Battling COVID-19 Pandemic: Sphingosine-1-Phosphate Analogs as an Adjunctive Therapy?
immunomodulators, Cytokine storm, SARS-CoV-2, COVID-19, S1P analogs
With the sudden outbreak of COVID-19 patient worldwide and associated mortality, it is critical to come up with an effective treatment against SARS-CoV-2. Studies suggest that mortality due to COVID 19 is mainly attributed to the hyper inflammatory response leading to cytokine storm and ARDS in infected patients. Sphingosine-1-phosphate receptor 1 (S1PR1) analogs, AAL-R and RP-002, have earlier provided in-vivo protection from the pathophysiological response during H1N1 influenza infection and improved mortality. Recently, it was shown that the treatment with sphingosine-1-phosphate receptor 1 analog, CYM5442, resulted in the significant dampening of the immune response upon H1N1 challenge in mice and improved survival of H1N1 infected mice in combination with an antiviral drug, oseltamivir. Hence, here we suggest to investigate the possible utility of using S1P analogs to treat COVID-19.
Battling COVID-19: using old weapons for a new enemy
Tocilizumab, hydroxychloroquine, Nitazoxanide, Lopinavir/ritonavir, SARS-CoV-2, Remdisivir
Abstract Coronavirus disease-19 (COVID-19) has reached pandemic proportions. Most of the drugs that are being tried for the treatment have not been evaluated in any randomized controlled trials. The purpose of this review was to summarize the in-vitro and in-vivo efficacy of these drugs on Severe Acute Respiratory Syndrome (SARS-CoV-2) and related viruses (SARS and Middle East Respiratory Syndrome) and evaluate their potential for re-purposing them in the management of COVID-19.
Nitin Gupta,, Rohit Kumar, Manish Soneja, Naveet Wig, Ankit Mittal, Parul Kodan
Tropical Diseases, Travel Medicine and Vaccines
Bayes' theorem, COVID19, and screening tests.
covid-19, Screening tests, Bayes' theorem
The COVID19 crisis has provided a portal to revisit and understand qualities of screening tests and the importance of Bayes' theorem in understanding how to interpret results and implications of next actions.
The American journal of emergency medicine
Bayesian inference of transmission chains using timing of symptoms, pathogen genomes and contact data.
There exists significant interest in developing statistical and computational tools for inferring 'who infected whom' in an infectious disease outbreak from densely sampled case data, with most recent studies focusing on the analysis of whole genome sequence data. However, genomic data can be poorly informative of transmission events if mutations accumulate too slowly to resolve individual transmission pairs or if there exist multiple pathogens lineages within-host, and there has been little focus on incorporating other types of outbreak data. We present here a methodology that uses contact data for the inference of transmission trees in a statistically rigorous manner, alongside genomic data and temporal data. Contact data is frequently collected in outbreaks of pathogens spread by close contact, including Ebola virus (EBOV), severe acute respiratory syndrome coronavirus (SARS-CoV) and Mycobacterium tuberculosis (TB), and routinely used to reconstruct transmission chains. As an improvement over previous, ad-hoc approaches, we developed a probabilistic model that relates a set of contact data to an underlying transmission tree and integrated this in the outbreaker2 inference framework. By analyzing simulated outbreaks under various contact tracing scenarios, we demonstrate that contact data significantly improves our ability to reconstruct transmission trees, even under realistic limitations on the coverage of the contact tracing effort and the amount of non-infectious mixing between cases. Indeed, contact data is equally or more informative than fully sampled whole genome sequence data in certain scenarios. We then use our method to analyze the early stages of the 2003 SARS outbreak in Singapore and describe the range of transmission scenarios consistent with contact data and genetic sequence in a probabilistic manner for the first time. This simple yet flexible model can easily be incorporated into existing tools for outbreak reconstruction and should permit a better integration of genomic and epidemiological data for inferring transmission chains.
Finlay Campbell, Anne Cori, Neil Ferguson, Thibaut Jombart
BCG Against SARS-CoV-2: Second Youth of an Old Age Vaccine?
covid-19, Clinical trials, IL-1β, BCG vaccine, trained immunity
The sudden outbreak of the COVID-19 pandemic, caused by SARS-CoV-2, has put the whole world into a difficult situation, asking for the immediate development of therapeutics and vaccines against the disease. Bacillus Calmette–Guérin (BCG), an attenuated strain of Mycobacterium bovis, has been administered for decades in many countries against tuberculosis. Today, when a solution against SARS-CoV-2 is urgently needed, the BCG vaccine has again come into the limelight owing to its earlier prevention of non-specific diseases. Data suggest a higher mortality rate of COVID-19 in non-BCG vaccinated countries, whereas the nations opting for BCG immunization have a comparatively lower mortality rate. The BCG vaccine is known to induce ‘trained immunity’ and generate ‘non-specific’ heterologous immune responses. It can confer anti-viral immunity by eliciting the production of pro-inflammatory cytokines, IL-6, TNF-α, IFN-γ, and IL-1β. Though the initial results look promising, a long trail still needs to be followed to avoid false promises. The accuracy of nationwide data, the role of an already activated immune system against ‘cytokine storms’, optimization and timing of vaccine dosage, and balancing demand-supply are some of the relevant issues that must be resolved before reaching a final conclusion.
BCG vaccination and COVID-19: Was flattening the curve just an illusion?
mortality, covid-19, Incidence, Tuberculosis, BCG vaccine, Correlation of data
BCG Vaccination and Mortality of COVID-19 across 173 Countries: An Ecological Study
Urbanization, covid-19, Coronavirus disease 2019, Vaccination, BCG, bacillus Calmette–Guérin
Ecological studies have suggested fewer COVID-19 morbidities and mortalities in Bacillus Calmette–Guérin (BCG)-vaccinated countries than BCG-non-vaccinated countries. However, these studies obtained data during the early phase of the pandemic and did not adjust for potential confounders, including PCR-test numbers per population (PCR-tests). Currently—more than four months after declaration of the pandemic—the BCG-hypothesis needs reexamining. An ecological study was conducted by obtaining data of 61 factors in 173 countries, including BCG vaccine coverage (%), using morbidity and mortality as outcomes, obtained from open resources. ‘Urban population (%)’ and ‘insufficient physical activity (%)’ in each country was positively associated with morbidity, but not mortality, after adjustment for PCR-tests. On the other hand, recent BCG vaccine coverage (%) was negatively associated with mortality, but not morbidity, even with adjustment for percentage of the population ≥ 60 years of age, morbidity, PCR-tests and other factors. The results of this study generated a hypothesis that a national BCG vaccination program seems to be associated with reduced mortality of COVID-19, although this needs to be further examined and proved by randomized clinical trials.
Mitsuyoshi Urashima, Katharina Otani, Yasutaka Hasegawa, Taisuke Akutsu
Be Aware, Be Alert, Be Prepared: Endoscopy during the COVID-2019 Pandemic
Diseases of the digestive system. Gastroenterology
Bebbington, Anthony (ed.). Minería, movimientos sociales y respuestas campesinas. Una ecología política de transformaciones territoriales
Bulletin de l'Institut Français d'Études Andines
http://journals.openedition.org/bifea/3751
Social sciences (General), Latin America. Spanish America
Bedside wireless lung ultrasound for the evaluation of COVID-19 lung injury in senior nursing home residents
lung ultrasound, COVID-19 pneumonia, elderly, nasal-pharyngeal swabs
Lung Ultrasound (LUS) is regarded to be potentially useful to diagnose lung injury in older adults living in nursing homes with suspected COVID-19 pneumonia. We aimed at evaluating presence lung injury among senior nursing home residents by LUS performed with portable wireless scanner echography. The study population consisted of 150 residents with a mean age of 88 years (85% female) residing in 12 nursing homes in Northern Italy. Subjects had to have a history of recent onset of symptoms compatible with COVID-19 pneumonia or have been exposed to the contagion of patients carrying the disease. COVID-19 testing was performed with SARS-CoV-2 nasal-pharyngeal (NP) swabs. Positive subjects to LUS scanning were considered those with non-coascelent B-lines in >3 zones, coalescent B-lines in >3 zones and with iperdensed patchy non-consolidated lungs. Sixty-three percent had positive NP testing and 65% had LUS signs of pulmonary injury. LUS had a sensitivity of 79% in predicting positive NP testing. Sixteen percent of residents tested negative for SARSCoV-2 carried the signs of COVID-19 lung injury at LUS. There were 92 patients (61%) with current or recent symptoms.Positivity to LUS scanning was reported in 73% of residents with symptoms, while it was 53% in those without (P=0.016). A positive NP testing was observed in 66% of residents with symptoms and in 57% of those without (P=0.27). We conclude that assessment of LUS by portable wireless scanner echography can be profitability utilized to diagnose lung injury among senior nursing home residents with or without symptoms compatible with COVID-19 pneumonia.
Mario Miccoli, Frank Lloyd Dini, Carlo Bergamini, Aldo Allegrini, Massimo Scopelliti, Gianmarco Secco, Stefano Boni, Raffaella Brigada, Stefano Perlini