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ANH-Intl Covid-19 information tracker - Week 19
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Science |
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Pathogenesis |
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Imbalanced host response to SARS-CoV-2 drives development of COVID-19 Authors: Blanco-Melo D et al Journal: Cell DOI: 10.1016/j.cell.2020.04.026 Viral pandemics, such as the one caused by SARS-CoV-2, pose an imminent threat to humanity. Because of its recent emergence, there is a paucity of information regarding viral behavior and host response following SARS-CoV-2 infection. Here, we offer an in- depth analysis of the transcriptional response to SARS-CoV-2 as it compares to other respiratory viruses. Cell and animal models of SARS-CoV-2 infections, in addition to transcriptional and serum profiling of COVID-19 patients, consistently revealed a unique and inappropriate inflammatory response. This response is defined by low levels of Type I and III interferons juxtaposed to elevated chemokines and high expression of IL- 6. Taken together, we propose that reduced innate antiviral defenses coupled with exuberant inflammatory cytokine production are the defining and driving feature of COVID-19. |
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Epidemiology |
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Authors: Bi Q et al Publication date: 27 April 2020 Journal: The Lancet Infectious Diseases DOI: 10.1016/ S1473-3099(20)30287-5 Interpretation: Our data on cases as well as their infected and uninfected close contacts provide key insights into the epidemiology of SARS-CoV-2. This analysis shows that isolation and contact tracing reduce the time during which cases are infectious in the community, thereby reducing the R. The overall impact of isolation and contact tracing, however, is uncertain and highly dependent on the number of asymptomatic cases. Moreover, children are at a similar risk of infection to the general population, although less likely to have severe symptoms; hence they should be considered in analyses of transmission and control. |
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Mutations |
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Authors: Holland LA et al Publication date: 01 May 2020 Journal: Journal of Virology DOI: 10.1128/JVI.00711-20 Like SARS-CoV, the SARS-CoV-2 genome encodes multiple open reading frames in the 3' region. We found that the SARS-CoV-2 AZ-ASU2923 genome has an 81 nucleotide deletion in the ORF7a gene resulting in a 27 amino-acid in-frame deletion (Figure 2B). The SARS-CoV ORF7a ortholog is a viral antagonist of host restriction factor BST-2/Tetherin and induces apoptosis (11-14). Based on the SARS-CoV ORF7a structure (15), the 27-aa deletion in SARS- CoV-2 ORF7a maps to the putative signal peptide (partial) and first two beta strands. To validate the deletion, we performed RT-PCR using primers spanning the region and verified by Sanger sequencing the amplicons (Figure 2C). Similar deletions in SARS-CoV-2 genomes are emerging, notably in the ORF8 gene (16) that may potentially reduce virus fitness (17). Hence, further experiments are needed to determine the functional consequences of the ORF7a deletion. Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2 Authors: Korber B et al Publication date: 30 April 2020 Journal: bioRxiv preprint DOI: 10.1101/2020.04.29.069054 We have developed an analysis pipeline to facilitate real-time mutation tracking in SARS-CoV-2, focusing initially on the Spike (S) protein because it mediates infection of human cells and is the target of most vaccine strategies and antibody-based therapeutics. To date we have identified fourteen mutations in Spike that are accumulating. Mutations are considered in a broader phylogenetic context, geographically, and over time, to provide an early warning system to reveal mutations that may confer selective advantages in transmission or resistance to interventions. Each one is evaluated for evidence of positive selection, and the implications of the mutation are explored through structural modeling. The mutation Spike D614G is of urgent concern; it began spreading in Europe in early February, and when introduced to new regions it rapidly becomes the dominant form. Also, we present evidence of recombination between locally circulating strains, indicative of multiple strain infections. These finding have important implications for SARS-CoV-2 transmission, pathogenesis and immune interventions. |
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Covid-19 patients |
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Vitamin D Level of Mild and Severe Elderly Cases of COVID-19: A Preliminary Report Author: El James Glicio Publication date: 05 May 2020 Journal: SSRN This preliminary report hypothesized that immune system’s response to infections in the lung may play a role in 25(OH)D levels of elderly patients infected with COVID-19. We performed a retrospective study in two tertiary medical centers in South Asia. The medical records of COVID- 19 patients were reviewed and a total of 176 subjects included were the elderly whose age is at least 60 years, with information in age, body mass index (BMI), sex, comorbidities, pre-hospital 25(OH)D level, and clinical characteristics. We reported that majority of the subjects had 25(OH)D level below 30 ng/ml, most of them were male, had diabetes, and were classified as severe. Most of the male and female subjects had 25(OH)D level below 30 ng/ml. Also, most of the subjects with pre-existing condition had 25(OH)D level below 30 ng/ml. Majority of subjects classified as severe had 25(OH)D level below 30 ng/ml. Age and 25(OH)D level were negatively related. Although clinical trials could provide more meaningful findings as to the causation of 25(OH)D levels and COVID-19 severity, basic healthy solutions such as Vitamin D supplementation could be raised even in the community level and awareness on Vitamin D benefits in fighting infections, such as COVID-19, should be disseminated especially to the vulnerable elderly population. UK report on 7542 patients critically ill with COVID-19 Institution: Intensive Care National Audit & Research Centre (ICNARC) Publication date: 01 May 2020 Read more... Clinical characteristics of asymptomatic and symptomatic patients with mild COVID-19 Authors: Kim GU et al Publication date: 30 April 2020 Journal: Clinical Microbiology and Infection DOI: 10.1016/j.cmi.2020.04.040 Objectives: Detailed knowledge on the prevalence of asymptomatic cases of COVID-19 and the clinical characteristics of mild COVID-19 is essential for effective control of the COVID-19 pandemic. We determined the prevalence of asymptomatic cases of COVID-19 and characterized the symptoms of patients with mild COVID-19. Methods: We recruited the study participants from a community facility designated for isolation of patients without moderate-to-severe symptoms of COVID-19 in South Korea. The prevalence of asymptomatic patients at admission and the detailed symptoms of mild COVID-19 were evaluated through a questionnaire-based survey. Diagnosis of COVID-19 was confirmed by real-time RT-PCR. Results: Of the 213 patients with COVID-19, 41 (19.2%) were asymptomatic until admission. Among the remaining patients with mild COVID-19, the most common symptom was cough (40.1% [69/172]), followed by hyposmia (39.5% [68/172]) and sputum (39.5%, [68/172]). Of the 68 patients with hyposmia, 61 (90%) patients had accompanying symptoms such as hypogeusia, nasal congestion, or rhinorrhea. Fever (>37.5 °C) was only observed in 20 (11.6%). Conclusions: As much as one-fifth of patients with COVID-19 had remained asymptomatic from exposure to admission. Hyposmia was quite frequent among patients with mild COVID-19, whereas fever was not. Social distancing should be strongly implemented to prevent disease transmission from asymptomatic patients or those with mild and inconspicuous symptoms. Association of Obesity with Disease Severity among Patients with COVID‐19 Authors: Kalligeros M et al Publication date: 30 April 2020 Journal: Obesity DOI: 10.1002/oby.22859 Objective: To explore the potential association of obesity and other chronic diseases with severe outcomes, such as intensive care unit (ICU) admission and invasive mechanical ventilation (IMV), in patients hospitalized with COVID‐19. Methods: Retrospective cohort of 103 patients hospitalized with COVID‐19. Demographic data, past medical history and hospital course were collected and analyzed. A multivariate logistic regression analysis was implemented to examine associations. Results: From February 17th to April 5th, 103 consecutive patients were hospitalized with COVID‐19. Among them, 41 patients (39.8%) were admitted to the ICU and 29 (70.7%) required (IMV). The prevalence of obesity was 47.5% (49/103). In a multivariate analysis, severe obesity (BMI ≥35 kg/m2) was associated with ICU admission (aOR 5.39; 95% CI:1.13‐25.64). Moreover, patients who required IMV, were more likely to have had heart disease (aOR 3.41; 95% CI:1.05‐11.06), obesity (BMI=30‐34.9 kg/m2) (aOR 6.85; 95% CI: 1.05‐44.82) or severe obesity (BMI≥35 kg/m2) (aOR 9.99; 95% CI:1.39‐71.69). Conclusion: In our analysis, severe obesity (BMI ≥35 kg/m2) was associated with ICU admission, while history of heart disease and obesity (BMI ≥30 kg/m2) were independently associated with the use of IMV. Increased vigilance and aggressive treatment of patients with obesity and COVID‐19 are warranted. |
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Therapeutics |
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Authors: Want Y, MD et al Publication date: 29 April 2020 Journal: The Lancet DOI: 10.1016/S0140-6736(20)31022-9 Findings: Between Feb 6, 2020, and March 12, 2020, 237 patients were enrolled and randomly assigned to a treatment group (158 to remdesivir and 79 to placebo); one patient in the placebo group who withdrew after randomisation was not included in the ITT population. Remdesivir use was not associated with a difference in time to clinical improvement (hazard ratio 1·23 [95% CI 0·87–1·75]). Although not statistically significant, patients receiving remdesivir had a numerically faster time to clinical improvement than those receiving placebo among patients with symptom duration of 10 days or less (hazard ratio 1·52 [0·95–2·43]). Adverse events were reported in 102 (66%) of 155 remdesivir recipients versus 50 (64%) of 78 placebo recipients. Remdesivir was stopped early because of adverse events in 18 (12%) patients versus four (5%) patients who stopped placebo early. Interpretation: In this study of adult patients admitted to hospital for severe COVID-19, remdesivir was not associated with statistically significant clinical benefits. However, the numerical reduction in time to clinical improvement in those treated earlier requires confirmation in larger studies. |
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Nutrient depletion |
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Authors: Carr AC et al Publication date: 06 May 2020 Journal: Nutrients DOI: 10.3390/nu12051318 Pneumonia is a severe lower respiratory tract infection that is a common complication and a major cause of mortality of the vitamin C-deficiency disease scurvy. This suggests an important link between vitamin C status and lower respiratory tract infections. Due to the paucity of information on the vitamin C status of patients with pneumonia, we assessed the vitamin C status of 50 patients with community-acquired pneumonia and compared these with 50 healthy community controls. The pneumonia cohort comprised 44 patients recruited through the Acute Medical Assessment Unit (AMAU) and 6 patients recruited through the Intensive Care Unit (ICU); mean age 68 ± 17 years, 54% male. Clinical, microbiological and hematological parameters were recorded. Blood samples were tested for vitamin C status using HPLC with electrochemical detection and protein carbonyl concentrations, an established marker of oxidative stress, using ELISA. Patients with pneumonia had depleted vitamin C status compared with healthy controls (23 ± 14 µmol/L vs. 56 ± 24 µmol/L, p < 0.001). The more severe patients in the ICU had significantly lower vitamin C status than those recruited through AMAU (11 ± 3 µmol/L vs. 24 ± 14 µmol/L, p = 0.02). The pneumonia cohort comprised 62% with hypovitaminosis C and 22% with deficiency, compared with only 8% hypovitaminosis C and no cases of deficiency in the healthy controls. The pneumonia cohort also exhibited significantly elevated protein carbonyl concentrations compared with the healthy controls (p < 0.001), indicating enhanced oxidative stress in the patients. We were able to collect subsequent samples from 28% of the cohort (mean 2.7 ± 1.7 days; range 1–7 days). These showed no significant differences in vitamin C status or protein carbonyl concentrations compared with baseline values (p = 0.6). Overall, the depleted vitamin C status and elevated oxidative stress observed in the patients with pneumonia indicates an enhanced requirement for the vitamin during their illness. Therefore, these patients would likely benefit from additional vitamin C supplementation to restore their blood and tissue levels to optimal. This may decrease excessive oxidative stress and aid in their recovery. Patterns of COVID-19 Mortality and Vitamin D: An Indonesian Study Authors: Raharusun et al Publication date: 30 April 2020 Journal: SSRN This is a retrospective cohort study which included two cohorts (active and expired) of 780 cases with laboratory-confirmed infection of SARS-CoV-2 in Indonesia. Age, sex, co-morbidity, Vitamin D status, and disease outcome (mortality) were extracted from electronic medical records. The aim was to determine patterns of mortality and associated factors, with a special focus on Vitamin D status. Results revealed that majority of the death cases were male and older and had pre-existing condition and below normal Vitamin D serum level. Univariate analysis revealed that older and male cases with pre-existing condition and below normal Vitamin D levels were associated with increasing odds of death. When controlling for age, sex, and comorbidity, Vitamin D status is strongly associated with COVID-19 mortality outcome of cases. Association between regional selenium status and reported outcome of COVID-19 cases in China Authors: Zhang J et al Publication date: 28 April 2020 Journal: The American Journal of Clinical Nutrition DOI: 10.1093/ajcn/nqaa095 Potentially relevant to the recent appearance of COVID-19 in China is the fact that there is a belt of selenium deficiency running from northeast to southwest in the country and, indeed, China has populations that have both the lowest and the highest selenium status in the world (1). A set of interesting studies published by the Beck laboratory in the 1990s showed that host selenium deficiency increased the virulence of RNA viruses such as coxsackievirus B3 and influenza A (2, 3). Passage through a selenium-deficient animal that was unable to produce sufficient antioxidant selenoproteins for its own protection resulted in the virus mutating to a virulent form that caused more severe pathology (2, 3). Those findings shed light on a human selenium-deficiency disease, a cardiomyopathy known as Keshan disease, named after the area in northeast China where it was endemic. The disease showed a seasonal variation, suggesting a viral cofactor that was later identified as coxsackievirus B3 (2). When the population was supplemented with selenium, the incidence of Keshan disease decreased dramatically (1, 2). Vitamin D Insufficiency is Prevalent in Severe COVID-19 Authors: Lau FH et al Publication date: 27 April 2020 Journal: medRxiv preprint DOI: 10.1101/2020.04.24.20075838 Background: COVID-19 is a major pandemic that has killed more than 196,000 people. The COVID-19 disease course is strikingly divergent. Approximately 80-85% of patients experience mild or no symptoms, while the remainder develop severe disease. The mechanisms underlying these divergent outcomes are unclear. Emerging health disparities data regarding African American and homeless populations suggest that vitamin D insufficiency (VDI) may be an underlying driver of COVID-19 severity. To better define the VDI-COVID-19 link, we determined the prevalence of VDI among our COVID-19 intensive care unit (ICU) patients. Methods: In an Institutional Review Board approved study performed at a single, tertiary care academic medical center, the medical records of COVID-19 patients were retrospectively reviewed. Subjects were included for whom serum 25-hydroxycholecalcifoerol (25OHD) levels were determined. COVID-19-relevant data were compiled and analyzed. We determined the frequency of VDI among COVID-19 patients to evaluate the likelihood of a VDI-COVID-19 relationship. Results: Twenty COVID-19 patients with serum 25OHD levels were identified; 65.0% required ICU admission.The VDI prevalence in ICU patients was 84.6%, vs. 57.1% in floor patients. Strikingly, 100% of ICU patients less than 75 years old had VDI. Coagulopathy was present in 62.5% of ICU COVID-19 patients, and 92.3% were lymphocytopenic. Conclusions: VDI is highly prevalent in severe COVID-19 patients. VDI and severe COVID-19 share numerous associations including hypertension, obesity, male sex, advanced age, concentration in northern climates, coagulopathy, and immune dysfunction. Thus, we suggest that prospective, randomized controlled studies of VDI in COVID-19 patients are warranted. Read more... |
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Contact Tracing |
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Impact of contact tracing on SARS-CoV-2 transmission Authors: Kaiyuan Sun and Cécile Viboud Publication date: 27 April 2020 Journal: The Lancet Infectious Disease DOI: 10.1016/S1473-3099(20)30357-1 As the far-reaching impacts of the coronavirus disease 2019 (COVID-19) pandemic expand to more and more countries, key questions about transmission dynamics and optimal intervention strategies remain unanswered. In particular, the age profile of susceptibility and infectivity, the frequency of super-spreading events, the amount of transmission in the household, and the contribution of asymptomatic individuals to transmission remain debated. The study by Qifang Bi and colleagues1 in The Lancet Infectious Diseases explores some of these questions by analysing detailed contact tracing data from Shenzhen, a large and affluent city in southern China at the border with Hong Kong. To dissect the drivers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, the authors modelled PCR-confirmed infections in 391 cases and 1286 of their close contacts from Jan 14 to Feb 12, 2020. |
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Testing |
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Authors: Chen Z et al Publication date: 23 April 2020 Journal: Analytical Chemistry DOI: 10.1021/acs.analchem.0c00784 The outbreak of 2019 coronavirus disease (COVID-19) has been a challenge for hospital laboratories because of the huge number of samples that must be tested for the presence of the causative pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Simple and rapid immunodiagnostic methods are urgently needed to identify positive cases. Here we report the development of a rapid and sensitive lateral flow immunoassay (LFIA) that uses lanthanide-doped polysterene nanoparticles (LNPs) to detect anti-SARV-CoV-2 IgG in human serum. A recombinant nucleocapsid phosphoprotein of SARS-CoV-2 was dispensed onto a nitrocellulose membrane to capture specific IgG. Mouse anti-human IgG antibody was labeled with self-assembled LNPs that served as a fluorescent reporter. A 100-μL aliquot of serum samples (1:1000 dilution) was used for this assay and the whole detection process took 10 min. The results of the validation experiment met the requirements for clinical diagnostic reagents. A value of 0.0666 was defined as the cutoff value by assaying 51 normal samples. We tested 7 samples that were positive by reverse-transcription (RT-)PCR and 12 that were negative but clinically suspicious for the presence of anti-SARS-CoV-2 IgG. One of the negative samples was determined to be SARS-CoV-2 IgG positive, while the results for the other samples were consistent with those obtained by RT-PCR. Thus, this assay can achieve rapid and sensitive detection of anti-SARS-CoV-2 IgG in human serum and allow positive identification in suspicious cases; it can also be useful for monitoring the progression COVID-19 and evaluating patients’ response to treatment. Dynamic profile of RT-PCR findings from 301 COVID-19 patients in Wuhan, China: A descriptive study Authors: Xiao AT et al Publication date: 11 April 2020 Journal: Journal of Clinical Virology DOI: 10.1016/j.jcv.2020.104346 Background: With the spread of Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection, its effect on society is amplified. We aimed to describe the viral detection results across different timepoints throughout the disease course. Methods: A retrospective study of 301 confirmed COVID-19 patients hospitalized at Tongji Hospital in Wuhan, China, were included. Demographic characteristics of the patients were collected. Upper respiratory specimens (throat and/or nasal swabs) were obtained and analyzed by real-time RT-PCR for SARS-CoV-2 infection. Period of viral infection and the contagious stage were analyzed. Results: Of 301 hospitalized COVID-19 patients, the median age was 58 years and 51.2 % were male. The median period between symptoms presence and positive SARS-CoV-2 RT-PCR results was 16 days (IQR, 10-23, N = 301). The median period between symptoms presence and an effective negative SARS-CoV-2 RT-PCR result was 20 days (IQR, 17-24; N = 216). Infected patient ≥65 years old stayed contagious longer (22 days vs 19 days, p = 0.015). Although two consecutive negative results were confirmed in 70 patients, 30 % of them had positive viral test results for the third time. Using specimens from nasal swabs to run the RT-PCR test showed a higher positive rate than using specimens from throat swabs. Conclusions: This large-scale investigation with 1113 RT-PCR test results from 301 COVID-19 patients showed that the average contagious period of SARS-CoV-2 infected patients was 20 days. Longer observation period and more than 2 series of negative viral test are necessary for patients ≥65 years. |
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Covd in children |
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COVID-19 infection in children Authors: Sinha IP et al Publication date: 01 May 2020 Journal: The Lancet Respiratory Medicine DOI: 10.1016/S2213-2600(20)30152-1 With rates of hospitalisation and mortality from novel coronavirus disease 2019 (COVID-19) increasing, there is understandable concern across the UK for medical professionals and the general public. We hope to highlight the challenges faced by children and health-care professionals involved in their care, and propose key strategies to address these challenges. Severe COVID-19 in children is rare. To date, the largest review of children with COVID-19 included 2143 children in China. Only 112 (5·6%) of 2143 children had severe disease (defined as hypoxia) and 13 (0·6%) children developed respiratory or multiorgan failure or acute respiratory distress syndrome (ARDS). At the time of writing, there have been two reported deaths in children testing positive for COVID-19 in China, and no deaths in Italy. We are waiting for formal reports of outcomes in children from other countries but to date, no deaths have been reported in the published literature. These figures are in stark contrast to the 4% global mortality rate in adults with COVID-19. Although the death rate from COVID-19 in children is low, medical professionals and parents are concerned about the health of children in the UK. Read more... |
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Media – Science related |
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Origins |
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Fauci: No scientific evidence the coronavirus was made in a Chinese lab Authors: Nsikan Akpan and Victoria Jaggard Publication date: 04 May 2020 Source: National Geographic ANTHONY “TONY” FAUCI has become the scientific face of America’s COVID-19 response, and he says the best evidence shows the virus behind the pandemic was not made in a lab in China. Fauci, the director of the U.S. National Institute of Allergy and Infectious Diseases, shot down the discussion that has been raging among politicians and pundits, calling it “a circular argument” in a conversation Monday with National Geographic. “If you look at the evolution of the virus in bats and what's out there now, [the scientific evidence] is very, very strongly leaning toward this could not have been artificially or deliberately manipulated … Everything about the stepwise evolution over time strongly indicates that [this virus] evolved in nature and then jumped species,” Fauci says. Based on the scientific evidence, he also doesn’t entertain an alternate theory—that someone found the coronavirus in the wild, brought it to a lab, and then it accidentally escaped. Evidence SARS-CoV-2 Emerged From a Biological Laboratory in Wuhan, China Publication date: 16 April 2020. Updated 02 May 2020 Source: Project Evidence The goal of this document is to examine evidence that may prove that (1) the SARS-CoV-2 virus was present at a biolaboratory in Wuhan, China, and (2) the SARS-CoV-2 virus was introduced into the greater Wuhan population by an infected lab worker or animal. These claims from this point on will be referred to as Claim 1 and Claim 2. This document does not attempt to provide a concrete conclusion on whether either claim is factually true. Rather, it examines the probability that each claim is true to allow the reader to make his or her own conclusions. While either claim cannot be irrevocably proven true, an attempt has been made to ensure the evidence used to support these claims is as factual as possible. If you would like to see a summarized version of every claim ("TL;DR") in this document, please see the Conclusion. Furthermore, this document does not attempt to investigate claims that SARS-CoV-2 is a "man-made bioweapon" or whether its release was intentional. See A Note on Biowarfare and "HIV Inserts". |
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Scientific advice |
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Author: Jon Stone Publication date: 4 May 2020 Source: The Independent Top scientists are setting up a shadow version of the government’s Scientific Advisory Group for Emergencies (Sage), amid concerns about “dangerous” political interference in advice to the government. Sir David King, a former government chief scientific adviser, has assembled a group of independent experts to look at how the UK could work its way out of the coronavirus lockdown. He said the 12-strong committee had been created “in response to concerns over the lack of transparency” from Sage. |
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Therapeutics |
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China is promoting coronavirus treatments based on unproven traditional medicines Author: David Cyranoski Publication date: 06 May 2020 Source: Nature The Chinese government is heavily promoting traditional medicines as treatments for COVID-19. The remedies, a major part of China’s health-care system, are even being sent to countries including Iran and Italy as international aid. But scientists outside China say it is dangerous to support therapies that have yet to be proved safe and effective. There are currently no proven treatments for the deadly respiratory disease caused by the new coronavirus, although many countries are trialling existing and experimental drugs. So far, only one — the antiviral remdesivir — has been shown, in randomized control trials, to have some potential to speed up recovery. Convalescent serum lines up as first-choice treatment for coronavirus Author: Cormac Sheridan Publication date: 01 May 2020 Source: Nature Biotechnology Antibodies from blood donated by people who recovered from the illness and hyper-immunoglobulins are becoming treatments of choice for COVID-19, with recombinant polyclonal antibody approaches to follow. A group of US academic researchers has sparked a nationwide effort to encourage people who have recovered from COVID-19 to donate plasma, which will be used to treat patients across the country. The convalescent plasma program was instigated by physicians and investigators from 40 institutions, including the Mayo Clinic, Johns Hopkins University, Washington University, Einstein Medical Center and the Icahn School of Medicine at Mount Sinai, among many others working closely with the US Food and Drug Administration (FDA) and industry partners. The UK’s National Health Service launched in April a program across its 23 main blood centers to collect convalescent plasma for testing in planned clinical trials. At the same time, a consortium of industry players — Takeda, CSL Behring, Biotest, Bio Products Laboratory, LFB, Octapharma and Microsoft — has come together to develop an unbranded polyclonal antibody product: hyperimmune globulin (H-Ig) purified from the pooled plasma of donors who have recovered from COVID-19. NIH clinical trial shows Remdesivir accelerates recovery from advanced COVID-19 Publication date: 29 April 2020 Source: National Institutes of Health Hospitalized patients with advanced COVID-19 and lung involvement who received remdesivir recovered faster than similar patients who received placebo, according to a preliminary data analysis from a randomized, controlled trial involving 1063 patients, which began on February 21. The trial (known as the Adaptive COVID-19 Treatment Trial, or ACTT), sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, is the first clinical trial launched in the United States to evaluate an experimental treatment for COVID-19. An independent data and safety monitoring board (DSMB) overseeing the trial met on April 27 to review data and shared their interim analysis with the study team. Based upon their review of the data, they noted that remdesivir was better than placebo from the perspective of the primary endpoint, time to recovery, a metric often used in influenza trials. Recovery in this study was defined as being well enough for hospital discharge or returning to normal activity level. |
| Perspectives on the Pandemic |
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The Bakersfield Doctors | Episode 6 Publication date: 28 April 2020 Source: Journeyman Pictures (YouTube) When Dr. Dan Erickson and Dr. Artin Massihi held a press conference on April 22nd about the results of testing they conducted at their urgent care facilities around Bakersfield, California, the video, uploaded by a local ABC news affiliate, went viral. After reaching five million views, YouTube took it down on the grounds that it "violated community standards." We followed up with the doctors to determine what was so dangerous about their message. What we discovered were reasonable and well-meaning professionals whose voices should be heard. Watch video... |
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Research roundup |
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COVID-19 Research in Brief: 24 April to 1 May, 2020 Author: Thiago Carvalho Publication date: 01 May 2020 Journal: Nature Medicine DOI: 10.1038/d41591-020-00016-y Nature Medicine summarizes all the research you need to know this week to keep on top of how science is responding to the COVID-19 pandemic. |
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Covid-19 patients |
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Draft government report projecting a surge of covid-19 cases (US) Publication date: 04 May 2020 Source: Washington Post A draft government report projects covid-19 cases will surge to about 200,000 per day by June 1, a staggering jump that would be accompanied by more than 3,000 deaths each day |
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Testing |
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How does a coronavirus antibody home test kit work, and how do I get one? Publication date: 06 May 2020 Source: The Telegraph The Government has outlined plans for Britons to conduct coronavirus antibody tests at home, with finger-prick kits that will be available from Amazon and Boots. But what are these tests – and do they work? What is an antibody test? An antibody test can detect if a person has had coronavirus before and has since recovered. The test, carried out by a device that pricks your finger for blood, works this out by testing your blood for coronavirus antibodies to see if they have already beaten the virus and gained some immunity to it. It can do this in about 15 minutes. The coronavirus swab test that the Government currently uses can only tell whether a person has the virus, not if they have had it and recovered. These swab tests also take much longer to get a result. The antibody test is also known as a "serological test". The Government had been hoping to roll out millions of antibody tests in the coming weeks, but supplies from China have so far failed to pass sensitivity and specificity tests. Why the Accuracy of SARS-CoV-2 Antibody Tests Varies So Much Author: Diana Kwon Publication date: 05 May 2020 Source: The Scientist Due to increasing demand from both researchers and policymakers, the number of antibody tests for SARS-CoV-2, the virus that causes COVID-19, has skyrocketed in recent weeks. According to a list kept by the nonprofit Foundation for Innovative New Diagnostics (FIND), more than 200 of these products, which are also known as serologic tests, are either now available or in development. Many of the test manufacturers are based in China, but there are also companies in a number of other countries, including South Korea, Germany, the US, and the UK. Only 12 have received emergency use authorization (EUA) from the US Food and Drug Administration (FDA), which gives companies permission to deploy a product without providing the same amount of supportive evidence as required in the typical approval process. In March, the FDA announced that, to expedite availability, companies could market these tests in the US without EUA as long as they conducted their own evaluation. Yesterday (May 4), the agency announced it would heighten the scrutiny of these tests after being criticized for the deluge of flawed tests that have become available in the US. Publication date: 03 May 2020 Source: Roche 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. “Thanks to the enormous efforts of our dedicated colleagues we are now able to deliver a high-quality antibody test in high quantities, so we can support healthcare systems around the world with an important tool to better manage the COVID-19 health crisis,” said Severin Schwan, CEO Roche Group. ”I am in particular pleased about the high specificity and sensitivity of our test, which is crucial to support health care systems around the world with a reliable tool to better manage the COVID-19 health crisis.” Quotient Limited Announces CE Mark for its SARS-CoV-2 (COVID-19) Antibody Microarray Publication date: 01 May 2020 Source: Quotient Quotient Limited (NASDAQ:QTNT), a commercial-stage diagnostics company (the Company), headquartered in Eysins, Switzerland, today announced that it has completed the process for declaring conformity to the essential requirements of the In Vitro Diagnostics Directive (IVDD 98/79/EC) and has CE marked (Conformité Européenne) its SARS-CoV-2 (COVID-19) antibody microarray. The test is now available for sale in Europe and Switzerland. The MosaiQ COVID-19 Antibody Microarray is designed as a serological disease screen specific to COVID-19. The assay detects the IgG and IgM antibodies directed at SARS-CoV-2. In addition to the concordance studies, the Company observed seroconversions (the generation of antibodies specific to SARS-CoV-2) in two patients where diagnosis was supported by a polymerase chain reaction (PCR) assay on the patients at the time of symptoms. Covid-19: Leading statistician slams UK’s reporting of swab tests as “travesty of science” Publication date: 27 April 2020 Source: The BMJ DOI: 10.1136/bmj.m1664 A leading statistician has criticised the UK government’s daily reporting of covid-19 swab test results, saying that no inference can be drawn reliably and that the failure to report by sample date could lead to serious misrepresentation of the pattern of the epidemic. “The UK’s data collection and reporting of swab testing is a travesty of statistical science, as you can draw no inferences whatsoever about the evolution of the epidemic,” said Sheila Bird, former programme leader at the MRC Biostatistics Unit, Cambridge Institute of Public Health. “Politicians only seem to be interested in the number of tests performed rather than what is actually happening in the epidemic,” she told The BMJ. The Department of Health and Social Care publishes the number of patients who have been tested for coronavirus and the number of positive tests. These are broken down into categories with figures reported daily for pillars 1, 2, and 41 (see box). Pillar 1 includes patients in hospital with a medical need, as well as the most critical workers and their households. |
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Media – Reporting |
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Transmission |
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Dr. Birx: ‘We Underestimated Very Early On The Number Of Asymptomatic Cases’ Publication date: 03 May 2020 Source: The Daily Wire White House Coronavirus Response Coordinator Dr. Deborah Birx told Fox News on Saturday night that the U.S. significantly underestimated the number of asymptomatic cases that existed of the coronavirus. “I think we’re learning every day about the virus and how it interacts with us as human hosts. And that’s been very important to constantly be triangulating data,” Birx said. “I think we underestimated very early on the number of asymptomatic cases. And I think we’re really beginning to understand there are people that get infected that those symptoms are so low-grade that they don’t even know that they’re infected.” |
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Therapeutics |
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Government researchers changed metric to measure coronavirus drug remdesivir during clinical trial Author: Christopher Rowland Publication date: 03 May 2020 Source: MSN News Government clinical trial investigators changed the primary metric for measuring the success of Gilead’s experimental drug remdesivir as a coronavirus treatment two weeks before Anthony S. Fauci’s announcement that the drug would be the new “standard of care.” Instead of counting how many people taking the drug were kept alive on ventilators or died, among other measures, the National Institute of Allergy and Infectious Diseases said it would judge the drug primarily on a different outcome: how long it took surviving patients to recover. COVID-19: Kerala government distributes homeopathy medicine to boost immunity Publication date: 28 April 2020 Source: Gulf News The Kerala Government is giving a big push to the homeopathic medicine industry; it is calling the medicine an immunity booster and has been distributing vials to around 4.5 million people across the state. The move comes as country reels under the surging coronavirus cases. "Thiruvananthapuram tops the list with medicine distributed to around 7 lakh [700,000] people with the help of residents' association[s] and MLAs spearheading the programme. The Homeopathy Department is giving Arsenicum Album 30C as a preventive medicine to boost immunity, [a measure] which the centre had approved. In Thiruvananthapuram, four mobile units have also been set up to distribute the medicine to homes," said CS Pradeep, District medical officer, Department of Homoeopathy. |
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Nutrient depletion |
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Author: Matt Ridley Publication date: 03 May 2020 Source: The Telegraph A suggestive set of numbers was published online in April by a medical scientist in the Philippines, Dr Mark Alipio. Of 49 patients with mild symptoms of Covid-19 in three hospitals in southern Asian countries, only two had low levels of vitamin D; of 104 patients with critical or severe symptoms, only four did not have low levels of vitamin D. The more severe the symptoms, the more likely a patient was to be not just low but deficient in the vitamin. Could vitamin D deficiency make the difference between getting very ill or not? There has long been evidence that a sufficiency of vitamin D protects against viruses, especially respiratory ones, including the common cold. Vitamin D increases the production of antiviral proteins and decreases cytokines, the immune molecules that can cause a “storm” of dangerous inflammation. It has long been suspected that most people’s low vitamin D levels in late winter partly explain the seasonal peaking of flu epidemics, and rising vitamin D levels in spring partly explain their sudden ending. |
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Testing |
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FDA steps up scrutiny of coronavirus antibody tests to ensure accuracy Author: Laurie McGinley Publication date: 05 May 2020 Source: Washington Post The Food and Drug Administration, under fire for allowing more than 100 commercial coronavirus antibody tests on the market without review, moved Monday to assert oversight, saying the tests will have to pass agency muster, including meeting standards for quality and accuracy. Officials said “unscrupulous actors” have been “marketing fraudulent test kits and using the pandemic as an opportunity to take advantage of Americans’ anxiety.” The action was the latest about-face in the administration’s coronavirus effort as it seeks to fix a flawed testing response that has been criticized as either too restrictive or too lenient. Earlier this year, the FDA was hammered for moving too slowly in allowing academic medical centers and others to develop diagnostic tests for the virus that might have made them more widely available. Then, critics say, it swung too far in the other direction in allowing the antibody tests to go unvetted. Tests in recovered patients found false positives, not reinfections, experts say Author: Kim Bo-gyung Publication date: 29 April 2020 Source: The Korea Herald South Korea’s infectious disease experts said Thursday that dead virus fragments were the likely cause of over 260 people here testing positive again for the novel coronavirus days and even weeks after marking full recoveries. Oh Myoung-don, who leads the central clinical committee for emerging disease control, said the committee members found little reason to believe that those cases could be COVID-19 reinfections or reactivations, which would have made global efforts to contain the virus much more daunting. “The tests detected the ribonucleic acid of the dead virus,” said Oh, a Seoul National University hospital doctor, at a press conference Thursday held at the National Medical Center. Read more... |
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Vaccines |
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Pharmaceutical giant Pfizer begins testing coronavirus vaccine in people Author: Carolyn Y Johnson Publication date: 05 May 2020 Source: The Washington Post Pharmaceutical giant Pfizer began testing multiple versions of an experimental coronavirus vaccine in healthy young people in the United States this week, a first step toward establishing the safety, dosage and most promising candidate to take into larger trials that will test effectiveness. In an unusual trial design that signals the pressing need to find a vaccine against covid-19, Pfizer is initially testing four versions of the vaccine, side by side. Typically, companies spend years on animal experiments and select a single promising candidate to put into human testing, but the drugmaker decided to create a flexible trial that could rapidly sift out the best option. “The pandemic came upon us, fast and furious, and we didn’t have a lot of time to do years of research,” said Kathrin Jansen, head of vaccine research and development at Pfizer. “Because of the urgency and the crisis, we said, ‘What can we do to shorten the development time for a vaccine?’ ” Coronavirus Act 2020: Does it permit mandatory vaccinations? Author: Louise Hooper Publication date: 01 May 2020 Source: Garden Court Chambers There are multiple human rights and civil liberties implications both globally and domestically arising from the response to COVID-19 and the current crisis. Some of them are very real and concerning. Others are scaremongering and simply not true. There is a video doing the rounds on social media which states that changes to the Control of Disease Act 1984, which came into force on the 27th April 2020 regarding vaccines and Covid-19 medical treatment, mean that the Government has the power to force medication on you and that this means vaccines. This is not correct and I set out below where the information in the YouTube video came from and why it is a misinterpretation or wrong. |
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Mortality |
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The UK Has The Most Coronavirus Deaths In Europe. But Is It A Fair Comparison? Author: Sarah Turnnidge Publication date: 05 May 2020 Source: HuffPost The UK has now paid the highest price in Europe for coronavirus, overtaking Italy as the European nation with the highest number of fatalities. Comparing the death toll in different countries has become a cornerstone of how the public measures the scale of the crisis, and the staggering figures are likely to bolster criticism of the government’s response – particularly because the UK has a younger population than Italy, and had more time to prepare for the outbreak. Government officials have argued, however, that different countries have tallied official coronavirus cases and deaths in different ways, making statistical comparisons challenging. On Tuesday, the head of health analysis at the UK’s Office for National Statistics cautioned about making international comparisons, describing it as “incredibly difficult to do”. |
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Censorship |
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Media freedom must not fall victim to Covid-19 Author: Antonio Zappulla Publication date: 04 May 2020 Source: EU Observer As the world grapples with the speed and scale of the devastation wreaked by Covid-19, the need for access to trusted, accurate and independent information has never been so acute. With global mortality rates showing no signs of slowing, the world's economy knocked off its axis, and society at a standstill, there is no precedent to this emergency. We are fighting it blindfolded. Each day is costing us thousands of lives. But without the vital free-flow of information – learnings from other countries, warnings from medics, expertise from scientists, guidance to the public – we stand no chance of fighting it at all. A free and vibrant media is more important than ever. Yet one of most catastrophic fallouts of this crisis is that it is paving the way for a crackdown on press freedoms across the world. A dangerous pattern seems to be emerging; it sees some governments increasingly taking advantage of the pandemic to instigate measures – on a sliding scale of severity – that place restrictions on news coverage. |
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Contact tracing |
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Coronavirus: Contact tracing app to be trialled on Isle of Wight Publication date: 3 May 2020 Source: BBC Health An NHS app aimed at limiting a second wave of coronavirus will be trialled on the Isle of Wight this week. It will be the first place where the new contact-tracing app will be used before being rolled out more widely this month, said Transport Secretary Grant Shapps. The government will be asking the whole of the UK to download it, he told the BBC's Andrew Marr Show. "That will help with a lot of the automation of the tracking." Epidemiologists advising the NHS say that about 56% of the UK population - equating to about 80% of smartphone owners - need to use the app in order to suppress the virus. However, they add that the spread of the disease could still be slowed even if the take-up is lower. |
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Lockdown |
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Administration to Phase Out Coronavirus Task Force Authors: Noah Weiland, Maggie Haberman and David E Sanger Publication date: 05 May 2020 Source: The New York Times Despite growing evidence that the pandemic is still raging, administration officials said on Tuesday that they had made so much progress in bringing it under control that they planned to wind down the coronavirus task force in the coming weeks and focus the White House on restarting the economy. Vice President Mike Pence, who has led the task force for two months, said it would probably wrap up its work around the end of the May, and shift management of the public health response back to the federal agencies whose work it was created to coordinate. Other administration officials said that under plans still in discussion, the White House would consult with medical experts on a more informal basis and that Jared Kushner, the president’s son-in-law and senior adviser, would help oversee a group pushing for progress in developing a vaccine and treatments for the virus. The end of lockdown: which rules are being lifted first around the world? Publication date: 04 May 2020 Source: The Times The first tentative steps out of lockdown are taking place around the world over the next fortnight, with governments weighing the frustrations of a population deprived of liberty and catastrophic economic forecasts against the risk of coronavirus spreading once freedoms are restored. Each country is taking its own approach. Some continue to warn of harsh fines and sanctions for failing to observe the rules. Others, however, place their faith in the goodwill and common sense of citizens to continue to observe social distancing in the fight against the pandemic. All are lifting restrictions in increments, as health authorities weigh the success of each measure before the next is introduced. Is evidence rising that Britain's lockdown could be a deadly mistake? Author: Sherelle Jacobs Publication date: 01 May 2020 Source: The Telegraph So concludes another surreal week of watching a government-by-focus-group pretend to “follow the science”. In particular, the Government overlooked two vital pieces of evidence that raise frightening questions about the impact of its draconian lockdown strategy – and whether lockdown was ever even necessary. First is the latest ONS data, which suggests that lockdown could be killing people insofar as people who are suffering from non-Covid diseases and conditions may not be seeking help. Figures for Week 16 (up to April 17) showed 11,854 excess deaths in Week 16 (compared with the five year average) – but just 8,758 were Covid-related. Are these other 3,096 non-Covid excess deaths anything to do with the fact that urgent referrals by GPs for cancer tests, and chemotherapy appointments have plummeted? Could it be that thousands of seriously ill people are not seeking treatment because they are following the Government's petrifying instructions to Stay At Home to deadly effect? UK government faces legal challenge to lockdown from businessman Author: Lisa O’Carroll Publication date: 01 May 2020 Source: The Guardian The government is facing a challenge to the legality of the coronavirus lockdown by a wealthy businessman who fears it will kill more people than it saves. Simon Dolan, whose Jota Aviation company has been delivering personal protective equipment (PPE) to the NHS, has put the health secretary on notice that he intends to issue proceedings for a judicial review, unless the government reverses some of the lockdown measures and reinstates freedom of movement. He is taking the action, which echoes that taken by Gina Miller over Brexit, on the grounds that the lockdown was both legally defective and disproportionate in law. He is also seeking minutes of the Scientific Advisory Group for Emergencies (Sage) meetings this year, some of which involved Boris Johnson’s adviser Dominic Cummings. A disproportionate interference with rights and freedoms: Coronavirus regulations and the ECHR Author: Francis Hoar Publication date: 20 April 2020 Source: Field Court Chambers The lockdown measures imposed by the Health Protection (Coronavirus, Restrictions) (England) Regulations are some of the most extreme restrictions on fundamental freedoms imposed in the modern era. They are a disproportionate interference with the rights and freedoms protected by the European Convention on Human Rights and therefore unlawful. In considering their proportionality, the failure to derogate from the European Convention on Human Rights (under Article 15) is a relevant factor, as it might suggest that the public health crisis is not one that threatened the ‘life of the nation’. Likewise, the failure to use the Civil Contingencies Act is both relevant to the question of whether the Regulations could lawfully have been passed under the delegated powers of the Public Health (Control of Disease) Act 1984 and to proportionality, given that the Civil Contingencies Act requires much more regular Parliamentary scrutiny and has specific limitations on the extent of any regulations passed under its delegated powers.
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