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ANH-Intl Covid-19 information tracker - Week 17
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Science |
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Origins |
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Authors: Hannah K Frank, David Enard and Scott D Boyd Publication date: 20 April 2020 Journal: bioRxiv preprint DOI: 10.1101/2020.04.20.051656 Pandemics originating from pathogen transmission between animals and humans highlight the broader need to understand how natural hosts have evolved in response to emerging human pathogens and which groups may be susceptible to infection. Here, we investigate angiotensin-converting enzyme 2 (ACE2), the host protein bound by SARS-CoV and SARS-CoV-2. We find that the ACE2 gene is under strong selection pressure in bats, the group in which the progenitors of SARS-CoV and SARS-CoV-2 are hypothesized to have evolved, particularly in residues that contact SARS-CoV and SARS-CoV-2. We detect positive selection in non-bat mammals in ACE2 but in a smaller proportion of branches than in bats, without enrichment of selection in residues that contact SARS-CoV or SARS-CoV-2. Additionally, we evaluate similarity between humans and other species in residues that contact SARS-CoV or SARS-CoV-2, revealing potential susceptible species but also highlighting the difficulties of predicting spillover events. This work increases our understanding of the relationship between mammals, particularly bats, and coronaviruses, and provides data that can be used in functional studies of how host proteins are bound by SARS-CoV and SARS-CoV-2 strains. |
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Mutations |
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Patient-derived mutations impact pathogenicity of SARS-CoV-2 Authors: Yao H et al Publication date: 19 April 2020 Journal: medRxiv preprint DOI: 10.1101/2020.04.14.20060160 The sudden outbreak of the severe acute respiratory syndrome-coronavirus (SARS-CoV-2) has spread globally with more than 1,300,000 patients diagnosed and a death toll of 70,000. Current genomic survey data suggest that single nucleotide variants (SNVs) are abundant. However, no mutation has been directly linked with functional changes in viral pathogenicity. Here we report functional characterizations of 11 patient-derived viral isolates, all of which have at least one mutation. Importantly, these viral isolates show significant variation in cytopathic effects and viral load, up to 270-fold differences, when infecting Vero-E6 cells. We observed intrapersonal variation and 6 different mutations in the spike glycoprotein (S protein), including 2 different SNVs that led to the same missense mutation. Therefore, we provide direct evidence that the SARS-CoV-2 has acquired mutations capable of substantially changing its pathogenicity. |
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Epidemiology |
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Authors: Cummings MJ MD et al Publication date: 20 April 2020 Journal: medRxiv preprint DOI: 10.1101/2020.04.15.20067157 Background: Nearly 30,000 patients with coronavirus disease-2019 (COVID-19) have been hospitalized in New York City as of April 14th, 2020. Data on the epidemiology, clinical course, and outcomes of critically ill patients with COVID-19 in this setting are needed. Methods: We prospectively collected clinical, biomarker, and treatment data on critically ill adults with laboratory-confirmed-COVID-19 admitted to two hospitals in northern Manhattan between March 2nd and April 1st, 2020. The primary outcome was in-hospital mortality. Secondary outcomes included frequency and duration of invasive mechanical ventilation, frequency of vasopressor use and renal-replacement-therapy, and time to clinical deterioration following hospital admission. The relationship between clinical risk factors, biomarkers, and in-hospital mortality was modeled using Cox-proportional-hazards regression. Each patient had at least 14 days of observation. Results: Of 1,150 adults hospitalized with COVID-19 during the study period, 257 (22%) were critically ill. The median age was 62 years (interquartile range [IQR] 51-72); 170 (66%) were male. Two-hundred twelve (82%) had at least one chronic illness, the most common of which were hypertension (63%; 162/257) and diabetes mellitus (36%; 92/257). One-hundred-thirty-eight patients (54%) were obese, and 13 (5%) were healthcare workers. As of April 14th, 2020, in-hospital mortality was 33% (86/257); 47% (122/257) of patients remained hospitalized. Two-hundred-one (79%) patients received invasive mechanical ventilation (median 13 days [IQR 9-17]), and 54% (138/257) and 29% (75/257) required vasopressors and renal-replacement-therapy, respectively. The median time to clinical deterioration following hospital admission was 3 days (IQR 1-6). Older age, hypertension, chronic lung disease, and higher concentrations of interleukin-6 and d-dimer at admission were independently associated with in-hospital mortality. Conclusions: Critical illness among patients hospitalized with COVID-19 in New York City is common and associated with a high frequency of invasive mechanical ventilation, extra-pulmonary organ dysfunction, and substantial in-hospital mortality. Estimating the burden of SARS-CoV-2 in France Authors: Salje H et al Publication date: 20 April 2020 Source: Institut Pasteur France has been heavily affected by the SARS-CoV-2 epidemic and went into lockdown on the 17th March 2020. Using models applied to hospital and death data, we estimate the impact of the lockdown and current population immunity. We find 2.6% of infected individuals are hospitalized and 0.53% die, ranging from 0.001% in those <20y to 8.3% in those >80y. Across all ages, men are more likely to be hospitalized, enter intensive care, and die than women. The lockdown reduced the reproductive number from 3.3 to 0.5 (84% reduction). By 11 May, when interventions are scheduled to be eased, we project 3.7 million (range: 2.3-6.7) people, 5.7% of the population, will have been infected. Population immunity appears insufficient to avoid a second wave if all control measures are released at the end of the lockdown Coronavirus Infections in Children Including COVID-19 An Overview of the Epidemiology, Clinical Features, Diagnosis, Treatment and Prevention Options in Children Authors: Zimmermann, Petra MD, PhD and Curtis, Nigel FRCPCH, PhD Publication date: May 2020 Journal: The Pediatric Infectious Disease Journal DOI: 10.1097/INF.0000000000002660 Coronaviruses (CoVs) are a large family of enveloped, single-stranded, zoonotic RNA viruses. Four CoVs commonly circulate among humans: HCoV2-229E, -HKU1, -NL63 and -OC43. However, CoVs can rapidly mutate and recombine leading to novel CoVs that can spread from animals to humans. The novel CoVs severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012. The 2019 novel coronavirus (SARS-CoV-2) is currently causing a severe outbreak of disease (termed COVID-19) in China and multiple other countries, threatening to cause a global pandemic. In humans, CoVs mostly cause respiratory and gastrointestinal symptoms. Clinical manifestations range from a common cold to more severe disease such as bronchitis, pneumonia, severe acute respiratory distress syndrome, multi-organ failure and even death. SARS-CoV, MERS-CoV and SARS-CoV-2 seem to less commonly affect children and to cause fewer symptoms and less severe disease in this age group compared with adults, and are associated with much lower case-fatality rates. Preliminary evidence suggests children are just as likely as adults to become infected with SARS-CoV-2 but are less likely to be symptomatic or develop severe symptoms. However, the importance of children in transmitting the virus remains uncertain. Children more often have gastrointestinal symptoms compared with adults. Most children with SARS-CoV present with fever, but this is not the case for the other novel CoVs. Many children affected by MERS-CoV are asymptomatic. The majority of children infected by novel CoVs have a documented household contact, often showing symptoms before them. In contrast, adults more often have a nosocomial exposure. In this review, we summarize epidemiologic, clinical and diagnostic findings, as well as treatment and prevention options for common circulating and novel CoVs infections in humans with a focus on infections in children. COVID-19 Antibody Seroprevalence in Santa Clara County, California Author: Bendavid E et al Publication date: 11 April 2020 Journal: MedRxiv preprint DOI: 10.1101/2020.04.14.20062463 Background: Addressing COVID-19 is a pressing health and social concern. To date, many epidemic projections and policies addressing COVID-19 have been designed without seroprevalence data to inform epidemic parameters. We measured the seroprevalence of antibodies to SARS-CoV-2 in Santa Clara County. Methods On 4/3-4/4, 2020, we tested county residents for antibodies to SARS-CoV-2 using a lateral flow immunoassay. Participants were recruited using Facebook ads targeting a representative sample of the county by demographic and geographic characteristics. We report the prevalence of antibodies to SARS-CoV-2 in a sample of 3,330 people, adjusting for zip code, sex, and race/ethnicity. We also adjust for test performance characteristics using 3 different estimates: (i) the test manufacturer's data, (ii) a sample of 37 positive and 30 negative controls tested at Stanford, and (iii) a combination of both. Results: The unadjusted prevalence of antibodies to SARS-CoV-2 in Santa Clara County was 1.5% (exact binomial 95CI 1.11-1.97%), and the population-weighted prevalence was 2.81% (95CI 2.24-3.37%). Under the three scenarios for test performance characteristics, the population prevalence of COVID-19 in Santa Clara ranged from 2.49% (95CI 1.80-3.17%) to 4.16% (2.58-5.70%). These prevalence estimates represent a range between 48,000 and 81,000 people infected in Santa Clara County by early April, 50-85-fold more than the number of confirmed cases. Conclusions: The population prevalence of SARS-CoV-2 antibodies in Santa Clara County implies that the infection is much more widespread than indicated by the number of confirmed cases. Population prevalence estimates can now be used to calibrate epidemic and mortality projections. Watch video of John Iaonnidis discussing the study results |
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Testing |
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Serological tests facilitate identification of asymptomatic SARS‐CoV‐2 infection in Wuhan, China Authors: Xiaodong Wu, Bo Fu, Lang Chen and Yong Feng Publication date: 20 April 2020 Journal: Medical Virology DOI: 10.1002/jmv.25904 The Wuhan City has ended the lockdown and people have been allowed to resume working since April 8 if meeting a set of COVID‐19‐associated tests including SARS‐CoV‐2 nucleic acid test (NAT) of nasopharyngeal swabs, chest CT scan or a SARS‐CoV‐2‐specific serological test. Here, we reported the positive rate of COVID‐19 tests based on NAT, chest CT scan and a serological SARS‐CoV‐2 test, from April 3 to 15 in one hospital in Qingshan Destrict, Wuhan. We observed a ~10% SARS‐CoV‐2‐specific IgG positive rate from 1,402 tests. Combination of SARS‐CoV‐2 NAT and a specific serological test might facilitate the detection of COVID‐19 infection, or the asymptomatic SARS‐CoV‐2‐infected subjects. Large‐scale investigation is required to evaluate the herd immunity of the city, for the resuming people and for the re‐opened city. The Promise and Peril of Antibody Testing for COVID-19 Author: Jennifer Abbasi Publication date: 17 April 2020 Journal: JAMA DOI: 10.1001/jama.2020.6170 As coronavirus disease 2019 (COVID-19) raged around the globe in late March, hundreds of San Miguel County, Colorado, residents turned out for a blood test. Standing 6 feet apart outside a Telluride school gym, they waited for the blood draw that would tell them whether they had mounted an immune response to the disease-causing virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—a sign that they’d been infected. In the first such community-wide campaign in the US, the San Miguel County Department of Health offered the voluntary screening to most of the area’s 8000 residents over 2 weeks. Just 8 of the 986 individuals tested on March 26 and 27 were positive for SARS-CoV-2 antibodies. Another 23 were borderline, suggesting that they’d recently been exposed to the virus and were just starting to make antibodies against it. But those were early days. The screenings, paid for by test manufacturer United Biomedical Inc and the county, eventually would be repeated to see how much things had changed. |
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Covid-19 patients |
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UK report on 5578 patients critically ill with COVID-19 Institution: Intensive Care National Audit & Research Centre (ICNARC) Publication date: 17 April 2020 Read more... Clinical Characteristics of Covid-19 in New York City Authors: Goyal P MD et al Publication date: 17 April 2020 Journal: The New England Journal of Medicine DOI: 10.1056/NEJMc2010419 The world is in the midst of the coronavirus disease 2019 (Covid-19) pandemic,1,2 and New York City has emerged as an epicenter. Here, we characterize the first 393 consecutive patients with Covid-19 who were admitted to two hospitals in New York City. This retrospective case series includes adults 18 years of age or older with confirmed Covid-19 who were consecutively admitted between March 3 (date of the first positive case) and March 27, 2020, at an 862-bed quaternary referral center and an affiliated 180-bed nonteaching community hospital in Manhattan. Both hospitals adopted an early-intubation strategy with limited use of high-flow nasal cannulae during this period. Cases were confirmed through reverse-transcriptase–polymerase-chain-reaction assays performed on nasopharyngeal swab specimens. Data were manually abstracted from electronic health records with the use of a quality-controlled protocol and structured abstraction tool (details are provided in the Methods section in the Supplementary Appendix, available with the full text of this letter at NEJM.org). Diarrhea is associated with prolonged symptoms and viral carriage in COVID-19 Authors: Wei XS et al Publication date: 17 April 2020 Journal: Clinical Gastroenterology and Hepatology DOI: 10.1016/j.cgh.2020.04.030 Background & Aims: We compared clinical, laboratory, radiological, and outcome features of patients with SARS-CoV-2 infection (COVID-19) with pneumonia, with vs without diarrhea. Conclusions: At a single center in Wuhan, China, 31% of patients with SARS-CoV-2 pneumonia had diarrhea. A significantly higher proportion of patients with diarrhea have virus RNA in stool than patients without diarrhea. Elimination of SARS-CoV-2 from stool takes longer than elimination from the nose and throat. COVID-19 pneumonia: ARDS or not? Authors: Luciano Gattinoni, Davide Chiumello & Sandra Rossi Publication date: 16 April 2020 Journal: Critical Care DOI: 10.1186/s13054-020-02880-z Even though it can meet the ARDS Berlin definition [1, 2], the COVID-19 pneumonia is a specific disease with peculiar phenotypes. Its main characteristic is the dissociation between the severity of the hypoxemia and the maintenance of relatively good respiratory mechanics. Indeed, the median respiratory system compliance is usually around 50 ml/cmH2O. Of note, the patients with respiratory compliance lower or higher than the median value experience hypoxemia of similar severity. We propose the presence of two types of patients (“non-ARDS,” type 1, and ARDS, type 2) with different pathophysiology. When presenting at the hospital, type 1 and type 2 patients are clearly distinguishable by CT scan (Fig. 1). If the CT scan is not available, the respiratory system compliance and possibly the response to PEEP are the only imperfect surrogates we may suggest. Targeting potential drivers of COVID-19: Neutrophil extracellular traps Authors: Barnes BJ et al Publication date: 16 April 2020 Journal: Journal of Experimental Medicine DOI: 10.1084/jem.20200652 Coronavirus disease 2019 (COVID-19) is a novel, viral-induced respiratory disease that in ∼10–15% of patients progresses to acute respiratory distress syndrome (ARDS) triggered by a cytokine storm. In this Perspective, autopsy results and literature are presented supporting the hypothesis that a little known yet powerful function of neutrophils—the ability to form neutrophil extracellular traps (NETs)—may contribute to organ damage and mortality in COVID-19. We show lung infiltration of neutrophils in an autopsy specimen from a patient who succumbed to COVID-19. We discuss prior reports linking aberrant NET formation to pulmonary diseases, thrombosis, mucous secretions in the airways, and cytokine production. If our hypothesis is correct, targeting NETs directly and/or indirectly with existing drugs may reduce the clinical severity of COVID-19. |
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Co-morbidities |
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Authors: Chen R, MD et al Publication date: 15 April 2020 Journal: Chest DOI: 10.1016/j.chest.2020.04.010 Methods: A retrospective cohort of 1590 hospitalized subjects with COVID-19 throughout China was established. The prognostic effects of variables, including clinical features and laboratory findings, were analyzed using Kapla-Meier method and Cox proportional hazard model. A prognostic nomogram was formulated to predict the survival of patient with COVID-19. Results: In this nationwide cohort, non-survivors showed higher incidence of elderly people, subjects with co-existing chronic illness, dyspnea and laboratory abnormalities on admission, compared with survivors. Multivariate Cox regression analysis showed that age≥75 (HR: 7.86, 95% CI: 2.44-25.35), age between 65-74 years (HR:3.43, 95%CI: 1.24-9.5), coronary heart disease (HR:4.28, 95%CI:1.14-16.13), cerebrovascular disease(HR:3.1, 95%CI:1.07-8.94), dyspnea (HR: 3.96, 95%CI:1.42-11), procalcitonin>0.5ng/ml(HR:8.72, 95%CI:3.42-22.28), aspartate aminotransferase>40U/liter (HR: 2.2, 95% CI: 1.1- 6.73) were independent risk factors associated with fatal outcome. A nomogram was established based on the results of multivariate analysis. The internal bootstrap resampling approach suggested the nomogram has sufficient discriminatory power with the C-index of 0.91 (95%CI 0.85-0.97). The calibration plots also demonstrated good consistence between the prediction and the observation. Conclusions: The proposed nomogram accurately predict clinical outcomes of patients with COVID-19 based on individual characteristics. Earlier identification, more intensive surveillance and appropriate therapy should be considered in patients with high risk. |
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Therapeutics |
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Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19 Authors: Magagnoli J et al Publication date: 21 April 2020 Journal: medRxiv preprint DOI: 10.1101/2020.04.16.20065920 Background: Despite limited and conflicting data on the use of hydroxychloroquine in patients with Covid-19, the U.S. Food and Drug Administration has authorized the emergency use of this drug when clinical trials are unavailable or infeasible. Hydroxychloroquine, alone or in combination with azithromycin, is being widely used in Covid-19 therapy based on anecdotal and limited observational evidence. Methods: We performed a retrospective analysis of data from patients hospitalized with confirmed SARS-CoV-2 infection in all United States Veterans Health Administration medical centers until April 11, 2020. Patients were categorized based on their exposure to hydroxychloroquine alone (HC) or with azithromycin (HC+AZ) as treatments in addition to standard supportive management for Covid-19. The two primary outcomes were death and the need for mechanical ventilation. We determined the association between treatment and the primary outcomes using competing risk hazard regression adjusting for clinical characteristics via propensity scores. Discharge and death were taken into account as competing risks and subdistribution hazard ratios are presented. Results: A total of 368 patients were evaluated (HC, n=97; HC+AZ, n=113; no HC, n=158). Rates of death in the HC, HC+AZ, and no HC groups were 27.8%, 22.1%, 11.4%, respectively. Rates of ventilation in the HC, HC+AZ, and no HC groups were 13.3%, 6.9%, 14.1%, respectively. Compared to the no HC group, the risk of death from any cause was higher in the HC group (adjusted hazard ratio, 2.61; 95% CI, 1.10 to 6.17; P=0.03) but not in the HC+AZ group (adjusted hazard ratio, 1.14; 95% CI, 0.56 to 2.32; P=0.72). The risk of ventilation was similar in the HC group (adjusted hazard ratio, 1.43; 95% CI, 0.53 to 3.79; P=0.48) and in the HC+AZ group (adjusted hazard ratio, 0.43; 95% CI, 0.16 to 1.12; P=0.09), compared to the no HC group. Conclusions: In this study, we found no evidence that use of hydroxychloroquine, either with or without azithromycin, reduced the risk of mechanical ventilation in patients hospitalized with Covid-19. An association of increased overall mortality was identified in patients treated with hydroxychloroquine alone. These findings highlight the importance of awaiting the results of ongoing prospective, randomized, controlled studies before widespread adoption of these drugs. |
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Nutrition |
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Nutrition amid the COVID-19 pandemic: a multi-level framework for action Authors: Farah Naja and Rena Hamadeh Publication date: 20 April 2020 Journal: European Journal of Clinical Nutrition DOI: 10.1038/s41430-020-0634-3 Experiences from previous outbreaks have shown that as an epidemic evolves, there is an urgent need to expand public health activities beyond direct clinical management and extend to cover basic principles of management and optimization of resource utilization [3]. Since the outbreak of the COVID-19, individual and community resilience emerged as a main resource while remaining the first line of defense in emergency preparedness. In fact, psychological and behavioral countermeasures of both the individual and the community are vital determinants to improve resilience and enhance the efficacy of public health approaches vis a vis a pandemic of a magnitude similar to that of COVID-19 [4]. The nutritional status of individuals has for long been considered as an indicator of resilience against destabilization [5]. The ecology of adversity and resilience demonstrates that substantial stressors, such as inadequate nutrition, can lead to long-lasting effects that are linked to health [6]. In fact, poor diet quality has been associated not only with physical but also mental health [7]. Optimal nutrition and dietary intake is a resource that transcends the individual, the community to reach global influence. |
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Social distancing |
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The Benefits and Costs of Using Social Distancing to Flatten the Curve for COVID-19 Authors: Thunstrom L et al Publication date: 14 April 2020 Institution: University of Wyoming Journal: Journal of Benefit Cost Analysis. DOI: 10.2139/ssrn.3561934 We examine the net benefits of social distancing to slow the spread of COVID-19 in the United States. Social distancing saves lives but imposes large costs on society due to reduced economic activity. We use epidemiological and economic forecasting to perform a rapid benefit-cost analysis of controlling the COVID-19 outbreak. Assuming that social distancing measures can substantially reduce contacts among individuals, we find net benefits of about $5.2 trillion in our benchmark case. We examine the magnitude of the critical parameters that might imply negative net benefits, including the value of statistical life and the discount rate. A key unknown factor is the speed of economic recovery with and without social distancing measures in place. A series of robustness checks also highlight the key role of the value of mortality risk reductions and discounting in the analysis and point to a need for effective economic stimulus when the outbreak has passed. |
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Environmental factors |
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Assessing nitrogen dioxide (NO2) levels as a contributing factor to coronavirus (COVID-19) fatality Author: Yaron Ogen Publication date: 15 July 2020 Journal: Science of The Total Environment DOI: 10.1016/j.scitotenv.2020.138605 Nitrogen dioxide (NO2) is an ambient trace-gas result of both natural and anthropogenic processes. Long-term exposure to NO2 may cause a wide spectrum of severe health problems such as hypertension, diabetes, heart and cardiovascular diseases and even death. The objective of this study is to examine the relationship between long-term exposure to NO2 and coronavirus fatality. The Sentinel-5P is used for mapping the tropospheric NO2 distribution and the NCEP/NCAR reanalysis for evaluating the atmospheric capability to disperse the pollution. The spatial analysis has been conducted on a regional scale and combined with the number of death cases taken from 66 administrative regions in Italy, Spain, France and Germany. Results show that out of the 4443 fatality cases, 3487 (78%) were in five regions located in north Italy and central Spain. Additionally, the same five regions show the highest NO2 concentrations combined with downwards airflow which prevent an efficient dispersion of air pollution. These results indicate that the long-term exposure to this pollutant may be one of the most important contributors to fatality caused by the COVID-19 virus in these regions and maybe across the whole world. Association between short-term exposure to air pollution and COVID-19 infection: Evidence from China Authors: Zhu Y et al Publication date: 15 April 2020 Journal: Science of The Total Environment DOI: 10.1016/j.scitotenv.2020.138704 The novel coronavirus pneumonia, namely COVID-19, has become a global public health problem. Previous studies have found that air pollution is a risk factor for respiratory infection by carrying microorganisms and affecting body's immunity. This study aimed to explore the relationship between ambient air pollutants and the infection caused by the novel coronavirus. Daily confirmed cases, air pollution concentration and meteorological variables in 120 cities were obtained from January 23, 2020 to February 29, 2020 in China. We applied a generalized additive model to investigate the associations of six air pollutants (PM2.5, PM10, SO2, CO, NO2 and O3) with COVID-19 confirmed cases. We observed significantly positive associations of PM2.5, PM10, NO2 and O3 in the last two weeks with newly COVID-19 confirmed cases. A 10-μg/m3 increase (lag0-14) in PM2.5, PM10, NO2, and O3 was associated with a 2.24% (95% CI: 1.02 to 3.46), 1.76% (95% CI: 0.89 to 2.63), 6.94% (95% CI: 2.38 to 11.51), and 4.76% (95% CI: 1.99 to 7.52) increase in the daily counts of confirmed cases, respectively. However, a 10-μg/m3 increase (lag0-14) in SO2 was associated with a 7.79% decrease (95% CI: -14.57 to -1.01) in COVID-19 confirmed cases. Our results indicate that there is a significant relationship between air pollution and COVID-19 infection, which could partially explain the effect of national lockdown and provide implications for the control and prevention of this novel disease. |
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Clinical trials |
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As at 22/04/20 745 clinical trials have been registered with the National Institutes of Health (NIH) ClinicalTrials.gov website: Covid-19 related trials Of those 28 (4%) are related to natural health interventions |
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Lockdown |
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Authors: Banholzer N et al Publication date: 21 April 2020 Journal: MedRxiv preprint DOI: 10.1101/2020.04.16.20062141 Background: The novel coronavirus (SARS-CoV-2) has rapidly evolved into a global epidemic. To control its spread, countries have implemented non-pharmaceutical interventions (NPIs), such as school or border closures, while others have even enforced a complete lockdown. Here we study the effectiveness of NPIs in reducing documented cases of COVID-19. Findings: Based on our model, we compare the effectiveness of NPIs in the early stages of the outbreak. The closure of venues is associated with a reduction in the number of new cases by 33 % (95% credible interval [CrI] 16–47 %). The reduction is lower for work bans on non-essential business activities (28 %; 95% CrI 10–42 %) and border closures (26 %; 95% CrI 13–37 %). School closures yield a reduction of only 11 % (95% CrI 0–27 %) and its relative impact is one of the lowest among the various policy measures considered in this analysis. Interpretation: This cross-country analysis provides early estimates regarding the effectiveness of different NPIs for controlling the COVID-19 epidemic. These findings are relevant for evaluating current health-policies and will be refined as more data become available. Authors: Sutherland, W.J. et al. Publication date: 16 April 2020 Institution: St Catharine’s College, Cambridge, CB2 1RL Source: BioRISC (Biosecurity Research Initiative at St Catharine’s) DOI: 10.17605/OSF.IO/CA5RH We have identified 275 options to reduce SARS-CoV-2 transmission in five key areas: (1) physical isolation, (2) reducing transmission through contaminated items, (3) enhancing cleaning and hygiene, (4) reducing spread through pets, and (5) restricting disease spread between areas. For any particular problem this long list will quickly be winnowed down to a much shorter list of potential options based on relevance and practicality; this bespoke shortlist will be the subject of more detailed consideration. |
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Covid reference |
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Seventeen years ago, in the middle of the outbreak, we decided to write a short medical text about the ongoing SARS drama, presenting the scientific data and providing real-time updates. After publishing three editions in 6months, a scientific magazine concluded that our SARS Reference (www.SARSReference.com) was “not fancy”, but presented “plenty of information”. When we became aware of the new coronavirus epidemic in mid-January 2020, we immediately felt that time had come to repeat our millenium exercise. Publication date: 1 April 2020 Publication date: 7 April 2020 Publication date: 21 April 2020 |
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Media – Science related |
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Pathogenesis |
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How does coronavirus kill? Clinicians trace a ferocious rampage through the body, from brain to toes Authors: Meredith Wadman, Jennifer Couzin-Frankel, Jocelyn Kaiser, Catherine Matacic Publication date: 17 April 2020 Source: Science DOI: 10.1126/science.abc3208 On rounds in a 20-bed intensive care unit one recent day, physician Joshua Denson assessed two patients with seizures, many with respiratory failure and others whose kidneys were on a dangerous downhill slide. Days earlier, his rounds had been interrupted as his team tried, and failed, to resuscitate a young woman whose heart had stopped. All shared one thing, says Denson, a pulmonary and critical care physician at the Tulane University School of Medicine. “They are all COVID positive.” As the number of confirmed cases of COVID-19 surges past 2.2 million globally and deaths surpass 150,000, clinicians and pathologists are struggling to understand the damage wrought by the coronavirus as it tears through the body. They are realizing that although the lungs are ground zero, its reach can extend to many organs including the heart and blood vessels, kidneys, gut, and brain. |
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Clinical trials |
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MolecularMatch Releases Free COVID-19 and Coronavirus Trial Tracking Tool Publication date: 14 April 2020 Source: MolecularMatch MolecularMatch, a leading clinical informatics company, has released a free, web-based portal to help researchers, physicians and patients find clinical trials for COVID-19 and coronavirus. The portal, available at VirusTrials.com, includes over 800 clinical trials across the globe for therapies and vaccines being tested for COVID-19. Physicians and patients can use their country, state or postal code to find enrolling trials nearest to the patient. Specific patient age, symptoms, severity and comorbidities are used to help find trials best suited to that individual. In addition to trials, the portal can also be used to search for literature and publications related to COVID-19. Check the COVID-19 Clinical Trials & Publications database |
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Therapeutics |
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Early Intervention Protocol for COVID-19 Can Save Lives Publication date: April 2020 Source: Front Line COVID-19 Critical Care Working Group This video describes the work of five critical care specialists who are treating coronavirus patients at academic centers and other major hospitals across the United States. Through their current work, past research, and studying the findings of the Shanghai expert protocols, they have concluded that a combination of corticosteroids, high dose intravenous ascorbic acid (vitamin C), and anticoagulants, given early in the ER or hospital, can prevent the progression of the disease and reduce the need for mechanical ventilators. Their findings have not yet been widely adopted in the U.S. and they want to get the word out to save lives now. Grassroots clinicians pick up on Vitamin C treatment for coronavirus Author: Jerome Burne Publication date: 20 April 2020 Source: HealthInsightUK We are all familiar with the popular idea that vitamin C can help with colds and flu. Equally familiar are the routine medical statements that any benefit is marginal at best. Over the last few weeks, however, the situation has been changing rapidly and it looks as if the wisdom of crowds about coronavirus had got it right. Responding to reports of trials and clinical use of high dose vitamin C on infected patients in China, a grassroots revolution by clinicians in America is underway to test its effectiveness. Meanwhile, official medical bodies in America and the UK are continuing to ignore the possibility that combinations of cheap supplements and old drugs could be useful. Video conference with Dr ZY Peng of the world’s first high-dose IVC trial Author: Richard Cheng, MD Publication date: 16 April 2020 Source: Cheng Integrative Health Center Blog We had the pleasure of having Dr ZY Peng as our guest in an international video conference to discuss his experience (in 3 different videos). Highlights: HD-IVC seems to reduce the inflammation of Covid-19 significantly HD-IVC seems to reduce Covid-19 patients’ ICU and hospital stays HD-IVC may also reduce the mortality rate of Covid-19 patients, although the number of patients may be too small Dr Peng also told the group that his hospital was giving Vit C powder to all healthcare providers and advised them to take 1-2grams of VC powder daily. He also said he believes all the major hospitals in Wuhan were giving Vit C powder to their healthcare providers. (I think this is significant because although the treatment of moderate to severe Covid-19 patients is very important, prevention or treatment of mild cases is probably even more important for obvious reasons – Richard Cheng, MD Early peek at data on Gilead coronavirus drug suggests patients are responding to treatment Author: Adam Feuersteing and Matthew Herper Publication date: 16 April 2020 Source: STATReports A Chicago hospital treating severe Covid-19 patients with Gilead Sciences’ antiviral medicine remdesivir in a closely watched clinical trial is seeing rapid recoveries in fever and respiratory symptoms, with nearly all patients discharged in less than a week, STAT has learned. Read more... |
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Testing |
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Early antibody testing suggests COVID-19 infections in L.A. County greatly exceed documented cases Author: Leigh Hopper Publication date: 20 April 2020 Source: University of Southern California USC and the Los Angeles County Department of Public Health on Monday released preliminary results from a collaborative scientific study that suggests infections from the new coronavirus are far more widespread — and the fatality rate much lower — in L.A. County than previously thought. The results are from the first round of an ongoing study by USC researchers and county health officials. They will be conducting antibody testing over time on a series of representative samples of adults to determine the scope and spread of the pandemic across the county. Based on the results of the first round of testing, the research team estimates that approximately 4.1% of the county’s adult population has an antibody to the virus. Adjusting this estimate for the statistical margin of error implies about 2.8% to 5.6% of the county’s adult population has an antibody to the virus — which translates to approximately 221,000 to 442,000 adults in the county who have been infected. That estimate is 28 to 55 times higher than the 7,994 confirmed cases of COVID-19 reported to the county at the time of the study in early April. The number of COVID-related deaths in the county has now surpassed 600. Will antibody tests for the coronavirus really change everything? Author: Smriti Mallapaty Publication date: 18 April 2020 Source: Nature DOI: 10.1038/d41586-020-01115-z British Prime Minister Boris Johnson called them a ‘game changer’. Antibody tests have captured the world’s attention for their potential to help life return to normal by revealing who has been exposed, and might now be immune, to the new coronavirus. Dozens of biotech companies and research laboratories have rushed to produce the blood tests. And governments around the world have bought millions of kits, in the hope that they could guide decisions on when to relax social-distancing measures and get people back to work. Some have even suggested that the tests could be used as an ‘immunity passport’, giving the owner clearance to interact with others again. Roche develops new serology test to detect COVID-19 antibodies Publication date: 17 April 2020 The new Elecsys Anti-SARS-CoV-2 serology test can support the detection of antibodies against SARS-CoV-2 in patients who have been exposed to the virus which causes COVID-19 The detection of these antibodies could help indicate if a person has gained immunity against the virus and inform treatment decisions Roche aims to have this test available by early May, in countries accepting the CE mark1 and is actively working with the US Food and Drug Administration for an Emergency Use Authorisation |
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Mortality & morbidity |
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COVID-19 Death Data in England – Update 20th April Authors: Jason Oke & Carl Heneghan Publication date: 20 April 2020 Source: The Centre for Evidence-Based Medicine Consistent with previous analyses, the peak day of deaths was the 8th of April. The structure of the data is similar across the regions, with the peak in London on the 4th of April, four days ahead of the rest of the country, the 8th of April. NHS England releases data at 2 pm each day and reports daily count up to the previous day as well as a total figure. We wrote about the problems with reconciling the different data here: Today’s reported figure is 429 deaths in hospitals in England. This figure is 36% less than last Monday (13th April) reported number of deaths (n= 667) in hospitals in England. |
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Vaccines |
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University of Waterloo developing DNA-based COVID-19 vaccine Publication date: 16 April 2020 Source: University of Waterloo Researchers at the University of Waterloo are developing a DNA-based vaccine that can be delivered through a nasal spray. The vaccine will work by using engineered bacteriophage, a process that will allow the vaccine to stimulate an immune response in the nasal cavity and target tissues in the lower respiratory tract. “When complete, our DNA-based vaccine will be administered non-invasively as a nasal spray that delivers nanomedicine engineered to immunize and decrease COVID-19 infections,” explains Roderick Slavcev, a professor in the School of Pharmacy who specializes in designing vaccines, pharmaceuticals and gene-therapy treatments. “This research combines the expertise of many and leverages existing technology developed by my team, which we’re reconfiguring for a COVID-19 application.” When completed, the researchers aim to have the DNA-based vaccine enter cells in targeted tissues and cause them to produce a virus-like particle (VLP) that will stimulate an immune response in people. News Feature: Avoiding pitfalls in the pursuit of a COVID-19 vaccine Author: Lynne Peeples Publication date: 14 April 2020 Journal: PNAS DOI: 10.1073/pnas.2005456117 As they race to devise a vaccine, researchers are trying to ensure that their candidates don’t spur a counterproductive, even dangerous, immune system reaction known as immune enhancement. The teams of researchers scrambling to develop a coronavirus disease 2019 (COVID-19) vaccine clearly face some big challenges, both scientific and logistical. One of the most pressing: understanding how the immune system interacts not only with the pathogen but with the vaccine itself—crucial insights when attempting to develop a safe and effective vaccine. |
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Lifting lockdowns |
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Publication date: 17 April 2020 Source: The BMJ European Union officials have unveiled their “roadmap” to phase out the ongoing coronavirus containment measures.1 But they warned of a “very long” exit from a crisis that has been a devastating double whammy to the continent’s health and economic wellbeing. The European Commission president, Ursula von der Leyen, warned that a failure by countries to work together on their exit strategies could lead to a dangerous second wave of covid-19. “If shops are open on one side of the border, we don’t want people moving from one member state to the next to use the shopping opportunity,” she said, urging authorities in EU member states not to erase the progress made from the painful lockdowns imposed over the past month. |
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Transmission |
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Vets would not manage Covid-19 this way Authors: Dick Sibley and Joe Brownlie Publication date: 16 April 2020 Journal: Vet Record DOI: 10.1136/vr.m3004 Veterinary surgeons with any experience in dealing with infectious disease and population medicine will be looking at the government’s current management of the Covid-19 epidemic with dismay. The current approach is to manage the epidemic to fit the critical care capacity of the NHS – something that has been under-resourced over many years. It is a strategy not so much to save lives but to delay deaths. But this policy could also wreck our economy and drive many businesses (including veterinary practices) into financial ruin. Livestock vets have experience of successfully managing national disease outbreaks. They understand the confounding factors that are important when determining strategies for delivering disease prevention and control on a major scale, including health, welfare, economics and political palatability: issues that are perplexing current policymakers. |
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Tracking |
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Publication date: 20 April 2020 Source: Ada Lovelace Institute A rapid evidence review published today by the Ada Lovelace Institute sets out proposals for whether, and how, the UK Government should use technology to transition from the COVID-19 global public health crisis. It concludes that there is no evidence to support the immediate deployment of digital contact tracing or immunity certification and calls for the establishment of a new Group of Advisors on Technology in Emergencies (GATE) to oversee the development and testing of any proposed digital tracing application. |
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Media – Reporting |
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Pathogenesis |
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Coronavirus clue? Most cases aboard U.S. aircraft carrier are symptom-free Authors: Phil Stewart and Idrees Ali Publication date: 16 April 2020 Source: Reuters Sweeping testing of the entire crew of the coronavirus-stricken U.S. aircraft carrier Theodore Roosevelt may have revealed a clue about the pandemic: The majority of the positive cases so far are among sailors who are asymptomatic, officials say. The possibility that the coronavirus spreads in a mostly stealthy mode among a population of largely young, healthy people showing no symptoms could have major implications for U.S. policy-makers, who are considering how and when to reopen the economy. |
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Therapeutics |
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Author: Rachel Ellis Publication date: 20 April 2020 (updated 21 April 2020) Source: Daily Mail The sunshine vitamin — vitamin D — is the latest target for researchers investigating treatment options for the coronavirus. Previous research has shown that the vitamin, which mainly comes from exposure to the sun and is essential for a healthy immune system, can help protect against other respiratory infections. Now, Spanish researchers have started a ten-week trial to see if vitamin D can also help with Covid-19. So should we all be taking a daily supplement to reduce our chances of getting the coronavirus or to help our bodies fight it? Local hospital using experimental drug treatment in hopes of saving lives of COVID-19 patients Author: Phil Archer Publication date: 16 April 2020 (updated 20 April 2020) Source: Click2Houston Because there is no known cure for COVID-19, doctors around the country are experimenting with treatments in an effort to save lives. One top doctor at United Memorial Medical Center said a cocktail of drugs used in the past to treat major infections is proving 100% success with his COVID-19 patients. That treatment is a combination of cortizone, large doses of vitamin C and a blood thinner. Dr. Joseph Varon says it shows great promises for treating COVID-19. Medics in fresh call to provide vitamin D for those in need Author: Kathleen Nutt Publication date: 17 April 2020 Source: The National Senior medics and experts have renewed an appeal for vitamin D to be distributed to groups of people who appear to be at a higher risk of becoming critically ill or dying if they catch the coronavirus. In an open letter, published in The National today, Barbara Boucher, Honorary Professor of Medicine at the Blizard Institute at Queen Mary University of London, joined Dr Peter Cobbold, Emeritus Professor, University of Liverpool and Helga Rhein, a retired GP in Edinburgh and others call for supplements to be given to the elderly, carers, night-shift workers and members of BAME communities in the UK who are more likely to have low levels of the nutrient. |
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Testing |
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No evidence that people who have survived coronavirus have immunity, says World Health Organisation Publication date: 18 April 2020 Source: The Telegraph There is currently no evidence to support the belief that people who have recovered from coronavirus then have immunity, the World Health Organisation has said. Senior WHO epidemiologists warned despite the hopes governments across the world have piled on antibody tests, there is no proof those who have been infected cannot be infected again. The British Government has bought 3.5 million serology tests, which measure levels of antibodies in blood plasma, even though they are not definitive of growing levels of herd immunity. Many tests being developed are pin-prick blood tests similar to widely used instant HIV tests and measure for raised levels of the antibodies the body uses to fight the virus. Speaking at a press conference in Geneva, Dr Maria van Kerkhove said: "There are a lot of countries that are suggesting using rapid diagnostic serological tests to be able to capture what they think will be a measure of immunity. Coronavirus: Double warning over antibody tests Publication date: 18 April 2020 Source: BBC Hopes that coronavirus antibody tests could help the UK end its lockdown have been dealt a blow - after the World Health Organization questioned whether they offer any guarantee of immunity. The UK has placed antibody tests - which check if someone has had Covid-19 - at the centre of an eventual "back-to-work" plan to restart normal life. But experts said they may not prove if someone is protected from reinfection. The UK's testing co-ordinator has also warned people not to buy private tests. The government has already paid for three-and-a-half million antibody tests, but has not yet found one that is reliable enough to use - and stresses that it will not approve the use of any test until it can be sure its findings can be fully depended on. Professor John Newton said the public should not purchase unapproved antibody tests until a working test is approved. |
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Mortality & morbidity |
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Swedish health agency says virus has peaked in Stockholm, no easing of restrictions yet Publication date: 21 April 2020 Source: Reuters Around one-third of Stockholm’s 1 million people will have had the novel coronavirus by the start of May and the disease may have already passed its peak in the capital, Sweden’s public health agency said on Tuesday. Stockholm accounts for around half of Sweden’s 15,300 confirmed cases of COVID-19, the respiratory disease caused by the virus, and a high proportion of its 1,765 deaths, including among very elderly people living in care homes. The public health agency said its modelling suggested the rate of new infections in the city had peaked on April 15, although a decline was not yet evident from its data. |
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Coronavirus agenda |
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The Dark Side Of The Coronavirus Scam Author: Bill Sardi Publication date: 22 April 2020 Source: Lew Rockwell This report reveals a collection of information that certainly throws a different light on the public’s understanding of this global COVID-19 coronavirus fiasco. For this report I will be referring to linked sources so readers can fact check as usual, and a primary source for this report I admiringly refer to as The Oracle Helena. As ancient history buffs may recall, Pythia was the female priestess at the Temple of Apollo at Delphin in ancient Greece (~1400 B.C.). The seat of the Oracle was dug into a pit where Pythia sat. She breathed terrestrial gases rising from the ground which altered her speech much like laughing gas does. People from all over Greece and points beyond trekked to Delphi to have their questions answered by the Priestess Pythia. |
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Second wave infections |
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Will there be a second wave of coronavirus? Author: Peter Beaumont Publication date: 20 April 2020 Source: The Guardian With more countries planning to loosen restrictions imposed due to coronavirus but the UK prime minister, Boris Johnson, and the German chancellor, Angela Merkel, concerned about the potential for a resurgence or second wave, here is what we know from the rest of the world about the risk of Covid-19 coming back. Will there be a second wave? Epidemics of infectious diseases behave in different ways but the 1918 influenza pandemic that killed more than 50 million people is regarded as a key example of a pandemic that occurred in multiple waves, with the latter more severe than the first. It has been replicated – albeit more mildly – in subsequent flu pandemics. Other flu pandemics – including in 1957 and 1968 – all had multiple waves. The 2009 H1N1 influenza A pandemic started in April and was followed, in the US and temperate northern hemisphere, by a second wave in the autumn. |
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Tracking |
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Bluetooth phone apps for tracking COVID-19 show modest early results Authors: Aradhana Aravindan and Sankalp Phartiyal Publication date: 21 April 2020 Source: Reuters When Singapore launched the first smartphone app of its kind last month to identify and alert people who had interacted with carriers of the novel coronavirus, the city-state of roughly 5.7 million people had 385 cases of infections. But even as cases in the country - which is in lockdown - have surged past 9,000, only about one in five people have downloaded the app, TraceTogether, which uses Bluetooth signals to log when people have been close to one another. The modest numbers in a tech-savvy country where trust in government is high shows the challenges facing public health authorities and technology experts around the world who are looking to exit lockdowns and believe contact-tracing apps can play an important role in restarting economies. |
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Vaccines |
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Don’t bet on vaccine to protect us from Covid-19, says world health expert Authors: Robin McKie, Toby Helm and Michael Savage Publication date: 18 April 2020 Source: The Guardian Professor of global health at Imperial College, London warns we ‘may have to adapt’ to virus. Humanity will have to live with the threat of coronavirus “for the foreseeable future” and adapt accordingly because there is no guarantee that a vaccine can be successfully developed, one of the world’s leading experts on the disease has warned. The stark message was delivered by David Nabarro, professor of global health at Imperial College, London, and an envoy for the World Health Organisation on Covid-19, as the number of UK hospital deaths from the virus passed 15,000. A further 888 people were reported on Saturday to have lost their lives – a figure described by communities secretary Robert Jenrick as “extremely sobering” – while the total number who have been infected increased by 5,525 to 114,217. |
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Lockdown |
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A sustainable exit strategy: Managing uncertainty, minimising harm Authors: Mulheirn I et al Publication date: 20 April 2020 Source: Tony Blair Institute for Global Change Lockdown saves lives, buying time... Across Europe, only full lockdown has worked to reduce the reproduction number below 1, slowing the rate of spread. ...but the UK now needs a sustainable strategy for Covid-19 OBR anticipates a 35% fall in GDP in Q2 if lockdown continues through June. Data on other conditions suggests that the health costs of lockdown are high. |
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