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Science |
| Origins |
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Sentinel surveillance of SARS-CoV-2 in wastewater anticipates the occurrence of COVID-19 cases Authors: Chavarria-Miró G et al Publication date: 13 June 2020 Journal: medRxiv preprint DOI: 10.1101/2020.06.13.20129627 SARS-CoV-2 was detected in Barcelona sewage long before the declaration of the first COVID-19 case, indicating that the infection was present in the population before the first imported case was reported. Sentinel surveillance of SARS-CoV-2 in wastewater would enable adoption of immediate measures in the event of future COVID-19 waves. Read more... |
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Pathogenesis |
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Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19) Authors: W Joost Wiersinga, MD, PhD, Andrew Rhodes, MD, PhD and Allen C Cheng, MD, PhD Publication date: 10 July 2020 Journal: JAMA DOI: 10.1001/jama.2020.12839 Importance: The coronavirus disease 2019 (COVID-19) pandemic, due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a worldwide sudden and substantial increase in hospitalizations for pneumonia with multiorgan disease. This review discusses current evidence regarding the pathophysiology, transmission, diagnosis, and management of COVID-19. Observations: SARS-CoV-2 is spread primarily via respiratory droplets during close face-to-face contact. Infection can be spread by asymptomatic, presymptomatic, and symptomatic carriers. The average time from exposure to symptom onset is 5 days, and 97.5% of people who develop symptoms do so within 11.5 days. The most common symptoms are fever, dry cough, and shortness of breath. Radiographic and laboratory abnormalities, such as lymphopenia and elevated lactate dehydrogenase, are common, but nonspecific. Diagnosis is made by detection of SARS-CoV-2 via reverse transcription polymerase chain reaction testing, although false-negative test results may occur in up to 20% to 67% of patients; however, this is dependent on the quality and timing of testing. Manifestations of COVID-19 include asymptomatic carriers and fulminant disease characterized by sepsis and acute respiratory failure. Approximately 5% of patients with COVID-19, and 20% of those hospitalized, experience severe symptoms necessitating intensive care. More than 75% of patients hospitalized with COVID-19 require supplemental oxygen. Treatment for individuals with COVID-19 includes best practices for supportive management of acute hypoxic respiratory failure. Emerging data indicate that dexamethasone therapy reduces 28-day mortality in patients requiring supplemental oxygen compared with usual care (21.6% vs 24.6%; age-adjusted rate ratio, 0.83 [95% CI, 0.74-0.92]) and that remdesivir improves time to recovery (hospital discharge or no supplemental oxygen requirement) from 15 to 11 days. In a randomized trial of 103 patients with COVID-19, convalescent plasma did not shorten time to recovery. Ongoing trials are testing antiviral therapies, immune modulators, and anticoagulants. The case-fatality rate for COVID-19 varies markedly by age, ranging from 0.3 deaths per 1000 cases among patients aged 5 to 17 years to 304.9 deaths per 1000 cases among patients aged 85 years or older in the US. Among patients hospitalized in the intensive care unit, the case fatality is up to 40%. At least 120 SARS-CoV-2 vaccines are under development. Until an effective vaccine is available, the primary methods to reduce spread are face masks, social distancing, and contact tracing. Monoclonal antibodies and hyperimmune globulin may provide additional preventive strategies. Conclusions and Relevance: As of July 1, 2020, more than 10 million people worldwide had been infected with SARS-CoV-2. Many aspects of transmission, infection, and treatment remain unclear. Advances in prevention and effective management of COVID-19 will require basic and clinical investigation and public health and clinical interventions. Predicting the Trajectory of Any COVID19 Epidemic From the Best Straight Line Authors: Michael Levitt1, Andrea Scaiewicz and Francesco Zonta Publication date: 26 June 2020 Source: medRxiv preprint DOI: 10.1101/2020.06.26.20140814 A pipeline involving data acquisition, curation, carefully chosen graphs and mathematical models, allows analysis of COVID-19 outbreaks at 3,546 locations world-wide (all countries plus smaller administrative divisions with data available). Comparison of locations with over 50 deaths shows all outbreaks have a common feature: H(t) defined as loge(X(t)/X(t-1)) decreases linearly on a log scale, where X(t) is the total number of Cases or Deaths on day, t (we use ln for loge). The downward slopes vary by about a factor of three with time constants (1/slope) of between 1 and 3 weeks; this suggests it may be possible to predict when an outbreak will end. Is it possible to go beyond this and perform early prediction of the outcome in terms of the eventual plateau number of total confirmed cases or deaths? We test this hypothesis by showing that the trajectory of cases or deaths in any outbreak can be converted into a straight line. Specifically Y (t) ≡ − ln(ln(N / X (t)) , is a straight line for the correct plateau value N, which is determined by a new method, Best-Line Fitting (BLF). BLF involves a straight-line facilitation extrapolation needed for prediction; it is blindingly fast and amenable to optimization. We find that in some locations that entire trajectory can be predicted early, whereas others take longer to follow this simple functional form. Fortunately, BLF distinguishes predictions that are likely to be correct in that they show a stable plateau of total cases or death (N value). We apply BLF to locations that seem close to a stable predicted N value and then forecast the outcome at some locations that are still growing wildly. Our accompanying web-site will be updated frequently and provide all graphs and data described here. |
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Epidemiology |
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Seroconversion of a city: Longitudinal monitoring of SARS-CoV-2 seroprevalence in New York City Authors: Stadlbauer D et al Publication date: 29 June 2020 Journal: medRxiv preprint DOI: 10.1101/2020.06.28.20142190 By conducting a retrospective, cross-sectional analysis of SARS-CoV-2 seroprevalence in a sentinel group (enriched for SARS-CoV-2 infections) and a screening group (representative of the general population) using >5,000 plasma samples from patients at Mount Sinai Hospital in New York City (NYC), we identified seropositive samples as early as in the week ending February 23, 2020. A stark increase in seropositivity in the sentinel group started the week ending March 22 and in the screening group in the week ending March 29. By the week ending April 19, the seroprevalence in the screening group reached 19.3%, which is well below the estimated 67% needed to achieve community immunity to SARS-CoV-2. These data potentially suggest an earlier than previously documented introduction of SARS-CoV-2 into the NYC metropolitan area. |
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Transmission |
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Airborne Transmission of SARS-CoV-2. Theoretical Considerations and Available Evidence Authors: Michael Klompas MD, Meghan A Baker, MD and Chanu Rhee MD Publication date: 13 July 2020 Journal: JAMA DOI: 10.1001/jama.2020.12458 The coronavirus disease 2019 (COVID-19) pandemic has reawakened the long-standing debate about the extent to which common respiratory viruses, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are transmitted via respiratory droplets vs aerosols. Droplets are classically described as larger entities (>5 μm) that rapidly drop to the ground by force of gravity, typically within 3 to 6 feet of the source person. Aerosols are smaller particles (≤5 μm) that rapidly evaporate in the air, leaving behind droplet nuclei that are small enough and light enough to remain suspended in the air for hours (analogous to pollen). Determining whether droplets or aerosols predominate in the transmission of SARS-CoV-2 has critical implications. If SARS-CoV-2 is primarily spread by respiratory droplets, wearing a medical mask, face shield, or keeping 6 feet apart from other individuals should be adequate to prevent transmission. If, however, SARS-CoV-2 is carried by aerosols that can remain suspended in the air for prolonged periods, medical masks would be inadequate (because aerosols can both penetrate and circumnavigate masks), face shields would provide only partial protection (because there are open gaps between the shield and the wearer’s face), and 6 feet of separation would not provide protection from aerosols that remain suspended in the air or are carried by currents. Authors: Stadnytskyi et al Publication date: 02 June 2020 Journal: PNAS DOI: 10.1073/pnas.2006874117 Speech droplets generated by asymptomatic carriers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are increasingly considered to be a likely mode of disease transmission. Highly sensitive laser light scattering observations have revealed that loud speech can emit thousands of oral fluid droplets per second. In a closed, stagnant air environment, they disappear from the window of view with time constants in the range of 8 to 14 min, which corresponds to droplet nuclei of ca. 4 μm diameter, or 12- to 21-μm droplets prior to dehydration. These observations confirm that there is a substantial probability that normal speaking causes airborne virus transmission in confined environments. |
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Covid-19 patients |
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Authors: Adams SH PhD et al Publication date: 13 July 2020 Journal: Journal of Adolescent Health DOI: 10.1016/j.jadohealth.2020.06.025 Purpose: COVID-19 morbidity and mortality reports in the U.S. have not included findings specific to young adults. The Centers for Disease Control and Prevention provides a list of conditions and associated behaviors, including smoking, conferring risk of severe COVID-19 illness regardless of age. This study examines young adults' medical vulnerability to severe COVID-19 illness, focusing on smoking-related behavior. Methods: A young adult subsample (aged 18e25 years) was developed from the National Health Interview Survey, a nationally representative data set, pooling years 2016e2108. The medical vulnerability measure (yes vs. no) was developed, guided by the Centers for Disease Control and Prevention risk indicators. The estimates of medical vulnerability were developed for the full sample, the nonsmoking sample, and the individual risk indicators. Logistic regressions were conducted to examine differences by sex, race/ethnicity, income, and insurance. Results: Medical vulnerability was 32% for the full sample and half that (16%) for the nonsmoking sample. Patterns and significance of some subgroup differences differed between the full and the nonsmoking sample. Male vulnerability was (33%) higher than female (30%; 95% CI: .7e.9) in the full sample, but lower in nonsmokers: male (14%) versus female (19%; 95% CI: 1.2e1.7). The white sub- group had higher vulnerability than Hispanic and Asian subgroups in both samplesdfull sample: white (31%) versus Hispanic (24%; 95% CI: .6e.9) and Asian (18%; 95% CI: .4e.5); nonsmokers: white (17%) versus Hispanic (13%; 95% CI: .06e.9) and Asian (10%; 95% CI: .3e.8). Conclusions: Notably, lower young adult medical vulnerability within nonsmokers versus the full sample underscores the importance of smoking prevention and mitigation. UK report on 10,421 patients critically ill with COVID-19 Institution: Intensive Care National Audit & Research Centre (ICNARC) Publication date: 10 July 2020 Authors: Wang S et al Publication date: 10 July 2020 Journal: Diabetologia DOI: 10.1007/s00125-020-05209-1 Aims/hypothesis: Hyperglycaemia is associated with an elevated risk of mortality in community-acquired pneumonia, stroke, acute myocardial infarction, trauma and surgery, among other conditions. In this study, we examined the relationship between fasting blood glucose (FBG) and 28-day mortality in coronavirus disease 2019 (COVID-19) patients not previously diagnosed as having diabetes. Methods: We conducted a retrospective study involving all consecutive COVID-19 patients with a definitive 28-day outcome and FBG measurement at admission from 24 January 2020 to 10 February 2020 in two hospitals based in Wuhan, China. Demographic and clinical data, 28-day outcomes, in-hospital complications and CRB-65 scores of COVID-19 patients in the two hospitals were analysed. CRB-65 is an effective measure for assessing the severity of pneumonia and is based on four indicators, i.e. confusion, respiratory rate (>30/min), systolic blood pressure (≤90 mmHg) or diastolic blood pressure (≤60 mmHg), and age (≥65 years). Results: Six hundred and five COVID-19 patients were enrolled, including 114 who died in hospital. Multivariable Cox regression analysis showed that age (HR 1.02 [95% CI 1.00, 1.04]), male sex (HR 1.75 [95% CI 1.17, 2.60]), CRB-65 score 1–2 (HR 2.68 [95% CI 1.56, 4.59]), CRB-65 score 3–4 (HR 5.25 [95% CI 2.05, 13.43]) and FBG ≥7.0 mmol/l (HR 2.30 [95% CI 1.49, 3.55]) were independent predictors for 28-day mortality. The OR for 28-day in-hospital complications in those with FBG ≥7.0 mmol/l and 6.1–6.9 mmol/l vs <6.1 mmol/l was 3.99 (95% CI 2.71, 5.88) or 2.61 (95% CI 1.64, 4.41), respectively. Conclusions/interpretation: FBG ≥7.0 mmol/l at admission is an independent predictor for 28-day mortality in patients with COVID-19 without previous diagnosis of diabetes. Glycaemic testing and control are important to all COVID-19 patients even where they have no pre-existing diabetes, as most COVID-19 patients are prone to glucose metabolic disorders. Author: Sheldon Cohen Publication date: 08 July 2020 Journal: Perspectives on Psychological Science DOI: 10.1177/1745691620942516 For 35 years, our laboratory has been involved in identifying psychosocial factors that predict who becomes ill when they are exposed to a virus affecting the upper respiratory tract. To pursue this question, we used a unique viral-challenge design in which we assessed behavioral, social, and psychological factors in healthy adults. We subsequently exposed these adults to a cold or influenza virus and then monitored them in quarantine for 5 to 6 days for onset of respiratory illness. Factors we found to be associated with greater risk of respiratory illnesses after virus exposure included smoking, ingesting an inadequate level of vitamin C, and chronic psychological stress. Those associated with decreased risk included social integration, social support, physical activity, adequate and efficient sleep, and moderate alcohol intake. We cautiously suggest that our findings could have implications for identifying who becomes ill when exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). This argument is based on evidence that the associations we report are replicable across multiple respiratory viruses and that the pathways found to link psychosocial factors to colds and influenza may play similar roles in COVID-19. |
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Mortality |
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Authors: Burton JK et al Publication date: 10 July 2020 Journal: medRxiv preprint DOI: 10.1101/2020.07.09.20149583 Background: COVID-19 has had large impact on care-home residents internationally. This study systematically examines care-home outbreaks of COVID-19 in a large Scottish health board. Methods: Analysis of testing, cases and deaths using linked care-home, testing and mortality data for 189 care-homes with 5843 beds in a large Scottish Health Board up to 15/06/20. Findings: 70 (37.0%) of care-homes experienced a COVID-19 outbreak, 66 of which were in care-homes for older people where care-home size was strongly associated with outbreaks (OR per 20-bed increase 3.50, 95%CI 2.06 to 5.94). There were 852 confirmed cases and 419 COVID-related deaths, 401 (95.7%) of which occurred in care-homes with an outbreak, 16 (3.8%) in hospital, and two in the 119 care-homes without a known outbreak. For non-COVID related deaths, there were 73 excess deaths in care-homes with an outbreak, but no excess deaths in care-homes without an outbreak, and 24 fewer deaths than expected of care-home residents in hospital. A quarter of COVID-19 related cases and deaths occurred in five (2.6%) care-homes, and half in 13 (6.9%) care-homes. Interpretation: The large impact on excess deaths appears to be primarily a direct effect of COVID-19, with cases and deaths are concentrated in a minority of care homes. A key implication is that there is a large pool of susceptible residents if community COVID-19 incidence increases again. Shielding residents from potential sources of infection and rapid action into minimise outbreak size where infection is introduced will be critical in any wave 2. OpenSAFELY: factors associated with COVID-19 death in 17 million patients Authors: Elizabeth J Williamson, Alex J Walker and Ben Goldacre Publication date: 08 July 2020 Journal: Nature DOI: 10.1038/s41586-020-2521-4 COVID-19 has rapidly affected mortality worldwide1. There is unprecedented urgency to understand who is most at risk of severe outcomes, requiring new approaches for timely analysis of large datasets. Working on behalf of NHS England, here we created OpenSAFELY: a secure health analytics platform covering 40% of all patients in England, holding patient data within the existing data centre of a major primary care electronic health records vendor. Primary care records of 17,278,392 adults were pseudonymously linked to 10,926 COVID-19-related deaths. COVID-19-related death was associated with: being male (hazard ratio (HR) 1.59, 95% confidence interval (CI) 1.53–1.65); older age and deprivation (both with a strong gradient); diabetes; severe asthma; and various other medical conditions. Compared with people with white ethnicity, Black and South Asian people were at higher risk even after adjustment for other factors (HR 1.48, 1.30–1.69 and 1.44, 1.32–1.58, respectively). We have quantified a range of clinical risk factors for COVID-19-related death in the largest cohort study conducted by any country to date. OpenSAFELY is rapidly adding further patients’ records; we will update and extend results regularly. |
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Nutrition and lifestyle |
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Gut microbiota and Covid-19- possible link and implications Authors: Debojyoti Dhar and Abhishek Mohanty Publication date: August 2020 Journal: Virus Research DOI: 10.1016/j.virusres.2020.198018 Covid-19 is a major pandemic facing the world today caused by SARS-CoV-2 which has implications on our understanding of infectious diseases. Although, SARS-Cov-2 primarily causes lung infection through binding of ACE2 receptors present on the alveolar epithelial cells, yet it was recently reported that SARS-CoV-2 RNA was found in the faeces of infected patients. Interestingly, the intestinal epithelial cells particularly the enterocytes of the small intestine also express ACE2 receptors. Role of the gut microbiota in influencing lung diseases has been well articulated. It is also known that respiratory virus infection causes perturbations in the gut microbiota. Diet, environmental factors and genetics play an important role in shaping gut microbiota which can influence immunity. Gut microbiota diversity is decreased in old age and Covid-19 has been mainly fatal in elderly patients which again points to the role the gut microbiota may play in this disease. Improving gut microbiota profile by personalized nutrition and supplementation known to improve immunity can be one of the prophylactic ways by which the impact of this disease can be minimized in old people and immune-compromised patients. More trials may be initiated to see the effect of co-supplementation of personalized functional food including prebiotics/probiotics along with current therapies. COVID-19 and metabolic syndrome: could diet be the key? Author: Maryanne Demasi Publication date: 10 July 2020 Journal: BMJ Evidence-Based Medicine DOI: 10.1136/bmjebm-2020-111451 In the current COVID-19 pandemic, governments mandate social distancing and good hand hygiene, but little attention is paid to the potential impact of diet on health outcomes. Poor diet is the most significant contributor to the burden of chronic, lifestyle-related diseases like obesity, type 2 diabetes and cardiovascular disease.1 As of 30 May 2020, the Centers for Disease Control and Prevention reported that among COVID-19 cases, the two most common underlying health conditions were cardiovascular disease (32%) and diabetes (30%).2 Hospitalisations were six times higher among patients with a reported underlying condition (45.4%) than those without reported underlying conditions (7.6%). Deaths were 12 times higher among patients with reported underlying conditions (19.5%) compared to those without reported underlying conditions (1.6%).2 Two-thirds of people in the UK who have fallen seriously ill with COVID-19 were overweight or obese and 99% of deaths in Italy have been in patients with pre-existing conditions, such as hypertension, diabetes and heart disease.3 These conditions, collectively known as metabolic syndrome, are linked to impaired immune function,4 and more severe symptoms and complications from COVID-19. Nutrients in prevention, treatment, and management of viral infections; special focus on Coronavirus Authors: BourBour et al Publication date: 09 July 2020 Journal: Archives of Physiology and Biochemistry DOI: 10.1080/13813455.2020.1791188 Background: The coronavirus disease 2019 (COVID-19) is a pandemic caused by coronavirus with mild to severe respiratory symptoms. This paper aimed to investigate the effect of nutrients on the immune system and their possible roles in the prevention, treatment, and management of COVID-19 in adults. Methods: This Systematic review was designed based on the guideline of the Preferred Reporting for Systematic Reviews (PRISMA). The articles that focussed on nutrition, immune system, viral infection, and coronaviruses were collected by searching databases for both published papers and accepted manuscripts from 1990 to 2020. Irrelevant papers and articles without English abstract were excluded from the review process. Results: Some nutrients are actively involved in the proper functioning and strengthening of the human immune system against viral infections including dietary protein, omega-3 fatty acids, vitamin A, vitamin D, vitamin E, vitamin B1, vitamin B6, vitamin B12, vitamin C, iron, zinc, and selenium. Few studies were done on the effect of dietary components on prevention of COVID-19, but supplementation with these nutrients may be effective in improving the health status of patients with viral infections. Conclusion: Following a balanced diet and supplementation with proper nutrients may play a vital role in prevention, treatment, and management of COVID-19. However, further clinical trials are needed to confirm these findings and presenting the strong recommendations against this pandemic. Making the Case for “COVID-19 Prophylaxis” With Lifestyle Medicine Authors: Elizabeth Peff Frates and Tim Rifai Publication date: 19 June 2020 Journal: American Journal of Health Promotion DOI: 10.1177/0890117120930536c Lifestyle (as) medicine has been increasingly recognized as a powerful therapy for prevention, control, and even reversal/remission of now well-established risk factors for COVID-19-associated morbidity and mortality.1 By lifestyle, in this context, we are primarily referring to effects of nutrition, activity, sleep, and smoking on individual metabolic health factors now clearly shown to be leading comorbidities associated with COVID-19 deaths, including, but not limited to, hypertension, diabetes, hyperlipidemia, and coronary artery disease2 (see Figure 1). As of April 6, 2020, hypertension appears to be the leading metabolic risk factor in New York’s 2020 COVID-19 experience. The Dietary Approaches to Stop Hypertension (DASH) eating pattern, of which the cornerstones are a high intake of whole fruits and vegetables combined with a substantially lower sodium intake than the US average, has been shown in multiple studies, including randomized controlled trials, to reduce blood pressure. This effect can approach the same potency as medications and with greater effect where there is higher baseline blood pressure or genetic predisposition. |
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Immunity |
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SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls Authors: Le Bert N et al Publication date: 15 July 2020 Journal: Nature DOI: 10.1038/s41586-020-2550-z Memory T cells induced by previous pathogens can shape the susceptibility to, and clinical severity of, subsequent infections1. Little is known about the presence of pre-existing memory T cells in humans with the potential to recognize SARS-CoV-2. Here, we first studied T cell responses to structural (nucleocapsid protein, NP) and non-structural (NSP-7 and NSP13 of ORF1) regions of SARS-CoV-2 in COVID-19 convalescents (n=36). In all of them we demonstrated the presence of CD4 and CD8 T cells recognizing multiple regions of the NP protein. We then showed that SARS-recovered patients (n=23) still possess long-lasting memory T cells reactive to SARS-NP 17 years after the 2003 outbreak, which displayed robust cross-reactivity to SARS-CoV-2 NP. Surprisingly, we also frequently detected SARS-CoV-2 specific T cells in individuals with no history of SARS, COVID-19 or contact with SARS/COVID-19 patients (n=37). SARS-CoV-2 T cells in uninfected donors exhibited a different pattern of immunodominance, frequently targeting the ORF-1-coded proteins NSP7 and 13 as well as the NP structural protein. Epitope characterization of NSP7-specific T cells showed recognition of protein fragments with low homology to “common cold” human coronaviruses but conserved amongst animal betacoranaviruses. Thus, infection with betacoronaviruses induces multispecific and long-lasting T cell immunity to the structural protein NP. Understanding how pre-existing NP- and ORF-1-specific T cells present in the general population impact susceptibility and pathogenesis of SARS-CoV-2 infection is of paramount importance for the management of the current COVID-19 pandemic. Longitudinal evaluation and decline of antibody responses in SARS-CoV-2 infection Authors: Seow J et al Publication date: 11 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. Pre-existing immunity to SARS-CoV-2: the knowns and unknowns Authors: Alessandro Sette and Shane Crotty Publication date: 07 July 2020 Journal: Nature Reviews Immunology DOI: 10.1038/s41577-020-0389-z T cell reactivity against SARS-CoV-2 was observed in unexposed people; however, the source and clinical relevance of the reactivity remains unknown. It is speculated that this reflects T cell memory to circulating ‘common cold’ coronaviruses. It will be important to define specificities of these T cells and assess their association with COVID-19 disease severity and vaccine responses. As data start to accumulate on the detection and characterization of SARS-CoV-2 T cell responses in humans, a surprising finding has been reported: lymphocytes from 20–50% of unexposed donors display significant reactivity to SARS-CoV-2 antigen peptide pools. 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: 0.1101/2020.06.29.174888 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. |
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Vaccines |
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An mRNA Vaccine against SARS-CoV-2 — Preliminary Report Authors: Jackson LA et al Publication date: 14 July 2020 Journal: New England Journal of Medicine DOI: 10.1056/NEJMoa2022483 Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and spread globally, prompting an international effort to accelerate development of a vaccine. The candidate vaccine mRNA-1273 encodes the stabilized prefusion SARS-CoV-2 spike protein. Methods: We conducted a phase 1, dose-escalation, open-label trial including 45 healthy adults, 18 to 55 years of age, who received two vaccinations, 28 days apart, with mRNA-1273 in a dose of 25 μg, 100 μg, or 250 μg. There were 15 participants in each dose group. Results: After the first vaccination, antibody responses were higher with higher dose (day 29 enzyme-linked immunosorbent assay anti–S-2P antibody geometric mean titer [GMT], 40,227 in the 25-μg group, 109,209 in the 100-μg group, and 213,526 in the 250-μg group). After the second vaccination, the titers increased (day 57 GMT, 299,751, 782,719, and 1,192,154, respectively). After the second vaccination, serum-neutralizing activity was detected by two methods in all participants evaluated, with values generally similar to those in the upper half of the distribution of a panel of control convalescent serum specimens. Solicited adverse events that occurred in more than half the participants included fatigue, chills, headache, myalgia, and pain at the injection site. Systemic adverse events were more common after the second vaccination, particularly with the highest dose, and three participants (21%) in the 250-μg dose group reported one or more severe adverse events. Conclusions: The mRNA-1273 vaccine induced anti–SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified. These findings support further development of this vaccine. Structural basis of a shared antibody response to SARS-CoV-2 Authors: Yuan M et al Publication date: 13 July 2020 Journal: Science DOI: 10.1126/science.abd2321 Molecular understanding of neutralizing antibody responses to SARS-CoV-2 could accelerate vaccine design and drug discovery. We analyzed 294 anti-SARS-CoV-2 antibodies and found that IGHV3-53 is the most frequently used IGHV gene for targeting the receptor-binding domain (RBD) of the spike protein. Co-crystal structures of two IGHV3-53 neutralizing antibodies with RBD, with or without Fab CR3022, at 2.33 to 3.20 Å resolution revealed that the germline-encoded residues dominate recognition of the ACE2 binding site. This binding mode limits the IGHV3-53 antibodies to short CDR H3 loops, but accommodates light-chain diversity. These IGHV3-53 antibodies show minimal affinity maturation and high potency, which is promising for vaccine design. Knowledge of these structural motifs and binding mode should facilitate design of antigens that elicit this type of neutralizing response. |
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Government/Health authorities |
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Mortality |
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Characteristics of Persons Who Died with COVID-19 — United States, February 12–May 18, 2020 Publication date: 10 July 2020 Source: Centers for Disease Control and Prevention What is already known about this topic? COVID-19 mortality is higher in persons with underlying medical conditions and in those aged ≥85 years. What is added by this report? Analysis of supplementary data for 10,647 decedents in 16 public health jurisdictions found that a majority were aged ≥65 years and most had underlying medical conditions. Overall, 34.9% of Hispanic and 29.5% of nonwhite decedents were aged <65 years, compared with 13.2% of white, non-Hispanic decedents. Among decedents aged <65 years, a total of 7.8% died in an emergency department or at home. What are the implications for public health practice? Understanding factors contributing to racial/ethnic mortality differences and out-of-hospital deaths might inform targeted communication to encourage persons in at-risk groups to practice preventive measures and promptly seek medical care if they become ill. |
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Media – Science related |
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Origins |
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Sentinel surveillance of SARS-CoV-2 in wastewater anticipates the occurrence of COVID-19 cases Authors: Carl Heneghan and Tom Jefferson Publication date: 13 July 2020 Source: The Centre for Evidence Based Medicine Bottom Line SARS-CoV-2 was detected in sewage 41 days before the declaration of the first COVID-19 case in Spain and in frozen samples dating back to 12 March 2019. If confirmed, the results suggest SARS CoV-2 has been around longer than first thought. Evidence Summary The copies or antigenic concentration closely resembled the shape of the epidemic curve apart from a break possibly due to dilution secondary to heavy rainfall. SARS-CoV-2 was detected in sewage 41 days (January 15th) before the reporting of the first COVID-19 case (February 25th), making wastewater surveillance a possible method to forecast cases of a disease with agents excreted in stools. Because most COVID-19 cases present with ILI and because there had been hypothesized cases before the index case, the researchers analysed frozen WWTP2 samples and found one positive, dating from 12th March 2019, some 10 months before the index case appearance. This suggested the presence of SARS-CoV-2 long before its appearance as a virulent infection. Of note is that earlier samples from January 2018 to January 2019 were negative for viral genome antigens. Read more... |
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Mortality |
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Why are US coronavirus deaths going down as covid-19 cases soar? Author: Michael Le Page Publication date: 14 July 2020 Source: New Scientist Coronavirus deaths are falling in the US even as cases skyrocket. In the UK, a lower proportion of people hospitalised with covid‑19 are dying. This has led to suggestions that the risk of dying if you are infected with the virus is falling, but the truth may be more complicated. “At this point, I don’t think we have conclusive evidence that the death rate is going down,” says Tessa Bold at Stockholm University in Sweden. Having plateaued at around 20,000 in May, the number of daily confirmed cases in the US began rising in June and has now exceeded 60,000. However, the number of deaths in the US reported as being due to covid-19 has fallen from more than 3000 a day in mid-April to well under 1000. |
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Environmental |
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Air pollution exposure linked to higher COVID-19 cases and deaths – new study Authors: Matt Cole, Ceren Ozgen and Eric Strobl Publication date: 13 July 2020 Source: The Conversation The global death toll from COVID-19 has now passed half a million. To slow the spread of the disease, we need to better understand why some places have higher numbers of cases and deaths than others. One factor that could partially explain this is air pollution. Research has shown that long term exposure to pollutants such as fine particulate matter (often called PM2.5, as these are particles smaller than 2.5 micrometres), nitrogen dioxide (NO₂) and sulphur dioxide (SO₂) can reduce lung function and cause respiratory illness. These pollutants have also been shown to cause a persistent inflammatory response even in the relatively young and to increase the risk of infection by viruses that target the respiratory tract. The pathogen that causes COVID-19 – SARS-CoV-2 – is one such virus. Several studies have already suggested that poor air quality can leave people at greater risk of contracting the virus, and at greater risk of serious illness and death. A study of the US found that even a small increase in PM2.5 concentrations of 1 microgram per cubic metre is associated with an 8% increase in the COVID-19 death rate. Our new research looked at the relationship between COVID-19 cases and exposure to air pollution in the Netherlands and found that the equivalent figure for that country could be up to 16.6%. |
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Media – Reporting |
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Second wave |
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If there is a second wave of Covid, the Swedish approach will have been right all along Author: Christopher Snowdon Publication date: 11 July 2020 Source: The Telegraph There have been times during this pandemic that I’ve felt as if my memory is playing tricks on me. I’m sure I remember scientists telling us that a second wave was inevitable. I could have sworn I saw a graph at the press briefings showing a scary bell curve of infections in the spring and an even scarier one in the winter. I’m sure I heard experts explaining that the only way COVID-19 would disappear would be when herd immunity was achieved, either through natural antibodies or vaccination. Official documents reassure me that I am not going mad. The minutes from a Sage meeting in March say: “Sage was unanimous that measures seeking to completely suppress the spread of Covid-19 will cause a second peak.” As far as I can tell, this is still their view. Suppressing a wintry virus during the sunniest spring on record could turn out to be no great achievement. The worst may be yet to come. Is there Really a Second Wave to Justify New Lock Downs? Not Even Close Author: J B Handley Publication date: 07 July 2020 Source: Health Impact News Why did politicians ever lockdown society in the first place? Can we all agree that the stated purpose was to “flatten the curve” so our hospital system could handle the inevitable COVID-19 patients who needed care? At that point, at least, back in early March, people were behaving rationally. They accepted that you can’t eradicate a virus, so let’s postpone things enough to handle it. The fact is, we have done that, and so much more. The headlines are filled with dire warnings of a “second wave” and trigger-happy Governors are rolling back regulations to try to stem the tide of new cases. But, is any of it actually true and should we all be worried? No, it’s not a second wave. The COVID-19 virus is on its final legs, and while I have filled this post with graphs to prove everything I just said, this is really the only graph you need to see, it’s the CDC’s data, over time, of deaths from COVID-19 here in the U.S., and the trend line is unmistakable: |
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Transmission |
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Probability of symptoms and critical disease after SARS-CoV-2 infection Authors: Poletti P et al Publication date: 22 June 2020 Journal: arXiv preprint DOI: arXiv:2006.08471 We quantified the probability of developing symptoms (respiratory or fever ≥37.5 °C) and critical disease (requiring intensive care or resulting in death) of SARS-CoV-2 positive subjects. 5,484 contacts of SARS-CoV-2 index cases detected in Lombardy, Italy were analyzed, and positive subjects were ascertained via nasal swabs and serological assays. 73.9% of all infected individuals aged less than 60 years did not develop symptoms (95% confidence interval: 71.8-75.9%). The risk of symptoms increased with age. 6.6% of infected subjects older than 60 years had critical disease, with males at significantly higher risk. |
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Testing |
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Author: Robert Guaderrama Publication date: 14 July 2020 Source: Fox35Orlando After FOX 35 News noticed errors in the state's report on positivity rates, the Florida Department of Health said that some laboratories have not been reporting negative test result data to the state. Countless labs have reported a 100 percent positivity rate, which means every single person tested was positive. Other labs had very high positivity rates. FOX 35 News found that testing sites like one local Centra Care reported that 83 people were tested and all tested positive. Then, NCF Diagnostics in Alachua reported 88 percent of tests were positive. How could that be? FOX 35 News investigated these astronomical numbers, contacting every local location mentioned in the report. The report showed that Orlando Health had a 98 percent positivity rate. However, when FOX 35 News contacted the hospital, they confirmed errors in the report. Orlando Health's positivity rate is only 9.4 percent, not 98 percent as in the report. |
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Therapeutics |
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Author: Guan Yu Lim Publication date: 08 July 2020 Source: Nutraingredients-asia Researchers at the Chinese University of Hong Kong (CUHK) are conducting three clinical studies to assess the effects of a probiotic formula on COVID-19 patients, people at higher-risk of contracting the virus and the general population. The probiotic formula was derived from a recent study by CUHK which found that COVID-19 patients were lacking a series of good bacteria, instead hosting a range of bad bacteria in their guts. Published in the Gastroenterology journal, researchers said patient had higher levels of Clostridium hathewayi, Bacteroides nordii and Actinomyces viscosus compare to the health population. |
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Immunity |
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If there is a second wave of Covid, the Swedish approach will have been right all along Author: Christopher Snowdon Publication date: 11 July 2020 Source: The Telegraph There have been times during this pandemic that I've felt as if my memory is playing tricks on me. I’m sure I remember scientists telling us that a second wave was inevitable. I could have sworn I saw a graph at the press briefings showing a scary bell curve of infections in the spring and an even scarier one in the winter. I’m sure I heard experts explaining that the only way COVID-19 would disappear would be when herd immunity was achieved, either through natural antibodies or vaccination. Official documents reassure me that I am not going mad. The minutes from a Sage meeting in March say: “Sage was unanimous that measures seeking to completely suppress the spread of Covid-19 will cause a second peak.” As far as I can tell, this is still their view. Suppressing a wintry virus during the sunniest spring on record could turn out to be no great achievement. The worst may be yet to come. 68% Have Antibodies in This Clinic. Can a Neighborhood Beat a Next Wave? Author: Joseph Goldstein Publication date: 09 July 2020 Source: New York Times At a clinic in Corona, a working-class neighborhood in Queens, more than 68 percent of people tested positive for antibodies to the new coronavirus. At another clinic in Jackson Heights, Queens, that number was 56 percent. But at a clinic in Cobble Hill, a mostly white and wealthy neighborhood in Brooklyn, only 13 percent of people tested positive for antibodies. As it has swept through New York, the coronavirus has exposed stark inequalities in nearly every aspect of city life, from who has been most affected to how the health care system cared for those patients. Many lower-income neighborhoods, where Black and Latino residents make up a large part of the population, were hard hit, while many wealthy neighborhoods suffered much less. But now, as the city braces for a possible second wave of the virus, some of those vulnerabilities may flip, with the affluent neighborhoods becoming most at risk of a surge. According to antibody test results from CityMD that were shared with The New York Times, some neighborhoods were so exposed to the virus during the peak of the epidemic in March and April that they might have some protection during a second wave. What are the biggest risks to society in the next 18 months? Author: Iman Ghosh Publication date: 03 July 2020 Source: World Economic Forum As the world continues to grapple with the effects of COVID-19, no part of society seems to be left unscathed. Fears are surmounting around the economy’s health, and dramatic changes in life as we know it are also underway. In today’s graphic, we use data from a World Economic Forum survey of 347 risk analysts on how they rank the likelihood of major risks we face in the aftermath of the pandemic. What are the most likely risks for the world over the next year and a half? The most likely risks In the report, a “risk” is defined as an uncertain event or condition with the potential for significant negative impacts on various countries and industries. The 31 risks have been grouped into five major categories: COVID-19 ‘herd immunity’ without vaccination? Teaching modern vaccine dogma old tricks Author: Andrew Boston Publication date: 25 June 2020 Source: Conservative Review Dr. Anthony Fauci has repeatedly emphasized vaccine development to control COVID-19 (Severe Acute Respiratory Syndrome Coronavirus-2 [SARS-Cov2]). His colleague, National Institutes of Health Director Dr. Francis Collins, subsequently interviewed by the Wall Street Journal, provided this caveat: “It would not be particularly encouraging if we have a vaccine that’s capable of protecting 20-year-olds who probably have a pretty low risk anyway of getting sick, and doesn’t work at all for people over 65.” Oxford University vaccine researcher and Regius Professor of Medicine Sir John Bell recently lamented that as COVID-19 cases rapidly dwindle in the U.K.,“You wouldn’t start (trials) in London now for sure.” Bell added that scientists might have to “chase” the virus around the nation for the vaccine trials to be successful. Vaccine enthusiast Fauci and the more sober Bell each conveniently ignore unsuccessful vaccine experiences with other coronaviruses over the past two decades: (Severe Acute Respiratory Syndrome) SARS-Cov1 and (Middle East Respiratory Syndrome) MERS-Cov. They also seem to have forgotten, amid the COVID-19 hysteria, reassuring, almost 100-year-old basic concepts of naturally acquired community immunization, made clear prior to modern-era mass vaccination campaigns. |
| Vaccines |
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New Docs: NIH Owns Half of Moderna Vaccine Author: Robert Kennedy Jr Publication date: 07 July 2020 Source: Children's Health Defense New documents obtained by Axios and Public Citizen suggest that the National Institute of Health (NIH) owns half the key patent for Moderna’s controversial COVID vaccine and could collect half the royalties. In addition, four NIH scientists have filed their own provisional patent application as co-inventors. Little known NIH regulations let agency scientists collect up to $150,000.00 annually in royalties from vaccines upon which they worked. These rules are recipes for regulatory corruption. NIH’s stake in the jab may explain why Anthony Fauci moved Moderna’s vaccine to the front of the line and to let Moderna skip animal trials despite the experimental technology and the inherent dangers of Coronavirus vaccines. Every prior coronavirus vaccine has proven problematic and can be lethal to animals due to COVID’s unique penchant for “pathogenic priming.” Death occurs only after a vaccinated animal encounters the wild virus. Public health advocates and scientists criticized Fauci’s decision to skip animal trials as reckless. It may also explain why Anthony Fauci arranged a $483 million grant to Moderna from a sister NIH agency, BARDA, despite the fact that Moderna has never brought a product to market or gotten approval. Read more... |
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Social Impacts |
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Another Deadly Cost of COVID-19 Lockdowns: "A Hidden Epidemic" of Drug Overdoses Author: Jon Miltimore Publication date: 13 July 2020 Source: Foundation for Economic Education Bodies are arriving at Anahi Ortiz’s office faster than he can process them. “We’ve literally run out of wheeled carts to put them on,” Ortiz, a coroner in Columbus, Ohio, recently told the Washington Post. The cause of death isn’t the coronavirus, however. It’s drug overdoses. Ortiz says sometimes his office will get as many as nine ODs in a day and a half. The story fits a pattern emerging around the US. Nationwide, the Post reports, public health officials are reporting alarming spikes in drug overdoses—”a hidden epidemic within the coronavirus pandemic.” The numbers are grim. According to the Overdose Detection Mapping Application Program, suspected overdoses in March were up 18 percent from the previous year nationally. In April, that figure ticked up to 29 percent. In May, the increase was 42 percent. In many instances, these overdoses are fatal. In Ortiz’s case, the surge resulted in about 50 percent more deaths than the same period over the previous year. Los Angeles and San Diego Schools to Go Online-Only in the Fall Authors: Shawn Hubler and Dana Goldstein Publication date: 13 July 2020 Source: The New York Times California’s two largest public school districts said on Monday that instruction would be online-only in the fall, in the latest sign that school administrators are increasingly unwilling to risk crowding students back into classrooms until the coronavirus is fully under control. The school districts in Los Angeles and San Diego, which together enroll some 825,000 students, are the largest in the country to abandon plans for even a partial physical return to classrooms when they reopen in August. The decision came as Gov. Gavin Newsom announced some of the most sweeping rollbacks yet of California’s plans to reopen. Indoor operations for restaurants, bars, wineries, movie theaters and zoos were shut down statewide on Monday, and churches, gyms, hair salons, malls and other businesses were shuttered for four-fifths of the population. Back to School? “No Thanks” Say Millions of New Homeschooling Parents Author: Kerry McDonald Publication date: 08 July 2020 Source: Forum for Economic Education Next month marks the beginning of the 2020/2021 academic year in several US states, and pressure is mounting to reopen schools even as the COVID-19 pandemic persists. Florida, for example, is now considered the nation’s No. 1 hot spot for the virus; yet on Monday, the state’s education commissioner issued an executive order mandating that all Florida schools open in August with in-person learning and their full suite of student services. Many parents are balking at back-to-school, choosing instead to homeschool their children this fall. Gratefully, this virus seems to be sparing most children, and prominent medical organizations such as the American Academy of Pediatrics have urged schools to reopen this fall with in-person learning. For some parents, fear of the virus itself is a primary consideration in delaying a child’s return to school, especially if the child has direct contact with individuals who are most vulnerable to COVID-19’s worst effects. School openings across globe suggest ways to keep coronavirus at bay, despite outbreaks Authors: Jennifer Couzin-Frankel, Gretchen Vogel and Meagan Weiland Publication date: 07 July 2020 Source: Science Early this spring, school gates around the world slammed shut. By early April, an astonishing 1.5 billion young people were staying home as part of broader shutdowns to protect people from the novel coronavirus. The drastic measures worked in many places, dramatically slowing the spread of SARS-CoV-2, the virus that causes COVID-19. However, as weeks turned into months, pediatricians and educators began to voice concern that school closures were doing more harm than good, especially as evidence mounted that children rarely develop severe symptoms from COVID-19. (An inflammatory condition first recognized in April, which seems to follow infection in some children, appears uncommon and generally treatable, although scientists continue to study the virus’ effect on youngsters.) |
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