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Science

Pathogenesis

From Anti-SARS-CoV-2 Immune Responses to COVID-19 via Molecular Mimicry

Author: Darja Kanduc

Publication date: 16 July 2020

Journal: Antibodies

DOI: 10.3390/antib9030033

Aim: To define the autoimmune potential of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection.

Methods: Experimentally validated epitopes cataloged at the Immune Epitope DataBase (IEDB) and present in SARS-CoV-2 were analyzed for peptide sharing with the human proteome. Results: Immunoreactive epitopes present in SARS-CoV-2 were mostly composed of peptide sequences present in human proteins that—when altered, mutated, deficient or, however, improperly functioning—may associate with a wide range of disorders, from respiratory distress to multiple organ failure.

Conclusions: This study represents a starting point or hint for future scientific–clinical investigations and suggests a range of possible protein targets of autoimmunity in SARS-CoV-2 infection. From an experimental perspective, the results warrant the testing of patients’ sera for autoantibodies against these protein targets. Clinically, the results warrant a stringent surveillance on the future pathologic sequelae of the current SARS-CoV-2 pandemic.

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Transmission

Contact Tracing during Coronavirus Disease Outbreak, South Korea, 2020

Authors: Park YJ et al

Publication date: 16 July 2020

Source: Emerging Infectious Diseases

DOI: 10.3201/eid2610.201315

We analyzed reports for 59,073 contacts of 5,706 coronavirus disease (COVID-19) index patients reported in South Korea during January 20–March 27, 2020. Of 10,592 household contacts, 11.8% had COVID-19. Of 48,481 nonhousehold contacts, 1.9% had COVID-19. Use of personal protective measures and social distancing reduces the likelihood of transmission.

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Pandemic peak SARS-CoV-2 infection and seroconversion rates in London frontline health-care workers

Authors: Houlihan CF et al

Publication date: 09 July 2020

Journal: The Lancet

DOI: 10.1016/S0140-6736(20)31484-7

Nosocomial transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major public health concern. Health-care workers (HCWs) are at high risk of developing COVID-19, and may themselves contribute to transmission.1

To evaluate these risks, we enrolled 200 patient-facing HCWs between March 26 and April 8, 2020, in SARS-CoV-2 Acquisition in Frontline Healthcare Workers—Evaluation to inform Response (SAFER), a prospective cohort study in high-risk frontline HCWs in an acute National Health Service hospital trust in London. We collected nasopharyngeal swabs for RT-PCR twice per week, symptom data, and blood samples monthly for high-sensitivity serology assays (ELISA and flow cytometry for spike glycoprotein). Further methodology, study participant demographics, and the length of participation are described in the appendix.

87 (44%) of 200 HCWs had evidence of SARS-CoV-2 infection at any timepoint, detected either by serology or RT-PCR. Of the 200 HCWs, 181 gave a valid blood sample at two timepoints. On the basis of the composite ELISA and flow-cytometry serological results, 82 (45%) of 181 HCWs were seropositive after 1 month. 36 (20%) of 181 HCWs seroconverted during the study, and 46 (25%) of 181 HCWs were already seropositive at study entry. 42 (21%) of 200 HCWs tested positive for SARS-CoV-2 by RT-PCR in at least one swab.

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Covid-19 patients

UK report on 10,492 patients critically ill with COVID-19

Institution: Intensive Care National Audit & Research Centre (ICNARC)

Publication date: 17 July 2020

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Histopathology and ultrastructural findings of fatal COVID-19 infections in Washington State: a case series

Authors: Bradley BT et al

Publication date: 16 July 2020

Journal: The Lancet

DOI: 10.1016/S0140-6736(20)31305-2

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of an ongoing pandemic, with increasing deaths worldwide. To date, documentation of the histopathological features in fatal cases of the disease caused by SARS-CoV-2 (COVID-19) has been scarce due to sparse autopsy performance and incomplete organ sampling. We aimed to provide a clinicopathological report of severe COVID-19 cases by documenting histopathological changes and evidence of SARS-CoV-2 tissue tropism.

Methods: In this case series, patients with a positive antemortem or post-mortem SARS-CoV-2 result were considered eligible for enrolment. Post-mortem examinations were done on 14 people who died with COVID-19 at the King County Medical Examiner's Office (Seattle, WA, USA) and Snohomish County Medical Examiner's Office (Everett, WA, USA) in negative-pressure isolation suites during February and March, 2020. Clinical and laboratory data were reviewed. Tissue examination was done by light microscopy, immunohistochemistry, electron microscopy, and quantitative RT-PCR.

Findings: The median age of our cohort was 73·5 years (range 42–84; IQR 67·5–77·25). All patients had clinically significant comorbidities, the most common being hypertension, chronic kidney disease, obstructive sleep apnoea, and metabolic disease including diabetes and obesity. The major pulmonary finding was diffuse alveolar damage in the acute or organising phases, with five patients showing focal pulmonary microthrombi. Coronavirus-like particles were detected in the respiratory system, kidney, and gastrointestinal tract. Lymphocytic myocarditis was observed in one patient with viral RNA detected in the tissue.

Interpretation: The primary pathology observed in our cohort was diffuse alveolar damage, with virus located in the pneumocytes and tracheal epithelium. Microthrombi, where observed, were scarce and endotheliitis was not identified. Although other non-pulmonary organs showed susceptibility to infection, their contribution to the pathogenesis of SARS-CoV-2 infection requires further examination.

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Factors Associated With Death in Critically Ill Patients With Coronavirus Disease 2019 in the US

Authors: Gupta S MD et al

Publication date: 15 July 2020

Journal: JAMA Internal Medicinet

DOI: 10.1001/jamainternmed.2020.3596

Question: What are the characteristics, outcomes, and factors associated with death among critically ill patients with coronavirus disease 2019 (COVID-19) in the US?

Findings: In a cohort of 2215 adults with COVID-19 who were admitted to intensive care units at 65 sites, 784 (35.4%) died within 28 days, with wide variation among hospitals. Factors associated with death included older age, male sex, obesity, coronary artery disease, cancer, acute organ dysfunction, and admission to a hospital with fewer intensive care unit beds.

Meaning: This study identified demographic, clinical, and hospital-level factors associated with death in critically ill patients with COVID-19 that may be used to facilitate the identification of medications and supportive therapies that can improve outcomes.

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New insights into genetic susceptibility of COVID-19: an ACE2 and TMPRSS2 polymorphism analysis

Authors: Hou Y et al

Publication date: 15 July 2020

Journal: BMC Medicine

DOI: 10.1186/s12916-020-01673-z

Background: Coronavirus Disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has now been confirmed worldwide. Yet, COVID-19 is strangely and tragically selective. Morbidity and mortality due to COVID19 rise dramatically with age and co-existing health conditions, including cancer and cardiovascular diseases. Human genetic factors may contribute to the extremely high transmissibility of SARS-CoV-2 and to the relentlessly progressive disease observed in a small but significant proportion of infected individuals, but these factors are largely unknown.

Main body: In this study, we investigated genetic susceptibility to COVID-19 by examining DNA polymorphisms in ACE2 and TMPRSS2 (two key host factors of SARS-CoV-2) from ~ 81,000 human genomes. We found unique genetic susceptibility across different populations in ACE2 and TMPRSS2. Specifically, ACE2 polymorphisms were found to be associated with cardiovascular and pulmonary conditions by altering the angiotensinogen-ACE2 interactions, such as p.Arg514Gly in the African/African-American population. Unique but prevalent polymorphisms (including p.Val160Met (rs12329760), an expression quantitative trait locus (eQTL)) in TMPRSS2, offer potential explanations for differential genetic susceptibility to COVID-19 as well as for risk factors, including those with cancer and the high-risk group of male patients. We further discussed that polymorphisms in ACE2 or TMPRSS2 could guide effective treatments (i.e., hydroxychloroquine and camostat) for COVID-19.

Conclusion: This study suggested that ACE2 or TMPRSS2 DNA polymorphisms were likely associated with genetic susceptibility of COVID-19, which calls for a human genetics initiative for fighting the COVID-19 pandemic.

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Mitigation strategies

Update Alert: Masks for Prevention of Respiratory Virus Infections, Including SARS-CoV-2, in Health Care and Community Settings

Authors: Chou R et al

Publication date: 20 July 2020

Journal: Annals of Internal Medicine

DOI: 10.7326/L20-0948

This is the first monthly update alert for a living rapid review on the use of masks for prevention of respiratory virus infections, including SARS-CoV-2, in health care and community settings (1). Searches were updated from 2 June 2020 to 2 July 2020, using the same search strategies as the original review. The update searches identified 321 citations. Due to the high volume of literature and to focus on higher-quality evidence, we modified selection criteria for this and future updates by restricting inclusion to peer-reviewed studies. Other inclusion criteria were unchanged. One study on the prevention of SARS-CoV-2 infection in a community setting was added for this update (2).

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Testing

Testing for SARS-CoV-2 in cellular components by routine nested RT-PCR followed by DNA sequencing

Author: Sin Hang Lee

Publication date: 17 July 2020

Journal: International Journal of Geriatrics and Rehabilitation

Currently, molecular tests for SARS-CoV-2 infection are primarily based on reverse transcription- quantitative polymerase chain reaction (RT-qPCR) on cell-free fluid samples of respiratory tract specimens. These tests measure the rate of fluorescent signal accumulation as a surrogate for direct DNA sequence determination and are known to generate false-negative and false-positive results. The author has developed a routine protocol to test the cellular components of respiratory tract specimens instead of cell-free fluids only and to use conventional nested RT-PCR to amplify the target nucleic acid for high detection sensitivity. A 398-bp heminested PCR amplicon is used as the template for direct DNA sequencing to ensure no false-positive test results. Using this protocol to re-test 20 reference samples prepared by the Connecticut State Department of Public Health, the author found 2 positives among 10 samples classified as negative by RT-qPCR assays. One of these two positive samples contained a mutant with a novel single nucleotide insertion in the N gene and a wild-type parental SARS-CoV-2. Of the 10 samples classified as positive by RT-qPCR assays, only 7 (7/10) were confirmed to contain SARS-CoV-2 by heminested PCR and DNA sequencing of a 398-bp amplicon of the N gene. One of the latter 7 positive SARS-CoV-2 isolates belongs to a newly discovered mutant first isolated from a specimen collected in the State of New York on March 17, 2020, according to information retrieved from the GenBank database. Routine sequencing of a 398-bp PCR amplicon can categorize any isolate into one of 6 clades of SARS-CoV-2 strains known to circulate in the United States. The author proposes that extremely accurate routine laboratory tests for SARS-CoV-2 be implemented as businesses attempt to return to normal operation in order to avoid raising false alarms of a re-emerging outbreak. False-positive laboratory test reports can easily create unnecessary panic resulting in negative impacts on local economies.

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Community prevalence of SARS-CoV-2 virus in England during May 2020: REACT study

Authors: Riley S et al

Publication date: 11 July 2020

Journal: medRxiv preprint

DOI: 10.1101/2020.07.10.20150524

Background England has experienced one of the highest rates of confirmed COVID-19 mortality in the world. SARS-CoV-2 virus has circulated in hospitals, care homes and the community since January 2020. Our current epidemiological knowledge is largely informed by clinical cases with far less understanding of community transmission. Methods The REal-time Assessment of Community Transmission (REACT) study is a nationally representative prevalence survey of SARS-CoV-2 virus swab-positivity in the community in England. We recruited participants regardless of symptom status. Results We found 159 positives from 120,610 swabs giving an average prevalence of 0.13% (95% CI: 0.11%,0.15%) from 1st May to 1st June 2020. We showed decreasing prevalence with a halving time of 8.6 (6.2, 13.6) days, implying an overall reproduction number R of 0.57 (0.45, 0.72). Adults aged 18 to 24 yrs had the highest swab-positivity rates, while those >64 yrs had the lowest. Of the 126 participants who tested positive with known symptom status in the week prior to their swab, 39 reported symptoms while 87 did not, giving an estimate that 69% (61%,76%) of people were symptom-free for the 7 days prior testing positive in our community sample. Symptoms strongly associated with swab-positivity were: nausea and/or vomiting, diarrhoea, blocked nose, loss of smell, loss of taste, headache, chills and severe fatigue. Recent contact with a known COVID-19 case was associated with odds of 24 (16, 38) for swab-positivity. Compared with non-key workers, odds of swab-positivity were 7.7 (2.4, 25) among care home (long-term care facilities) workers and 5.2 (2.9, 9.3) among health care workers. However, some of the excess risk associated with key worker status was explained by recent contact with COVID-19 cases. We found no strong evidence for geographical variability in positive swab results. Conclusion Our results provide a reliable baseline against which the impact of subsequent relaxation of lockdown can be assessed to inform future public health efforts to control transmission.

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Immunity

Longitudinal evaluation and decline of antibody responses in SARS-CoV-2 infection

Authors: Seow J et al

Publication date: 09 July 2020

Journal: medRxiv preprint

DOI: 10.1101/2020.07.09.20148429

Antibody (Ab) responses to SARS-CoV-2 can be detected in most infected individuals 10-15 days following the onset of COVID-19 symptoms. However, due to the recent emergence of this virus in the human population it is not yet known how long these Ab responses will be

maintained or whether they will provide protection from re-infection. Using sequential serum samples collected up to 94 days post onset of symptoms (POS) from 65 RT-qPCR confirmed SARS-CoV-2-infected individuals, we show seroconversion in >95% of cases and neutralizing antibody (nAb) responses when sampled beyond 8 days POS. We demonstrate that the magnitude of the nAb response is dependent upon the disease severity, but this does not affect the kinetics of the nAb response. Declining nAb titres were observed during the follow up period. Whilst some individuals with high peak ID50 (>10,000) maintained titres >1,000 at >60 days POS, some with lower peak ID50 had titres approaching baseline within the follow up period. A similar decline in nAb titres was also observed in a cohort of seropositive healthcare workers from Guy’s and St Thomas’ Hospitals. We suggest that this transient nAb response is a feature shared by both a SARS-CoV-2 infection that causes low disease severity and the circulating seasonal coronaviruses that are associated with common colds. This study has important implications when considering widespread serological testing, Ab protection against re-infection with SARS-CoV-2 and the durability of vaccine protection.

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Covid and pregnancy

Reduction in preterm births during the COVID-19 lockdown in Ireland: a natural experiment allowing analysis of data from the prior two decades

Authors: Philip RK et al

Publication date: 05 June 2020

Journal: medRxiv preprint

DOI: 10.1101/2020.06.03.20121442

Background: Aetiology of preterm birth (PTB) is heterogeneous and preventive strategies remain elusive. Socio-environmental measures implemented as Ireland s prudent response to the SARS-CoV-2 virus (COVID-19) pandemic represented, in effect, a national lockdown and have possibly influenced the health and wellbeing of pregnant women and unborn infants. Cumulative impact of such socio-environmental factors operating contemporaneously on PTB has never been assessed before. Methods: Regional PTB trends of very low birth weight (VLBW) infants in one designated health area of Ireland over two decades were analysed. Poisson regression and rate ratio analyses with 95% CI were conducted. Observed regional data from January to April 2020 were compared to historical regional and national data and forecasted national figures for 2020. Results: Poisson regression analysis found that the regional historical VLBW rate per 1000 live births for January to April, 2001 to 2019 was 8.18 (95% CI: 7.21, 9.29). During January to April 2020, an unusually low VLBW rate of just 2.17 per 1000 live births was observed. The rate ratio of 3.77 (95% CI: 1.21, 11.75), p = 0.022, estimates that for the last two decades there was, on average, 3.77 times the rate of VLBW, compared to the period January to April 2020 during which there is a 73% reduction. National Irish VLBW rate for 2020 is forecasted to be reduced to 400 per 60,000 births compared to historical 500 to 600 range. Conclusion: An unprecedented reduction in PTB of VLBW infants was observed in one health region of Ireland during the COVID-19 lockdown. Potential determinants of this unique temporal trend reside in the summative socio-environmental impact of the COVID-19 dictated lockdown. Our findings, if mirrored in other regions that have adopted similar measures to combat the pandemic, demonstrate the potential to evaluate these implicated interdependent behavioural and socio-environmental modifiers to positively influence PTB rates globally.

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Changes in premature birth rates during the Danish nationwide COVID-19 lockdown: a nationwide register-based prevalence proportion study

Author: Hedermann G et al

Publication date: 23 May 2020

Journal: medRxiv preprint

DOI: 10.1101/2020.05.22.20109793

Objectives To explore the impact of COVID-19 lockdown on premature birth rates in Denmark Design Nationwide register-based prevalence proportion study. Participants 31,180 live singleton infants born in Denmark between March 12, and April 14, from 2015 to 2020 Main outcome measures The Main outcome measure was the odds ratio of premature birth, per preterm category, during the lockdown period compared with the calendar match period in the five previous years. Results A total of 31 180 newborns were included in the study period, of these 58 were born extremely premature (gestational age below 28 weeks). The distribution of gestational ages was significantly different (p = 0.004) during the lockdown period compared to the previous five years. The extremely premature birth rate during the lockdown was significantly lower than the corresponding mean rate for the same dates in the previous years (odds ratio 0.09 [95 % CI 0.01 - 0.04], p < 0.001). No significant difference between the lockdown and previous years was found for other gestational age categories. Conclusions The birth rate of extremely premature infants decreased significantly (~90 % reduction) during the Danish nationwide lockdown from a stable rate in the preceding five years. The reasons for this decrease are unclear. Identification of possible causal mechanisms might stimulate changes in clinical practice. Ideally, some cases of extreme prematurity are preventable which may decrease infant morbidity and mortality.

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Vaccines

An alphavirus-derived replicon RNA vaccine induces SARS-CoV-2 neutralizing antibody and T cell responses in mice and nonhuman primates

Authors: Erasmus JH et al

Publication date: 20 July 2020

Journal: Science Translational Medicine

DOI: 10.1126/scitranslmed.abc9396

The COVID-19 pandemic, caused by infection with the SARS-CoV-2 coronavirus, is having a deleterious impact on health services and the global economy, highlighting the urgent need for an effective vaccine. Such a vaccine would need to rapidly confer protection after one or two doses and would need to be manufactured using components suitable for scale-up. Here, we developed an alphavirus-derived replicon RNA vaccine candidate, repRNA-CoV2S, encoding the SARS-CoV-2 spike (S) protein. The RNA replicons were formulated with Lipid InOrganic Nanoparticles (LION) that were designed to enhance vaccine stability, delivery, and immunogenicity. We show that a single intramuscular injection of the LION/repRNA-CoV2S vaccine in mice elicited robust production of anti-SARS-CoV-2 S protein IgG antibody isotypes indicative of a Type 1 T helper cell response. A prime/boost regimen induced potent T cell responses in mice including antigen-specific responses in lung and spleen. Prime-only immunization of aged (17-month old) mice induced smaller immune responses compared to young mice, but this difference was abrogated by booster immunization. Importantly, in nonhuman primates, prime-only immunization in one intramuscular injection site or prime/boost immunizations in 5 intramuscular injection sites elicited modest T cell responses and robust antibody responses. The antibody responses persisted for at least 70 days and neutralized SARS-CoV-2 at titers comparable to those in human serum samples collected from individuals convalescing from COVID-19. These data support further development of LION/repRNA-CoV2S as a vaccine candidate for prophylactic protection against SARS-CoV-2 infection.

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Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial

Author: Folegatti PM

Publication date: 20 July 2020

Journal: The Lancet

DOI: 10.1016/S0140-6736(20)31604-4

Background: The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might be curtailed by vaccination. We assessed the safety, reactogenicity, and immunogenicity of a viral vectored coronavirus vaccine that expresses the spike protein of SARS-CoV-2.

Methods: We did a phase 1/2, single-blind, randomised controlled trial in five trial sites in the UK of a chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19) expressing the SARS-CoV-2 spike protein compared with a meningococcal conjugate vaccine (MenACWY) as control. Healthy adults aged 18–55 years with no history of laboratory confirmed SARS-CoV-2 infection or of COVID-19-like symptoms were randomly assigned (1:1) to receive ChAdOx1 nCoV-19 at a dose of 5 × 1010 viral particles or MenACWY as a single intramuscular injection. A protocol amendment in two of the five sites allowed prophylactic paracetamol to be administered before vaccination. Ten participants assigned to a non-randomised, unblinded ChAdOx1 nCoV-19 prime-boost group received a two-dose schedule, with the booster vaccine administered 28 days after the first dose. Humoral responses at baseline and following vaccination were assessed using a standardised total IgG ELISA against trimeric SARS-CoV-2 spike protein, a muliplexed immunoassay, three live SARS-CoV-2 neutralisation assays (a 50% plaque reduction neutralisation assay [PRNT50]; a microneutralisation assay [MNA50, MNA80, and MNA90]; and Marburg VN), and a pseudovirus neutralisation assay. Cellular responses were assessed using an ex-vivo interferon-γ enzyme-linked immunospot assay. The co-primary outcomes are to assess efficacy, as measured by cases of symptomatic virologically confirmed COVID-19, and safety, as measured by the occurrence of serious adverse events. Analyses were done by group allocation in participants who received the vaccine. Safety was assessed over 28 days after vaccination. Here, we report the preliminary findings on safety, reactogenicity, and cellular and humoral immune responses. The study is ongoing, and was registered at ISRCTN, 15281137, and ClinicalTrials.gov, NCT04324606.

Findings: Between April 23 and May 21, 2020, 1077 participants were enrolled and assigned to receive either ChAdOx1 nCoV-19 (n=543) or MenACWY (n=534), ten of whom were enrolled in the non-randomised ChAdOx1 nCoV-19 prime-boost group. Local and systemic reactions were more common in the ChAdOx1 nCoV-19 group and many were reduced by use of prophylactic paracetamol, including pain, feeling feverish, chills, muscle ache, headache, and malaise (all p<0·05). There were no serious adverse events related to ChAdOx1 nCoV-19. In the ChAdOx1 nCoV-19 group, spike-specific T-cell responses peaked on day 14 (median 856 spot-forming cells per million peripheral blood mononuclear cells, IQR 493–1802; n=43). Anti-spike IgG responses rose by day 28 (median 157 ELISA units [EU], 96–317; n=127), and were boosted following a second dose (639 EU, 360–792; n=10). Neutralising antibody responses against SARS-CoV-2 were detected in 32 (91%) of 35 participants after a single dose when measured in MNA80 and in 35 (100%) participants when measured in PRNT50. After a booster dose, all participants had neutralising activity (nine of nine in MNA80 at day 42 and ten of ten in Marburg VN on day 56). Neutralising antibody responses correlated strongly with antibody levels measured by ELISA (R2=0·67 by Marburg VN; p<0·001).

Interpretation: ChAdOx1 nCoV-19 showed an acceptable safety profile, and homologous boosting increased antibody responses. These results, together with the induction of both humoral and cellular immune responses, support large-scale evaluation of this candidate vaccine in an ongoing phase 3 programme.

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Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial

Author: Zhu FC et al

Publication date: 20 July 2020

Journal: The Lancet

DOI: 10.1016/S0140-6736(20)31605-6

Background: This is the first randomised controlled trial for assessment of the immunogenicity and safety of a candidate non-replicating adenovirus type-5 (Ad5)-vectored COVID-19 vaccine, aiming to determine an appropriate dose of the candidate vaccine for an efficacy study.

Methods: This randomised, double-blind, placebo-controlled, phase 2 trial of the Ad5-vectored COVID-19 vaccine was done in a single centre in Wuhan, China. Healthy adults aged 18 years or older, who were HIV-negative and previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-free, were eligible to participate and were randomly assigned to receive the vaccine at a dose of 1 × 1011 viral particles per mL or 5 × 1010 viral particles per mL, or placebo. Investigators allocated participants at a ratio of 2:1:1 to receive a single injection intramuscularly in the arm. The randomisation list (block size 4) was generated by an independent statistician. Participants, investigators, and staff undertaking laboratory analyses were masked to group allocation. The primary endpoints for immunogenicity were the geometric mean titres (GMTs) of specific ELISA antibody responses to the receptor binding domain (RBD) and neutralising antibody responses at day 28. The primary endpoint for safety evaluation was the incidence of adverse reactions within 14 days. All recruited participants who received at least one dose were included in the primary and safety analyses. This study is registered with ClinicalTrials.gov, NCT04341389.

Findings: 603 volunteers were recruited and screened for eligibility between April 11 and 16, 2020. 508 eligible participants (50% male; mean age 39·7 years, SD 12·5) consented to participate in the trial and were randomly assigned to receive the vaccine (1 × 1011 viral particles n=253; 5 × 1010 viral particles n=129) or placebo (n=126). In the 1 × 1011 and 5 × 1010 viral particles dose groups, the RBD-specific ELISA antibodies peaked at 656·5 (95% CI 575·2–749·2) and 571·0 (467·6–697·3), with seroconversion rates at 96% (95% CI 93–98) and 97% (92–99), respectively, at day 28. Both doses of the vaccine induced significant neutralising antibody responses to live SARS-CoV-2, with GMTs of 19·5 (95% CI 16·8–22·7) and 18·3 (14·4–23·3) in participants receiving 1 × 1011 and 5 × 1010 viral particles, respectively. Specific interferon γ enzyme-linked immunospot assay responses post vaccination were observed in 227 (90%, 95% CI 85–93) of 253 and 113 (88%, 81–92) of 129 participants in the 1 × 1011 and 5 × 1010 viral particles dose groups, respectively. Solicited adverse reactions were reported by 183 (72%) of 253 and 96 (74%) of 129 participants in the 1 × 1011 and 5 × 1010 viral particles dose groups, respectively. Severe adverse reactions were reported by 24 (9%) participants in the 1 × 1011 viral particles dose group and one (1%) participant in the 5 × 1010 viral particles dose group. No serious adverse reactions were documented.

Interpretation: The Ad5-vectored COVID-19 vaccine at 5 × 1010 viral particles is safe, and induced significant immune responses in the majority of recipients after a single immunisation.

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Social Impact

Mental health before and during the COVID-19 pandemic: a longitudinal probability sample survey of the UK population

Authors: Pierce M PhD et al

Publication date: 21 July 2020

Journal: The Lancet Psychiatry

DOI: 10.1016/S2215-0366(20)30308-4

Background: The potential impact of the COVID-19 pandemic on population mental health is of increasing global concern. We examine changes in adult mental health in the UK population before and during the lockdown.

Methods: In this secondary analysis of a national, longitudinal cohort study, households that took part in Waves 8 or 9 of the UK Household Longitudinal Study (UKHLS) panel, including all members aged 16 or older in April, 2020, were invited to complete the COVID-19 web survey on April 23–30, 2020. Participants who were unable to make an informed decision as a result of incapacity, or who had unknown postal addresses or addresses abroad were excluded. Mental health was assessed using the 12-item General Health Questionnaire (GHQ-12). Repeated cross-sectional analyses were done to examine temporal trends. Fixed-effects regression models were fitted to identify within-person change compared with preceding trends.

Findings: Waves 6–9 of the UKHLS had 53 351 participants. Eligible participants for the COVID-19 web survey were from households that took part in Waves 8 or 9, and 17 452 (41·2%) of 42 330 eligible people participated in the web survey. Population prevalence of clinically significant levels of mental distress rose from 18·9% (95% CI 17·8–20·0) in 2018–19 to 27·3% (26·3–28·2) in April, 2020, one month into UK lockdown. Mean GHQ-12 score also increased over this time, from 11·5 (95% CI 11·3–11·6) in 2018–19, to 12·6 (12·5–12·8) in April, 2020. This was 0·48 (95% CI 0·07–0·90) points higher than expected when accounting for previous upward trends between 2014 and 2018. Comparing GHQ-12 scores within individuals, adjusting for time trends and significant predictors of change, increases were greatest in 18–24-year-olds (2·69 points, 95% CI 1·89–3·48), 25–34-year-olds (1·57, 0·96–2·18), women (0·92, 0·50–1·35), and people living with young children (1·45, 0·79–2·12). People employed before the pandemic also averaged a notable increase in GHQ-12 score (0·63, 95% CI 0·20–1·06).

Interpretation: By late April, 2020, mental health in the UK had deteriorated compared with pre-COVID-19 trends. Policies emphasising the needs of women, young people, and those with preschool aged children are likely to play an important part in preventing future mental illness.

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Government/Health authorities

Mitigation strategies

COVID-19-EPIDEMIC: Should individuals in the community without respiratory symptoms wear facemasks to reduce the spread of COVID-19? – a rapid review

Publication date: June 2020

Source: Norwegian Institute of Public Health

Health authorities have given conflicting recommendations regarding the use of facemasks by asymptomatic individuals in the community to reduce the spread of COVID-19. For ex- ample, the World Health Organization (WHO) states that “at present, there is no direct evi- dence (from studies on COVID-19 and in healthy people in the community) on the effective- ness of universal masking of healthy people in the community to prevent infection with res- piratory viruses, including COVID-19”. Yet, “WHO has updated its guidance to advise that to prevent COVID-19 transmission effectively in areas of community transmission, govern- ments should encourage the general public to wear masks in specific situations and settings as part of a comprehensive approach to suppress SARS-CoV-2 transmission”. This includes settings where individuals are unable to keep a physical distance of at least 1 meter. WHO is also strongly encouraging countries to conduct research on this critical topic.

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Vaccines

Millions could be vaccinated against COVID-19 as UK secures strong portfolio of promising vaccines

Publication date: 20 July 2020

Source: UK Government

  • The UK government has secured early access to 90 million vaccine doses from the BioNTech/Pfizer alliance and Valneva with more in the pipeline as part of its strategy to build a portfolio of promising new vaccines to protect the UK from COVID-19
  • In addition, treatments containing COVID-19-neutralising antibodies have been secured from AstraZeneca to protect those who cannot receive vaccines
  • UK public encouraged to sign up to a new NHS website to make it quicker and easier for potential volunteers to join vital studies that could help save lives – the aim is to get 500,000 people signed up by October

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Social Impacts

Unintended Consequences of Lockdowns: COVID-19 and the Shadow Pandemic

Authors: Saravana Ravindran and Manisha Shah

Publication date: July 2020

Source: The National Bureau of Economic Research (US)

Violence against women is a problem worldwide, with economic costs ranging from 1-4% of global GDP. Using variation in the intensity of government-mandated lockdowns in India, we show that domestic violence complaints increase by 0.47 SD in districts with the strictest lockdown rules. We find similarly large increases in cybercrime complaints. Interestingly, rape and sexual assault complaints decrease 0.4 SD during the same period in districts with the strictest lockdowns, consistent with decreased female mobility in public spaces, public transport, and workplaces. Attitudes toward domestic violence play an important role in the reporting and incidence of domestic violence during the lockdown.

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Media – Science related

Pandemic

Month Four of the Panic: Where Is the Evidence?

Author: Roger W Koops

Publication date: 19 July 2020

Source: American Institute for Economic Research

Dr. Carl Sagan was one of the premier scientists when it came to trying to bridge the gap of hard science with general public understanding. In the process, his personal enthusiasm for the wonder of science became evident to all. He also understood that science could be hijacked and that the highest standards of evidence were required when fantastic claims were being made.

In just a few short months, the world has gone from a normal functioning society to one of extreme panic and chaos (maybe The Twilight Zone could not have conceived of this to such a degree). We have seen the very foundations of human existence cracked, some might say disintegrated. There has been induced panic and hysteria, cultural and social disintegration, censorship, political hijacking, economic collapse and hardship, imposition of laws in free societies incurred beyond the usual process of lawmaking and resembling totalitarian regimes. In short, human existence has been turned upside down. Fortunately, there have been some zones of sanity around the world, but far too few.

The panic that has been induced has been directed towards trying to convince the public that SARS-COV-2, which I will refer to simply as coronavirus, is an apocalyptic virus that will doom anyone that gets it. This effort continues to this day.

Avoiding the virus, or run and hide, has been the major theme of the inducement. Therefore, the message is that all of these extreme measures are necessary to save people from the horrors of the disease. This is truly an extraordinary claim. So, where is the extraordinary evidence?

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Mitigation strategies

The Independent SAGE Report 8. Policy for England on face coverings to reduce transmission of SARS-CoV-2

Publication date: 15 July 2020

Source: The Independent SAGE Group

An Independent SAGE Report following public consultation on 14th July 2020

Aims

This report sets out recommendations for maximizing the benefits of face coverings while minimizing their risks, taking into account evolving evidence and the behavioural factors that must be addressed. It raises issues that need to be tackled by Government involving, and in partnership with, employers, communities, and relevant organisations.

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Mortality

Why no-one can ever recover from COVID-19 in England – a statistical anomaly

Authors: Yoon K Loke and Carl Heneghan

Publication date: 16 July 2020

Source: Centre for Evidence-Based Medicine

People living in England have become increasingly concerned in the face of Public Health England’s (PHE) figures demonstrating a relentless daily toll of more than a hundred COVID-associated deaths several days a week (see Figure 1).

This is in stark contrast to the more reassuring recovery in neighbouring regions (Wales, Scotland and Northern Ireland), where there are days with no COVID-associated deaths whatsoever.

One reason for this due is a statistical flaw in the way that PHE compiles ‘out of hospital’ deaths data, rather than any genuine difference between the regions of the UK:

“Linking data on confirmed positive cases (identified through testing by NHS and PHE laboratories and commercial partners) to the NHS Demographic Batch Service: when a patient dies, the NHS central register of patients is notified (this is not limited to deaths in hospitals). The list of all lab-confirmed cases is checked against the NHS central register each day, to check if any of the patients have died.”

Here, it seems that PHE regularly looks for people on the NHS database who have ever tested positive, and simply checks to see if they are still alive or not. PHE does not appear to consider how long ago the COVID test result was, nor whether the person has been successfully treated in hospital and discharged to the community. Anyone who has tested COVID positive but subsequently died at a later date of any cause will be included on the PHE COVID death figures.

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Therapeutics

Synairgen announces positive results from trial of SNG001 in hospitalised COVID-19 patients

Publication date: 20 July 2020

Source: Synairgen

Synairgen plc (LSE: SNG), the respiratory drug discovery and development company which originated from research at the University of Southampton, is pleased to announce positive results from its clinical trial of SNG001, its wholly-owned inhaled formulation of interferon beta, in hospitalised COVID-19 patients.

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Vaccines

National Academies Launch Study on Equitable Allocation of a COVID-19 Vaccine – First Meeting July 24

Publication date: 21 July 2020

Source: The National Academies of Sciences Engineering Medicine

In response to a request from the National Institutes of Health (NIH) and Centers for Disease Control and Prevention (CDC), the National Academies of Sciences, Engineering, and Medicine and the National Academy of Medicine (NAM) have formed a committee that will develop an overarching framework to assist policymakers in the U.S. and global health communities in planning for equitable allocation of vaccines against COVID-19.  The committee will hold its first meeting on July 24.

As part of the study, the committee will consider what criteria should be used to set priorities for equitable distribution among groups of potential vaccine recipients, taking into account factors such as population health disparities; individuals at higher risk because of health status, occupation, or living conditions; and geographic distribution of active virus spread.  In addition, the committee will consider how communities of color can be assured access to COVID-19 vaccines in the U.S. and recommend strategies to mitigate vaccine hesitancy among the American public.

“While there has been a worldwide effort to accelerate development of safe and effective SARS-CoV-2 vaccines, there will inevitably be limited doses available for the first several months,” said NAM President Victor J. Dzau.  “We are pleased to be able to mobilize expertise quickly to respond to the government’s request for an independent study of priority-setting for the equitable allocation of potential vaccines for SARS-CoV-2.  We look forward to providing a framework to advise policymakers and health authorities as they plan for these allocation decisions, as well as to help inform the American public’s understanding of this critical issue.”

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COVID-19 Vaccine Frontrunners

Author: Jef Akst

Publication date: 07 April 2020 | Updated 20 July 2020

Source: The Scientist

Stay up-to-date on the progress of dozens of vaccine candidates that are currently undergoing clinical testing.

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Second wave

Preparing for a challenging winter 2020/21

Publication date: 14 July 2020

Source: The Academy of Medical Sciences

July and August must be a period of intense preparation for our reasonable worst-case scenario for health in the winter that we set out in this report, including a resurgence of COVID-19, which might be greater than that seen in the spring. The assumptions that we have made should be tested as new evidence emerges (including analysis of the evidence from the first wave) to enable prevention and mitigation strategies to be adapted and refined. Mitigation strategies should not pose further disadvantage to the most vulnerable in society or the highest risk patients for communities. To maximise their effectiveness (and to ensure they do no exacerbate inequalities), preparations for winter must be informed by engagement with patients, carers, public and healthcare professionals (as we have benefitted from in this report); and, whenever possible, be developed through co-production. Implementation or prevention and mitigation strategies requires enhanced coordination, collaboration and data sharing between central and local initiatives.

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Media – Reporting

Endemic virus

Coronavirus: 'Infection here for many years to come'

Publication date: 21 July 2020

Source: BBC

The UK will be living with coronavirus for many years to come and even a vaccine is unlikely to eliminate it for good, experts are warning.

Wellcome Trust director Prof Sir Jeremy Farrar told the House of Commons' Health Committee "things will not be done by Christmas".

He went on to say humanity would be living with the virus for "decades".

It comes after the prime minister said last week he hoped for a return to normality by Christmas.

Boris Johnson made the comments as he set out plans to further ease restrictions, including the opening of leisure centres and indoor swimming pools later this month and the prospect of mass gatherings being allowed from the autumn.

But experts giving evidence to the cross-party group of MPs said it was important to be realistic that the virus would still be here.

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Transmission

Hundreds gather in Hyde Park to protest against wearing masks

Authors: Patrick Grafton-Green and Rebecca Speare-Cole

Publication date: 20 July 2020

Source: Evening Standard

Hundreds of people have gathered in Hyde Park in central London to protest against wearing masks.

Crowds started congregating at about 1pm on Sunday ahead of an expected march organised by campaign group Keep Britain Free.

They initially hovered around Marble Arch in the capital to listen to speeches for around two hours.

People held placards reading "I will be not be masked, tested, tracked" and "no mask".

Face coverings will also become mandatory in shops and supermarkets in England from July 24.

Those who fail to wear a mask face fine of up to £100.

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Masks Likely Do Not Inhibit Viral Spread

Author: Dr Joseph Mercola

Publication date: 19 July 2020

Source: Mercola.com

  • Not a single randomized controlled trial with verified outcome has been able to detect a statistically significant advantage of wearing a mask versus not wearing a mask, when it comes to preventing infectious viral illness
  • If there were any significant advantage to wearing a mask to reduce infection risk to either the wearer or others in the vicinity, then it would have been detected in at least one of these trials, yet there's no sign of such a benefit
  • There is no evidence that masks are of any utility for preventing infection by either stopping the aerosol particles from coming out, or from going in. You're not helping the people around you by wearing a mask, and you're not helping yourself avoid the disease by wearing a mask
  • Infectious viral respiratory diseases primarily spread via very fine aerosol particles that are in suspension in the air. Any mask that allows you to breathe therefore allows for transmission of aerosolized viruses
  • All-cause mortality data are not affected by reporting bias. A detailed study of the current data of all-cause mortality shows the all-cause mortality this past winter was no different, statistically, from previous decades. COVID-19 is not a killer disease, and this pandemic has not brought anything out of the ordinary in terms of death toll

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Why coronavirus deaths remain low in the US despite surge in new cases

Author: Josie Ensor

Publication date: 17 July 2020

Source: The Telegraph

Dr Joseph Varon has never seen so many patients in his intensive care unit. Most of the beds are occupied by cases of Covid-19.

But although his hospital in Houston, Texas, has found itself in the new epicentre of the US outbreak, he is not as worried as you might imagine.

“Our ward is full of coronavirus patients, but we’ve had amazing success in treating them,” said Dr Varon, chief medical officer at United Memorial Medical Center. “Around 95 per cent of people who have come in here have walked out.”

The US has been reporting record numbers of virus cases - hitting 77,000 in one day on Thursday - yet deaths have not been rising at the rate many had expected.

The country averaged just over 700 deaths a day the week to Wednesday - up from 500 in the first week of July but far lower than the 2,200 recorded during the deadliest phase of the outbreak in April.

According to the most recent death certificate data released by the Centers for Disease Control and Prevention (CDC), the percentage of deaths caused by Covid-19 and conditions linked to the virus decreased from 6.9 per cent for the last week of June to 5.5 per cent the first week of July, representing the eleventh consecutive week of decline.

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Study reveals extent of coronavirus spread in hospitals during pandemic peak

Publication date: 10 July 2020

Source: The Francis Crick Institute

Researchers studying the spread of SARS-CoV-2 among healthcare workers have found high levels of asymptomatic infections during the peak of the pandemic in London. These results, published as part of correspondence in The Lancet today, highlight the importance of routinely screening healthcare staff for the virus to protect frontline workers and their patients.

As part of the SAFER study, researchers at University College London Hospitals (UCLH) NHS Foundation Trust, collected twice-weekly self-administered nose and throat swabs and monthly blood samples from 200 frontline healthcare staff. These staff are caring for patients in a variety of roles within A&E, intensive care, and the acute medical unit at UCLH.

In partnership with the Francis Crick Institute, swabs were tested to assess whether staff were currently infected, and blood serum was tested for antibodies to the virus spike protein, which would indicate exposure to the virus.

Initial analysis of samples taken between 26 March and 8 April 2020, the peak of the pandemic in London, revealed that 25% of healthcare staff tested had already had the infection, and a further 20% acquired infection within the first month of follow up.

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Mortality

Axios-Ipsos poll: The skeptics are growing

Author: Margaret Talev

Publication date: 21 July 2020

Source: Axios

A rising number of Americans — now nearly one in three — don't believe the virus' death toll is as high as the official count, despite surging new infections and hospitalizations, per this week's installment of the Axios-Ipsos Coronavirus Index.

Between the lines: Republicans, Fox News watchers and people who say they have no main source of news are driving this trend.

Why it matters: It shows President Trump's enduring influence on his base, even as Americans overall say they are increasingly dissatisfied with his handling of the virus and political support is shifting toward Joe Biden.

What they're saying: "We live in highly tribal and partisan times, and people are more likely to believe cues and signals from their political leaders than the scientists or the experts," says Cliff Young, president of Ipsos U.S. Public Affairs.

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Therapeutics

Coronavirus: millions of Britons should be taking ‘sunshine nutrient’ vitamin D

Author: Andrew Gregory

Publication date: 19 July 2020

Source: The Times

Millions of Britons should be encouraged to take vitamin D supplements this winter because they could help fight the coronavirus, according to a report commissioned by the government’s chief scientific adviser.

In the review, ordered by Sir Patrick Vallance on how to stop hospitals being overwhelmed, the Academy of Medical Scientists urges ministers to bolster public health messages on vitamin D, known as the “sunshine” nutrient.

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Environment

‘It was so gross, I nearly cried’: Meet the UK’s litter-picking army – fighting our rising tide of filth

Author: Sam Wollaston

Publication date: 21 July 2020

Source: The Guardian

Thousands of volunteers are trying to keep Britain clean as people go wild after lockdown. We join some in Bournemouth, as they face the discarded plastic, PPE, pants – and human poo.

On a promising July morning, Bournemouth’s East Cliff limbers up for the day: dog walkers, power walkers, an outdoor gym class on a patch of grass. Four people in hi-vis vests beetle about purposefully, looking at the ground. They carry buckets and bags, and each has a tool – a stick with a handle at one end and a grabber at the other.

One of them, Lea Baker, 62, nimbly scales the clifftop fence to grab a Coke can. “Sometimes, when there is a really difficult one and I get it, I’m like: ‘Yes, I win!’” she says, giving it a little fist pump.

Baker is a retired teacher, originally from Holland. “I love England, but this is one aspect I hate,” she says, nodding at her bucket, now nearly full of cans and bottles, plastic, fag ends, wipes and other horrors. Cigarette butts are her bugbear. “There are so many of them, and they take so long to pick up.” She’s not a fan of dog poo either, tied up in plastic bags and then discarded or hung on the fence. “It’s actually better to leave the poo.”

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The COVID-19 masks threatening the lives of whales

Author: Rosie Greenaway

Publication date: 08 July 2020

Source: Natural Products News

Billions of disposable masks and gloves are ending up in the sea during the coronavirus pandemic, according to international non-profit Ocean Conservancy which warns we could be heading for a surge in ocean pollution.

Divers and environmental observers have witnessed an increasing number of surgical masks and latex gloves washing up on foreshores and polluting the world’s waters.

Across the planet – from the Soko Islands in Hong Kong and the Bosphorus in Turkey, to the Cote D’Azur in France and even the banks of London’s River Thames – the PPE now commonplace in everyday life is encroaching on the natural habitats of species such as birds and sea creatures.

The glove or the mask that you take off … could easily be the glove or the mask that kills a whale

“It’s important to understand we had a tremendously grave crisis before the pandemic even started in terms of plastic waste in the ocean – and now you take the global pandemic. At the current rate, we’re putting 129 billion – and I’m saying billion – face masks into the environment every single month [and] 65 billion plastic gloves. A significant portion of those would be disposed of improperly and wind up in the ocean,” says Doug Cress, vice president of conservation for Ocean Conservancy.

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Covid and pregnancy

During Coronavirus Lockdowns, Some Doctors Wondered: Where Are the Preemies?

Author: Elizabeth Preston

Date: 19 July 2020

Source: The New York Times

This spring, as countries around the world told people to stay home to slow the spread of the coronavirus, doctors in neonatal intensive care units were noticing something strange: Premature births were falling, in some cases drastically.

It started with doctors in Ireland and Denmark. Each team, unaware of the other’s work, crunched the numbers from its own region or country and found that during the lockdowns, premature births — especially the earliest, most dangerous cases — had plummeted. When they shared their findings, they heard similar anecdotal reports from other countries.

They don’t know what caused the drop in premature births, and can only speculate as to the factors in lockdown that might have contributed. But further research might help doctors, scientists and parents-to-be understand the causes of premature birth and ways to prevent it, which have been elusive until now. Their studies are not yet peer reviewed, and have been posted only on preprint servers. In some cases the changes amounted to only a few missing babies per hospital. But they represented significant reductions from the norm, and some experts in premature birth think the research is worthy of additional investigation.

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Vaccines

Africa Demonstrates Against Oxford Vaccine Trial

Publication date: 04 July 2020

Source: Covid Watching

Demonstrations have broken out in South Africa regarding the proposed vaccine trials being run by the University of Oxford, one of the competitors in the race to bring a COVID19 vaccine to market. The demonstrators at Witwatersrand University in Johannesburg, questioned the safety and ethics behind the trials, and held banners saying they didn’t want a Gates Foundation vaccine. They expressed concern that the testing was going to be done on poor people and noted that the vaccine hadn’t even been tested yet in Europe or the USA, where the outbreak is more serious. Demonstrators also raised the comments made by a French researcher two months ago, regarding testing new vaccines on Africans first. The researcher had said “If I can be provocative, shouldn’t we be doing this study in Africa, where there are no masks, no treatments, no resuscitation?” He compared it to some AIDS studies: “In prostitutes, we try things because we know that they are highly exposed and that they do not protect themselves.”

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Social Impacts

The Living Standards Audit 2020

Publication date: 21 July 2020

Source: Resolution Foundation

This report is the latest in a series of annual Living Standards Audits, highlighting recent trends in household incomes. This year’s report looks at how households were faring before the coronavirus crisis, but also presents our nowcast of how the incomes of different groups were affected during the height of the lockdown. We also look to the future, and discuss the importance of maintaining – and even improving – the safety net in order to protect incomes against the effects of rising unemployment in the months ahead.

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Social Perceptions and behaviours

COVID-19 UK Perceptions and Behaviour - Week 18 (15-16 JULY)

Publication date: 20 June 2020

Source: ORB International

Our latest data from 2,065 adults across the UK shows:

There is a slight decline in opinion of the way that the Government is handling the crisis (39% agree the Govt. was handling it well on June 24-25th, whereas the figure this week was 36%). Slightly fewer people also feel that it is under control currently (32% from June 24-25th vs 28% this week).

There is broad support for making masks compulsory. Only one in five (18%) oppose this, while more than half (54%) would support.

Likewise it seems that people want to see politicians and celebrities wearing masks – 80% have this view.

In terms of behaviours, there is little change from three weeks ago when we last ran the survey – the vast majority see taking a summer holiday (84%), going to the cinema (83%), or going to the pub (81%) as risky activities, while people saying that eating in a restaurant is risky has dropped by only 5% (82% on June 24-25th vs 77% this week). Again, it seems that people are more prepared to go to work (53%) than they are to take risks socially – not ideal for the hospitality industry.

Around one in seven (14%) would not want to be vaccinated should one be available. A similar proportion (13%) say they are unsure whether or not they would get vaccinated.

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