Results: Among 465 COVID‐19 patients, median age was 45 years while hypertension, diabetes, and chronic liver disease were the most common comorbidities. History of exposure to the epidemic area was present in 170 (36.56%) and 185 (39.78%) patients were clustered in 77 families. Severe/critical type of COVID‐19 developed in 49 (10.54%) patients. Fever and cough were the most common symptoms while diarrhea/vomiting were reported in 58 (12.47%) patients. Multivariate analysis revealed eight risk factors for severe/critical COVID‐19. Glucocorticoids and antibiotics were administered to 60 (12.90%) and 218(46.88%) patients, respectively. Bioinformatics showed four single amino acid mutations and one amino acid position loss in SARS‐CoV‐2 from Zhejiang province, with more similarity to humans than to viruses.
Conclusions: SARS‐CoV‐2 showed virological mutations and more human transmission in Zhejiang province, indicating considerable epidemiological and clinical changes. Caution in glucocorticoid and antibiotics use is advisable.
The lung pathology seen in patients with coronavirus disease 2019 (COVID-19) shows marked microvascular thrombosis and haemorrhage linked to extensive alveolar and interstitial inflammation that shares features with macrophage activation syndrome (MAS). We have termed the lung-restricted vascular immunopathology associated with COVID-19 as diffuse pulmonary intravascular coagulopathy, which in its early stages is distinct from disseminated intravascular coagulation. Increased circulating D-dimer concentrations (reflecting pulmonary vascular bed thrombosis with fibrinolysis) and elevated cardiac enzyme concentrations (reflecting emergent ventricular stress induced by pulmonary hypertension) in the face of normal fibrinogen and platelet levels are key early features of severe pulmonary intravascular coagulopathy related to COVID-19. Extensive immunothrombosis over a wide pulmonary vascular territory without confirmation of COVID-19 viraemia in early disease best explains the adverse impact of male sex, hypertension, obesity, and diabetes on the prognosis of patients with COVID-19. The immune mechanism underlying diffuse alveolar and pulmonary interstitial inflammation in COVID-19 involves a MAS-like state that triggers extensive immunothrombosis, which might unmask subclinical cardiovascular disease and is distinct from the MAS and disseminated intravascular coagulation that is more familiar to rheumatologists.
Authors: Lauren M Madigan, MD, Robert G Micheletti, MD and Kanade Shinkai MD, PhD
Publication date: 30 April 2020
Journal: JAMA Dermatology
In this issue of JAMA Dermatology, clinical cases and images of rashes in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are presented.1,2 Although these early observations are not comprehensive of all skin manifestations seen, our intention in publishing them is to help dermatologists recognize emerging patterns of rashes in patients with coronavirus disease 2019 (COVID-19). The reported prevalence of cutaneous signs in association with this pandemic is conflicting; one study reported a rash in only 0.2% of a cohort of Chinese patients,3 whereas the estimated prevalence in a cross-sectional Italian study was 20.4%.4 In the latter study, performed by dermatologists, the cutaneous manifestations were most commonly described as an erythematous rash; however, a range of additional morphologic features were observed, including generalized urticaria and vesicular eruptions. A predilection for the trunk was also noted.4 It may not be possible to determine the exact prevalence of skin findings in infected patients until serologic testing is more widely available, given that some individuals may lack the typical respiratory signs of COVID-19.
In the past month we found a 30-fold increased incidence of Kawasaki-like disease. Children diagnosed after the SARS-CoV-2 epidemic began showed evidence of immune response to the virus, were older, had a higher rate of cardiac involvement, and features of MAS. The SARS-CoV-2 epidemic was associated with high incidence of a severe form of Kawasaki disease. A similar outbreak of Kawasaki-like disease is expected in countries involved in the SARS-CoV-2 epidemic.
Authors: Yanuck SF, Pizzorno J, Messier H, Fitzgerald KN
Journal: Integrative Medicine Journal
This paper presents an evidence-based strategy for improving clinical outcomes in COVID-19. Recommendations are based on the phases of the disease, because optimal interventions for one phase may not be appropriate for a different phase. The four phases addressed are: Prevention, Infection, Inflammation and Recovery.
Underlying this phased approach is recognition of emerging evidence for two different components of pathophysiology, early infection and late stage severe complications. These two aspects of the disease suggest two different patterns of clinical emphasis that seem on the surface to be not entirely concordant. We describe the application of therapeutic strategies and appropriate tactics that address four main stages of disease progression for COVID-19.
Emerging evidence in COVID-19 suggests that the SARS-CoV-2 virus may both evade the innate immune response and kill macrophages. Delayed innate immune response and a depleted population of macrophages can theoretically result in a blunted antigen presentation, delaying and diminishing activation of the adaptive immune response. Thus, one clinical strategy involves supporting patient innate and adaptive immune responses early in the time course of illness, with the goal of
improving the timeliness, readiness, and robustness of both the innate and adaptive immune responses.
At the other end of the disease pathology spectrum, risk of fatality in COVID-19 is driven by excessive and persistent upregulation of inflammatory mechanisms associated with cytokine storm. Thus, the second clinical strategy is to prevent or mitigate excessive inflammatory response to prevent the cytokine storm associated with high mortality risk.
Clinical support for immune system pathogen clearance mechanisms involves obligate activation of immune response components that are inherently inflammatory. This puts the goals of the first clinical strategy (immune activation) potentially at odds with the goals of the second strategy (mitigation of proinflammatory effects). This creates a need for discernment about the time course of the illness and with that, understanding of which components of an overall strategy to apply at each phase of the time course of the illness.
We review evidence from early observational studies and the existing literature on both outcomes and mechanisms of disease, to inform a phased approach to support the patient at risk for infection, with infection, with escalating inflammation during infection, and at risk of negative sequelae as they move into recovery.
Authors: Petre Cristian Ilie, Simina Stefanescu and Lee Smith
Publication date: 06 May 2020
Journal: Aging Clinical and Experimental Research
WHO declared SARS-CoV-2 a global pandemic. The present aim was to propose an hypothesis that there is a potential association between mean levels of vitamin D in various countries with cases and mortality caused by COVID-19. The mean levels of vitamin D for 20 European countries and morbidity and mortality caused by COVID-19 were acquired. Negative correlations between mean levels of vitamin D (average 56 mmol/L, STDEV 10.61) in each country and the number of COVID-19 cases/1 M (mean 295.95, STDEV 298.7, and mortality/1 M (mean 5.96, STDEV 15.13) were observed. Vitamin D levels are severely low in the aging population especially in Spain, Italy and Switzerland. This is also the most vulnerable group of the population in relation to COVID-19. It should be advisable to perform dedicated studies about vitamin D levels in COVID-19 patients with different degrees of disease severity.
Authors: Richard L Horowitz, Phyllis R Freeman and James Bruzzese
Publication date: 21 April 2020
Journal: Respiratory Medicine Case Reports
Two patients living in New York City (NYC) with a history of Lyme and tick-borne co-infections experienced a cough and dyspnea and demonstrated radiological findings consistent with novel coronavirus pneumonia (NCP). A trial of 2 g of PO or IV glutathione was used in both patients and improved their dyspnea within 1 h of use. Repeated use of both 2000 mg of PO and IV glutathione was effective in further relieving respiratory symptoms.
Oral and IV glutathione, glutathione precursors (N-acetyl-cysteine) and alpha lipoic acid may represent a novel treatment approach for blocking NF-κB and addressing “cytokine storm syndrome” and respiratory distress in patients with COVID-19 pneumonia.
Background Large-scale data show that the mortality of COVID-19 varies dramatically across populations, although the cause of these disparities is not well understood. In this study we investigated whether severe COVID-19 is linked to Vitamin D (Vit D) deficiency. Method Daily admission, recovery and deceased rate data for patients with COVID-19 from countries with a large number of confirmed patients (Germany, South Korea (S. Korea), China (Hubei), Switzerland, Iran, UK, US, France, Spain, Italy) as of April 20, 2020 were used. The time-adjusted case mortality ratio (T-CMR) was estimated as the number of deceased patients on day N divided by the number of confirmed cases on day N-8. The adaptive average of T-CMR (A-CMR) was further calculated as a metric of COVID-19 associated mortality in different countries. Although data on Vit D level is not currently available for COVID-19 patients, we leveraged the previously established links between Vit D and C-Reactive Protein (CRP) and between CRP and severe COVID-19, respectively, to estimate the potential impact of Vit D on the reduction of severe COVID-19. Findings A link between Vit D status and COVID-19 A-CMR in the US, France, and the UK (countries with similar screening status) may exist. Combining COVID-19 patient data and prior work on Vit D and CRP levels, we show that the risk of severe COVID-19 cases among patients with severe Vit D deficiency is 17.3% while the equivalent figure for patients with normal Vit D levels is 14.6% (a reduction of 15.6%). Interpretation Given that CRP is a surrogate marker for severe COVID-19 and is associated with Vit D deficiency, our finding suggests that Vit D may reduce COVID-19 severity by suppressing cytokine storm in COVID-19 patients. Further research is needed to account for other factors through direct measurement of Vit D levels.
Social distancing measures, with varying degrees of restriction, have been imposed around the world in order to stem the spread of COVID-19. In this work we analyze the effect of current social distancing measures in the United States. We quantify the reduction in doubling rate, by state, that is associated with social distancing. We find that social distancing is associated with a statistically-significant reduction in the doubling rate for all but three states. At the same time, we do not find significant evidence that social distancing has resulted in a reduction in the number of daily confirmed cases. Instead, social distancing has merely stabilized the spread of the disease. We provide an illustration of our findings for each state, including point estimates of the effective reproduction number, R, both with and without social distancing. We also discuss the policy implications of our findings.
A UK trial – testing whether low-risk treatment in the community can help people at higher risk of complications from COVID-19 to get better quicker, reducing the need for hospital admission – is today announcing that older people who have had coronavirus symptoms for 15 days or less can now also screen for the trial online.
More than 500 GP surgeries are already recruiting people aged 50–64 with a pre-existing illness, or aged 65 and over, into the trial.
It is the first trial of COVID-19 treatments to take place in primary care, one of the UK Government’s four national priority platform trials on the disease, and is funded by the UK Research and Innovation (UKRI) and National Institute for Health Research (NIHR) COVID-19 rapid response.
France has been heavily affected by the SARS-CoV-2 epidemic and went into lockdown on the 17 March 2020. Using models applied to hospital and death data, we estimate the impact of the lockdown and current population immunity. We find 3.6% of infected individuals are hospitalized and 0.7% die, ranging from 0.001% in those <20 years of age (ya) to 10.1% in those >80ya. Across all ages, men are more likely to be hospitalized, enter intensive care, and die than women. The lockdown reduced the reproductive number from 2.90 to 0.67 (77% reduction). By 11 May 2020, when interventions are scheduled to be eased, we project 2.8 million (range: 1.8–4.7) people, or 4.4% (range: 2.8–7.2) 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.
ENE-Covid19 es un amplio estudio longitudinal sero-epidemiológico, de base poblacional, cuyos objetivos son estimar la prevalencia de infección por SARS-Cov2 mediante la determinación de anticuerpos frente al virus en España y evaluar su evolución temporal.
Los resultados presentados hoy, para la primera ronda se refieren a la lectura de la banda de IgG del test rápido, ya que sólo disponemos de resultados parciales del análisis por inmunoensayo.
En la primera ronda de ENE-Covid19 (27 de abril a 11 de mayo) se han reclutado 60983 participantes en la muestra nacional y 3234 en el estudio específico insular, no incluido en este informe. La tasa de participación entre los individuos elegibles ha sido 62,3%, y considerando solamente las personas que han podido ser contactadas alcanza el 74,7%.
La prevalencia estimada de anticuerpos IgG frente a SARS-Cov2 en España es de un 5,0% (95% IC: 4,7%- 5,4%), siendo muy similar en hombres y mujeres( 5,0% (95% IC: 4,6%-5,4%) versus 5,1% (95% IC: 4,7%) . En relación con la edad, la prevalencia es menor en bebes, niños y en jóvenes, permaneciendo bastante estable en grupos de más edad.
La proporción de positivos es mayor en residentes de grandes ciudades (>100.000 habitantes) 6,4% (IC 95%: 5,8-7,1).
ENE-Covid19 is a large population-based sero-epidemiological longitudinal study, the objectives of which are to estimate the prevalence of SARS-Cov2 infection by determining antibodies against the virus in Spain and evaluating its temporal evolution.
The results presented today for the first round refer to the reading of the IgG band of the rapid test, since we only have partial results of the analysis by immunoassay.
In the first round of ENE-Covid19 (April 27 to May 11), 60,983 participants in the national sample and 3,234 in the island-specific study, not included in this report, were recruited. The participation rate among eligible individuals has been 62.3%, and considering only the people who have been contacted, it reaches 74.7%.
The estimated prevalence of IgG antibodies against SARS-Cov2 in Spain is 5.0% (95% CI: 4.7% - 5.4%), being very similar in men and women (5.0% (95 % CI: 4.6% -5.4%) versus 5.1% (95% CI: 4.7%). In relation to age, the prevalence is lower in babies, children and young people, remaining quite stable in older age groups.
The proportion of positives is higher in residents of large cities (> 100,000 inhabitants) 6.4% (95% CI: 5.8-7.1).
The serology test has a specificity greater than 99.8% and sensitivity of 100% (14 Days post-PCR confirmation)
The high specificity of the test is crucial to determine reliably if a person has been exposed to the virus and if the patient has developed antibodies
Roche will provide high double-digit millions of tests already in May for countries accepting the CE mark and in the U.S. under Emergency Use Authorization, further ramping up capacities thereafter
The test is available on Roche’s cobas e analysers which are widely available around the world
Basel, 03 May 2020 - Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA)1 for its new Elecsys® Anti-SARS-CoV-2 antibody test. The test is designed to help determine if a patient has been exposed to the SARS-CoV-2 virus and if the patient has developed antibodies against SARS-CoV-2. Roche has already started shipping the new antibody test to leading laboratories globally and will ramp up production capacity to high double-digit millions per month to serve healthcare systems in countries accepting the CE mark2 as well as the U.S.
Fresh air and sunshine are protective against coronavirus, one of the Government's chief scientific advisers has said.
The decision to release some of the UK's lockdown restrictions, allowing people to spend more time outdoors, have faced criticism from those claiming that will reverse the benefits of lockdown and help spread the virus.
On Wednesday, new rules came into effect, allowing people to exercise outdoors as much as they like and take part in sports such as golf, tennis and fishing. People can also meet up with one person from outside their household.
Giving evidence at the science and technology select committee, Professor Alan Penn, the chief scientific adviser at the Ministry of Housing, Communities and Local Government and a member of the Scientific Advisory Group for Emergencies (Sage), said being outdoors will help prevent people from contracting the virus.
he World Health Organization (WHO) welcomes innovations around the world including repurposing drugs, traditional medicines and developing new therapies in the search for potential treatments for COVID-19.
WHO recognizes that traditional, complementary and alternative medicine has many benefits and Africa has a long history of traditional medicine and practitioners that play an important role in providing care to populations. Medicinal plants such as Artemisia annua are being considered as possible treatments for COVID-19 and should be tested for efficacy and adverse side effects. Africans deserve to use medicines tested to the same standards as people in the rest of the world. Even if therapies are derived from traditional practice and natural, establishing their efficacy and safety through rigorous clinical trials is critical.
African governments through their Ministers of Health adopted a resolution urging Member States to produce evidence on the safety, efficacy and quality of traditional medicine at the Fiftieth Session of the WHO Regional Committee for Africa in 2000. Countries also agreed to undertake relevant research and require national medicines regulatory agencies to approve medicines in line with international standards, which include the product following a strict research protocol and undergoing tests and clinical trials. These studies normally involve hundreds of people under the monitoring of the national regulatory authorities and may take quite a few months in an expedited process.
Authors: Adelina Comas-Herrera and Jose-Luis Fernández
Publication date: 12 May 2020
Source: London School of Economics
New report estimating the mortality impact of the COVID-19 pandemic on people who live in care homes in England.
Data on deaths in care homes directly attributed to COVID-19 underestimate the impact of the pandemic on care home residents, as they do not take account of indirect mortality effects of the pandemic and/or because of problems with the identification of the disease as the cause of death.
Data on registered COVID-19 deaths in care homes in England and Wales only accounts for an estimated 41.6% of all excess deaths in care homes.
Not all care home residents die in care homes, (according to CQC data, 15% of all deaths of care home residents are found to happen in hospitals). Deaths of care home residents in hospitals are not currently accounted for in publicly available estimates of the number of deaths in care homes linked to the pandemic.
Calculating total excess mortality in care homes since 28th December (19,038, 46% of all excess mortality in England and Wales), and adjusting this by the assumption that 15% of care home residents die in hospital, suggests that by the 1st May there had been in excess of 22,000 deaths of care home residents during the COVID-19 pandemic (54% of all excess mortality) in England and Wales.
The drug maker Gilead Sciences released a bombshell two weeks ago: A study conducted by a U.S. government agency had found that the company’s experimental drug, remdesivir, was the first treatment shown to have even a small effect against Covid-19.
Behind that ray of hope, though, was one of the toughest quandaries in medicine: how to balance the need to rigorously test a new medicine for safety and effectiveness with the moral imperative to get patients a treatment that works as quickly as possible. At the heart of the decision was a process that was — as is often in the case in clinical trials — by turns secretive and bureaucratic.
The National Institute of Allergy and Infectious Diseases has described to STAT in new detail how it made its fateful decision: to start giving remdesivir to patients who had been assigned to receive a placebo in the study, essentially limiting researchers’ ability to collect more data about whether the drug saves lives — something the study, called ACTT-1, suggests but does not prove. In the trial, 8% of the participants given remdesivir died, compared with 11.6% of the placebo group, a difference that was not statistically significant
For a few fleeting moments during the New York governor Andrew Cuomo’s daily coronavirus briefing on Wednesday 6 May, the sombre grimace that has filled our screens for weeks was briefly replaced by something resembling a smile.
“We are ready, we’re all-in,” the governor gushed. “We are New Yorkers, so we’re aggressive about it, we’re ambitious about it … We realise that change is not only imminent, but it can actually be a friend if done the right way.”
The inspiration for these uncharacteristically good vibes was a video visit from the former Google CEO Eric Schmidt, who joined the governor’s briefing to announce that he will be heading up a panel to reimagine New York state’s post-Covid reality, with an emphasis on permanently integrating technology into every aspect of civic life.
The Government's coronavirus warnings have "effectively terrorised" Britons "into believing that this is a disease that is going to kill you" even though most those infected will not be hospitalised, one of its advisers has warned.
Professor Robert Dingwall also told Friday's Chopper's Politics podcast – which you can listen to on the player below – that the Government should let people come within 1.5 metres of each other inside and outside as part of measures to ease the lockdown.
The public authorities face a challenge to manage the British people out of the levels of fear and anxiety that they have helped create through their "Stay Home, Protect the NHS, Save Lives" messaging, he warned.
Teacher, health practitioner and founder of The New School, Lucy Stephens, shares her concerns about the impact the new proposals for schools could have on child development, emotional health and wellbeing