that need ICUs will overpass the current capacity set at 2000 beds for ICU hospital beds in the city. The model predicts that the death toll by the same date will reach 1752 people and the number of cases will be 54652 inhabitants by then. We provide a Shiny app available in (https://claudia-rivera-rodriguez.shinyapps.io/shinyappcovidclinic/). The original values in the app reproduce the results of this paper, but the parameters and starting values can be changed according to the users needs.


title: Modeling geographical spread of COVID-19 in India using network-based approach

text: COVID-19 pandemic is a global concern, due to its high spreading and alarming fatality rate. Mathematical models can play a decisive role in mitigating the spread and predicting the growth of the epidemic. India is a large country, with a highly variable inter-state mobility, and dynamically varying infection cases in different locations; thus, the existing models, based solely on the aspects of growth rates, or generalized network concepts, may not provide desired predictions. The internal mobility of a country must be considered, for accurate prediction. Herein, we propose a framework for predicting the geographical spread of COVID-19, using reported COVID-19 cases, census migration data, and monthly airline data of passengers. We discover that spreading depends on the spatial distribution of existing cases, human mobility patterns, and administrative decisions. In India, the mobility towards professional sites can surge incoming cases at Maharastra and Karnataka, while migration towards the native places can risk Uttar Pradesh and Bihar. We anticipate that the state Kerala, with one of the highest cases of COVID-19, may not receive significant incoming cases, while Karnataka and Haryana may receive the challenge of high incoming cases, with medium cases so far. Using airline passenger's data, we also estimate the number of potential incoming cases at various airports. The study predicts that the airports located in the region of north India are vulnerable, whereas in northeast India and in some south India are relatively safe. The detailed analysis in this direction will guide policymakers for prior planning of transport, and minimize the spread of COVID-19.


title: Statistical and network-based analysis of Italian COVID-19 data: communities detection and temporal evolution

text: Coronavirus disease (COVID-19) outbreak started at Wuhan, China, and it has rapidly spread across China and many other countries. Italy is one of the European countries most affected by the COVID-19 disease, and it has registered high COVID-19 death rates and the death toll. In this article, we analyzed different Italian COVID-19 data at the regional level for the period February 24 to March 29, 2020. The analysis pipeline includes the following steps. After individuating groups of similar or dissimilar regions with respect to the ten types of available COVID-19 data using statistical test, we built several similarity matrices (reported in Supplementary file). Then, we mapped those similarity matrices into networks where nodes represent Italian regions and edges represent similarity relationships (edge length is inversely proportional to similarity). Then, network-based analysis was performed mainly discovering communities of regions that show similar behaviour. Then, network-based analysis was performed by running several community detection algorithms on those networks and by underlying communities of regions that show similar behaviour. The network-based analysis of Italian COVID-19 data is able to elegantly show how regions form communities, i.e. how they join and leave them, along time and how community consistency changes along time and with respect to the different available data.


title: Potent neutralizing antibodies in the sera of convalescent COVID-19 patients are directed against conserved linear epitopes on the SARS-CoV-2 spike protein

text: The ongoing SARS-CoV-2 pandemic demands rapid identification of immunogenic targets for the design of efficient vaccines and serological detection tools. In this report, using pools of overlapping linear peptides and functional assays, we present two immunodominant regions on the spike glycoprotein that were highly recognized by neutralizing antibodies in the sera of COVID-19 convalescent patients. One is highly specific to SARS-CoV-2, and the other is a potential pan-coronavirus target.


title: Development and clinical application of a rapid and sensitive loop-mediated isothermalamplification test for SARS-CoV-2 infection

text: Background The outbreak of SARS-CoV-2 urgently requires sensitive and convenient COVID-19 diagnostics to assure the containment and timely treatment of patients. We aimed to develop and validate a novel reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay to detect SARS-CoV-2 in both qualified laboratories and point-of-care settings. Methods Patients with suspected COVID-19 and close contacts between Jan 26 and April 8, 2020, were recruited from two hospitals. Respiratory samples were collected and tested with LAMP and the results were compared with those obtained by RT-qPCR. The inconsistent samples between these two methods were subjected to next-generation sequencing for confirmation. In addition, we tested the RT-LAMP on an asymptomatic COVID-19 carrier and patients with other respiratory viral infections. Results We finally collected a cohort of 129 cases (329 nasopharyngeal swabs) and the independent cohort of 76 patients (152 nasopharyngeal swabs and sputum samples). RT-LAMP was validated to be accurate (overall sensitivity and specificity: 88.89% and 99.00%; positive and negative predictive values: 94.74% and 97.78%) and diagnostically useful (positive and negative likelihood ratios: 88.89 and 0.11). RT-LAMP showed an increased sensitivity (88.89% vs 81.48%) and high consistency (kappa 0.92) compared with RT-qPCR for SARS-CoV-2 screening while requiring only constant temperature heating and visual inspection. The median time required for RT-LAMP was less than 1 h from sample to result. Further analyses indicated that RT-LAMP was feasible for asymptomatic patients and did not cross-react with other respiratory pathogen infections. Conclusion The RT-LAMP assay offers a rapid, sensitive and straightforward detection for SARS-CoV-2 infection, which could aid the expansion of COVID-19 testing in the public domain and hospitals.


Art in time of Corona virus


title: Pulmonary post-mortem findings in a large series of COVID-19 cases from Northern Italy

text: Importance. The analysis of lung tissues of patients with COVID-19 may help understand pathogenesis and clinical outcomes in this life-threatening respiratory illness. Objective. To determine the histological patterns in lung tissue of patients with severe COVID-19. Design and participants. Lungs tissues of 38 cases who died for COVID-19 in two hospital of Northern Italy were systematically analysed. Hematoxylin-eosin staining, immunohistochemistry for the inflammatory infiltrate and cellular components, electron microscopy were performed. Results. The features of the exudative and proliferative phases of Diffuse Alveolar Disease (DAD) were found: capillary congestion, necrosis of pneumocytes, hyaline membrane, interstitial oedema, pneumocyte hyperplasia and reactive atypia, platelet-fibrin thrombi. The inflammatory infiltrate was composed by macrophages in alveolar lumens and lymphocytes mainly in the interstitium. Electron microscopy revealed viral particles within cytoplasmic vacuoles of pneumocytes. Conclusions and relevance. The predominant pattern of lung lesions in COVID-19 patients is DAD, as described for the other two coronavirus that infect humans, SARS-CoV and MERS-CoV. Hyaline membrane formation and pneumocyte atypical hyperplasia are frequently found. The main relevant finding is the presence of platelet-fibrin thrombi in small arterial vessels; this important observation fits into the clinical context of coagulopathy which dominates in these patients and which is one of the main targets of therapy.


title: COVID-19: Impact of Obesity and Diabetes in Disease Severity

text: Background: The Coronavirus disease 2019 (COVID19) pandemic is straining the healthcare system, particularly for patients with severe outcomes who require admittance to the intensive care unit (ICU). This study aimed to investigate the potential associations of obesity and diabetes with COVID19 severe outcomes, assessed as ICU admittance. Subjects: Demographic and patient characteristics from a retrospective cohort of 1158 patients hospitalized with COVID19 in a single center in Kuwait, along with their medical history, were analyzed. Univariate and multivariate analyses were performed to explore the associations between different variables and ICU admittance. Results: From the 1158 hospitalized patients, 271 (23.4%) had diabetes, 236 (20.4%) had hypertension and 104 (9%) required admittance into the ICU. From patients with available measurements, 157 (21.6%) had body mass index (BMI)[≥]25 kg/m2. Univariate analysis showed that overweight (BMI=25.0~29.9 kg/m2), obesity class I (BMI=30~34.9 kg/m2) and morbid obesity (BMI[≥]40 kg/m2) associated with ICU admittance (odds ratio (OR) [95% confidence intervals (CI)]: 2.45 [1.26~4.74] p value=0.008; OR [95% CI]: 3.51 [1.60~7.69] p value=0.002; and OR [95% CI]: 5.18 [1.50~17.85] p value=0.009], respectively). Patients with diabetes were more likely to be admitted to ICU (OR [95% CI]: 9.38 [5.49~16.02]). Two models for multivariate regression analysis were used, assessing either BMI or diabetes on ICU outcomes. In the BMI model, class I obesity and morbid obesity were associated with ICU admittance (adjusted OR (AOR) [95% CI]: 2.7 [1.17~6.20] p value=0.019 and AOR [95% CI]: 3.95 [1.00~15.20] p value=0.046, respectively). In the diabetes model, diabetes was associated with higher ICU admittance (AOR [95% CI]: 5.49 [3.13~9.65] p value<0.001) whereas hypertension had a protective effect on ICU admittance (AOR [95% CI]: 0.51 (0.28-0.91). Conclusions: In our cohort, overweight, obesity and diabetes in patients with COVID19 were associated with ICU admittance, putting these patients at higher risk of poor outcomes.


title: High-surety isothermal amplification and detection of SARS-CoV-2, including with crude enzymes

text: Isothermal nucleic acid amplification tests (iNAT), such as loop-mediated isothermal amplification (LAMP), are good alternatives to polymerase chain reaction (PCR)-based amplification assays, especially for point-of-care and low resource use, in part because they can be carried out with relatively simple instrumentation. However, iNATs can generate spurious amplicons, especially in the absence of target sequences, resulting in false positive results. This is especially true if signals are based on non-sequence-specific probes, such as intercalating dyes or pH changes. In addition, pathogens often prove to be moving, evolving targets, and can accumulate mutations that will lead to inefficient primer binding and thus false negative results. Internally redundant assays targeting different regions of the target sequence can help to reduce such false negatives. Here we describe rapid conversion of three previously described SARS-CoV-2 LAMP assays that relied on non-sequence-specific readout into assays that can be visually read using sequence-specific fluorogenic oligonucleotide strand exchange (OSD) probes. We evaluate one-pot operation of both individual and multiplex LAMP-OSD assays and demonstrate detection of SARS-CoV-2 virions in crude human saliva.


title: Anosmia and dysgeusia in patients with mild SARS-CoV-2 infection

text: In this cohort of 42 patients with mild COVID19 we describe the unique clinical feature of acute anosmia and dysgeusia in more than third of patients. Median onset of these features was 3.3 days after onset of illness (range 0-7) with rapid recovery in most patient.


Drug Supply During COVID-19 Pandemic: Remember Not to Run With Your Tank Empty


title: Preparedness and response to Pediatric CoVID-19 in European Emergency Departments: a survey of the REPEM and PERUKI networks

text: Study objective: We aimed to describe the preparedness and response to the COVID-19 pandemic in referral EDs caring for children across Europe. Methods: We did a cross-sectional point prevalence survey, which was developed and disseminated through the pediatric emergency medicine research networks for Europe (REPEM) and the United Kingdom and Ireland (PERUKI). We included a pre-determined number of centers based on each country population: five to ten EDs for countries with > 20 million inhabitants and one to five EDs for the other countries. ED directors or named delegates completed the survey between March 20th and 21st to report practice in use one month after the outbreak in Northern Italy. We used descriptive statistics to analyse data. Results: Overall 102 centers from 18 countries completed the survey: 34% did not have an ED contingency plan for pandemics and 36% had never had simulations for such events. Wide variation on PPE items was shown for recommended PPE use at pre-triage and for patient assessment, with 62% of centers experiencing shortage in one or more PPE items. COVID-19 positive ED staff was reported in 25% of centers. Only 17% of EDs had negative pressure isolation rooms. Conclusion: We identified variability and gaps in preparedness and response to the COVID-19 epidemic across European referral EDs for children. Early availability of a documented contingency plan, provision of simulation training, appropriate use of PPE, and appropriate isolation facilities emerged as key factors that should be optimized to improve preparedness and inform responses to future pandemics.


title: Hypoferremia predicts hospitalization and oxygen demand in COVID-19 patients

text: Background: Iron metabolism might play a crucial role in cytokine release syndrome in COVID-19 patients. Therefore we assessed iron metabolism markers in COVID-19 patients for their ability to predict disease severity. Methods: COVID-19 patients referred to the Heidelberg University Hospital were retrospectively analyzed. Patients were divided into outpatients (cohort A, n=204), inpatients (cohort B, n=81), and outpatients later admitted to hospital because of health deterioration (cohort C, n=23). Results: Iron metabolism parameters were severely altered in patients of cohort B and C compared to cohort A. In multivariate regression analysis including age, gender, CRP and iron-related parameters only serum iron and ferritin were significantly associated with hospitalization. ROC analysis revealed an AUC for serum iron of 0.894 and an iron concentration <6micromol/l as the best cutoff-point predicting hospitalization with a sensitivity of 94.7% and a specificity of 67.9%. When stratifying inpatients in a low- and high oxygen demand group serum iron levels differed significantly between these two groups and showed a high negative correlation with the inflammatory parameters IL-6, procalcitonin, and CRP. Unexpectedly, serum iron levels poorly correlate with hepcidin. Conclusion: We conclude that measurement of serum iron can help predicting the severity of COVID-19. The differences in serum iron availability observed between the low and high oxygen demand group suggest that disturbed iron metabolism likely plays a causal role in the pathophysiology leading to lung injury.


title: Comparison of the Accula SARS-CoV-2 Test with a Laboratory-Developed Assay for Detection of SARS-CoV-2 RNA in Clinical Nasopharyngeal Specimens

text: Background Several point-of-care (POC) molecular tests have received emergency use authorization (EUA) from the Food and Drug Administration (FDA) for diagnosis of SARS-CoV-2. The test performance characteristics of the Accula (Mesa Biotech) SARS-CoV-2 POC test need to be evaluated to inform its optimal use. Objectives The aim of this study was to assess test performance of the Accula SARS-CoV-2 test. Study design The performance of the Accula test was assessed by comparing results of 100 nasopharyngeal swab samples previously characterized by the Stanford Health Care EUA laboratory-developed test (SHC-LDT) targeting the envelope (E) gene. Assay concordance was assessed by overall percent agreement, positive percent agreement (PPA), negative percent agreement (NPA), and Cohen’s kappa coefficient. Results Overall percent agreement between the assays was 84.0% (95% confidence interval [CI] 75.3 to 90.6%), PPA was 68.0% (95% CI 53.3 to 80.5%) and the kappa coefficient was 0.68 (95% CI 0.54 to 0.82). Sixteen specimens detected by the SHC-LDT were not detected by the Accula test, and showed low viral load burden with a median cycle threshold value of 37.7. NPA was 100% (95% CI 94.2 to 100%). Conclusion Compared to the SHC-LDT, the Accula SARS-CoV-2 test showed excellent negative agreement. However, positive agreement was low for samples with low viral load. The false negative rate of the Accula POC test calls for a more thorough evaluation of POC test performance characteristics in clinical settings, and for confirmatory testing in individuals with moderate to high pre-test probability of SARS-CoV-2 who test negative on Accula.


Impact of the COVID-19 outbreak on endoscopy training in a tertiary care centre in Germany


Lymphopenia predicts disease severity of COVID-19: a descriptive and predictive study


title: Sustained virome diversity in Antarctic penguins and their ticks: geographical connectedness and no evidence for low pathogen pressure

text: Despite its isolation and extreme climate, Antarctica is home to diverse fauna and associated microorganisms. It has been proposed that the most iconic Antarctic animal, the penguin, experiences low pathogen pressure, accounting for their disease susceptibility in foreign environments. However, there is a limited understanding of virome diversity in Antarctic species, the extent of in situ virus evolution, or how it relates to that in other geographic regions. To test the idea that penguins have limited microbial diversity we determined the viromes of three species of penguins and their ticks sampled on the Antarctic peninsula. Using total RNA-Sequencing we identified 107 viral species, comprising likely penguin associated viruses (n = 13), penguin diet and microbiome associated viruses (n = 82) and tick viruses (n = 8), two of which may have the potential to infect penguins. Notably, the level of virome diversity revealed in penguins is comparable to that seen in Australian waterbirds, including many of the same viral families. These data therefore reject the theory that penguins are subject to lower pathogen pressure. The repeated detection of specific viruses in Antarctic penguins also suggests that rather than being simply spill-over hosts, these animals may act as key virus reservoirs.


title: Changing workplace geographies in the COVID-19 crisis

text: COVID-19 has fundamentally changed workplace geographies with large proportions of people working at home during the ‘Great Lockdown’. This commentary argues that working at home has emerged as a key policy response and one in which inequalities are embedded. We outline the nature of these social and spatial inequalities by examining existing evidence and data for the Global North, and consider some of the economic and policy challenges ahead.


title: A dynamic nomenclature proposal for SARS-CoV-2 to assist genomic epidemiology

text: The ongoing pandemic spread of a novel human coronavirus, SARS-COV-2, associated with severe pneumonia disease (COVID-19), has resulted in the generation of thousands of virus genome sequences. The rate of genome generation is unprecedented, yet there is currently no coherent nor accepted scheme for naming the expanding phylogenetic diversity of SARS-CoV-2. We present a rational and dynamic virus nomenclature that uses a phylogenetic framework to identify those lineages that contribute most to active spread. Our system is made tractable by constraining the number and depth of hierarchical lineage labels and by flagging and declassifying virus lineages that become unobserved and hence are likely inactive. By focusing on active virus lineages and those spreading to new locations this nomenclature will assist in tracking and understanding the patterns and determinants of the global spread of SARS-CoV-2.


title: Trimeric SARS-CoV-2 Spike interacts with dimeric ACE2 with limited intra-Spike avidity

text: A serious public health crisis is currently unfolding due to the SARS-CoV-2 pandemic. SARS-CoV-2 viral entry depends on an interaction between the receptor binding domain of the trimeric viral Spike protein (Spike-RBD) and the dimeric human angiotensin converting enzyme 2 (ACE2) receptor. While it is clear that strategies to block the Spike/ACE2 interaction are promising as anti-SARS-CoV-2 therapeutics, our current understanding is insufficient for the rational design of maximally effective therapeutic molecules. Here, we investigated the mechanism of Spike/ACE2 interaction by characterizing the binding affinity and kinetics of different multimeric forms of recombinant ACE2 and Spike-RBD domain. We also engineered ACE2 into a split Nanoluciferase-based reporter system to probe the conformational landscape of Spike-RBDs in the context of the Spike trimer. Interestingly, a dimeric form of ACE2, but not monomeric ACE2, binds with high affinity to Spike and blocks viral entry in pseudotyped virus and live SARS-CoV-2 virus neutralization assays. We show that dimeric ACE2 interacts with an RBD on Spike with limited intra-Spike avidity, which nonetheless contributes to the affinity of this interaction. Additionally, we demonstrate that a proportion of Spike can simultaneously interact with multiple ACE2 dimers, indicating that more than one RBD domain in a Spike trimer can adopt an ACE2-accessible “up” conformation. Our findings have significant implications on the design strategies of therapeutic molecules that block the Spike/ACE2 interaction. The constructs we describe are freely available to the research community as molecular tools to further our understanding of SARS-CoV-2 biology.


title: Asynchronicity of endemic and emerging mosquito-borne disease outbreaks in the Dominican Republic

text: Mosquito-borne viruses pose a perpetual public health threat to countries and territories in the Carribean due to the region's tropical climate and seasonal reception of international tourists. Outbreaks of the emerging viruses chikungunya and Zika in 2014 and 2016, respectively, demonstrated the rapidity with which these viruses can spread between islands. At the same time, the number of reported dengue fever cases, caused by the endemic dengue virus, has steadily climbed over the past decade, and a large dengue outbreak that began sweeping through this region in 2019 continues in 2020. Sustainable disease and mosquito control measures are urgently needed to quell virus transmission in the long term and prevent future outbreaks from occurring. To improve upon current surveillance methods, we analyzed temporal and spatial patterns of chikungunya, Zika, and dengue outbreaks reported in the Dominican Republic between 2012 and 2018. The viruses that caused these outbreaks are transmitted by Aedes mosquitoes, which are sensitive to seasonal climatological variability. In this study, we evaluated whether climate and the spatio-temporal dynamics of past dengue outbreaks could inform when and where future emerging disease outbreaks might occur. We found that the temporal and spatial distribution of emerging disease outbreaks did not conform to those of seasonal dengue outbreaks. Rather, the former occurred when climatological conditions were suboptimal for Aedes activity. Provincial dengue attack rates did not correspond to those of emerging diseases. Our study also provides evidence for under-reporting of dengue cases, especially following the 2016 Zika outbreak. We advocate for the implementation of a sustainable and long-term surveillance system to monitor the spread of known mosquito-borne viruses and to identify emerging threats before they cause outbreaks. Specifically, we recommend the use of febrile illness incidence, case fatality rates, and serosurveys during inter-outbreak periods to better understand rates of transmission and asymptomatic infection.


title: Feasibility Study of Mitigation and Suppression Intervention Strategies for Controlling COVID-19 Outbreaks in London and Wuhan

text: Recent outbreaks of coronavirus disease 2019 (COVID-19) has led a global pandemic cross the world. Most countries took two main interventions: suppression like immediate lockdown cities at epicentre or mitigation that slows down but not stopping epidemic for reducing peak healthcare demand. Both strategies have their apparent merits and limitations; it becomes extremely hard to conduct one intervention as the most feasible way to all countries. Targeting at this problem, this paper conducted a feasibility study by defining a mathematical model named SEMCR that can access effectiveness of mitigation, suppression and hybrid interventions for controlling COVID-19 outbreaks in London and Wuhan. It extended traditional SEIR (Susceptible-Exposed Infectious-Recovered) model by adding two key features: a direct connection between Exposed and Recovered populations, and separating infections into mild and critical cases. It defined parameters to classify two stages of COVID-19 control: active contain by isolation of cases and contacts, passive contain by suppression or mitigation. The model was fitted and evaluated with public dataset containing daily number of confirmed active cases including Wuhan and London during January, 2020 and March 2020. The simulated results showed that 1) Immediate suppression taken in Wuhan significantly reduced the total exposed and infectious populations to 119610, but it has to be consistently maintained at least 90 days (by the middle of April 2020). Its success heavily relied on sufficiently external support from other places of China. This mode were not suitable to other countries that have no sufficient health resources. 2) In London, it is possible to take a hybrid intervention of suppression and mitigation for every 2 or 3 weeks over a longer period to balance the total infections and economic loss. While the total infectious populations in this scenario would be possibly 2 times than the one taking suppression, economic loss and recovery of London would be less affected. 3) Both in Wuhan and London cases, one important issue of fitting practical data was that there were a large portion (probably 62.9% in Wuhan) of self-recovered populations that were asymptomatic or mild symptomatic. These people might think they have been healthy at home and did not go to hospital for COVID-19 tests. Early release of intervention intensity potentially increased a risk of the second outbreak. One limitation of our model was that our prediction of infections and deaths depended on a parameter estimation of intervention intensity that presented by average number contacts with susceptible individuals as infectious individuals in a certain region. It assumed that each intervention had equivalent effects on the reproduction number R in different regions over time. Practical effectiveness of implementing intervention intensity might be varied with respect to cultures or other issues of certain county.


title: Health Literacy, Social Media and Pandemic Planning

text: The novel coronavirus and resulting global pandemic serves to underscore the importance of health literacy As more Americans are urged to self-isolate as a way of combating the spread of the virus, they turn to the internet and social networks for information, support, and community However, previous estimates of limited or low health literacy of Americans may mean that many who use the internet for information may not be accessing or interpreting information correctly and more disturbingly, may be facilitating the spread of misinformation Health literacy must be established as an integral part of the public health response to disaster planning


Organ transplantation management in the midst of the COVID-19 outbreak: a synopsis


title: Clinical Course and Risk Factors for Recurrence of Positive SARS-CoV-2 RNA: A Retrospective Cohort Study from Wuhan, China

text: Background Coronavirus Disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has developed into a full-blown global pandemic. It has been reported that patients with COVID-19 meeting the criteria for hospital discharge (including two consecutive negative RT-PCR results) have experienced recurrent PCR positivity. However, the clinical course and risk factors for these patients have not been well described. Methods In this retrospective cohort study, consecutive patients with COVID-19 confirmed by RT-PCR from the Guanggu Branch of Hubei Province Maternity and Childcare Hospital from February 24, 2020 to March 31, 2020 were enrolled. The epidemiological, radiographic, laboratory, treatment, and outcome data were extracted from medical records. Univariate and multivariable logistic regression methods were used to elucidate risk factors for patients with recurrence of positive SARS-CoV-2 RNA. Results 1087 COVID-19 patients were included in this study. Of these, 20 (1.8%) died and 1067 (98.2%) were discharged from the hospital. Among the discharged cases, there were 81 (7.6%) patients found to develop a repeat positive SARS-Cov-2 RNA result. Older age was obviously associated with death. For patients with recurrent RT-PCR positivity, the median duration from illness onset to onset of complete RNA negative was 33.0 days (range, 6.0-82.0 days; IQR, 20.0-41.0 days), while that from illness onset to recurrence was 50.0 days (range, 21.0-95.0 days; IQR, 36.5-59.5 days). Multivariate regression analysis identified recurrence of positive SARS-Cov-2 RNA was associated with elevated IL-6 levels (P=0.004, OR=3.050; 95% CI, 1.432-6.499), increased lymphocyte count (P=0.038, OR=2.321; 95% CI, 1.048-5.138) and CT imaging features of lung consolidation (P=0.038, OR=1.641; 95% CI, 1.028-2.620) during hospitalization. Conclusion Elevated lymphocyte counts and IL-6 levels in blood, and consolidation features on CT imaging are useful risk factors for clinicians to identify patients at risk of developing recurrent positivity of SARS-CoV-2 RNA. This is speculated to be caused by a balance in immune regulation when fighting virus toxicity. For patients with a high risk of recurrent positivity, a prolonged observation and additional preventative measures should be implemented for at least 50 days after illness onset to prevent future outbreaks.


title: Getting it right in the pandemic

text: The pandemic is far from over, but it’s already obvious some countries have done better than others Germany is one, with fewer infections and lower mortality from covid-19 than many of its European neighbours Well timed lockdown measures and an extensive, community based system of testing and contact tracing have paid off, says Ralph Reintjes 1 There’s still time to get this right in the UK, argue Peter Roderick and colleagues 2 They emphasise the need to “think local” and reintegrate testing and contact tracing into established regional systems Meanwhile, the current centralised approach and reliance on commercially run tests mean that results are not reliably communicated to patients’ GPs or those doing local contact tracing Another example of getting …


title: COVID-19 is a complex disease with wide spectrum of clinical patterns and an emerging problem for nephrologist

text: Implication for health policy/practice/research/medical education: In December 2019, an outbreak of coronavirus disease (COVID-19) due to the novel SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) virus began in China and spread rapidly worldwide. After China, Italy is the country with the highest number of cases so far. There are only limited data on COVID-19 in patients affected by chronic kidney disease. Herein, we report the outcomes of two patients with COVID-19 pneumonia who required renal replacement therapy. It is unknown whether hemodialysis patients represent a distinct group of patients with certain characteristics that may make them susceptible to infection or severe disease. In this letter, we describe our clinical experience with COVID-19 patients.


title: Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients

text: Background: The dynamic changes of lymphocyte subsets and cytokines profiles of patients with novel coronavirus disease (COVID-19) and their correlation with the disease severity remain unclear. Method: Peripheral blood samples were longitudinally collected from 40 confirmed COVID-19 patients and examined for lymphocyte subsets by flow cytometry and cytokine profiles by specific immunoassays. Findings: Of the 40 COVID-19 patients enrolled, 13 severe cases showed significant and sustained decreases in lymphocyte counts but increases in neutrophil counts than 27 mild cases. Further analysis demonstrated significant decreases in the counts of T cells, especially CD8 + T cells, as well as increases in IL-6, IL-10, IL-2 and IFN-γ levels in the peripheral blood in the severe cases compared to those in the mild cases. T cell counts and cytokine levels in severe COVID-19 patients who survived the disease gradually recovered at later time points to levels that were comparable to those of the mild cases. Moreover, the neutrophil-to-CD8+ T cell ratio (N8R) were identified as the most powerful prognostic factor affecting the prognosis for severe COVID-19. Conclusion: The degree of lymphopenia and a proinflammatory cytokine storm is higher in severe COVID-19 patients than in mild cases, and is associated with the disease severity. N8R may serve as a useful prognostic factor for early identification of severe COVID-19 cases.


title: Oxygen and mortality in COVID-19 pneumonia: a comparative analysis of supplemental oxygen policies and health outcomes across 26 countries.

text: Introduction Hypoxia is the main cause of morbidity and mortality in COVID-19. During the COVID-19 pandemic some countries have reduced access to supplemental oxygen (e.g. oxygen rationing), whereas other nations have maintained and even improved access to supplemental oxygen. We examined whether such variation in the access to supplemental oxygen had any bearing on mortality in COVID-19. Methods Three independent investigators searched for, identified and extracted the nationally recommended target oxygen levels for the commencement of oxygen in COVID-19 pneumonia from the 29 worst affected countries. Mortality estimates were calculated from three independent sources. We then applied linear regression analysis to examine for potential association between national targets for the commencement of oxygen and case fatality rates. Results Of the 26 nations included, 15 had employed conservative oxygen strategies to manage COVID-19 pneumonia. Of them, Belgium, France, USA, Canada, China, Germany, Mexico, Spain, Sweden and the UK guidelines advised commencing oxygen when oxygen saturations (SpO2) fell to 91% or less. Target SpO2 ranged from 92% to 95% in the other 16 nations. Linear regression analysis demonstrated a strong inverse correlation between the national target for the commencement of oxygen and national case fatality rates (Spearmans Rho = -0.622, p < 0.001). Conclusion Our study highlights the disparity in oxygen provision for COVID-19 patients between the nations analysed, and indicates such disparity in access to supplemental oxygen may represent a modifiable factor associated with mortality during the pandemic.


title: Phenotype of SARS-CoV-2-specific T-cells in COVID-19 patients with acute respiratory distress syndrome

text: COVID-19 is associated with lymphopenia and cytokine storm, but no information is available on specific cellular immune responses to SARS-CoV-2. Here, we characterized SARS-CoV-2-specific CD4+ and CD8+ T-cells in patients with acute respiratory distress syndrome. The spike protein (S) proved a potent T-cell antigen and specific T-cells predominantly produced Th1 cytokines. These novel data are important in vaccine design and will facilitate evaluation of vaccine candidate immunogenicity.


title: Prediction of Spreads of COVID-19 in India from Current Trend

text: The article describe modelling efforts for evaluating the current level of COVID-19 infections in India, using exponential model. The Data from 15 march 2020 to 30 April 2020 are used for validating the model, where intrinsic rise rate is kept constant. It is observed that some states of India, like Maharastra, Gujarat and Delhi have a much higher daily infection cases. This is modelled by assuming an initial higher infections, keeping rise rate same. The sudden outbursts are captured using offset of values for these three states. Data from other states like Madhya Pradesh, Uttar Pradesh and Rajasthan are also analysed and they are found to be following the same constants as India is following. Worldwide, many attempts are made to predict outburst of COVID-19 and in the model, described in this paper, turning point is not predicted, as cases in India are still rising. The developed model is based on daily confirmed infections and not on cumulative infections and rationalization is carried out for the population of various regions, while predicting infections for various states. Assigning a decay constant at this stage will be a premature exercise and keeping that in mind, exponential model predicts that India will attain 1 lakh case by 15 May 2020. The figure of 2 lakh and 3 lakh will be attained on 22 May 2020 and 26 May 2020, respectively.


title: Genome Analysis of SARS-CoV-2 Isolate from Bangladesh

text: Recently the first genome sequence for a Severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2 isolate from Bangladesh became available. The sequencing was carried out by the Child Health Research Foundation and provided the first insight into the genetic details of the viral strain responsible for the SARS-CoV-2 infections in Bangladesh. Here we carried out a comparative study were we explored the phylogenetic relationship between the Bangladeshi isolate with other isolates from different parts of the world. Afterwards we identified single nucleotide variants in the Bangladeshi isolate, using the Wuhan virus reference sequence. We found a total of 9 variants in the Bangladeshi isolate using 2 separate tools. Barring 2, the rest of these variants were also observed in other isolates from different countries. Most of the variants occurred in the ORF1ab gen. Another noteworthy finding was a sequence of three consecutive variants in the N protein gene that were observed in other isolates as well. Lastly the phylogenetic analysis revealed a close relationship between the Bangladeshi isolate and those from Taiwan, Kazakhstan, Greece, California, Spain, Israel, and Sri Lanka.


title: Genetic variants in TMPRSS2 and Structure of SARS-CoV-2 spike glycoprotein and TMPRSS2 complex

text: SARS-CoV-2, a highly transmittable pathogen has infected over 3.8 million people around the globe. The spike glycoprotein of SARS-CoV-2 engages host ACE2 for adhesion, TMPRSS2 for activation and entry. With the aid of whole-exome sequencing, we report a variant rs12329760 in TMPRSS2 gene and its mutant V160M, which might impede viral entry. Furthermore, we identified TMPRSS2 cleavage sites in S2 domain of spike glycoprotein and report the structure of TMPRSS2 in complex with spike glycoprotein. We also report the structures of protease inhibitors in complex with TMPRSS2, which could hamper the interaction with spike protein. These findings advance our understanding on the role of TMPRSS2 and in the development of potential therapeutics.


title: Progression / remission of Coronavirus disease 2019: Data driven recommendations for repeating SARS-CoV-2 nucleic acid amplification tests.

text: This short study was performed to better understand the time frame associated with changes in SARS-CoV-2 nucleic acid testing and provide recommendations for repeat testing. Recommendations were useful as little guidance is available for repeat testing in patients being followed expectantly for changes in disease. A review of laboratory data of tests for SARS-CoV-2 nucleic acid was performed selecting patients who had changing results. Time between changes in test results was determined to provide guidance for repeat testing. The interquartile range of data for patients who had a negative to positive change in lab testing ("progression") was 6-16 days (Median 9). The interquartile range of data for patients who had a positive to negative change in test results ("remission") was 9-21 days (Median 14). Because sampling of the nares or nasopharynx can be variable, repeat testing should be performed swiftly when symptomatic patients are negative. The data in this short study varies widely, so authors recommend repeat testing during a period of time associated with the interquartile range or median (see results above).


title: Integrative Network Biology Framework Elucidates Molecular Mechanisms of SARS-CoV-2 Pathogenesis

text: COVID-19 (Coronavirus disease 2019) is a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While the pathophysiology of this deadly virus is complex and largely unknown, we employ a network biology-fueled approach and integrated multiomics data pertaining to lung epithelial cells-specific coexpression network and human interactome to generate Calu-3-specific human-SARS-CoV-2 Interactome (CSI). Topological clustering and pathway enrichment analysis show that SARS-CoV-2 target central nodes of host-viral network that participate in core functional pathways. Network centrality analyses discover 28 high-value SARS-CoV-2 targets, which are possibly involved in viral entry, proliferation and survival to establish infection and facilitate disease progression. Our probabilistic modeling framework elucidates critical regulatory circuitry and molecular events pertinent to COVID-19, particularly the host modifying responses and cytokine storm. Overall, our network centric analyses reveal novel molecular components, uncover structural and functional modules, and provide molecular insights into SARS-CoV-2 pathogenicity.


Using the Surviving Sepsis Coronavirus Disease 2019 Guidelines—Anything New Yet?


COVID-19 and endoscopy training


title: Evaluating the efficacy of RT-qPCR SARS-CoV-2 direct approaches in comparison to RNA extraction

text: SARS-CoV-2 genetic identification is based on viral RNA extraction prior to RT-qPCR assay, however recent studies support the elimination of the extraction step. Herein, we assessed the RNA extraction necessity, by comparing RT-qPCR efficacy in several direct approaches vs. the gold standard RNA extraction, in detection of SARS-CoV-2 from laboratory samples as well as clinical Oro-nasopharyngeal SARS-CoV-2 swabs. Our findings show advantage for the extraction procedure, however a direct no-buffer approach might be an alternative, since it identified up to 70% of positive clinical specimens.


title: Adaptive cyclic exit strategies from lockdown to suppress COVID-19 and allow economic activity

text: Many countries have applied lockdown that helped suppress COVID-19, but with devastating economic consequences. Here we propose exit strategies from lockdown that provide sustainable, albeit reduced, economic activity. We use mathematical models to show that a cyclic schedule of 4-day work and 10-day lockdown, or similar variants, can prevent resurgence of the epidemic while providing part-time employment. The cycle pushes the reproduction number R below one by reduced exposure time and by exploiting the virus latent period: those infected during work days reach peak infectiousness during lockdown days. The number of work days can be adapted in response to observations. Throughout, full epidemiological measures need to continue including hygiene, physical distancing, compartmentalization, testing and contact tracing. This conceptual framework, when combined with other interventions to control the epidemic, can offer the beginnings of predictability to many economic sectors.


title: Giving voice to those directly affected by the COVID-19 pandemic – the experience and reflections of a person with dementia

text: The coronavirus disease 2019 (COVID-19) pandemic presents unprecedented challenges to society. Behind the daily tally of deaths and cases of infection are individuals and families who are experiencing the ultimate consequence of this disease. Every aspect of our lives has been affected and these affects are amplified for those who have to cocoon and have conditions such as dementia. There is little opportunity to directly hear the experience of those ‘vulnerable adults’ who have been self-isolating for many weeks now. This letter takes the form of a reflective conversation with a person living with dementia. Honouring the principles of public and patient involvement (PPI), it is an attempt to give voice to the experience of one of the many thousands of vulnerable people during the COVID-19 pandemic. As well as describing the effect on her daily life, Helen describes what supports would help at this time. While the focus of attention at the moment is rightly on dealing with the effects of the virus in nursing homes, the many thousands of people living with dementia in the community should not be forgotten.


title: Epidemiological characteristics of 1212 COVID-19 patients in Henan, China

text: Based on publicly released data for 1212 patients, we investigated the epidemiological characteristics of COVID-19 in Henan of China. The following findings are obtained: 1) COVID-19 patients in Henan show gender (55% vs 45%) and age (81% aged between 21 and 60) preferences, possible causes were explored; 2) Statistical analysis on 483 patients reveals that the estimated average, mode and median incubation periods are 7.4, 4 and 7 days; Incubation periods of 92% patients were no more than 14 days; 3) The epidemic of COVID-19 in Henan has undergone three stages and showed high correlations with the numbers of patients that recently return from Wuhan; 4) Network analysis on the aggregate outbreak phenomena of COVID-19 revealed that 208 cases were clustering infected, and various people's Hospital are the main force in treating patients. The related investigations have potential implications for the prevention and control of COVID-19.


title: Behaviors and attitudes in response to the COVID-19 pandemic: Insights from a cross-national Facebook survey

text: In the absence of medical treatment and vaccination, the mitigation and containment of the ongoing COVID-19 pandemic relies on behavioral changes. Timely data on attitudes and behaviors are thus necessary to develop optimal intervention strategies and to assess the consequences of the pandemic for different demographic groups. We developed a rapid response monitoring system via a continuously run online survey (the "COVID-19 Health Behavior Survey") across eight countries (Belgium, France, Germany, Italy, the Netherlands, Spain, the United Kingdom, the United States). The survey was specifically designed to collect key information on people's health status, behaviors, close social contacts, and attitudes in response to the COVID-19 pandemic. We developed an innovative approach to recruit participants via targeted Facebook advertisement campaigns in order to generate balanced samples for post-stratification. In this paper, we present results for the period from March 13-April 19, 2020. We estimate important differences by sex: women show a substantially higher perception of threat along with a lower level of confidence in the health system. This is paralleled by sex-specific behaviors, with women more likely to adopt a wide range of preventive behaviors. We thus expect behavior to serve as a protective factor for women. Our findings also show a higher level of awareness and concern among older respondents, in line with the evidence that the elderly are at highest risk of severe complications following infection from COVID-19. While across all the samples respondents were less concerned for themselves than for their country or for the world, we also observed substantial temporal and spatial heterogeneity in terms of confidence in institutions and responses to non-pharmaceutical interventions.


title: Optimal upper respiratory tract sampling time for novel coronavirus pneumonia suspects

text: Objective: Explore best upper respiratory tract sampling time of suspected novel coronavirus pneumonia cases. Methods: We collected dates of patients from Hangzhou, Shenzhen, Jinhua city and so on who had the clear exposure history of a novel coronavirus pneumonia(COVID-19). We retrospected demographic data, exposure time, onset time, visiting time and positive time for novel coronavirus nucleic acid detection in respiratory specimens. There were 256 patients from January 20, 2020-February 12,2020 from eight cities included in our study. 106 cases appeared symptoms before January 25th and 150 after. Results: There were 136(53.1%)male infected cases. The mean age of all patients was 43.80 {+/-} 14.85.The median time from exposure to onset was 5(3,8)days.The median time of the first time of positive nucleic acid detection was 11(9,14)days and mode number was 13.The median time from onset to the first time of positive nucleic acid detection was 6(4,8)days and mode number was 5. The time from onset to definite diagnosis was 5(3,7) days before January 25th while it was 7.5(5,10)days after which was significantly shorter before January 25th(U=3885.5,P<0.001). The time from exposure to definite diagnosis was 11(9,14)days and 11(9,14)days before January 25th and after and without significant difference. The time from exposure to definite diagnosis was 11(9,13)days in first-tier cities and 13(11,15)days in second and third-tier cities. The difference was significantly shorter of first-tier cities(U=1355.5 P=0.039). And also the time was short from visiting to definite diagnosis which was 2(2,3)days in first-tier cities and 3(2,4)days in second and third-tier cities but without significant difference(U=842.5P=0.054). Conclusions: From our study we found that the best upper respiratory tract sampling time for novel coronavirus pneumonia suspects was 13days after exposure. The time from onset to definite diagnosis was shorter after January 25th. The patients were diagnosed faster in the first-tier cities after exposure.


title: First two months of the 2019 Coronavirus Disease (COVID-19) epidemic in China: real-time surveillance and evaluation with a second derivative model

text: BACKGROUND: Similar to outbreaks of many other infectious diseases, success in controlling the novel 2019 coronavirus infection requires a timely and accurate monitoring of the epidemic, particularly during its early period with rather limited data while the need for information increases explosively. METHODS: In this study, we used a second derivative model to characterize the coronavirus epidemic in China with cumulatively diagnosed cases during the first 2 months. The analysis was further enhanced by an exponential model with a close-population assumption. This model was built with the data and used to assess the detection rate during the study period, considering the differences between the true infections, detectable and detected cases. RESULTS: Results from the second derivative modeling suggest the coronavirus epidemic as nonlinear and chaotic in nature. Although it emerged gradually, the epidemic was highly responsive to massive interventions initiated on January 21, 2020, as indicated by results from both second derivative and exponential modeling analyses. The epidemic started to decelerate immediately after the massive actions. The results derived from our analysis signaled the decline of the epidemic 14 days before it eventually occurred on February 4, 2020. Study findings further signaled an accelerated decline in the epidemic starting in 14 days on February 18, 2020. CONCLUSIONS: The coronavirus epidemic appeared to be nonlinear and chaotic, and was responsive to effective interventions. The methods used in this study can be applied in surveillance to inform and encourage the general public, public health professionals, clinicians and decision-makers to take coordinative and collaborative efforts to control the epidemic.


title: Evaluating epidemiological scenarios of isolation and further releases considering protection actions to control transmission of CoViD-19 in Sao Paulo State, Brazil.

text: A mathematical model was formulated based on nonlinear ordinary differential equations considering young (below 60 years old) and elder (above 60 years) subpopulations, aiming to describe the introduction, dissemination and control of new coronavirus in Sao Paulo State, Brazil. In Sao Paulo State, the first case of CoViD-19 was confirmed on 26 February, the first death due to CoViD-19 was registered on 16 March, on 24 March the Sao Paulo State authorities implemented the isolation of persons in non-essential activities, which is programmed to end on June 1. The deterministic model used the data collected in Sao Paulo State to estimate the model parameters to describe the current epidemiological status in the State under isolation. We concluded that the proportion in isolation influenced the number of new cases in around 9 days ahead. We evaluate the suitability of lockdown in Sao Paulo State and concluded that this extreme measure should be efficient if lower transmission is occurring among isolated persons. Nevertheless, the isolated persons must be released one day. Based on this model, we studied the potential epidemiological scenarios of release by varying the release proportions of young and elder persons. We evaluated three releases divided in equal proportions elapsed 14 days between releases, and three strategies: the first release occurring on June 1, 15 and 23. We concluded that these three strategies are equivalent (little difference) in reducing the number of hospitalization due to severe CoViD-19 and deaths, due to presenting the effective reproduction number near one. However, if protection actions as using face mask and hygiene (washing hands, for instance) could be massively disseminated in the population, we concluded there health care system may not collapse.


title: Reacting to outbreaks at neighboring localities

text: We study the dynamics of epidemics in a networked metapopulation model. In each subpopulation, representing a locality, disease propagates according to a modified susceptible-exposed-infected-recovered (SEIR) dynamics. We assume that individuals reduce their number of contacts as a function of the weighted sum of cumulative number of cases within the locality and in neighboring localities. The susceptible and exposed (pre-symptomatic and infectious) individuals are allowed to travel between localities undetected. To investigate the combined effects of mobility and contact reduction on disease progression within interconnected localities, we consider a scenario with two localities where disease originates in one and is exported to the neighboring locality via travel of undetected pre-symptomatic individuals. We associate the behavior change at the disease-importing locality due to the outbreak size at the origin with the level of preparedness of the locality. Our results show that restricting mobility is valuable if the importing locality is increasing its level of preparedness with respect to the outbreak size at the origin. Moreover, increased levels of preparedness can yield lower total outbreak size by further reducing the outbreak size at the importing locality, even when the response at the origin is weak. Our results highlight that public health decisions on social distancing at localities with less severe outbreaks should strongly account for potential impact of neighbouring localities with a poor response to the outbreak rather than localities with successful responses.


title: Estimation of the percentages of asymptomatic patients and undiagnosed patients of the novel coronavirus (SARS-CoV-2) infection in Hokkaido, Japan by using birth-death process with recursive full tracing

text: Estimating the percentages of undiagnosed and asymptomatic patients is essential for controlling the outbreak of SARS-CoV-2, and for assessing any strategy for controlling the disease. In this paper, we propose a novel analysis based on the birth-death process with recursive full tracing. We estimated the numbers of undiagnosed symptomatic patients and total infected individuals per diagnosed patient before and after the declaration of the state of emergency in Hokkaido, Japan. The median of the estimated number of undiagnosed symptomatic patients per diagnosed patient decreased from 1.9 to 0.77 after the declaration, and the median of the estimated number of total infected individuals per diagnosed patient decreased from 4.7 to 2.4. We will discuss the limitations and possible expansions of the model.


Variation of 2019 novel coronavirus complete genomes recorded in the 1(st) month of outbreak: Implication for mutation


title: Rates relief campaign continues

text: BVA is continuing to push hard for veterinary practices to be granted access to further financial support for businesses affected by Covid-19.


title: In vivo recellularization of xenogeneic vascular grafts decellularized with high hydrostatic pressure method in a porcine carotid arterial interpose model

text: Autologous vascular grafts are widely used in revascularization surgeries for small caliber targets. However, the availability of autologous conduits might be limited due to prior surgeries or the quality of vessels. Xenogeneic decellularized vascular grafts from animals potentially substitute for autologous vascular grafts. Decellularization with high hydrostatic pressure (HHP) is reported to highly preserve extracellular matrix (ECM) which would be feasible for recellularization and vascular remodeling after implantation. In the present study, we conducted xenogeneic implantation of HHP-decellularized bovine vascular grafts from dorsalis pedis arteries to porcine carotid arteries then evaluated graft patency, ECM preservation and recellularization. Surgical procedure not to damage luminal surface of the grafts from drying significantly increased the graft patency at 4 weeks after implantation (P = 0.0079). After the technical improvement, all grafts (N = 5) were patent with mild stenosis due to intimal hyperplasia at 4 weeks after implantation. Neither aneurysmal change nor massive thrombosis was observed even without administration of anticoagulants nor anti-platelet agents. Elastica van Gieson and Sirius-red stainings revealed fair preservation of ECM proteins including elastin and collagen after implantation. Luminal surface of grafts was thoroughly covered with von Willebrand factor-positive endothelium. Scanning electron microscopy on luminal surface of implanted grafts exhibited cobblestone-like endothelial cell layer which is similar to native vascular endothelium. Recellularization of tunica media with alpha-smooth muscle actin-positive smooth muscle cells was partly observed. Thus, we confirmed that HHP-decellularized grafts are feasible for xenogeneic implantation accompanied by recellularization by recipient cells.


Challenges to neonatal care in Cambodia amid the COVID-19 pandemic