title: Isolation of SARS-CoV-2-related coronavirus from Malayan pangolins

text: The current outbreak of COVID-19 poses unprecedented challenges to global health1. The new coronavirus responsible for this outbreak-SARS-CoV-2-shares high sequence identity to SARS-CoV and a bat coronavirus, RaTG132. Although bats may be the reservoir host for a variety of coronaviruses3,4, it remains unknown whether SARS-CoV-2 has additional host species. Here we show that a coronavirus, which we name pangolin-CoV, isolated from a Malayan pangolin has 100%, 98.6%, 97.8% and 90.7% amino acid identity with SARS-CoV-2 in the E, M, N and S proteins, respectively. In particular, the receptor-binding domain of the S protein of pangolin-CoV is almost identical to that of SARS-CoV-2, with one difference in a noncritical amino acid. Our comparative genomic analysis suggests that SARS-CoV-2 may have originated in the recombination of a virus similar to pangolin-CoV with one similar to RaTG13. Pangolin-CoV was detected in 17 out of the 25 Malayan pangolins that we analysed. Infected pangolins showed clinical signs and histological changes, and circulating antibodies against pangolin-CoV reacted with the S protein of SARS-CoV-2. The isolation of a coronavirus from pangolins that is closely related to SARS-CoV-2 suggests that these animals have the potential to act as an intermediate host of SARS-CoV-2. This newly identified coronavirus from pangolins-the most-trafficked mammal in the illegal wildlife trade-could represent a future threat to public health if wildlife trade is not effectively controlled.


text: The current outbreak of coronavirus disease-2019 (COVID-19) poses unprecedented challenges to global health1. The new coronavirus responsible for this outbreak-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-shares high sequence identity to SARS-CoV and a bat coronavirus, RaTG132. Although bats may be the reservoir host for a variety of coronaviruses3,4, it remains unknown whether SARS-CoV-2 has additional host species. Here we show that a coronavirus, which we name pangolin-CoV, isolated from a Malayan pangolin has 100%, 98.6%, 97.8% and 90.7% amino acid identity with SARS-CoV-2 in the E, M, N and S proteins, respectively. In particular, the receptor-binding domain of the S protein of pangolin-CoV is almost identical to that of SARS-CoV-2, with one difference in a noncritical amino acid. Our comparative genomic analysis suggests that SARS-CoV-2 may have originated in the recombination of a virus similar to pangolin-CoV with one similar to RaTG13. Pangolin-CoV was detected in 17 out of the 25 Malayan pangolins that we analysed. Infected pangolins showed clinical signs and histological changes, and circulating antibodies against pangolin-CoV reacted with the S protein of SARS-CoV-2. The isolation of a coronavirus from pangolins that is closely related to SARS-CoV-2 suggests that these animals have the potential to act as an intermediate host of SARS-CoV-2. This newly identified coronavirus from pangolins-the most-trafficked mammal in the illegal wildlife trade-could represent a future threat to public health if wildlife trade is not effectively controlled.


Prolonged Viral RNA Shedding Duration in COVID-19


title: Could Intravenous Immunoglobulin Collected from Recovered Coronavirus Patients Protect against COVID-19 and Strengthen the Immune System of New Patients?

text: The emergence of the novel coronavirus in Wuhan, China, which causes severe respiratory tract infections in humans (COVID-19), has become a global health concern Most coronaviruses infect animals but can evolve into strains that cross the species barrier and infect humans At the present, there is no single specific vaccine or efficient antiviral therapy against COVID-19 Recently, we showed that intravenous immunoglobulin (IVIg) treatment reduces inflammation of intestinal epithelial cells and eliminates overgrowth of the opportunistic human fungal pathogen Candida albicans in the murine gut Immunotherapy with IVIg could be employed to neutralize COVID-19 However, the efficacy of IVIg would be better if the immune IgG antibodies were collected from patients who have recovered from COVID-19 in the same city, or the surrounding area, in order to increase the chance of neutralizing the virus These immune IgG antibodies will be specific against COVID-19 by boosting the immune response in newly infected patients Different procedures may be used to remove or inactivate any possible pathogens from the plasma of recovered coronavirus patient derived immune IgG, including solvent/detergent, 60 °C heat-treatment, and nanofiltration Overall, immunotherapy with immune IgG antibodies combined with antiviral drugs may be an alternative treatment against COVID-19 until stronger options such as vaccines are available


In the Limelight: June 2020


title: Co-infections in people with COVID-19: a systematic review and meta-analysis

text: OBJECTIVES: In previous influenza pandemics, bacterial co-infections have been a major cause of mortality. We aimed to evaluate the burden of co-infections in patients with COVID-19. METHODS: We systematically searched Embase, Medline, Cochrane Library, LILACS and CINAHL for eligible studies published from 1 January 2020 to 17 April 2020. We included patients of all ages, in all settings. The main outcome was the proportion of patients with a bacterial, fungal or viral co-infection. . RESULTS: Thirty studies including 3834 patients were included. Overall, 7% of hospitalised COVID-19 patients had a bacterial co-infection (95% CI 3-12%, n=2183, I2=92·2%). A higher proportion of ICU patients had bacterial co-infections than patients in mixed ward/ICU settings (14%, 95% CI 5-26, I2=74·7% versus 4%, 95% CI 1-9, I2= 91·7%). The commonest bacteria were Mycoplasma pneumonia, Pseudomonas aeruginosa and Haemophilus influenzae. The pooled proportion with a viral co-infection was 3% (95% CI 1-6, n=1014, I2=62·3%), with Respiratory Syncytial Virus and influenza A the commonest. Three studies reported fungal co-infections. CONCLUSIONS: A low proportion of COVID-19 patients have a bacterial co-infection; less than in previous influenza pandemics. These findings do not support the routine use of antibiotics in the management of confirmed COVID-19 infection.


title: Chloroquine for SARS-CoV-2: Implications of Its Unique Pharmacokinetic and Safety Properties

text: Since in vitro studies and a preliminary clinical report suggested the efficacy of chloroquine for COVID-19-associated pneumonia, there is increasing interest in this old antimalarial drug. In this article, we discuss the pharmacokinetics and safety of chloroquine that should be considered in light of use in SARS-CoV-2 infections. Chloroquine is well absorbed and distributes extensively resulting in a large volume of distribution with an apparent and terminal half-life of 1.6 days and 2 weeks, respectively. Chloroquine is metabolized by cytochrome P450 and renal clearance is responsible for one third of total clearance. The lack of reliable information on target concentrations or doses for COVID-19 implies that for both adults and children, doses that proved effective and safe in malaria should be considered, such as 'loading doses' in adults (30 mg/kg over 48 h) and children (70 mg/kg over 5 days), which reported good tolerability. Here, plasma concentrations were < 2.5 µmol/L, which is associated with (minor) toxicity. While the influence of renal dysfunction, critical illness, or obesity seems small, in critically ill patients, reduced absorption may be anticipated. Clinical experience has shown that chloroquine has a narrow safety margin, as three times the adult therapeutic dosage for malaria can be lethal when given as a single dose. Although infrequent, poisoning in children is extremely dangerous where one to two tablets can potentially be fatal. In conclusion, the pharmacokinetic and safety properties of chloroquine suggest that chloroquine can be used safely for an acute virus infection, under corrected QT monitoring, but also that the safety margin is small, particularly in children.


title: A retrospective study of the initial 25 COVID-19 patients in Luoyang, China

text: PURPOSE: To summarize the chest CT imaging and clinical features of the initial COVID-19 patients and provide a clinical diagnostic method that is more effective and can be performed earlier. METHODS: This retrospective study investigated the clinical, laboratory and imaging information of 25 patients in the Luoyang area. There were 15 (60%) male and 10 (40%) female patients ranging from 24 to 88 years old (52 ± 19.30). Data were analyzed by Microsoft Excel and are expressed as the mean ± standard deviation or percentage. RESULTS: Thirteen (52%) patients had been in Wuhan or were in contact with people who had been in Wuhan, and ten (40%) patients were infected by their families or colleagues. The median time from initial symptoms to diagnosis was 7 days. Ninety-two percent of patients had respiratory symptoms, and 8% of them had digestive symptoms. Fever (92%), cough (60%) and fatigue (56%) were the most common symptoms. Most patients had a normal or reduced WBC (96%), reduced lymphocyte count (60%), increased CRP (48%) and increased ESR (44%). Ground glass opacity (GGO) was the typical radiological finding on chest CT. CONCLUSION: Characteristic chest CT imaging features could appear earlier than the viral nucleic acid assay results.


title: Inequalities in access to water and soap matter for the COVID-19 response in sub-Saharan Africa

text: The COVID-19 pandemic has spread rapidly since the first case notification of the WHO in December 2019. Lacking an effective treatment, countries have implemented non-pharmaceutical interventions including social distancing measures and have encouraged maintaining adequate and frequent hand hygiene to slow down the disease transmission. Although access to clean water and soap is universal in high-income settings, it remains a basic need many do not have in low- and middle-income settings.We analyzed data from Demographic and Health Surveys (DHS) of 16 countries in sub-Saharan Africa, using the most recent survey since 2015. Differences in the percentage of households with an observed handwashing place with water and soap were estimated by place of residence and wealth quintiles. Equiplots showed wide within-country disparities, disproportionately affecting the poorest households and rural residents, who represent the majority of the population in most of the countries.Social inequalities in access to water and soap matter for the COVID-19 response in sub-Saharan Africa. Interventions such as mass distribution of soap and ensuring access to clean water, along with other preventive strategies should be scaled up to reach the most vulnerable populations.


title: Care, Convenience, Comfort, Confidentiality, and Contagion: The 5 C's that Will Shape the Future of Telemedicine

text: The COVID-19 pandemic has driven rapid, widespread adoption of telemedicine. The distribution of clinicians, long travel distances, and disability all limit access to care, especially for persons with Parkinson's disease. Telemedicine is not a panacea for all of these challenges but does offer advantages. These advantages can be summarized as the 5 C's: accessible care, increased convenience, enhanced comfort, greater confidentiality to patients and families, and now reduced risk of contagion. Telemedicine also has its limitations, including the inability to perform parts of the physical examination and inequitable access to the Internet and related technologies. Future models will deliver care to patients from a diverse set of specialties. These will include mental health specialists, physiotherapists, neurosurgeons, speech-language therapists, dieticians, social workers, and exercise coaches. Along with these new care models, digital therapeutics, defined as treatments delivered through software programs, are emerging. Telemedicine is now being introduced as a bridge to restart clinical trials and will increasingly become a normal part of future research studies. From this pandemic will be a wealth of new telemedicine approaches which will fundamentally change and improve care as well as research for individuals with Parkinson's disease.


title: Low-Contact & High-Interconnectivity Pathology (LC&HI Path): Post-COVID19-Pandemic Practice of Pathology

text: The COVID-19 pandemic situation may be viewed as an opportunity to accelerate some of the ongoing transformations in modern Pathology. This refers primarily to the digitalization of the practice of tissue and cellular pathology diagnostics. However, it is also an opportunity to analyse the modus operandi of a discipline that has practiced in a similar manner for over 100 years. The challenge is to define the next generation of interconnectivity tools that would be necessary to achieve a new operational model that, while ensuring low face-to-face interaction between the main players of the diagnostic pipeline, allows maximum interconnectivity to serve our patients and the immediate teaching and research needs associated with clinical tissue/cellular samples. This viewpoint aims to describe what this new paradigm, a low-contact & high-interconnectivity pathology (LC&HC Path) operation, may require in the near future.


title: Geospatial Spread of the COVID-19 Pandemic in Mexico

text: COVID-19 is an infectious respiratory disease that the World Health Organization has declared a pandemic. Although a global phenomenon, there is the need to react locally with swift and informed actions, as some of the essential plans are highly dependent on factors such as culture, geography, laws, and customs. This paper presents our approach to mapping the geospatial spread of COVID-19 in Mexico at the state and municipal level, the highest allowed possible resolution in the publicly available dataset provided by the Health Ministry. To visualize the magnitude of the infection, we offer a map for the confirmed positive, pending, and deceases cases, while to support mobility, we provide a geospatial visualization of $R_t$, the basic reproduction number. This document describes the structure of the dataset, the software tools employed, and a description of the functionality of the maps, which definition we make publicly available.


title: The Lung Macrophage in SARS-CoV-2 Infection: A Friend or a Foe?

text: Respiratory, circulatory, and renal failure are among the gravest features of COVID-19 and are associated with a very high mortality rate. A common denominator of all affected organs is the expression of angiotensin-converting enzyme 2 (ACE2), a protease responsible for the conversion of Angiotensin 1-8 (Ang II) to Angiotensin 1-7 (Ang 1-7). Ang 1-7 acts on these tissues and in other target organs via Mas receptor (MasR), where it exerts beneficial effects, including vasodilation and suppression of inflammation and fibrosis, along an attenuation of cardiac and vascular remodeling. Unfortunately, ACE2 also serves as the binding receptor of SARS viral spike glycoprotein, enabling its attachment to host cells, with subsequent viral internalization and replication. Although numerous reports have linked the devastating organ injuries to viral homing and attachment to organ-specific cells widely expressing ACE2, little attention has been given to ACE-2 expressed by the immune system. Herein we outline potential adverse effects of SARS-CoV2 on macrophages and dendritic cells, key cells of the immune system expressing ACE2. Specifically, we propose a new hypothesis that, while macrophages play an important role in antiviral defense mechanisms, in the case of SARS-CoV, they may also serve as a Trojan horse, enabling viral anchoring specifically within the pulmonary parenchyma. It is tempting to assume that diverse expression of ACE2 in macrophages among individuals might govern the severity of SARS-CoV-2 infection. Moreover, reallocation of viral-containing macrophages migrating out of the lung to other tissues is theoretically plausible in the context of viral spread with the involvement of other organs.


The first locally acquired novel case of 2019-nCoV infection in a healthcare worker in the Paris area


[Chronic granulocytic leukemia with COVID-19 pneumonia: a case report]


title: Marine natural compounds as potents inhibitors against the main protease of SARS-CoV-2-a molecular dynamic study

text: Sever acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single-stranded RNA (ssRNA) virus, responsible for severe acute respiratory disease (COVID-19). A large number of natural compounds are under trial for screening compounds, possessing potential inhibitory effect against the viral infection. Keeping in view the importance of marine compounds in antiviral activity, we investigated the potency of some marine natural products to target SARS-CoV-2 main protease (Mpro) (PDB ID 6MO3). The crystallographic structure of Mpro in an apo form was retrieved from Protein Data Bank and marine compounds from PubChem. These structures were prepared for docking and the complex with good docking score was subjected to molecular dynamic (MD) simulations for a period of 100 ns. To measure the stability, flexibility, and average distance between the target and compounds, root mean square deviations (RMSD), root mean square fluctuation (RMSF), and the distance matrix were calculated. Among five marine compounds, C-1 (PubChem CID 11170714) exhibited good activity, interacting with the active site and surrounding residues, forming many hydrogen and hydrophobic interactions. The C-1 also attained a stable dynamic behavior, and the average distance between compound and target remains constant. In conclusion, marine natural compounds may be used as a potential inhibitor against SARS-CoV-2 for better management of COVID-19.[Figure: see text].


title: Mutations strengthened SARS-CoV-2 infectivity

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity is a major concern in coronavirus disease 2019 (COVID-19) prevention and economic reopening. However, rigorous determination of SARS-COV-2 infectivity is essentially impossible owing to its continuous evolution with over 13752 single nucleotide polymorphisms (SNP) variants in six different subtypes. We develop an advanced machine learning algorithm based on the algebraic topology to quantitatively evaluate the binding affinity changes of SARS-CoV-2 spike glycoprotein (S protein) and host angiotensin-converting enzyme 2 (ACE2) receptor following the mutations. Based on mutation-induced binding affinity changes, we reveal that five out of six SARS-CoV-2 subtypes have become either moderately or slightly more infectious, while one subtype has weakened its infectivity. We find that SARS-CoV-2 is slightly more infectious than SARS-CoV according to computed S protein-ACE2 binding affinity changes. Based on a systematic evaluation of all possible 3686 future mutations on the S protein receptor-binding domain (RBD), we show that most likely future mutations will make SARS-CoV-2 more infectious. Combining sequence alignment, probability analysis, and binding affinity calculation, we predict that a few residues on the receptor-binding motif (RBM), i.e., 452, 489, 500, 501, and 505, have very high chances to mutate into significantly more infectious COVID-19 strains.


COVID-19 and informal settlements: an urgent call to rethink urban governance


title: Medical Student Concerns Relating to Neurosurgery Education During COVID-19

text: BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has created significant obstacles within medical education. For medical students interested in pursuing neurosurgery as a specialty, the educational policies surrounding COVID-19 have resulted in unique challenges. The present study used a nationwide survey to identify the concerns of medical students interested in pursuing neurosurgery during the COVID-19 pandemic. METHODS: Students who had previously registered for medical student neurosurgery training camps were sent an online Qualtrics survey requesting them to assess how the COVID-19 pandemic was affecting their neurosurgical education. The Pearson χ2 test and post hoc pairwise Fisher exact test were used for analysis of categorical variables, and the 2-tailed paired Student t test was used for continuous variables. RESULTS: The survey was distributed to 852 medical students, with 127 analyzed responses. Concerns regarding conferences and networking opportunities (63%), clinical experience (59%), and board examination scores (42%) were most frequently cited. Of the third-year medical students, 76% reported ≥1 cancelled or postponed neurosurgery rotation. On average, students were more likely to take 1 year off from medical school after than before the start of the COVID-19 pandemic, measured from 0 to 100 (25.3 ± 36.0 vs. 39.5 ± 37.5; P = 0.004). Virtual mentorship pairing was the highest rated educational intervention suggested by first- and second-year medical students. The third- and fourth-year medical students had cited virtual surgical skills workshops most frequently. CONCLUSIONS: The results from the present nationwide survey have highlighted the concerns of medical students regarding their neurosurgery education during the COVID-19 pandemic. With these findings, neurosurgery organizations can consider targeted plans for students of each year to continue their education and development.


title: [Biological Product Development Strategies for Prevention and Treatment of Coronavirus Disease 2019]

text: Coronavirus disease 2019 (COVID-19) caused by the novel coronavirus, also known as severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), has become a Public Health Emergency of International Concern. Due to the large infection population, broad transmissibility and high mortality, it is urgent to find out the efficient and specific methods to prevent and treat COVID-19. As biological products have broadly applied in the prevention and treatment of severe epidemic diseases, they are promising in blocking novel coronavirus infection. According to the research advances of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), we reviewed the potential application of biological products such as interferon, convalescent plasma, intestinal micro-ecological regulators, vaccines and therapeutic antibodies, etc. , on prevention and treatment of COVID-19. May this review be helpful for conquering COVID-19 in the near future.


Leadership in the Aftermath of Coronavirus Disease 2019 (COVID-19): Next Steps Post Surge


title: Spread of infectious disease and social awareness as parasitic contagions on clustered networks

text: There is a rich history of models for the interaction of a biological contagion like influenza with the spread of related information such as an influenza vaccination campaign. Recent work on the spread of interacting contagions on networks has highlighted that these interacting contagions can have counter-intuitive interplay with network structure. Here we generalize one of these frameworks to tackle three important features of the spread of awareness and disease: one, we model the dynamics on highly clustered, cliquish, networks to mimic the role of workplaces and households; two, the awareness contagion affects the spread of the biological contagion by reducing its transmission rate where an aware or vaccinated individual is less likely to be infected; and three, the biological contagion also affects the spread of the awareness contagion but by increasing its transmission rate where an infected individual is more receptive and more likely to share information related to the disease. Under these conditions, we find that increasing network clustering, which is known to hinder disease spread, can actually allow them to sustain larger epidemics of the disease in models with awareness. This counter-intuitive result goes against the conventional wisdom suggesting that random networks are justifiable as they provide worst-case scenario forecasts. To further investigate this result, we provide a closed-form criterion based on a two-step branching process (i.e., the numbers of expected tertiary infections) to identify different regions in parameter space where the net effect of clustering and co-infection varies. Altogether, our results highlight once again the need to go beyond random networks in disease modeling and illustrate the type of analysis that is possible even in complex models of interacting contagions.


title: Changes of Laboratory Cardiac Markers and Mechanisms of Cardiac Injury in Coronavirus Disease 2019

text: Some patients with coronavirus disease 2019 (COVID-19) show abnormal changes in laboratory myocardial injury markers, suggesting that patients with myocardial injury have a higher mortality rate than those without myocardial injury. This article reviews the possible mechanism of myocardial injury in patients with COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects the patients with COVID-19 in aspects of direct infection of myocardial injury, specific binding to functional receptors on cardiomyocytes, and immune-mediated myocardial injury. During hospitalization, the monitoring of laboratory myocardial injury markers in patients of COVID-19 should be strengthened.


title: An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice

text: Coronaviruses (CoVs) traffic frequently between species resulting in novel disease outbreaks, most recently exemplified by the newly emerged SARS-CoV-2, the causative agent of COVID-19. Here, we show that the ribonucleoside analog ß-d-N4-hydroxycytidine (NHC; EIDD-1931) has broad-spectrum antiviral activity against SARS-CoV-2, MERS-CoV, SARS-CoV, and related zoonotic group 2b or 2c bat-CoVs, as well as increased potency against a CoV bearing resistance mutations to the nucleoside analog inhibitor remdesivir. In mice infected with SARS-CoV or MERS-CoV, both prophylactic and therapeutic administration of EIDD-2801, an orally bioavailable NHC prodrug (ß-d-N4-hydroxycytidine-5'-isopropyl ester), improved pulmonary function and reduced virus titer and body weight loss. Decreased MERS-CoV yields in vitro and in vivo were associated with increased transition mutation frequency in viral, but not host cell RNA, supporting a mechanism of lethal mutagenesis in CoV. The potency of NHC/EIDD-2801 against multiple CoVs and oral bioavailability highlights its potential utility as an effective antiviral against SARS-CoV-2 and other future zoonotic CoVs.


title: Beyond the virus: Ensuring continuity of care for people with diabetes during COVID-19

text: The current COVID-19 pandemic is a major concern for the diabetes community. A meta-analysis in China found that the proportions of people with COVID-19 and diabetes was 9.7% and that having diabetes resulted in a two-fold increased risk of having a severe case. Global guidance on confinement measures for the prevention of COVID-19 have a particular emphasis on vulnerable populations which include people with diabetes. These recommendations are coherent to avoid the spread of SARSCoV-2 infection, but are in contradiction with comprehensive diabetes care, which requires regular patient-provider interactions for patient education, prescriptions and possible management of complications or mental health. Moreover, confinement drives risk for unhealthy diets, decreased physical activity, mental health related concerns, in parallel to delayed care-seeking due to fear of contracting COVID-19. Another weakness in the current COVID-19 response is the focus on hospital care which overlooks the importance of Primary Care in guaranteeing continuity of care. Ensuring the availability of insulin, other medicines, self-monitoring and diagnostic tools is another challenge. These are all global concerns for the diabetes community, as well as for those suffering from other chronic conditions. Undoubtedly, the global priority is to contain the spread and impact of COVID-19. However, health systems still need to meet the needs of the entire population, including individuals with diabetes. Clear guidance for preparedness, crisis and post-crisis management of diabetes and chronic diseases during mass disruptions to health systems are lacking. Therefore, in parallel to the epidemic response efforts to ensure existing healthcare services keep running should be supported to avoid health consequences that might be worse than the epidemic itself. This includes targeted messaging for people with diabetes and vulnerable populations with regards to possible risk of infection as well as their disease-related management; continued support via telephone, video conferencing or even home visits; ensuring access to insulin and other medicines and supplies both nationally and individually; and most importantly, preparing for the future.


title: Incomplete and late recovery of sudden olfactory dysfunction in COVID-19

text: INTRODUCTION: Sudden olfactory dysfunction is a new symptom related to COVID-19, with little data on its duration or recovery rate. OBJECTIVE: To characterize patients with sudden olfactory dysfunction during the COVID-19 pandemic, especially their recovery data. METHODS: An online survey was conducted by the Brazilian Society of Otorhinolaryngology and Cervico-Facial Surgery, and Brazilian Academy of Rhinology, including doctors who assessed sudden olfactory dysfunction patients starting after February 1st, 2020. Participants were posteriorly asked by e-mail to verify data on the recovery of sudden olfactory loss and test for COVID-19 at the end of the data collection period. RESULTS: 253 sudden olfactory dysfunction patients were included, of which 59.1% were females with median age of 36 years, with a median follow-up period of 31 days. 183 patients (72.3%) had been tested for COVID-19, and of those 145 (79.2%) tested positive. Patients that tested positive for COVID-19 more frequently showed non-specific inflammatory symptoms (89.7% vs. 73.7%; p=0.02), a lower rate of total recovery of sudden olfactory dysfunction (52.6% vs. 70.3%; p=0.05) and a longer duration to achieve total recovery (15 days vs. 10 days; p=0.0006) than the ones who tested negative for COVID-19. Considering only positive-COVID-19 patients, individuals with sudden hyposmia completely recovered more often than the ones with sudden anosmia (68.4% vs. 50.0%; p=0.04). CONCLUSION: Positive-COVID-19 patients with sudden olfactory dysfunction showed lower total recovery rate and longer duration than negative-COVID-19 patients. Additionally, total recovery was seen more frequently in positive-COVID-19 patients with sudden hyposmia than the ones with sudden anosmia.


The preventive strategies of community hospital in the battle of fighting pandemic COVID-19 in Taiwan


title: Epidemiological study of novel coronavirus (COVID-19)

text: We report a statistical analysis of some highly infected countries by the novel coronavirus (COVID-19). The cumulative infected data were fitted with various growth models (e.g. Logistic equation, Weibull equation and Hill equation) and obtained the power index of top ten highly infected countries. The newly infected data were fitted with Gaussian distribution with the peak at ~40 days for the countries whose infection curves are seem to be saturated. The similarity in growth kinetics of infected people of different countries provides first-hand guidelines to take proper precautions to minimize human damage.


title: The potential role of Th17 immune responses in coronavirus immunopathology and vaccine-induced immune enhancement

text: Increasing evidence points to host Th17 inflammatory responses as contributing to the severe lung pathology and mortality of lower respiratory tract infections from coronaviruses. This includes host inflammatory and cytokine responses to COVID-19 caused by the SARS-2 coronavirus (SARS CoV2). From studies conducted in laboratory animals, there are additional concerns about immune enhancement and the role of potential host immunopathology resulting from experimental human COVID-19 vaccines. Here we summarize evidence suggesting there may be partial overlap between the underlying immunopathologic processes linked to both coronavirus infection and vaccination, and a role for Th17 in immune enhancement and eosinophilic pulmonary immunopathology. Such findings help explain the link between viral-vectored coronavirus vaccines and immune enhancement and its reduction through alum adjuvants. Additional research may also clarify links between COVID-19 pulmonary immunopathology and heart disease.


title: Determination of the order of fractional derivative for subdiffusion equation

text: The identification of the right order of the equation in applied fractional modeling plays an important role. In this paper we consider an inverse problem for determining the order of time fractional derivative in a subdiffusion equation with an arbitrary second order elliptic differential operator. We prove that the additional information about the solution at a fixed time instant at a monitoring location, as"the observation data", identifies uniquely the order of the fractional derivative.


title: COVID-19: impact on and recommendations for breast cancer care: the Singapore experience

text: The ensuing COVID-19 pandemic poses unprecedented and daunting challenges to the routine delivery of oncological and supportive care to patients with breast cancer. Considerations include the infective risk of patients who are inherently immunosuppressed from their malignancy and therapies, long-term oncological outcomes from the treatment decisions undertaken during this extraordinary period, and diverted healthcare resources to support a coordinated whole-of-society outbreak response. In this review, we chronicle the repercussions of the COVID-19 outbreak on breast cancer management in Singapore and describe our approach to triaging and prioritising care of breast tumours. We further propose adaptations to established clinical processes and practices across the different specialties involved in breast oncology, with references to the relevant evidence base or expert consensus guidelines. These recommendations have been developed within the unique context of Singapore's public healthcare sector. They can serve as a resource to guide breast cancer management for future contingencies in this city-state, while certain elements therein may be extrapolatable to other medical systems during this global public health emergency.


Drug treatment of SARS-Cov2: Potential effects in patients with substance use disorders (SUD)


New clinical manifestation of COVID-19 related Guillain-Barrè syndrome highly responsive to intravenous immunoglobulins: two Italian cases


title: Evaluation of novel coronavirus disease (COVID-19) using quantitative lung CT and clinical data: prediction of short-term outcome

text: BACKGROUND: Computed tomography (CT) enables quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, helping in outcome prediction. METHODS: From 1 to 22 March 2020, patients with pneumonia symptoms, positive lung CT scan, and confirmed SARS-CoV-2 on reverse transcription-polymerase chain reaction (RT-PCR) were consecutively enrolled. Clinical data was collected. Outcome was defined as favourable or adverse (i.e., need for mechanical ventilation or death) and registered over a period of 10 days following CT. Volume of disease (VoD) on CT was calculated semi-automatically. Multiple linear regression was used to predict VoD by clinical/laboratory data. To predict outcome, important features were selected using a priori analysis and subsequently used to train 4 different models. RESULTS: A total of 106 consecutive patients were enrolled (median age 63.5 years, range 26-95 years; 41/106 women, 38.7%). Median duration of symptoms and C-reactive protein (CRP) was 5 days (range 1-30) and 4.94 mg/L (range 0.1-28.3), respectively. Median VoD was 249.5 cm3 (range 9.9-1505) and was predicted by lymphocyte percentage (p = 0.008) and CRP (p < 0.001). Important variables for outcome prediction included CRP (area under the curve [AUC] 0.77), VoD (AUC 0.75), age (AUC 0.72), lymphocyte percentage (AUC 0.70), coronary calcification (AUC 0.68), and presence of comorbidities (AUC 0.66). Support vector machine had the best performance in outcome prediction, yielding an AUC of 0.92. CONCLUSIONS: Measuring the VoD using a simple CT post-processing tool estimates SARS-CoV-2 burden. CT and clinical data together enable accurate prediction of short-term clinical outcome.


title: Best behaviour

text: Scientists are trying to control our actions in this pandemic, but what happens when they get things wrong? Graham Lawton reports.


Preventing bat-born viral outbreaks in future using ecological interventions


The Sexual and Reproductive Health of Adolescents and Young Adults During the COVID-19 Pandemic


title: From Easing Lockdowns to Scaling-Up Community-Based COVID-19 Screening, Testing, and Contact Tracing in Africa - Shared Approaches, Innovations, and Challenges to Minimize Morbidity and Mortality

text: The arrival of COVID-19 to the African continent resulted in a range of locally relevant lockdown measures, which curtailed the spread of SARS-CoV-2 but caused economic hardship for large sections of the population. African countries now face difficult choices regarding easing of lockdowns and sustaining effective public health control measures and surveillance. Control of the COVID-19 pandemic will require efficient community screening, testing, contact tracing, and behavioral change interventions, adequate resources, and a well-supported, community-based team of trained, protected personnel. We discuss COVID-19 screening-testing-contact tracing approaches used in selected African countries and the need for shared, affordable, innovative methods to overcome challenges and minimize mortality rates. This crisis presents a unique opportunity to align COVID-19 services with those already in place for HIV, TB, Malaria, and other non-communicable diseases (NCDs) through mobilization of Africa's inter-professional healthcare workforce to contain the pandemic. By addressing the challenges, the detrimental effect of the COVID-19 pandemic on African citizens can be minimized.


title: Estimation of airborne viral emission: Quanta emission rate of SARS-CoV-2 for infection risk assessment

text: Airborne transmission is a pathway of contagion that is still not sufficiently investigated despite the evidence in the scientific literature of the role it can play in the context of an epidemic. While the medical research area dedicates efforts to find cures and remedies to counteract the effects of a virus, the engineering area is involved in providing risk assessments in indoor environments by simulating the airborne transmission of the virus during an epidemic. To this end, virus air emission data are needed. Unfortunately, this information is usually available only after the outbreak, based on specific reverse engineering cases. In this work, a novel approach to estimate the viral load emitted by a contagious subject on the basis of the viral load in the mouth, the type of respiratory activity (e.g. breathing, speaking, whispering), respiratory physiological parameters (e.g. inhalation rate), and activity level (e.g. resting, standing, light exercise) is proposed. The results showed that high quanta emission rates (>100 quanta h-1) can be reached by an asymptomatic infectious SARS-CoV-2 subject performing vocalization during light activities (i.e. walking slowly) whereas a symptomatic SARS-CoV-2 subject in resting conditions mostly has a low quanta emission rate (<1 quantum h-1). The findings in terms of quanta emission rates were then adopted in infection risk models to demonstrate its application by evaluating the number of people infected by an asymptomatic SARS-CoV-2 subject in Italian indoor microenvironments before and after the introduction of virus containment measures. The results obtained from the simulations clearly highlight that a key role is played by proper ventilation in containment of the virus in indoor environments.


Haemorrhagic enteritis and COVID-19: causality or coincidence


Chronic myeloid leukaemia and the use of tyrosine kinase inhibitors in the days of COVID-19 pandemic


How technology can help in oncologic patient management during COVID-19 outbreak


title: Protecting children from iatrogenic harm during COVID19 pandemic

text: Critical care management of patients with COVID-19 has been influenced by a mixture of public, media and societal pressure, as well as clinical and anecdotal observations from many prominent researchers and key opinion leaders. These factors may have affected the principles of evidence-based medicine and encouraged the widespread use of non-tested pharmacological and aggressive respiratory support therapies, even in intensive care units (ICUs). The COVID-19 pandemic has predominantly affected adult populations, while children appear to be relatively spared of severe disease. Notwithstanding, paediatric intensive care (PICU) clinicians may already have been influenced by changes in practices of adult ICUs, and these changes may pose unintended consequences to the vulnerable population in the PICU. In this article, we analyse several potential iatrogenic causes of the detrimental effects of the current pandemic to children and highlight the risks underlying a sudden change of clinical practice.


title: Beyond Contact Tracing: Community-Based Early Detection for Ebola Response

text: The 2014 Ebola outbreak in west Africa raised many questions about the control of infectious disease in an increasingly connected global society. Limited availability of contact information made contact tracing difficult or impractical in combating the outbreak. We consider the development of multi-scale public health strategies and simulate policies for community-level response aimed at early screening of communities rather than individuals, as well as travel restrictions to prevent community cross-contamination. Our analysis shows the policies to be effective even at a relatively low level of compliance. In our simulations, 40% of individuals conforming to these policies is enough to stop the outbreak. Simulations with a 50% compliance rate are consistent with the case counts in Liberia during the period of rapid decline after mid September, 2014. We also find the travel restriction to be effective at reducing the risks associated with compliance substantially below the 40% level, shortening the outbreak and enabling efforts to be focused on affected areas. Our results suggest that the multi-scale approach can be used to further evolve public health strategy for defeating emerging epidemics.


title: The coronavirus (COVID-19) pandemic's impact on mental health

text: Throughout the world, the public is being informed about the physical effects of SARS-CoV-2 infection and steps to take to prevent exposure to the coronavirus and manage symptoms of COVID-19 if they appear. However, the effects of this pandemic on one's mental health have not been studied at length and are still not known. As all efforts are focused on understanding the epidemiology, clinical features, transmission patterns, and management of the COVID-19 outbreak, there has been very little concern expressed over the effects on one's mental health and on strategies to prevent stigmatization. People's behavior may greatly affect the pandemic's dynamic by altering the severity, transmission, disease flow, and repercussions. The present situation requires raising awareness in public, which can be helpful to deal with this calamity. This perspective article provides a detailed overview of the effects of the COVID-19 outbreak on the mental health of people.


Evaluation of the Level of Anxiety among Iranian Multiple Sclerosis Fellowships During the Outbreak of COVID-19


title: What Is the Role for Algorithmics and Computational Biology in Responding to the COVID-19 Pandemic?

text: We asked speakers from the Annual International Conference on Research in Computational Molecular Biology (RECOMB) about how computational biology as a discipline is being affected by COVID-19 and how the expertise of their community can help in the global response to the pandemic.


Pandemic could add noise to clinical trial data


title: Predicting COVID-19 Incidence Through Analysis of Google Trends Data in Iran: Data Mining and Deep Learning Pilot Study

text: BACKGROUND: The recent global outbreak of coronavirus disease (COVID-19) is affecting many countries worldwide. Iran is one of the top 10 most affected countries. Search engines provide useful data from populations, and these data might be useful to analyze epidemics. Utilizing data mining methods on electronic resources' data might provide a better insight into the COVID-19 outbreak to manage the health crisis in each country and worldwide. OBJECTIVE: This study aimed to predict the incidence of COVID-19 in Iran. METHODS: Data were obtained from the Google Trends website. Linear regression and long short-term memory (LSTM) models were used to estimate the number of positive COVID-19 cases. All models were evaluated using 10-fold cross-validation, and root mean square error (RMSE) was used as the performance metric. RESULTS: The linear regression model predicted the incidence with an RMSE of 7.562 (SD 6.492). The most effective factors besides previous day incidence included the search frequency of handwashing, hand sanitizer, and antiseptic topics. The RMSE of the LSTM model was 27.187 (SD 20.705). CONCLUSIONS: Data mining algorithms can be employed to predict trends of outbreaks. This prediction might support policymakers and health care managers to plan and allocate health care resources accordingly.


Reduction in healthcare-associated respiratory viral infections during a COVID-19 outbreak


COVID-19: Lessons to be learnt from a once-in-a-century global pandemic


Why is hyperglycaemia worsening COVID-19 and its prognosis?


title: Gaining resilience and reducing stress in the age of COVID-19

text: PURPOSE OF REVIEW: The world is experiencing the evolving situation associated with the outbreak of the Corona Virus Disease-2019 (COVID-19) virus, and there is more of need than ever for stress management and self-care. In this article, we will define the physiological, psychological and social aspects, stages, and components of stress reactions in the context of COVID-19, review the relevant literature on stress reactions, and offer some guidance on how to help patients mitigate the physiological and psychological impact of the pandemic through resilience-building techniques. RECENT FINDINGS: There is continued evidence that the fight or flight response involves activation throughout the body at physiological, biochemical and immune levels. This response can be mitigated through increasing parasympathetic nervous system activation as well as cognitive and behavioral interventions. SUMMARY: This article will review the stress, provide a theoretical layout to predict upcoming response, and offer clinicians some practical interventions to employ as the stress of the COVID-19 pandemic continues.


Frontal encephalopathy related to hyperinflammation in COVID-19


title: Considerations for Postacute Rehabilitation for Survivors of COVID-19

text: Coronavirus disease (COVID-19), the infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported on December 31, 2019. Because it has only been studied for just over three months, our understanding of this disease is still incomplete, particularly regarding its sequelae and long-term outcomes. Moreover, very little has been written about the rehabilitation needs of patients with COVID-19 after discharge from acute care. The objective of this report is to answer the question "What rehabilitation services do survivors of COVID-19 require?" The question was asked within the context of a subacute hospital delivering geriatric inpatient and outpatient rehabilitation services. Three areas relevant to rehabilitation after COVID-19 were identified. First, details of how patients may present have been summarized, including comorbidities, complications from an intensive care unit stay with or without intubation, and the effects of the virus on multiple body systems, including those pertaining to cardiac, neurological, cognitive, and mental health. Second, I have suggested procedures regarding the design of inpatient rehabilitation units for COVID-19 survivors, staffing issues, and considerations for outpatient rehabilitation. Third, guidelines for rehabilitation (physiotherapy, occupational therapy, speech-language pathology) following COVID-19 have been proposed with respect to recovery of the respiratory system as well as recovery of mobility and function. A thorough assessment and an individualized, progressive treatment plan which focuses on function, disability, and return to participation in society will help each patient to maximize their function and quality of life. Careful consideration of the rehabilitation environment will ensure that all patients recover as completely as possible.


title: Effects of Three Needling Manipulations of Zusanli (ST 36) on Deqi Sensations and Surface Myoelectricity in Healthy Participants

text: OBJECTIVE: To investigate the effects of different acupuncture manipulations on Deqi sensations and surface myoelectricity, and explore the correlation between Deqi sensations and needling manipulations. METHODS: Forty-five healthy participants accepted twirling, lifting-thrusting, and twirling plus lifting-thrusting manipulanions at right Zusanli (ST 36), respectively. The acupuncturist's and participants' Deqi sensations were collected by MGH Acupuncture Sensation Scale (MASS). The intensity and occurrence rate of soreness, dull pain, pressure, heaviness, fullness, numbness, sharp pain, warmth, coolness, and throbbing feelings of participants, and tightness, smooth, and tangle feelings of acupuncturist were measured. The correlation between the acupuncturist's and participant's Deqi sensations was analyzed. Surface electromyogram (EMG) were recorded before, during and after needling in 30 participants. The integrated EMG (iEMG), mean power frequency (MPF) and media frequency (MF) were analyzed. RESULT: Both fullness and soreness of participants and tightness of acupuncturist were the most frequently occurred ones. A positive correlation between participants' fullness and acupuncturist's tightness was observed during the three aforementioned needling manipulations (P<0.05, OR>1). Almost all the needling sensations measured in the present study could be induced by the three needling manipulations. However, strength of Deqi sensations was exhibited as lifting-thrusting > twirling plus lifting-thrusting > twirling according to MASS index. The iEMG values were increased and MPF, MF values were decreased during needling compaired to those before needling, especially during lifting-thrusting (P<0.01). CONCLUSIONS: The intensity and occurrence rate of the different Deqi sensations induced by different needling manipulations were basically similar. The fullness and soreness were both the most frequently induced Deqi sensations. The strongest Deqi sensation could be induced by lifting-thrusting manipulation. There is a positive correlation between participants' fullness and acupuncturist's tightness during the three needling manipulations. The myoelectricity around the acupoint is related to Deqi responses. (Registration No. AMCTR-IOR-20000314).


title: Heparin resistance in COVID-19 patients in the intensive care unit

text: Patients with COVID-19 have a coagulopathy and high thrombotic risk. In a cohort of 69 intensive care unit (ICU) patients we investigated for evidence of heparin resistance in those that have received therapeutic anticoagulation. 15 of the patients have received therapeutic anticoagulation with either unfractionated heparin (UFH) or low molecular weight heparin (LMWH), of which full information was available on 14 patients. Heparin resistance to UFH was documented in 8/10 (80%) patients and sub-optimal peak anti-Xa following therapeutic LMWH in 5/5 (100%) patients where this was measured (some patients received both anticoagulants sequentially). Spiking plasma from 12 COVID-19 ICU patient samples demonstrated decreased in-vitro recovery of anti-Xa compared to normal pooled plasma. In conclusion, we have found evidence of heparin resistance in critically unwell COVID-19 patients. Further studies investigating this are required to determine the optimal thromboprophylaxis in COVID-19 and management of thrombotic episodes.


Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China


title: Integration of palliative care into COVID-19 pandemic planning

text: The COVID-19 pandemic is expected to surpass the healthcare system's capacity to provide intensive care to all patients who deteriorate as a result of the disease. This poses a unique challenge to healthcare teams of rationing care during pandemic when resources are scarce. Healthcare providers will need to acquire new skills in care decision making and effective symptom control for patients who do not receive life-saving measures. In this review, we describe some of the important palliative care considerations that need to be incorporated into COVID-19 pandemic planning. The main aspects to be considered include decision algorithms for rationing care, training on effective symptoms management, alternative delivery methods of palliative care services such as telemedicine and finally death and bereavement support for surviving family members who are likely to be isolated from their loved one at the moment of death.


Letter to the Editor: Obesity as a risk factor for greater severity of COVID-19 in patients with metabolic associated fatty liver disease


title: Coronavirus Disease 2019 (COVID-19) and Pregnancy: Responding to a Rapidly Evolving Situation

text: As the world confronts coronavirus disease 2019 (COVID-19), an illness caused by yet another emerging pathogen (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]), obstetric care providers are asking what this means for pregnant women. The global spread has been swift, and many key questions remain. The case-fatality rate for persons cared for in the United States and whether asymptomatic persons transmit the virus are examples of questions that need to be answered to inform public health control measures. There are also unanswered questions specific to pregnant women, such as whether pregnant women are more severely affected and whether intrauterine transmission occurs. Although guidelines for pregnant women from the American College of Obstetricians and Gynecologists and the Centers for Disease Control and Prevention have been rapidly developed based on the best available evidence, additional information is critically needed to inform key decisions, such as whether pregnant health care workers should receive special consideration, whether to temporarily separate infected mothers and their newborns, and whether it is safe for infected women to breastfeed. Some current recommendations are well supported, based largely on what we know from seasonal influenza: patients should avoid contact with ill persons, avoid touching their face, cover coughs and sneezes, wash hands frequently, disinfect contaminated surfaces, and stay home when sick. Prenatal clinics should ensure all pregnant women and their visitors are screened for fever and respiratory symptoms, and symptomatic women should be isolated from well women and required to wear a mask. As the situation with COVID-19 rapidly unfolds, it is critical that obstetricians keep up to date.


How should we treat pregnant women infected with SARS-CoV-2?


title: Characterize of production systems and milk quality of production units in the semiarid region of Ceará/ Caracterização dos sistemas de produção e qualidade do leite de unidades produtoras no semiárido do Ceará

text: The aim of this study was to characterize the production systems and milk quality of eight milk production units (MPU) in the semiarid region of the state of Ceará, Brazil. Individual interviews were conducted through a questionnaire on the characteristics of the properties and production systems. Samples of milk and water were collected for a period of 12 months. Four MPUs were classified as semi-specialized and four as non-specialized. No differences were observed in milk composition between the two production systems, and both showed protein, fat, and solids-not-fat levels. Differences were observed for somatic cell count. The semi-specialized systems showed an average somatic cell and total bacterial count which is above the limit established by the 62nd Normative Instruction. All water samples showed presence of Escherichia coli. Somatic cell count was positively correlated (fat) and negatively (lactose). For total bacterial count, correlations were negative for fat, total solids, and somatic cell count. The microbiological quality of milk is not in accordance with the 62st and 7th Normative Instructions. The specialization of the production systems did not result in improved microbiological aspects of milk.(AU)


Administration of umbilical cord mesenchymal stem cells in patients with severe COVID-19 pneumonia


ST-Segment-Elevation Myocardial Infarction Care and COVID-19: The Value Proposition of Fibrinolytic Therapy and the Pharmacoinvasive Strategy


title: Compartmental model with loss of immunity: analysis and parameters estimation for Covid-19

text: The outbreak of Covid-19 led the world to an unprecedent health and economical crisis. In an attempt to responde to this emergency researchers worldwide are intensively studying the Covid-19 pandemic dynamics. In this work, a SIRSi compartmental model is proposed, which is a modification of the known classical SIR model. The proposed SIRSi model considers differences in the immunization within a population, and the possibility of unreported or asymptomatic cases. The model is adjusted to three major cities of S\~ao Paulo State, in Brazil, namely, S\~ao Paulo, Santos and Campinas, providing estimates on the duration and peaks of the outbreak.


title: COVID-19-Impact on DNR Orders in the Largest Cancer Center in Jordan

text: The COVID-19 pandemic requires health care teams to rethink how they can continue to provide high-quality care for all patients, whether they are suffering from a COVID-19 infection or other diseases with clinical uncertainty. Although the number of COVID-19 cases in Jordan remains relatively low compared to many other countries, our team introduced significant changes to team operations early, with the aim of protecting patients, families, and health care staff from COVID-19 infections, while preparing to respond to the needs of patients suffering from severe COVID-19 infections. This paper describes the changes made to our "do not resuscitate" policy for the duration of the pandemic.


Covid-19: Black people and other minorities are hardest hit in US


title: The endosomal lipid bis(monoacylglycero) phosphate as a potential key player in the mechanism of action of chloroquine against SARS-COV-2 and other enveloped viruses hijacking the endocytic pathway

text: The anti-malarial drug Chloroquine (CQ) and its derivative hydroxychloroquine have shown antiviral activities in vitro against many viruses, including coronaviruses, dengue virus and the biosafety level 4 Nipah and Hendra paramyxoviruses. The in vivo efficacy of CQ in the treatment of COVID-19 is currently a matter of debate. CQ is a lysosomotrophic compound that accumulates in lysosomes, as well as in food vacuoles of Plasmodium falciparum. In the treatment of malaria, CQ impairs the digestion and growth of the parasite by increasing the pH of the food vacuole. Similarly, it is assumed that the antiviral effects of CQ results from the increase of lysosome pH and the inhibition of acidic proteases involved in the maturation of virus fusion protein. CQ has however other effects, among which phospholipidosis, characterized by the accumulation of multivesicular bodies within the cell. The increase in phospholipid species particularly concerns bis(monoacylglycero)phosphate (BMP), a specific lipid of late endosomes involved in vesicular trafficking and pH-dependent vesicle budding. It was shown previously that drugs like progesterone, the cationic amphiphile U18666A and the phospholipase inhibitor methyl arachidonyl fluoro phosphonate (MAFP) induce the accumulation of BMP in THP-1 cells and decrease cell infection by human immunodeficiency virus. HIV viral particles were found to be retained into large endosomal-type vesicles, preventing virus spreading. Since BMP was also reported to favour virus entry through hijacking of the endocytic pathway, we propose here that BMP could play a dual role in viral infection, with its antiviral effects triggered by lysosomotropic drugs like CQ.


title: SARS-CoV-2 RNA detection in the air and on surfaces in the COVID-19 ward of a hospital in Milan, Italy

text: The COVID-19 outbreak has rapidly progressed worldwide finding the health system, scientists and society unprepared to face a little-known, fast spreading, and extremely deadly virus. Italy is one of the countries hardest hit by the pandemic, resulting in healthcare facilities bearing heavy burdens and severe restrictive measures. Despite efforts to clarify the virus transmission, especially in indoor scenarios, several aspects of SARS-CoV-2 spread are still rudimentary. This study evaluated the contamination of the air and surfaces by SARS-CoV-2 RNA in the COVID-19 isolation ward of a hospital in Milan, Italy. A total of 42 air and surface samples were collected inside five different zones of the ward including contaminated (COVID-19 patients' area), semi-contaminated (undressing room), and clean areas. SARS-CoV-2 RNA detection was performed using real time reverse transcription polymerase chain reaction. Overall, 24.3% of swab samples were positive, but none of these were collected in the clean area. Thus, the positivity rate was higher in contaminated (35.0%) and semi-contaminated (50.0%) areas than in clean areas (0.0%; P<0.05). The most contaminated surfaces were hand sanitizer dispensers (100.0%), medical equipment (50.0%), medical equipment touch screens (50.0%), shelves for medical equipment (40.0%), bedrails (33.3%), and door handles (25.0%). All the air samples collected from the contaminated area, namely the intensive care unit and corridor, were positive while viral RNA was not detected in either semi-contaminated or clean areas. These results showed that environmental contamination did not involve clean areas, but the results also support the need for strict disinfection, hand hygiene and protective measures for healthcare workers as well as the need for airborne isolation precautions.


title: ISeeU2: Visually Interpretable ICU mortality prediction using deep learning and free-text medical notes

text: Accurate mortality prediction allows Intensive Care Units (ICUs) to adequately benchmark clinical practice and identify patients with unexpected outcomes. Traditionally, simple statistical models have been used to assess patient death risk, many times with sub-optimal performance. On the other hand deep learning holds promise to positively impact clinical practice by leveraging medical data to assist diagnosis and prediction, including mortality prediction. However, as the question of whether powerful Deep Learning models attend correlations backed by sound medical knowledge when generating predictions remains open, additional interpretability tools are needed to foster trust and encourage the use of AI by clinicians. In this work we show a Deep Learning model trained on MIMIC-III to predict mortality using raw nursing notes, together with visual explanations for word importance. Our model reaches a ROC of 0.8629 (+/-0.0058), outperforming the traditional SAPS-II score and providing enhanced interpretability when compared with similar Deep Learning approaches.


Leading in the COVID-19 Crisis: Challenges and Solutions for State Health Leaders


Acute myocardial infarction due to coronary stent thrombosis in a symptomatic COVID-19 patient


title: Diferentes fontes energéticas durante o período de transição de vacas primíparas e os seus efeitos sobre metabólitos sanguíneos e hormônios/ Different energy sources during the primiparous dairy cow transition period and its effects on blood metabolites and hormones

text: Objetivou-se com este estudo comparar os efeitos do fornecimento de dietas glicogênicas ou lipogênicas sobre metabolitos sanguíneos e hormônios em vacas primíparas (n=40) durante o período de transição. Os animais foram aleatoriamente distribuídos em quatro tratamentos: controle, sais de cálcio de ácidos graxos poli-insaturados (Megalac-E, 100g pré-parto e 250g pós-parto), soja tostada (400g pré-parto e 800g pós-parto) e propilenoglicol (300ml pré e pós-parto). Os suplementos foram fornecidos individualmente. Foram realizadas coletas de sangue para determinação das concentrações plasmáticas de insulina, glicose, ácidos graxos não esterificados (AGNE) e IGF-I. As concentrações de insulina e de glicose foram maiores nos animais do tratamento com sais de cálcio de ácidos graxos poli-insaturados. A maior concentração de AGNE foi observada no grupo controle. A concentração plasmática de IGF-I foi mais elevada para os animais do tratamento que receberam suplementos lipogênicos. A adição de sais de cálcio de ácidos graxos poli-insaturados a dieta foi capaz de amenizar as mudanças hormonais e metabólicas características do período de transição.(AU)


title: Breast cancer care during a pandemic: an opportune time for cryoablation?

text: PURPOSE: Cryoablation is a minimally-invasive percutaneous procedure that is capable of reducing the psychosocial burden of surgical delay while also decreasing the morbidity of breast cancer therapy. The purpose of this editorial is to discuss the potential role of cryoablation for reducing the psychosocial burden of surgical delay during the COVID-19 pandemic by expediting the management of breast cancer while also lessening demand on limited healthcare resources. METHODS: This editorial critiques current expert opinion recommendations that aim to reduce viral transmission and preserve healthcare resources during the COVID-19 pandemic by advocating delay of elective breast cancer surgery. RESULTS: The editorial summarizes the current state of the evidence that supports the selective use of cryoablation as a definite or stopgap measure in the management of breast cancer during the COVID-19 pandemic or when healthcare resources are limited. CONCLUSIONS: As an office-based procedure performed under local anesthesia, cryoablation eliminates the need for operating room personnel and equipment while also reducing the psychosocial impact of delayed breast cancer surgery. By reducing the number of patient and healthcare provider interactions, cryoablation not only decreases the risk of viral transmission but also the need for personal protective devices during resource-limited times.


Bedside rapid placement of nasointestinal feeding tube via ultrasound-guided stylet positioning in critical COVID-19 patients


title: The WetNet: What the Oral Polio Vaccine Hypothesis Exposes about Globalized Interspecies Fluid Bonds

text: The author analyzes the aftermath of Edward Hooper's suggestion that the trial of an oral polio vaccine (OPV) in the Belgian colonies of Africa engendered the pandemic form of the AIDS virus, HIV-1. In response to Hooper's book, The River (1999), the Royal Society in London held a conference to debate the origins of HIV. Examination of the quick dismissal of the OPV theory opens a space for legitimately challenging the widely held belief that the vaccine contamination question was convincingly resolved. This article interrogates the relationship between historiography and the making of scientific facts and history, suggesting that historians have been too credulous of scientists' testimony. The further result of the lack of a thorough analysis of the evidence backing the OPV hypothesis has resulted in a missed opportunity to read The River as one of the few detailed accounts of the immense social, political, technological, and interspecies infrastructure constituted by Cold War vaccine production. This biomedical infrastructure dramatically changed the geographic and interspecies mobility of viruses in ways that may be impossible to reconstruct. Yet these potential transmission routes remain crucial to acknowledge. The COVID-19 pandemic draws attention to the critical importance of studying The WetNet, a concept coined by the author to name the conceptual and material infrastructures of inter- and intraspecies fluid bonding.


title: Genetic characterization and phylogenetic analysis of porcine deltacoronavirus (PDCoV) in Shandong Province, China

text: Porcine deltacoronavirus (PDCoV) is the etiological agent of acute diarrhoea and vomiting in pigs, threatening the swine industry worldwide. Although several PDCoV studies have been conducted in China, more sequence information is needed to understand the molecular characterization of PDCoV. In this study, the partial ORF1a, spike protein (S) and nucleocapsid protein (N) were sequenced from Shandong Province between 2017 and 2018. The sequencing results for the S protein from 10 PDCoV strains showed 96.7 %-99.7 % nucleotide sequence identity with the China lineage strains, while sharing a lower level of nucleotide sequence identity, ranging from 95.7 to 96.8%, with the Vietnam/Laos/Thailand lineage strains. N protein sequencing analysis showed that these strains showed nucleotide homologies of 97.3%-99.3% with the reference strains. Phylogenetic analyses based on S protein sequences showed that these PDCoV strains were classified into the China lineage. The discontinuous 2 + 3 aa deletions at 400-401 and 758-760 were found in the Nsp2 and Nsp3 coding region in five strains, respectively, with similar deletions having been identified in Vietnam, Thailand, and Laos. Three novel patterns of deletion were observed for the first time in the Nsp2 and Nsp3 regions. Importantly, those findings suggest that PDCoV may have undergone a high degree of variation since PDCoV was first detected in China.


title: The early experiences of a single tertiary Italian emergency department treating COVID-19 in children

text: Italy has been badly affected by COVID-19, despite strict quarantine measures. Up to 1 June 2020, 2.1% of the positive cases in Italy were aged 0-18 years, with no paediatric deaths (1). This paper focuses on the clinical features, laboratory and imaging data and outcomes of 24 patients admitted to the Emergency Department (ED) at IRCCS Gaslini Children's Hospital, Genoa, Italy, from 24 February to 16 April 2020.


title: Porcine Deltacoronavirus Infection and Transmission in Poultry, United States1

text: Coronaviruses cause respiratory and gastrointestinal diseases in diverse host species. Deltacoronaviruses (DCoVs) have been identified in various songbird species and in leopard cats in China. In 2009, porcine deltacoronavirus (PDCoV) was detected in fecal samples from pigs in Asia, but its etiologic role was not identified until 2014, when it caused major diarrhea outbreaks in swine in the United States. Studies have shown that PDCoV uses a conserved region of the aminopeptidase N protein to infect cell lines derived from multiple species, including humans, pigs, and chickens. Because PDCoV is a potential zoonotic pathogen, investigations of its prevalence in humans and its contribution to human disease continue. We report experimental PDCoV infection and subsequent transmission among poultry. In PDCoV-inoculated chicks and turkey poults, we observed diarrhea, persistent viral RNA titers from cloacal and tracheal samples, PDCoV-specific serum IgY antibody responses, and antigen-positive cells from intestines.


Recovery from COVID-19 in a patient with spondyloarthritis treated with TNF-alpha inhibitor etanercept


title: Caring for the Carers of COVID-19

text: none.


title: Cytokine storm induced by SARS-CoV-2

text: Coronavirus disease 2019 (COVID-19), caused by the virus designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread widely throughout the world. Despite the strict global outbreak management and quarantine measures that have been implemented, the incidence of COVID-19 continues to rise, resulting in more than 290,000 deaths and representing an extremely serious threat to human life and health. The clinical symptoms of the affected patients are heterogeneous, ranging from mild upper respiratory symptoms to severe pneumonitis and even acute respiratory distress syndrome (ARDS) or death. Systemic immune over activation due to SARS-CoV-2 infection causes the cytokine storm, which is especially noteworthy in severely ill patients with COVID-19. Pieces of evidence from current studies have shown that the cytokine storm may be an important factor in disease progression, even leading to multiple organ failure and death. This review provides an overview of the knowledge on the COVID-19 epidemiological profile, the molecular mechanisms of the SARS-CoV-2-induced cytokine storm and immune responses, the pathophysiological changes that occur during infection, the main antiviral compounds used in treatment strategies and the potential drugs for targeting cytokines, this information is presented to provide valuable guidance for further studies and for a therapeutic reduction of this excessive immune response.


title: SARS-CoV-2 spread in Northern Italy: what about the pollution role?

text: The recent epidemic of the new SARS-CoV-2 in the northern regions of Italy is putting the organization of the Italian health system under serious attack. The current emergency requires all possible efforts to stem the spread of the virus. In this context, it is clear that we have the urgent need to rely upon etiopathogenetic data, in order to do all possible efforts to block the epidemic. However, observing the trend of the infections in China and the geographic areas of the main outbreaks, it could be hypothesized that air pollution plays a role. In particular, it has been previously demonstrated, in specific populations, a role of particulate matter in worsening clinical presentation of virus infection in airways. Without prejudice to the ascertained virus spread by air droplets or contaminated surfaces, the factors that could have favored its spread remain to be investigated. Moreover, if these observations were to be confirmed, when the health emergency is resolved, it will be mandatory to redesign an economic-productive model in balance with the environment.


title: Time-dependent changes in the clinical characteristics and prognosis of hospitalized COVID-19 patients in Wuhan, China: A retrospective study

text: Cases of coronavirus disease 2019 (COVID-19) have been breaking out around the world recently. However, the dynamic changes in the clinical symptoms and prognosis of COVID-19 patients remain unknown. According to the onset time of clinical symptoms, 843 COVID-19 patients admitted between Jan 22 and Feb 14, 2020 were divided into three groups: group A (Jan 21 to Jan 25, nâ¯=â¯324), group B (Jan 26 to Jan 31, nâ¯=â¯358) and group C (Feb 1 to Feb 10, nâ¯=â¯161). Data on the demographics, symptoms, first laboratory results, treatments and outcomes (within 12â¯days of hospitalization) were collected. The results showed that the median duration from symptom onset to admission shortened over time (12.5, 10 and 5â¯days, respectively, pâ¯<â¯0.05). Fewer patients had fever symptoms and bilateral pneumonia in group C than in the group A and B. Laboratory results showed that white blood cell, neutrophil, and platelet counts, lactic acid and D-dimer levels were lower, while lymphocyte, CD3, and CD8 counts were higher in group C. In addition, group C had more mild-moderate cases and fewer severe cases than the other two groups. More importantly, the incidence of complications (18.5%, 14.2% and 11.2%, respectively, pâ¯<â¯0.05) and all-cause mortality (11.7%, 8.4%, and 5.6%, respectively, pâ¯<â¯0.05) decreased over time. The clinical characteristics and prognosis of COVID-19 patients changed over time. Improved prognosis was found at a later stage.


Coronaviruses that are always present


Ventilación mecánica no invasiva y oxigenoterapia de alto flujo en la pandemia COVID-19: El valor de un empate./ Ventilación mecánica no invasiva y oxigenoterapia de alto flujo en la pandemia COVID-19: El valor de un empate./ Non-invasive mechanical ventilation and high-flow oxygen therapy in the COVID-19 pandemic: the value of a draw


title: Double-Membrane Vesicles as Platforms for Viral Replication

text: Viruses, as obligate intracellular parasites, exploit cellular pathways and resources in a variety of fascinating ways. A striking example of this is the remodelling of intracellular membranes into specialized structures that support the replication of positive-sense ssRNA (+RNA) viruses infecting eukaryotes. These distinct forms of virus-induced structures include double-membrane vesicles (DMVs), found during viral infections as diverse and notorious as those of coronaviruses, enteroviruses, noroviruses, or hepatitis C virus. Our understanding of these DMVs has evolved over the past 15 years thanks to advances in imaging techniques and modern molecular biology tools. In this article, we review contemporary understanding of the biogenesis, structure, and function of virus-induced DMVs as well as the open questions posed by these intriguing structures.


Mask wearing to complement social distancing and save lives during COVID-19


Covid-19 and Racial Disparities: Moving Towards Surgical Equity


title: Safeguarding children with long-term conditions from COVID-19

text: Professor Alan Glasper, from the University of Southampton, discusses strategies to protect children with long-term health conditions from acquiring the disease caused by the SARS-CoV-2 virus.


title: Spatiotemporal distribution and trend of COVID-19 in the Yangtze River Delta region of the People's Republic of China

text: An outbreak of atypical pneumonia, now called COVID-19 and known to be caused by the novel coronavirus SARS-CoV-2, first detected in Wuhan, Hubei Province of the People's Republic of China in December 2019 and afterwards rapidly spread worldwide. Wuhan and the Yangtze River Delta (YRD) region implemented first-level public health emergency responses to stop the spread of the virus on January 23rd, 2020. We tracked the geographical gravity centre of the disease and calculated spatial autocorrelation to explore the spatiotemporal patterns of distribution of imported and locally disseminated COVID-19 cases under the emergency-response control measure. We also applied polynomial regression analysis to estimate the trend of the COVID-19 in the YRD region before and after the control activities against the spread of the infection were instituted. The results show that the control measures applied have been effective. And, in the YRD region, areas with a large influx of population flow from Wuhan and Hubei Province had high risks of COVID-19. Therefore, identification of the spatiotemporal trends should be the first step when developing effective policies to manage and control any new epidemic. The results are not only informative locally but also useful for the rest of the world.


title: Rapid establishment of a COVID-19 biobank in NHRI by National Biobank Consortium of Taiwan

text: By the request of the Minister of Health and Welfare, NHRI Biobank was assigned to establish a COVID-19 biobank in early Feb, 2020 to collect COVID-19 patients' blood samples for Taiwan researchers and industries in an emergent way. It was set up in less than 3 weeks and quickly opened for application. This biobank can provide applicants with biosamples, such as serum, DNA and RNA, and also the clinical and genomic data, so as to accelerate the COVID-19 treatment and prevention research in Taiwan. This COID-19 biobank already received 7 applications. It has become a very important research resource for the COVID-19 pandemic in Taiwan, including disease mechanism, the variable human responses and epidemic preventions.


Getting to a New Normal: Mandating That Patients Wear Masks as Hospitals Fully Reopen during the Coronavirus Pandemic


title: Coalition for medical education-A call to action: A proposition to adapt clinical medical education to meet the needs of students and other healthcare learners during COVID-19

text: With the ongoing coronavirus, journals and the media have extensively covered the impacts on doctors, nurses, physician assistants, and other healthcare workers. However, one group that has rarely been mentioned despite being significantly impacted is medical students and medical education overall. This piece, prepared by both a medical student and a cardiothoracic surgeon with a long career in academic medicine, discusses the recent history of medical education and how it has led to issues now with distance-based learning due to COVID-19. It concludes with a call to action for the medical education system to adapt so it can meet the needs of healthcare learners during COVID-19 and even beyond.


Reply to Sánchez-Pacheco et al., Chookajorn, and Mavian et al.: Explaining phylogenetic network analysis of SARS-CoV-2 genomes


A Frail Health Care System for an Old Population: Lesson form the COVID-19 Outbreak in Italy


How Institutions Can Protect the Mental Health and Psychosocial Well-Being of Their Healthcare Workers in the Current COVID-19 Pandemic


Children's mortality from COVID-19 compared with all-deaths and other relevant causes of death: epidemiological information for decision-making by parents, teachers, clinicians and policymakers


title: First impressions of the foundation interim year 1 postings: positives, pitfalls, and perils

text: COVID-19 has placed an increased burden on the NHS. Changes were made to expand patient capacity including hospital restructuring, cancellation of most elective surgeries and early graduation of final year medical students. 1 The UK foundation programme (UKFP) curated a new training position for graduates as foundation interim year 1 (FiY1) doctors, where they voluntarily work in paid positions prior to entering formal foundation year 1 (FY1) roles. 2 Expediting the process of fulfilling these positions, the General Medical Council facilitated early provisional registration of doctors. We discuss the positives, pitfalls, and perils of the new roles and the first impressions of three newly qualified FiY1 s in medical, obstetrics and gynaecology and surgical posts, a surgical FY1 doctor and a clinical supervisor in surgery.


Cutaneous small-vessel vasculitis associated with novel 2019 coronavirus SARS-CoV-2 infection (COVID-19)


Public and Private Health Services: Wait Times for Health Services and the Risk of Inequality from the Italian Perspective


COVID-19: Risk groups, mechanistic insights and challenges


title: Symptom management for patients awaiting joint replacement surgery

text: BACKGROUND: Joint replacement surgery is a highly effective treatment option for patients with severe osteoarthritis (OA) of the hip and knee when other treatments have failed. Unfortunately, as a result of the COVID-19 pandemic, a temporary suspension of non-urgent elective surgery was implemented. Thousands of patients currently awaiting hip and knee replacements have been affected. Many of these patients will present to their general practitioners for symptom management during this interim period. OBJECTIVE: The purpose of this article is to summarise current recommendations for the non-operative management of patients with symptomatic OA. DISCUSSION: Non-operative treatment modalities for OA include education, lifestyle modification and exercise, mass reduction, physiotherapy, orthoses, psychology, pharmaceuticals and injections. Multimodal therapy is required for patients with severe symptoms. A number of useful online resources are presented, as access to public allied health services may be limited because of the COVID-19 pandemic.


Evolving status of the 2019 novel coronavirus infection: Proposal of conventional serologic assays for disease diagnosis and infection monitoring


title: Early Outbreak Detection for Proactive Crisis Management Using Twitter Data: COVID-19 a Case Study in the US

text: During a disease outbreak, timely non-medical interventions are critical in preventing the disease from growing into an epidemic and ultimately a pandemic. However, taking quick measures requires the capability to detect the early warning signs of the outbreak. This work collects Twitter posts surrounding the 2020 COVID-19 pandemic expressing the most common symptoms of COVID-19 including cough and fever, geolocated to the United States. Through examining the variation in Twitter activities at the state level, we observed a temporal lag between the rises in the number of symptom reporting tweets and officially reported positive cases which varies between 5 to 19 days.


title: Early Phase of the COVID-19 Outbreak in Hungary and Post-Lockdown Scenarios

text: COVID-19 epidemic has been suppressed in Hungary due to timely non-pharmaceutical interventions, prompting a considerable reduction in the number of contacts and transmission of the virus. This strategy was effective in preventing epidemic growth and reducing the incidence of COVID-19 to low levels. In this report, we present the first epidemiological and statistical analysis of the early phase of the COVID-19 outbreak in Hungary. Then, we establish an age-structured compartmental model to explore alternative post-lockdown scenarios. We incorporate various factors, such as age-specific measures, seasonal effects, and spatial heterogeneity to project the possible peak size and disease burden of a COVID-19 epidemic wave after the current measures are relaxed.


Position paper ANMCO: Gestione dei pazienti con sospetto o conclamato COVID-19 e necessità di procedure di elettrofisiologia e/o elettrostimolazione urgenti./ [ANMCO Position paper: Guidance for the management of suspected or confirmed COVID-19 patients requiring urgent electrophysiological procedures]


title: Let's talk about sex in the context of COVID-19

text: In recent months, the coronavirus disease 2019 (COVID-19) pandemic has sent many countries into crisis. Studies have shown that this virus causes worse outcomes and a higher mortality in men than in women. It has been recognized that sex can affect the immune response to a pathogenic agent, as well as the susceptibility for some respiratory diseases. These different responses in males and females may be related to the actions of sex hormones. Angiotensin-converting enzyme 2 (ACE2) acts as the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19. The expression of ACE2 is influenced by sex hormones; therefore, we discuss in this article that this could be one of the reasons why COVID-19 is more prevalent in men than in women.


To keep a COVID-19-free hospital ward: mission possible?


Coronavirus: the first three months as it happened


Coronavirus Disease (COVID-19) hospitalized patients with acute kidney injury (AKI) treated with acute peritoneal dialysis do not have infectious PD effluent


title: Long-term potentiation prevents ketamine-induced aberrant neurophysiological dynamics in the hippocampus-prefrontal cortex pathway in vivo

text: N-methyl-D-aspartate receptor (NMDAr) antagonists such as ketamine (KET) produce psychotic-like behavior in both humans and animal models. NMDAr hypofunction affects normal oscillatory dynamics and synaptic plasticity in key brain regions related to schizophrenia, particularly in the hippocampus and the prefrontal cortex. It has been shown that prior long-term potentiation (LTP) occluded the increase of synaptic efficacy in the hippocampus-prefrontal cortex pathway induced by MK-801, a non-competitive NMDAr antagonist. However, it is not clear whether LTP could also modulate aberrant oscillations and short-term plasticity disruptions induced by NMDAr antagonists. Thus, we tested whether LTP could mitigate the electrophysiological changes promoted by KET. We recorded HPC-PFC local field potentials and evoked responses in urethane anesthetized rats, before and after KET administration, preceded or not by LTP induction. Our results show that KET promotes an aberrant delta-high-gamma cross-frequency coupling in the PFC and an enhancement in HPC-PFC evoked responses. LTP induction prior to KET attenuates changes in synaptic efficiency and prevents the increase in cortical gamma amplitude comodulation. These findings are consistent with evidence that increased efficiency of glutamatergic receptors attenuates cognitive impairment in animal models of psychosis. Therefore, high-frequency stimulation in HPC may be a useful tool to better understand how to prevent NMDAr hypofunction effects on synaptic plasticity and oscillatory coordination in cortico-limbic circuits.


Dr. Li Wenliang and the Time of COVID-19


title: Brief Report: Anti-phospholipid antibodies in critically ill patients with Coronavirus Disease 2019 (COVID-19)

text: OBJECTIVES: Coagulopathy is one of the characteristics of critically ill patients with Coronavirus Disease 2019 (COVID-19). Antiphospholipid antibodies (aPLs) contribute to coagulopathy, but their role in COVID-19 remains unclear. We aimed to determine the prevalence and characteristics of aPLs in patients with COVID-19. METHODS: Sera collected from 66 critically ill and 13 non-critically ill patients with COVID-19 were tested for anti-cardiolipin (aCL) and anti-ß2-glycoprotein 1 (aß2GP1) (IgG, IgM, and IgA) and IgG aß2GP1-D1 by the chemiluminescence assay (CIA) and IgM and IgG anti-phosphatidylserine/prothrombin (aPS/PT) by ELISA. RESULTS: aPLs were detected in 47.0% of critically ill patients (31/66), but not in patients with non-critical conditions. IgA aß2GP1 was the most common aPL, present in 28.8% (19/66) critically ill patients, followed by IgA aCL (25.8%,17/66) and IgG aß2GP1 (18.2%,12/66). For multiple aPLs, IgA aß2GP1+IgA aCL was the most common type (22.7%, 15/66), followed by IgA aß2GP1+IgA aCL+ IgG aß2GP1 (15.2%, 10/66). aPLs emerge around 35-39 days post-disease onset. Dynamic analysis of aPLs revealed 4 patterns based on persistence or transient appearance of the aPLs. Patients with multiple aPLs displayed significantly higher incidence of cerebral infarction (p=0.023). CONCLUSIONS: aPLs were common in critically ill patients. Multiple medium or high levels aPLs may help identify patients at risk of developing cerebral infarction. aPLs may be transient and disappear within a few weeks, but in genetically predisposed patients, COVID-19 may trigger the development of "COVID-19-induced-APS-like-syndrome". Long-term follow-up on COVID-19 patients positive for aPLs would be of great importance.


title: Hypoxemia in COVID-19 patients: An hypothesis

text: The current SARS-Cov-2 virus pandemic challenges critical care physicians and other caregivers to find effective treatment for desperately ill patients - especially those with sudden and extreme hypoxemia. Unlike patients with other forms of Acute Respiratory Distress Syndrome, these patients do not exhibit increased lung stiffness or dramatic dyspnea., even in the presence of arterial blood oxygen levels lower than that seen normally in mixed venous blood. Urgent intubation and mechanical ventilation with high inflation pressures and raised inhaled oxygen concentration have proved unhelpful or worse, but why? Our Hypothesis is that sudden opening of a previously undetected probe-patent foramen ovale (PPFO) may explain this mystery. As hypoxemia without acidosis is a rather weak stimulus of dyspnea or increased ventilation, and opening of such an intracardiac shunt would not worsen lung mechanical properties, the absence of dramatic symptom changes would not be surprising. We point out the high frequency of PFO both in life and at autopsy, and the physiological evidence of large shunt fractions found in Covid-19 patients. Published evidence of hypercoagulability and abundant evidence of pulmonary emboli found at autopsy are in accord with our hypothesis, as they would contribute to raised pressure in the pulmonary arteries and right heart chambers, potentially causing a shunt to open. We review the interaction between viral corona spike protein and ACE-2 receptors present on the surface of alveolar lining cells, and contribution to hypercoagulabilty caused by the spike protein. Search for an open PFO after a large drop in arterial oxygen saturation can be performed at the bedside with a variety of well-established techniques including bedside echocardiography, nitrogen washout test, and imaging studies. Potential treatments might include balloon or patch closure of the shunt, and various drug treatments to lower pulmonary vascular resistance.


title: Geo-temporal distribution of 1,688 Chinese healthcare workers infected with COVID-19 in severe conditions-A secondary data analysis

text: INTRODUCTION: The COVID-19 outbreak is posing an unprecedented challenge to healthcare workers. This study analyzes the geo-temporal effects on disease severity for the 1,688 Chinese healthcare workers infected with COVID-19. METHODS: Using the descriptive results recently reported by the Chinese CDC, we compare the percentage of infected healthcare workers in severe conditions over time and across three areas in China, and the fatality rate of infected healthcare workers with all the infected individuals in China aged 22-59 years. RESULTS: Among the infected Chinese healthcare workers whose symptoms onset appeared during the same ten-day period, the percentage of those in severe conditions decreased significantly from 19.7% (Jan 11-20) to 14.4% (Jan 21-31) to 8.7% (Feb 1-11). Across the country, there was also a significant difference in the disease severity, with Wuhan being the most severe (17.3%), followed by Hubei Province (10.2%), and the rest of China (6.6%). The case fatality rate for the 1,688 infected Chinese healthcare workers was significantly lower than that for the 29,798 infected patients aged 20-59 years-0.3% (5/1,688) vs. 0.65% (193/29,798), respectively. CONCLUSION: The disease severity among infected healthcare workers improved considerably over a short period of time in China. The more severe conditions in Wuhan compared to the rest of the country may be attributable to the draconian lockdown. The clinical outcomes of infected Chinese healthcare workers may represent a more accurate estimation of the severity of COVID-19 for those who have access to quality healthcare.


title: Risk of the Brazilian health care system over 5572 municipalities to exceed health care capacity due to the 2019 novel coronavirus (COVID-19)

text: The spread of the 2019 novel coronavirus (COVID-19) has challenged governments to develop public policies to reduce the load of the COVID-19 on health care systems, which is commonly referred to as "flattening the curve". This study aims to address this issue by proposing a spatial multicriteria approach to estimate the risk of the Brazilian health care system, by municipality, to exceed the health care capacity because of an influx of patients infected with the COVID-19. We estimated this risk for 5572 municipalities in Brazil using a combination of a multicriteria decision-making approach with spatial analysis to estimate the exceedance risk, and then, we examined the risk variation by designing 5 control intervention scenarios (3 scenarios representing reduction on social contacts, and 2 scenarios representing investment on health care system). For the baseline scenario using an average infection rate across Brazil, we estimated a mean Hospital Bed Capacity (HBC) value of -16.73, indicating that, on average, the Brazilian municipalities will have a deficit of approximately 17 beds. This deficit is projected to occur in 3338 municipalities with the north and northeast regions being at the greatest risk of exceeding health care capacity due to the COVID-19. The intervention scenarios indicate across all of Brazil that they could address the bed shortage, with an average of available beds between 23 and 32. However, when we consider the shortages at a municipal scale, bed exceedances still occur for at least 2119 municipalities in the most effective intervention scenario. Our findings are essential to identify priority areas, to compare populations, and to provide options for government agencies to act. This study can be used to provide support for the creation of effective health public policies for national, regional, and local intervention.