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ANH-Intl Covid-19 information tracker - Week 27
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Science |
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Pathogenesis |
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Authors: Justin D Silverman, Nathaniel Hupert and Alex D Washburne Publication date: 22 June 2020 Journal: Science Translational Medicine DOI: 10.1126/scitranslmed.abc1126 Detection of SARS-CoV-2 infections to date has relied heavily on RT-PCR testing. However, limited test availability, high false-negative rates, and the existence of asymptomatic or sub-clinical infections have resulted in an under-counting of the true prevalence of SARS-CoV-2. Here, we show how influenza-like illness (ILI) outpatient surveillance data can be used to estimate the prevalence of SARS-CoV-2. We found a surge of non-influenza ILI above the seasonal average in March 2020 and showed that this surge correlated with COVID-19 case counts across states. If 1/3 of patients infected with SARS-CoV-2 in the US sought care, this ILI surge would have corresponded to more than 8.7 million new SARS-CoV-2 infections across the US during the three-week period from March 8 to March 28, 2020. Combining excess ILI counts with the date of onset of community transmission in the US, we also show that the early epidemic in the US was unlikely to have been doubling slower than every 4 days. Together these results suggest a conceptual model for the COVID-19 epidemic in the US characterized by rapid spread across the US with over 80% infected patients remaining undetected. We emphasize the importance of testing these findings with seroprevalence data and discuss the broader potential to use syndromic surveillance for early detection and understanding of emerging infectious diseases. Authors: Nina Schwalbe, Susanna Lehtimakin and Juan Pablo Gutiérrez Publication date: 15 June 2020 Journal: The Lancet Global Health DOI: 10.1016/S2214-109X(20)30276-X The burden of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues to grow, both in terms of morbidity and mortality from the pandemic itself and the effects of mitigation strategies.1 Tailoring policies on the basis of emerging evidence about conditions associated with COVID-19 severity is key to informing the actions of both policy makers and individuals. This means moving from generalised population-based mitigation strategies to focusing on those most at risk of severe outcomes from COVID-19. In The Lancet Global Health, Andrew Clark and colleagues2 produce a model-based estimate of populations at increased risk of severe COVID-19. The authors focus on the central role played by 11 predominantly non-communicable disease (NCD) categories in predicting risk and the need to tailor the response accordingly. Understanding the heterogeneities of risk helps to contextualise the response and focus resources and actions on those most susceptible to severe disease, who are a fraction of the total number of people considered at risk.3 A particular strength of the model underlying this analysis is that, while based on currently available data and assumptions about the pandemic, it can be modified as new evidence emerges and allows for the much needed further stratification of risk to inform a precision public health approach. |
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Transmission |
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Back to Normal: An Old Physics Route to Reduce SARS-CoV-2 Transmission in Indoor Spaces Authors: García de Abajo FJ Publication date: 18 June 2020 Journal: ACS Nano DOI: 10.1021/acsnano.0c04596 We advocate the widespread use of UV-C light as a short-term, easily deployable, and affordable way to limit virus spread in the current SARS-CoV-2 pandemic. Radical social distancing with the associated shutdown of schools, restaurants, sport clubs, workplaces, and traveling has been shown to be effective in reducing virus spread, but its economic and social costs are unsustainable in the medium term. Simple measures like frequent handwashing, facial masks, and other physical barriers are being commonly adopted to prevent virus transmission. However, their efficacy may be limited, particularly in shared indoor spaces, where, in addition to airborne transmission, elements with small surface areas such as elevator buttons, door handles, and handrails are frequently used and can also mediate transmission. We argue that additional measures are necessary to reduce virus transmission when people resume attending schools and jobs that require proximity or some degree of physical contact. Among the available alternatives, UV-C light satisfies the requirements of rapid, widespread, and economically viable deployment. Its implementation is only limited by current production capacities, an increase of which requires swift intervention by industry and authorities. Authors: Perski O et al Publication date: 01 May 2020 Journal: Qeios preprint DOI: 10.32388/1SC5L4 Background: Face masks have been proposed as an important way of reducing transmission of viral respiratory infections, including SARS-CoV-2. Objective: To assess the likelihood that wearing face masks in community settings reduces transmission of viral respiratory infections. Methods: We conducted a rapid evidence review and used a Bayesian statistical approach to analysing experimental and observational studies conducted in community-dwelling children and adults that assessed the effectiveness of face mask wearing (vs. no face masks) on self-reported, laboratory-confirmed, or clinically diagnosed viral respiratory infections. Results: Eleven RCTs and 10 observational studies met the inclusion criteria. The calculation of Bayes factors and cumulative posterior odds from the RCTs showed a moderate likelihood of a small effect of wearing surgical face masks in community settings in reducing self-reported influenza-like illness (ILI) (cumulative posterior odds = 3.61). However, the risk of reporting bias was high and evidence of reduction of clinically- or laboratory-confirmed infection was equivocal (cumulative posterior odds = 1.07 and 1.22, respectively). Observational studies yielded evidence of a negative association between face mask wearing and ILI but with high risk of confounding and reporting bias. Conclusions: Available evidence from RCTs is equivocal as to whether or not wearing face masks in community settings results in a reduction in clinically- or laboratory-confirmed viral respiratory infections. No relevant studies concerned SARS-CoV-2 or were undertaken in community settings in the UK. |
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Covid-19 patients |
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Authors: Bhasin et al Publication date: 01 July 2020 Journal: Obesity DOI: 10.1002/oby.22947 Objective: Obesity has been found to be a risk factor for hospitalization with COVID‐19. We were interested in understanding whether patients hospitalized with COVID‐19 differed in BMI at older versus younger ages, and if trends were independent of diabetes and hypertension. Methods: We performed a cross‐sectional analysis of patients hospitalized with moderate to severe COVID‐19 at Northwestern Memorial Hospital from March 19th, 2020 until April 4th, 2020. We compared patients hospitalized with COVID‐19 above and below the age of 50, and to those hospitalized without COVID‐19. Results: We found patients younger than 50 years of age hospitalized with COVID‐19 without diabetes or hypertension had mean BMI greater than those older than 50 years of age, with BMI 43.1 (95%CI 34.5 – 51.7) kg/m2 vs 30.1 (95%CI 27.7 – 32.5) kg/m2 (p=0.02). Furthermore, BMI appears to inversely correlate with increasing age amongst patients hospitalized with COVID‐19. We did not detect the same difference or trend for patients hospitalized without COVID‐19. Conclusion: We found younger patients (age <50 years) with COVID‐19 had higher mean BMI than older patients with COVID‐19, with and without diabetes and hypertension. This trend did not exist in patients without COVID‐19 hospitalized during the same time‐period. Authors: Deng M et al Publication date: 29 June 2020 Journal: Obesity DOI: 10.1002/oby.22943 Objective: To explore the indicators for severity in young COVID‐19 patients age between 18 to 40. Methods: This retrospective cohort study includes 65 consecutively admitted COVID‐19 patients age between 18 to 40 in Zhongnan Hospital of Wuhan University. Among them, 53 were moderate cases, 12 were severe or critical cases. Epidemiological, clinical and laboratory characteristics and treatment data were collected. A multivariate logistic regression analysis was implemented to explore risk factors. Results: The severe/critical cases have obviously higher BMI (average 29.23 vs. 22.79kg/m2) and lower liver CT value (average 50.00 vs. 65.00mU) than moderate cases group. The severe/critical cases have higher fasting glucose, alanine aminotransferase (ALT) , aspartate aminotransferase (AST) , and creatinine (Cr) compared with moderate cases (All P<0.01) . More severe/critical cases (58.33% vs. 1.92%) have positive urine protein. The severe/critical cases will experience a significant process of serum albumin decline. Logistic regression analysis showed that male, high body mass index (especially obesity), elevated fasting blood glucose and urinary protein positive are all risk factors for severe young COVID‐19 patients. Conclusion: Obesity is an important predictor of severity in young COVID‐19 patients. The main mechanism is related to the damage of liver and kidney. UK report on 10,130 patients critically ill with COVID-19 Institution: Intensive Care National Audit & Research Centre (ICNARC) Publication date: 26 June 2020 Read more... Authors: Varatharaj A et al Publication date: 25 June 2020 Journal: The Lancet Psychiatry DOI: 10.1016/ S2215-0366(20)30287-X Background: Concerns regarding potential neurological complications of COVID-19 are being increasingly reported, primarily in small series. Larger studies have been limited by both geography and specialty. Comprehensive characterisation of clinical syndromes is crucial to allow rational selection and evaluation of potential therapies. The aim of this study was to investigate the breadth of complications of COVID-19 across the UK that affected the brain. Interpretation: To our knowledge, this is the first nationwide, cross-specialty surveillance study of acute neurological and psychiatric complications of COVID-19. Altered mental status was the second most common presentation, comprising encephalopathy or encephalitis and primary psychiatric diagnoses, often occurring in younger patients. This study provides valuable and timely data that are urgently needed by clinicians, researchers, and funders to inform immediate steps in COVID-19 neuroscience research and health policy. |
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Mortality |
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Authors: Weinberger DM et al Publication date: 01 July 2020 Journal: JAMA International Medicine DOI: 10.1001/jamainternmed.2020.3391 Importance: Efforts to track the severity and public health impact of coronavirus disease 2019 (COVID-19) in the United States have been hampered by state-level differences in diagnostic test availability, differing strategies for prioritization of individuals for testing, and delays between testing and reporting. Evaluating unexplained increases in deaths due to all causes or attributed to nonspecific outcomes, such as pneumonia and influenza, can provide a more complete picture of the burden of COVID-19. Objective: To estimate the burden of all deaths related to COVID-19 in the United States from March to May 2020. Design, Setting, and Population: This observational study evaluated the numbers of US deaths from any cause and deaths from pneumonia, influenza, and/or COVID-19 from March 1 through May 30, 2020, using public data of the entire US population from the National Center for Health Statistics (NCHS). These numbers were compared with those from the same period of previous years. All data analyzed were accessed on June 12, 2020. Main Outcomes and Measures: Increases in weekly deaths due to any cause or deaths due to pneumonia/influenza/COVID-19 above a baseline, which was adjusted for time of year, influenza activity, and reporting delays. These estimates were compared with reported deaths attributed to COVID-19 and with testing data. Results: There were approximately 781 000 total deaths in the United States from March 1 to May 30, 2020, representing 122 300 (95% prediction interval, 116 800-127 000) more deaths than would typically be expected at that time of year. There were 95 235 reported deaths officially attributed to COVID-19 from March 1 to May 30, 2020. The number of excess all-cause deaths was 28% higher than the official tally of COVID-19–reported deaths during that period. In several states, these deaths occurred before increases in the availability of COVID-19 diagnostic tests and were not counted in official COVID-19 death records. There was substantial variability between states in the difference between official COVID-19 deaths and the estimated burden of excess deaths. Conclusions and Relevance: Excess deaths provide an estimate of the full COVID-19 burden and indicate that official tallies likely undercount deaths due to the virus. The mortality burden and the completeness of the tallies vary markedly between states. Authors: Neil M et al Publication date: 26 May 2020 Source: medRxiv preprint DOI: 10.1101/2020.05.25.20112466 Widely reported statistics on Covid-19 across the globe fail to take account of both the uncertainty of the data and possible explanations for this uncertainty. In this paper we use a Bayesian Network (BN) model to estimate the Covid-19 infection prevalence rate (IPR) and infection fatality rate (IFR) for different countries and regions, where relevant data are available. This combines multiple sources of data in a single model. The results show that Chelsea Mass. USA and Gangelt Germany have relatively higher infection prevalence rates (IPR) than Santa Clara USA, Kobe, Japan and England and Wales. In all cases the infection prevalence is significantly higher than what has been widely reported, with much higher community infection rates in all locations. For Santa Clara and Chelsea, both in the USA, the most likely IFR values are 0.3-0.4%. Kobe, Japan is very unusual in comparison with the others with values an order of magnitude less than the others at, 0.001%. The IFR for Spain is centred around 1%. England and Wales lie between Spain and the USA/German values with an IFR around 0.8%. There remains some uncertainty around these estimates but an IFR greater than 1% looks remote for all regions/countries. We use a Bayesian technique called "virtual evidence" to test the sensitivity of the IFR to two significant sources of uncertainty: survey quality and uncertainty about Covid-19 death counts. In response the adjusted estimates for IFR are most likely to be in the range 0.3%-0.5%. |
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Testing |
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The Global Phosphorylation Landscape of SARS-CoV-2 Infection Authors: Bouhaddou M et al Publication date: 28 June 2020 Journal: Cell DOI: 10.1016/j.cell.2020.06.034 The causative agent of the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected millions and killed hundreds of thousands of people worldwide, highlighting an urgent need to develop antiviral therapies. Here, we present a quantitative mass spectrometry-based phosphoproteomics survey of SARS-CoV-2 infection in Vero E6 cells, revealing dramatic rewiring of phosphorylation on host and viral proteins. SARS-CoV-2 infection promoted casein kinase II (CK2) and p38 MAP kinase activation, production of diverse cytokines, and shutdown of mitotic kinases resulting in cell cycle arrest. Infection also stimulated a marked induction of CK2-containing filopodia protrusions possessing budding viral particles. Eighty-seven drugs and compounds were identified by mapping global phosphorylation profiles to dysregulated kinases and pathways. We found pharmacologic inhibition of p38, CK2, CDKs, AXL and PIKFYVE kinases to possess antiviral efficacy, representing potential COVID-19 therapies. |
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Vaccines |
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Authors: Mulligant MJ et al Publication date: 01 July 2020 Journal: medRxiv preprint DOI: 10.1101/2020.06.30.20142570 In March 2020, the WHO declared a pandemic of coronavirus disease 2019 (COVID-19), due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).1 With >8.8 million cases and >450,000 deaths reported globally, a vaccine is urgently needed. We report the available safety, tolerability, and immunogenicity data from an ongoing placebo-controlled, observer-blinded dose escalation study among healthy adults, 18-55 years of age, randomized to receive 2 doses, separated by 21 days, of 10 μg, 30 μg, or 100 μg of BNT162b1, a lipid nanoparticle-formulated, nucleoside-modified, mRNA vaccine that encodes trimerized SARS-CoV-2 spike glycoprotein RBD. Local reactions and systemic events were dose-dependent, generally mild to moderate, and transient. RBD-binding IgG concentrations and SARS-CoV-2 neutralizing titers in sera increased with dose level and after a second dose. Geometric mean neutralizing titers reached 1.8- to 2.8-fold that of a panel of COVID-19 convalescent human sera. These results support further evaluation of this mRNA vaccine candidate. |
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Mental health and covid |
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Mental health during the COVID-19 pandemic in two longitudinal UK population cohorts Authors: Kwong ASF et al Publication date: 18 June 2020 Source: medRxiv preprint DOI: 0.1101/2020.06.16.20133116 Background: The impact of COVID-19 on mental health is unclear. Evidence from longitudinal studies with pre pandemic data are needed to address (1) how mental health has changed from pre-pandemic levels to during the COVID-19 pandemic and (2), whether there are groups at greater risk of poorer mental health during the pandemic? Methods: We used data from COVID-19 surveys (completed through April/May 2020), nested within two large longitudinal population cohorts with harmonised measures of mental health: two generations of the Avon Longitudinal Study of Parents and Children (ALPSAC): the index generation ALSPAC-G1 (n= 2850, mean age 28) and the parents generation ALSPAC-G0 (n= 3720, mean age = 59) and Generation Scotland: Scottish Family Health Study (GS, (n= 4233, mean age = 59), both with validated pre-pandemic measures of mental health and baseline factors. To answer question 1, we used ALSPAC-G1, which has identical mental health measures before and during the pandemic. Question 2 was addressed using both studies, using pre-pandemic and COVID-19 specific factors to explore associations with depression and anxiety in COVID-19. Findings: In ALSPAC-G1 there was evidence that anxiety and lower wellbeing, but not depression, had increased in COVID-19 from pre-pandemic assessments. The percentage of individuals with probable anxiety disorder was almost double during COVID-19: 24% (95% CI 23%, 26%) compared to pre-pandemic levels (13%, 95% CI 12%, 14%), with clinically relevant effect sizes. In both ALSPAC and GS, depression and anxiety were greater in younger populations, women, those with pre-existing mental and physical health conditions, those living alone and in socio-economic adversity. We did not detect evidence for elevated risk in key workers or health care workers. Interpretation: These results suggest increases in anxiety and lower wellbeing that may be related to the COVID-19 pandemic and/or its management, particularly in young people. This research highlights that specific groups may be disproportionally at risk of elevated levels of depression and anxiety during COVID-19 and supports recent calls for increasing funds for mental health services. Funding: The UK Medical Research Council (MRC), the Wellcome Trust and University of Bristol. Read more... |
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Therapeutics |
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SARS-CoV-2: An Update on Potential Antivirals in Light of SARS-CoV Antiviral Drug Discoveries Author: Hatem A Elshabrawy Publication date: 23 June 2020 Journal: Vaccines DOI: 10.3390/vaccines8020335 Coronaviruses (CoVs) are a group of RNA viruses that are associated with different diseases in animals, birds, and humans. Human CoVs (HCoVs) have long been known to be the causative agents of mild respiratory illnesses. However, two HCoVs associated with severe respiratory diseases are Severe Acute Respiratory Syndrome-CoV (SARS-CoV) and Middle East Respiratory Syndrome-CoV (MERS-CoV). Both viruses resulted in hundreds of deaths after spreading to several countries. Most recently, SARS-CoV-2 has emerged as the third HCoV causing severe respiratory distress syndrome and viral pneumonia (known as COVID-19) in patients from Wuhan, China, in December 2019. Soon after its discovery, SARS-CoV-2 spread to all countries, resulting in millions of cases and thousands of deaths. Since the emergence of SARS-CoV, many research groups have dedicated their resources to discovering effective antivirals that can treat such life-threatening infections. The rapid spread and high fatality rate of SARS-CoV-2 necessitate the quick discovery of effective antivirals to control this outbreak. Since SARS-CoV-2 shares 79% sequence identity with SARS-CoV, several anti-SARS-CoV drugs have shown promise in limiting SARS-CoV-2 replication in vitro and in vivo. In this review, we discuss antivirals described for SARS-CoV and provide an update on therapeutic strategies and antivirals against SARS-CoV-2. The control of the current outbreak will strongly depend on the discovery of effective and safe anti-SARS-CoV-2 drugs. |
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Nutrients |
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Authors: Wen Tan C et al Publication date: 10 June 2020 Journal: medRxiv preprint DOI: 10.1101/2020.06.01.20112334 Objective: To determine the clinical outcomes of older COVID-19 patients who received DMB compared to those who did not. We hypothesized that fewer patients administered DMB would require oxygen therapy and/or intensive care support than those who did not. Methodology: Cohort observational study of all consecutive hospitalized COVID-19 patients aged 50 and above in a tertiary academic hospital who received DMB compared to a recent cohort who did not. Patients were administered oral vitamin D3 1000 IU OD, magnesium 150mg OD and vitamin B12 500mcg OD (DMB) upon admission if they did not require oxygen therapy. Primary outcome was deterioration post-DMB administration leading to any form of oxygen therapy and/or intensive care support. Results: Between 15 January and 15 April 2020, 43 consecutive COVID-19 patients aged ≥50 were identified. 17 patients received DMB and 26 patients did not. Baseline demographic characteristics between the two groups was significantly different in age. In univariate analysis, age and hypertension showed significant influence on outcome while DMB retained protective significance after adjusting for age or hypertension separately in multivariate analysis. Fewer DMB patients than controls required initiation of oxygen therapy during their hospitalization (17.6% vs 61.5%, P=0.006). DMB exposure was associated with odds ratios of 0.13 (95% CI: 0.03 − 0.59) and 0.20 (95% CI: 0.04 − 0.93) for oxygen therapy and/or intensive care support on univariate and multivariate analyses respectively. Conclusions: DMB combination in older COVID-19 patients was associated with a significant reduction in proportion of patients with clinical deterioration requiring oxygen support and/or intensive care support. This study supports further larger randomized control trials to ascertain the full benefit of DMB in ameliorating COVID-19 severity. |
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Children and covid |
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Multisystem Inflammatory Syndrome in U.S. Children and Adolescents Authors: Feldstein LR PhD Publication date: 29 June 2020 Journal: New England Journal of Medicine DOI: 10.1056/NEJMoa2021680 Background: Understanding the epidemiology and clinical course of multisystem inflammatory syndrome in children (MIS-C) and its temporal association with coronavirus disease 2019 (Covid-19) is important, given the clinical and public health implications of the syndrome. Methods: We conducted targeted surveillance for MIS-C from March 15 to May 20, 2020, in pediatric health centers across the United States. The case definition included six criteria: serious illness leading to hospitalization, an age of less than 21 years, fever that lasted for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on reverse-transcriptase polymerase chain reaction (RT-PCR), antibody testing, or exposure to persons with Covid-19 in the past month. Clinicians abstracted the data onto standardized forms. Results: We report on 186 patients with MIS-C in 26 states. The median age was 8.3 years, 115 patients (62%) were male, 135 (73%) had previously been healthy, 131 (70%) were positive for SARS-CoV-2 by RT-PCR or antibody testing, and 164 (88%) were hospitalized after April 16, 2020. Organ-system involvement included the gastrointestinal system in 171 patients (92%), cardiovascular in 149 (80%), hematologic in 142 (76%), mucocutaneous in 137 (74%), and respiratory in 131 (70%). The median duration of hospitalization was 7 days (interquartile range, 4 to 10); 148 patients (80%) received intensive care, 37 (20%) received mechanical ventilation, 90 (48%) received vasoactive support, and 4 (2%) died. Coronary-artery aneurysms (z scores ≥2.5) were documented in 15 patients (8%), and Kawasaki’s disease–like features were documented in 74 (40%). Most patients (171 [92%]) had elevations in at least four biomarkers indicating inflammation. The use of immunomodulating therapies was common: intravenous immune globulin was used in 144 (77%), glucocorticoids in 91 (49%), and interleukin-6 or 1RA inhibitors in 38 (20%). Conclusions: Multisystem inflammatory syndrome in children associated with SARS-CoV-2 led to serious and life-threatening illness in previously healthy children and adolescents. (Funded by the Centers for Disease Control and Prevention.) Multisystem Inflammatory Syndrome in Children in New York State Authors: Dufort EM MD Publication date: 29 June 2020 Journal: New England Journal of Medicine DOI: 10.1056/NEJMoa2021756 Background: A multisystem inflammatory syndrome in children (MIS-C) is associated with coronavirus disease 2019. The New York State Department of Health (NYSDOH) established active, statewide surveillance to describe hospitalized patients with the syndrome. Methods: Hospitals in New York State reported cases of Kawasaki’s disease, toxic shock syndrome, myocarditis, and potential MIS-C in hospitalized patients younger than 21 years of age and sent medical records to the NYSDOH. We carried out descriptive analyses that summarized the clinical presentation, complications, and outcomes of patients who met the NYSDOH case definition for MIS-C between March 1 and May 10, 2020. Results: As of May 10, 2020, a total of 191 potential cases were reported to the NYSDOH. Of 95 patients with confirmed MIS-C (laboratory-confirmed acute or recent severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection) and 4 with suspected MIS-C (met clinical and epidemiologic criteria), 53 (54%) were male; 31 of 78 (40%) were black, and 31 of 85 (36%) were Hispanic. A total of 31 patients (31%) were 0 to 5 years of age, 42 (42%) were 6 to 12 years of age, and 26 (26%) were 13 to 20 years of age. All presented with subjective fever or chills; 97% had tachycardia, 80% had gastrointestinal symptoms, 60% had rash, 56% had conjunctival injection, and 27% had mucosal changes. Elevated levels of C-reactive protein, d-dimer, and troponin were found in 100%, 91%, and 71% of the patients, respectively; 62% received vasopressor support, 53% had evidence of myocarditis, 80% were admitted to an intensive care unit, and 2 died. The median length of hospital stay was 6 days. Conclusions: The emergence of multisystem inflammatory syndrome in children in New York State coincided with widespread SARS-CoV-2 transmission; this hyperinflammatory syndrome with dermatologic, mucocutaneous, and gastrointestinal manifestations was associated with cardiac dysfunction. Authors: Lynn RM et al Publication Date: 25 June 2020 Journal: Archives of Disease in Childhood DOI: 10.1136/archdischild-2020-319848 The UK has witnessed large reductions in children attending emergency departments (ED) and paediatric assessment units (PAU) during the COVID-19 pandemic,1 which began in late January and peaked in mid-April before declining.2 These reductions raised concerns about the late presentation of critical illness in children. To address this, the British Paediatric Surveillance Unit undertook a snapshot electronic survey on 24 April 2020 of 4075 paediatric consultants representing >90% of paediatric consultants in the UK and Ireland, asking whether, during the previous 14 days, they had seen any children who, in their opinion, presented later than they would have expected prior to the COVID-19 pandemic (ie, delayed presentation). Over the next 7 days, 2433 (60%) paediatricians responded. Overall, 241 (32%) of 752 paediatricians working in ED/PAU had witnessed delayed presentations, with 57 (8%) reporting ≥3 patients with delayed presentation. Delayed presentation reports ranged between 14% in Wales and 47% in the Midlands (figure 1). Free text responses revealed diabetes mellitus (new diagnosis/diabetic ketoacidosis) as by far the most common delayed presentation,3 but also sepsis and malignancy (table 1). There were also nine deaths where delayed presentation was considered a contributing factor, resulting mainly from sepsis and malignancy. COVID-19 in 7780 pediatric patients: A systematic review Authors: Hoang A et al Publication date: 26 June 2020 Journal: EClinicalMedicine DOI: 10.1016/j.eclinm.2020.100433 Background: Studies summarizing the clinical picture of COVID-19 in children are lacking. This review char- acterizes clinical symptoms, laboratory, and imaging findings, as well as therapies provided to confirmed pediatric cases of COVID-19. Methods: Adhering to PRISMA guidelines, we searched four medical databases (PubMed, LitCovid, Scopus, WHO COVID-19 database) between December 1, 2019 to May 14, 2020 using the keywords “novel coronavi- rus”, “COVID-19” or “SARS-CoV-2”. We included published or in press peer-reviewed cross-sectional, case series, and case reports providing clinical signs, imaging findings, and/or laboratory results of pediatric patients who were positive for COVID-19. Risk of bias was appraised through the quality assessment tool published by the National Institutes of Health. PROSPERO registration # CRD42020182261. Findings: We identified 131 studies across 26 countries comprising 7780 pediatric patients. Although fever (59¢1%) and cough (55¢9%) were the most frequent symptoms 19¢3% of children were asymptomatic. Patchy lesions (21¢0%) and ground-glass opacities (32¢9%) depicted lung radiograph and computed tomography find- ings, respectively. Immunocompromised children or those with respiratory/cardiac disease comprised the largest subset of COVID-19 children with underlying medical conditions (152 of 233 individuals). Coinfec- tions were observed in 5.6% of children and abnormal laboratory markers included serum D-dimer, procalci- tonin, creatine kinase, and interleukin-6. Seven deaths were reported (0¢09%) and 11 children (0¢14%) met inclusion for multisystem inflammatory syndrome in children. Interpretation: This review provides evidence that children diagnosed with COVID-19 have an overall excel- lent prognosis. Future longitudinal studies are needed to confirm our findings and better understand which patients are at increased risk for developing severe inflammation and multiorgan failure. |
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Immunity |
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Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19 Authors: Sekine T et al Publication date: 29 June 2020 Journal: bioRxiv preprint DOI: 10.1101/2020.06.29.174888 SARS-CoV-2-specific memory T cells will likely prove critical for long-term immune protection against COVID-19. We systematically mapped the functional and phenotypic landscape of SARS-CoV-2-specific T cell responses in a large cohort of unexposed individuals as well as exposed family members and individuals with acute or convalescent COVID-19. Acute phase SARS-CoV-2-specific T cells displayed a highly activated cytotoxic phenotype that correlated with various clinical markers of disease severity, whereas convalescent phase SARS-CoV-2-specific T cells were polyfunctional and displayed a stem-like memory phenotype. Importantly, SARS-CoV-2-specific T cells were detectable in antibody-seronegative family members and individuals with a history of asymptomatic or mild COVID-19. Our collective dataset shows that SARS-CoV-2 elicits robust memory T cell responses akin to those observed in the context of successful vaccines, suggesting that natural exposure or infection may prevent recurrent episodes of severe COVID-19 also in seronegative individuals. Authors: Grifoni et al Publication date: 23 June 2020 Journal: Cell DOI: 10.1016/j.cell.2020.05.015 Understanding adaptive immunity to SARS-CoV-2 is important for vaccine development, interpreting coro-navirus disease 2019 (COVID-19) pathogenesis, and calibration of pandemic control measures. Using HLAclass I and II predicted peptide ‘‘megapools,’’ circulating SARS-CoV-2-specific CD8+and CD4+T cellswere identified in70% and 100% of COVID-19 convalescent patients, respectively. CD4+T cell responsesto spike, the main target of most vaccine efforts, were robust and correlated with the magnitude of the anti-SARS-CoV-2 IgG and IgA titers. The M, spike, and N proteins each accounted for 11%–27% of the total CD4+response, with additional responses commonly targeting nsp3, nsp4, ORF3a, and ORF8, among others. ForCD8+T cells, spike and M were recognized, with at least eight SARS-CoV-2 ORFs targeted. Importantly, wedetected SARS-CoV-2-reactive CD4+T cells in ~40%–60% of unexposed individuals, suggesting cross-reactive T cell recognition between circulating ‘‘common cold’’ coronaviruses and SARS-CoV-2. Authors: Tom Britton, Frank Ball and Pieter Trapman Publication date: 23 June 2020 Journal: Science DOI: 10.1126/science.abc6810 Despite various levels of preventive measures, in 2020 many countries have suffered severely from the coronavirus 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. We show that population heterogeneity can significantly impact disease-induced immunity as the proportion infected in groups with the highest contact rates is greater than in groups with low contact rates. We estimate that if R0 = 2.5 in an age-structured community with mixing rates fitted to social activity then the disease-induced herd immunity level can be around 43%, which is substantially less than the classical herd immunity level of 60% obtained through homogeneous immunization of the population. Our estimates should be interpreted as an illustration of how population heterogeneity affects herd immunity, rather than an exact value or even a best estimate. |
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Government/Health authorities |
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Vaccines |
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Publication date: 23 June 2020 Source: UK Research and Innovation The Pirbright Institute, working in collaboration with the University of Oxford have successfully shown that two doses of the ChAdOx1 nCoV-19 (AZD1222) vaccine produce a greater antibody response than a single dose in pigs. The emergence and subsequent spread of SARS-CoV-2 has caused a global pandemic that continues to have a huge impact on human health and welfare, and the world economy. Vaccines to protect against COVID-19 and to reduce SARS-CoV-2 transmission are urgently required to combat this global emergency. The ChAdOx1 nCoV-19 vaccine developed by researchers at the University of Oxford is being tested in humans and it is hoped an effective vaccine could be produced as early as later this year. The new vaccine, ChAdOx1 nCoV-19 which was developed by a team of scientists at the Jenner Institute, is a chimpanzee adenovirus vaccine vector that contains the spike protein from SARS-CoV-2. Phase 1 human clinical trials of the single dose vaccine have already begun following research that showed that macaques were protected against lung disease after a single immunisation. Volunteers are now being recruited for the next phase of human trials. Studies carried out at Pirbright were designed to establish whether two doses of the new vaccine in pigs (prime and boost), might elicit an even greater immune response and therefore maybe a more effective approach to developing a protective response. Pigs provide a useful model having previously been shown to predict vaccine outcome in humans, particularly in influenza studies. |
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Media – Science related |
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Immunity |
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Studies Report Rapid Loss of COVID-19 Antibodies Author: Amanda Heidt Publication date: 19 June 2020 Source: The Scientist A pair of studies published this week is shedding light on the duration of immunity following COVID-19, showing patients lose their IgG antibodies—the virus-specific, slower-forming antibodies associated with long-term immunity—within weeks or months after recovery. With COVID-19, most people who become infected do produce antibodies, and even small amounts can still neutralize the virus in vitro, according to earlier work. These latest studies could not determine if a lack of antibodies leaves people at risk of reinfection. One of the studies found that 10 percent of nearly 1,500 COVID-positive patients registered undetectable antibody levels within weeks of first showing symptoms, while the other of 74 patients found they typically lost their antibodies two to three months after recovering from the infection, especially among those who tested positive but were asymptomatic. In contrast, infections caused by coronavirus cousins such as SARS and MERS result in antibodies that remain in the body for nearly a year, according to The New York Times. The first study, published June 16 on the preprint server medRxiv, screened for antibodies in almost 1,500 coronavirus patients in Wuhan, China. The researchers compared their levels to three other groups: nearly 20,000 members of the general population; more than 1,600 patients hospitalized for reasons other than COVID-19; and more than 3,800 medical workers, whom the authors assumed had “inevitably” been exposed to the virus in its early days, meaning they should have developed antibodies. |
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Covd-19 patients |
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Why strange and debilitating coronavirus symptoms can last for months Author: Linda Geddes Publication date: 24 June 2020 Source: New Scientist Within 24 hours of asking an online covid-19 support group if anyone had been experiencing prolonged or unusual symptoms, I had been messaged by 140 people. The list was mind-boggling and deeply upsetting. “I feel like I’m in the middle of a waking nightmare,” said Zoe Wall, who was previously fit and healthy. Two months after developing covid-19-like symptoms, she was still experiencing chest pains and “fatigue beyond description”. Harry’s symptoms started with a terrible headache and itchy body, followed by shortness of breath. He was still experiencing breathing difficulties, chest pain, numbness in his arm and bloating 10 weeks later. Jenn had had no sense of smell or taste since testing positive for covid-19 on 31 March. Abbi had minimal respiratory symptoms, but very bad gastric ones and lost 19 kilograms in two months. Others reported fatigue, headaches, tingling fingertips and brain fog. As the months tick by since the start of the coronavirus pandemic and we learn more about covid-19, it is becoming increasingly evident that even mild cases can have distressing and long-lasting effects. “There’s clearly something going on here. It is not their imagination or hypochondria. It doesn’t even seem to be linked to how severely they had the disease, as far as I can see,” says Danny Altmann, an immunologist at Imperial College London. All this means we need to rethink how we diagnose and treat covid-19. The long list of symptoms also seems to suggest there might even be several subtypes of the disease, which could help us predict which cases will become serious. |
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Transmission |
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Lockdown measures return as covid-19 cases spike in several countries Author: Adam Vaughan Publication date: 30 June 2020 Source: New Scientist More than half a million people are now confirmed to have died from the coronavirus, as local outbreaks around the world trigger fears of a second wave of covid-19. Globally, a record 189,077 cases were reported on 27 June, and cases are rising in Africa, Asia and North and South America. Some of the surge is due to greater testing, and the rate of deaths is yet to see an equivalent increase. However, the World Health Organization (WHO) believes the growth in daily cases is down to a genuine acceleration in the spread of the virus. “Intense transmission is going on in many communities in many parts of the world,” a spokesperson says. There are also flare-ups in countries that successfully lowered infection rates but have since relaxed restrictions. Azra Ghani at Imperial College London notes that in many countries that rapidly introduced lockdowns, such as South Korea, only around 5 per cent of people have had the virus. “Which means as soon as you start to open up and connections start to come back between countries, it’s very likely to take off again,” she says. The South Korean government declared the start of a “second wave” of infections last week, due to small clusters of cases after an easing of restrictions in May. A jump in cases in the Australian state of Victoria has led to the reintroduction of lockdown in some areas of Melbourne. China has reimposed a lockdown on 400,000 people in Anxin county near Beijing after 18 new cases. Mapping coronavirus in sewage could reveal disease hotspots Author: Hayley Dunning Publication date: 24 June 2020 Source: Imperial College London A new project to model the SARS-CoV-2 virus in raw sewage could help efforts to map the prevalence of COVID-19 in humans and potential animal hosts. The project will also sample the virus in nearby freshwater ecosystems to assess the potential for the disease to be transmitted via raw sewage, which could become increasingly important during the winter as drains overflow in storms. COVID-19 is typically characterised by respiratory symptoms such as persistent cough, but fragments of the virus are also detectable in the faeces of some patients for prolonged periods. This provides the potential to monitor the prevalence of COVID-19 using sewage samples, but could also be a route for transmission of the disease. |
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Social impact |
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COVID-19 might trigger diabetes in otherwise healthy people Author: Siobhán Dunphy Publication date: 26 June 2020 Source: European Scientist People with diabetes are known to be at increased risk of developing COVID-19 and those with the condition are more likely to die from the infection (1, 2). Now, a growing body of evidence suggests the novel coronavirus might trigger type 1 diabetes. At present, the hypothesis is based on a number of anecdotal reports of a handful of people who have spontaneously developed diabetes following a COVID-19 infection. In one such case report in China, a previously healthy young man presented with new-onset, severe diabetes after contracting COVID-19 (3). Other viral infections such as mumps, enterovirus infections, and the SARS coronavirus have long been suspected of enhancing or even eliciting diabetes symptoms. The viruses can disrupt the function of key cells involved in diabetes by either destroying the cells that control blood sugar levels or triggering an immune response. Five things we learnt from our polling on public perceptions during COVID-19 Author: Tim Gardner Publication date: 25 June 2020 Source: The Health Foundation The changes to daily life brought about by COVID-19 and the far-reaching restrictions introduced to slow the spread of the virus are without precedent in modern times. To understand how public attitudes have been affected by the pandemic and the measures taken in response to it, the Health Foundation commissioned Ipsos MORI to conduct a representative national poll. The survey was conducted by telephone between 1–10 May 2020 with a representative sample of 1,983 adults in Great Britain. The chart story below summarises five things we have learnt from the polling so far, with further detail about each finding further down the page. |
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Media – Reporting |
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Immunity |
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Fauci says Covid-19 vaccine may not get US to herd immunity if too many people refuse to get it Author: Elizabeth Cohen Publication date: 29 June 2020 Source: CNN Dr. Anthony Fauci says he would "settle" for a Covid-19 vaccine that's 70% to 75% effective, but that this incomplete protection, coupled with the fact that many Americans say they won't get a coronavirus vaccine, makes it "unlikely" that the US will achieve sufficient levels of immunity to quell the outbreak. With government support, three coronavirus vaccines are expected to be studied in large-scale clinical trials in the next three months. "The best we've ever done is measles, which is 97 to 98 percent effective," said Fauci, the director of the National Institute of Allergy and Infectious Diseases. "That would be wonderful if we get there. I don't think we will. I would settle for [a] 70, 75% effective vaccine." A CNN poll last month found one-third of Americans said they would not try to get vaccinated against Covid, even if the vaccine is widely available and low cost. Lockdown and social distancing could make our immune system weaker, says scientist Author: Steve Bird Publication date: 27 June 2020 Source: The Telegraph Prolonged periods of lockdown cocooning the public from germs could leave people dangerously vulnerable to new viruses, a leading epidemiologist has warned. Sunetra Gupta, professor of theoretical epidemiology at the University of Oxford, fears intense social distancing could actually weaken immune systems because people are not exposed to germs and so do not develop defences that could protect them against future pandemics. The scientist rose to prominence in March after her team’s modelling created a best case scenario where coronavirus arrived in the UK in December and spread quickly through the population creating “herd immunity”, already partly acquired through exposure to different strains of the virus.... |
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Testing |
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Author: Paige Winfield Cunningham Publication date: 26 June 2020 Source: The Washington Post The Trump administration is weighing a new testing strategy as coronavirus cases mount: testing groups of people together. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, told me in an interview last night that health officials are having “intense discussions” about what’s known as “pool testing.” The idea is that by testing samples from many people all together, officials could test more people with fewer resources. And those who are infected could be more quickly found and isolated. Pool testing would allow officials to cast a much broader net to find cases faster. It would represent a dramatic shift from how coronavirus testing is currently being carried out in the United States – but one that may be sorely needed as virus hot spots worsen and new ones appear. |
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Covid infection rates |
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Coronavirus: US hits record high in daily cases Publication date: 26 June 2020 Source: BBC News The United States recorded an all-time daily high of 40,000 coronavirus infections on Thursday, figures from Johns Hopkins University (JHU) show. A recent surge in infections and hospitalisations has prompted the states of Texas, Florida and Arizona to pause reopening plans. Texas's governor ordered bars to close and announced other "targeted measures" on Friday to bring infections down. Florida announced it was suspending alcohol consumption at its bars. JHU's previous high of 36,400 was on 24 April when less testing took place. The US has 2.4 million confirmed infections and 122,370 deaths - more than any other country. While some of the increase in daily cases recorded is down to increased testing, the rate of positive tests in some areas is also increasing. CDC Head Estimates U.S. Coronavirus Cases Might be 10 Times Higher Than Data Show Author: Alice Park Publication date: 25 June 2020 Source: Time In a press briefing on June 25, Dr. Robert Redfield, director of the U.S. Centers for Disease Control and Prevention (CDC), said that the current official count of COVID-19 cases in the U.S. may actually be a drastic underestimate. Redfield said the new, much-higher estimate, is based on growing data from antibody testing, which picks up the presence of immune cells that react to SARS-CoV-2, the virus that causes COVID-19. People will test positive for antibodies to the virus if they have been infected—whether or not they ever got sick or even developed symptoms. Previously, testing was focused only on those with symptoms. But because so many who become infected with SARS-CoV-2 could either have mild disease or not know they were infected at all, Redfield said, current information on the burden of cases is an underestimate. “The traditional approach of looking for symptomatic illness, and diagnoses obviously under estimated the total number of infections,” Redfield said. “Now that serology tests are available, which test for antibodies, the estimates we have right now show about 10 times more people have antibodies in the jurisdictions tested than had documented infections.” |
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Mortality |
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Virus patients less likely to die now than at peak of crisis Author: Tom Whipple Publication date: 26 June 2020 Source: The Times The death rate for coronavirus patients in English hospitals has fallen to a quarter of the level at the peak of the outbreak, which may mean that doctors are getting better at treating it. Researchers said it was also possible that the data had a less optimistic explanation, possibly reflecting changes in those being admitted to hospital. At the beginning of April, when there were 15,000 people in hospital with Covid-19, about 6 per cent died. Since then, the number in hospital has fallen by 2.4 per cent a day, meaning numbers have halved every 29 days. At the same time the number of deaths has reduced by 4.3 per cent a day, meaning that it has halved every 16 days. As a consequence, in the latest figures the hospital death rate has fallen to 1.5 per cent. |
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Schools |
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Schools to scrap social distancing in September Author: Camilla Turner Publication date: 24 June 2020 Source: The Telegraph Social distancing will not be applied in schools and "bubbles" will be expanded to enable all pupils to return to their classes full-time in September, the Government will announce next week. Pupils will not be expected to keep two metres or even one metre apart at all times while in school buildings, The Telegraph understands. Instead, schools will be asked to focus on limiting the extent to which children mix outside their class or year group and on implementing strict hygiene regimes. The solution to reopening schools will involve groups of children being placed in "bubbles" – as is already the case in primaries – and is seen by the Government as removing the need for social distancing. |
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Social Impacts |
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NHS treatment delays linked to more child deaths than coronavirus Author: Sarah Knapton Publication date: 25 June 2020 Source: The Telegraph More children died after failing to get timely medical treatment during lockdown than lost their lives because of coronavirus, new research by the Royal College of Paediatrics and Child Health (RCPCH) suggests. Six children under the age of 16 have died from Covid-19 in Britain since the pandemic began, according to the Office for National Statistics (ONS). However, seeking medical help too late was a contributory factor in the deaths of nine children in paediatric care new analysis has found, with the figure likely to be higher. A survey of 2,433 paediatricians, carried out by the RCPCH, found that one in three handling emergency admissions had dealt with children who turned up later than usual for diagnosis or treatment. Experts said the Government's "Stay Home, protect the NHS" message had made parents anxious about taking their children to hospital. Nine children died of cancer, sepsis (blood poisoning) and metabolic disease in the fortnight before the survey. |
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