17 June, 2021

VAERS data reveals no increased risk of neuroautoimmune adverse events from COVID-19 vaccines -

Neuroautoimmune disorders, such as multiple sclerosis and Guillain-Barre syndrome, have been documented in relation to various vaccines in the past. This paper uses passive reporting information from the CDC/FDA9s VAERS system to analyse whether neuroautoimmune presentations are reported at a relatively higher or lower rate, vis-a-vis other adverse effects, for COVID-19 vaccines than for other vaccines. Through computing the reporting odds ratios for a range of symptoms and comparator vaccines, a clear indication in favour of the safety of COVID-19 vaccines emerges, with reports of neuroautoimmune adverse events in relation to other adverse events being over 70% less likely for COVID-19 than for comparator vaccines (ROR: 0.292, p < 0.0001). In comparison with other vaccines given as part of routine care in adulthood, COVID-19 vaccines have the lowest reporting odds ratio of neuroautoimmune adverse effects (median ROR: 0.246).

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Similar Rates of AKI during the First Two Waves of COVID-19 in Northern Italy: a single-center study -

Introduction: Two waves of COVID-19 cases have overwhelmed most European countries during 2020. It is unclear if the incidence of acute kidney injury (AKI) has changed during the COVID-19 outbreaks. This study aims to evaluate the differences in incidence, risk factors and outcome of AKI in patients with SARS-CoV-2 infection during the first and second wave of COVID-19. Method: We reviewed the health medical records of 792 consecutive patients with COVID-19 hospitalized at the University Hospital of Modena, Italy, from February 25 to December 14, 2020. Results: AKI was diagnosed in 122 (15.4%) patients. Incidence of AKI remained steady rate during wave-1 (15.9%) and wave-2 (14.7%) (P=0.89). AKI patients were older (P=<0.001) and had a more severe respiratory impairment (PO2/FO2) (P=≤0.001) than their non-AKI counterparts. AKI led to a longer hospital stay (P=0.001), complicated with a higher rate of ICU admission. COVID-19-related AKI was associate with 59.7% of deaths during wave-1 and 70.6% during wave-2. At the end of the period of observation, 24% (wave-1) and 46.7% (wave-2) of survivors were discharged with a not fully recovered kidney function. Risk factors for AKI in patients with COVID-19 were diuretics (HR=5.3; 95%CI, 1.2-23.3; P=0.025) and cardiovascular disease (HR, 2.23; 95%CI, 1.05-5.1; P=0.036). Conclusion: The incidence of AKI (about 15%) remained unchanged during 2020, regardless of the trend of COVID-19. AKI occurred in patients with severe COVID-19 symptoms and was associated with a higher incidence of deaths than non-AKI patients. The risk factors of COVID-19-related AKI were diuretic therapy and cardiovascular disease.

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Understanding microvascular thrombosis in COVID-19 via massive single-cell imaging of circulating platelets -

A characteristic clinical feature of COVID-19 is the frequent incidence of microvascular thrombosis. In fact, COVID-19 autopsy reports have shown widespread thrombotic microangiopathy characterized by extensive diffuse microthrombi within peripheral capillaries and arterioles in lungs, hearts, and other organs, resulting in multiorgan failure. However, the underlying process of COVID-19-associated microvascular thrombosis remains elusive due to the lack of tools to statistically examine platelet aggregation (i.e., the initiation of microthrombus formation) in detail. Here we present a method for massive image-based profiling, temporal monitoring, and big data analysis of circulating platelets and platelet aggregates in the blood of COVID-19 patients at single-cell resolution, to provide previously unattainable insights into the disease. In fact, our analysis of the image data from 110 hospitalized patients shows the anomalous presence of excessive platelet aggregates in nearly 90% of all COVID-19 patients. Furthermore, results indicate strong links between the concentration of platelet aggregates and the severity, mortality, and respiratory condition of patients with COVID-19. Finally, high-dimensional analysis based on deep learning shows that the disease behaves as systemic thrombosis.

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Effect of control measures on the pattern of COVID-19 Epidemics in Japan -

Background. COVID-19 has spread worldwide since its emergence in 2019. In contrast to many other countries with epidemics, Japan differed in that it avoided lockdowns and instead asked people for self-control. A travel campaign was conducted with a sizable budget, but the number of PCR tests was severely limited. These choices may have influenced the course of the epidemic. Methods. The increase or decrease in the classes of SARS-CoV-2 variants was estimated by analyzing the published sequences with an objective multivariate analysis. This approach observes the samples in multiple directions, digesting complex differences into simpler forms. The results were compared over time with the number of confirmed cases, PCR tests, and overseas visitors. The kinetics of infection were analyzed using the logarithmic growth rate. Results. The declared states of emergency failed to alter the movement of the growth rate. Three epidemic peaks were caused by domestically mutated variants. In other countries, there are few cases in which multiple variants have peaked. However, due to the relaxation of immigration restrictions, several infective variants have been imported from abroad and are currently competing for expansion, creating the fourth peak. By April 2021, these foreign variants exceeded 80%. The chaotic situation in Japan will continue for some time, in part because no effort has been made to identify asymptomatic carriers, and details of the vaccination program are undecided.

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Maintaining trust in a pandemic: Blood collection agency messaging to donors and the public during the early days of COVID-19 -

COVID-19 has posed unprecedented challenges to health systems around the world, including blood collection agencies (BCAs). Many countries, such as Canada and Australia, that rely on non-remunerated voluntary donors, saw an initial drop in donors in the early days of the pandemic followed by a return to sufficient levels of the blood supply. BCA messaging plays a key role in communicating the needs of the blood operator, promoting and encouraging donation, educating, and connecting with the public and donors. This paper reports on discourse analysis (Bloor and Bloor, 2013) of BCA messaging in Canada and Australia from March 1-July 31, 2020 to understand how BCAs constructed donation to encourage donation during this period and what this can tell us about public trust and blood operators. Drawing on multiple sources of online content and print media, our analysis identified four dominant messages during the study period: 1) blood donation is safe; 2) blood donation is designated an essential activity; 3) blood is needed; and 4) blood donation is a response to the pandemic. In Canada and Australia, our analysis suggests that: 1) implicit within constructions of blood donation as safe is the message that BCAs can be trusted; 2) messages that construct blood donation as essential and needed implicitly ask donors to trust BCAs in order to share in the commitment of meeting patient needs; and 3) the pandemic has made possible the construction of blood donation as both an exceptional and commonplace activity. For BCAs, our analysis supports donor communications that are transparent and responsive to public concerns, and the local context, to support public trust. Beyond BCAs, health organizations and leaders cannot underestimate the importance of building and maintaining public trust as countries continue to struggle with containment of the virus and encourage vaccine uptake.

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Ceylon cinnamon and its major compound Cinnamaldehyde can limit overshooting inflammatory signaling and angiogenesis in vitro: implications for COVID-19 treatment -

Overshooting immune reactions can occur during inflammatory responses that accompany severe infections, such as COVID-19. Cytokines, damage-associated molecular patterns (DAMPs), and reactive oxygen and nitrogen species can generate positive feedback loops of inflammation, leading to long-term complications such as vascular endothelialitis, thrombosis, endothelial dysfunction, neurological impairments, and chronic fatigue. Dexamethasone can limit inflammation by inhibiting the activation of pro-inflammatory transcription factors. High dose dexamethasone, however, has undesirable side effects. Here, we show that Ceylon cinnamon and its major compound cinnamaldehyde can mitigate inflammatory signaling in vitro. Cinnamaldehyde interferes with the dimerization of toll-like receptor 4 (TLR4), which can be activated by DAMPs like HSP60 and HMGB1. Our results suggest that supplementary treatment with Ceylon cinnamon may allow administration of lower doses of dexamethasone to avoid high dose steroid side effects. Moreover, preliminary results indicate that Ceylon cinnamon modulates angiogenesis, which is a reactive phenomenon in COVID-19.

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A new combination testing methodology to identify accurate and economical point-of-care testing strategies -

Background: Quick, cheap and accurate point-of-care testing is urgently needed to enable frequent, large-scale testing to contain COVID-19. Lateral flow tests for antigen and antibody detection are an obvious candidate for use in community-wide testing, because they are quick and cheap relative to lab-processed tests. However, their low accuracy has limited their adoption. We develop a new methodology to increase the diagnostic accuracy of a combination of cheap, quick and inaccurate index tests with correlated or discordant outcomes, and illustrate its performance on commercially available lateral flow immunoassays (LFIAs) for Sars-CoV-2 antibody detection. Methods and Findings: We analyze laboratory test outcomes of 300 serum samples from health care workers detected with PCR-confirmed SARS-Cov-2 infection at least 21 days prior to sample collection, and 500 pre-pandemic serum samples, from a national seroprevalence survey, tested using eight LFIAs (Abbott, Biosure/Mologic, Orientgene-Menarini, Fortress, Biopanda I, Biopanda II, SureScreen and Wondfo) and Hybrid DABA as reference test. For each of 14 two-test combinations (e.g., Abbott, Fortress) and 16 three-test combinations (e.g., Abbott, Fortress, Biosure/Mologic) used on at least 100 positive and 100 negative samples, we classify an outcome sequence – e.g., (+,-) for (Abbott, Fortress) – as positive if its combination positive predictive value (CPPV) exceeds a given threshold, set between 0 and 1. Our main outcome measures are the sensitivity and specificity of different classification rules for classifying the outcomes of a combination test. We define testing possibility frontiers which represent sensitivity and false positive rates for different thresholds. The envelope of frontiers further enables test selection. The eight index tests individually meet neither the UK Medicines and Healthcare Products Regulatory Agency9s 98% sensitivity and 98% specificity criterion, nor the US Center for Disease Control9s 99.5% specificity criterion. Among these eight tests, the highest single-test LFIA specificity is 99.4% (with a sensitivity of 65.2%) and the highest single-test LFIA sensitivity is 93.4% (with a specificity of 97.4%). Using our methodology, a two-test combination meets the UK Medicines and Healthcare Products Regulatory Agency9s criterion, achieving sensitivity of 98.4% and specificity of 98.0%. While two-test combinations meeting the US Center for Disease Control9s 99.5% specificity criterion have sensitivity below 83.6%, a three-test combination delivers a specificity of 99.6% and a sensitivity of 95.8%. Conclusions: Current CDC guidelines suggest combining tests, noting that 9performance of orthogonal testing algorithms has not been systematically evaluated9 and highlighting discordant outcomes. Our methodology combines available LFIAs to meet desired accuracy criteria, by identifying testing possibility frontiers which encompass benchmarks, enabling cost savings. Our methodology applies equally to antigen testing and can greatly expand testing capacity through combining less accurate tests, especially for use cases needing quick, accurate tests, e.g., entry to public spaces such as airports, nursing homes or hospitals.

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Nafamostat-interferon-alpha combination suppresses SARS-CoV-2 infection in vitro and in vivo -

SARS-CoV-2 and its vaccine/immune-escaping variants continue to pose a serious threat to public health due to a paucity of effective, rapidly deployable, and widely available treatments. Here we address these challenges by combining Pegasys (IFNa) and nafamostat to effectively suppress SARS-CoV-2 infection in cell culture and hamsters. Our results indicate that Serpin E1 is an important mediator of the antiviral activity of IFNa and that both Serpin E1 and camostat can target the same cellular factor TMPRSS2, which plays a critical role in viral replication. The low doses of the drugs in combination may have several clinical advantages, including fewer adverse events and improved patient outcome. Thus, our study may provide a proactive solution for the ongoing pandemic and potential future coronavirus outbreaks, which is still urgently required in many parts of the world.

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A SARS-CoV-2 spike ferritin nanoparticle vaccine protects against heterologous challenge with B.1.1.7 and B.1.351 virus variants in Syrian golden hamsters -

The emergence of SARS-CoV-2 variants of concern (VOC) requires adequate coverage of vaccine protection. We evaluated whether a spike ferritin nanoparticle vaccine (SpFN), adjuvanted with the Army Liposomal Formulation QS21 (ALFQ), conferred protection against the B.1.1.7 and B.1.351 VOCs in Syrian golden hamsters. SpFN-ALFQ was administered as either single or double-vaccination (0 and 4 week) regimens, using a high (10 g) or low (0.2 g) immunogen dose. Animals were intranasally challenged at week 11. Binding antibody responses were comparable between high- and low-dose groups. Neutralizing antibody titers were equivalent against WA1, B.1.1.7, and B.1.351 variants following two high dose two vaccinations. SpFN-ALFQ vaccination protected against SARS-CoV-2-induced disease and viral replication following intranasal B.1.1.7 or B.1.351 challenge, as evidenced by reduced weight loss, lung pathology, and lung and nasal turbinate viral burden. These data support the development of SpFN-ALFQ as a broadly protective, next-generation SARS-CoV-2 vaccine.

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SARS-CoV-2 Viral Replication in a High Throughput Human Primary Epithelial Airway Organ Model -

COVID-19 emerged as a worldwide pandemic early in 2020, and at this writing has caused over 170 million cases and 3.7 million deaths worldwide, and almost 600,000 deaths in the United States. The rapid development of several safe and highly efficacious vaccines stands as one of the most extraordinary achievements in modern medicine, but the identification and administration of efficacious therapeutics to treat patients suffering from COVID-19 has been far less successful. A major factor limiting progress in the development of effective treatments has been a lack of suitable preclinical models for the disease, currently reliant upon various animal models and in vitro culture of immortalized cell lines. Here we report the first successful demonstration of SARS-CoV-2 infection and viral replication in a human primary cell-based organ-on-chip, leveraging a recently developed tissue culture platform known as PREDICT96. This successful demonstration of SARS-CoV-2 infection in human primary airway epithelial cells derived from a living donor represents a powerful new pathway for disease modeling and an avenue for screening therapeutic candidates in a high throughput platform.

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INCIDENCE OF THROMBOTIC EVENTS IN A COMMERCIALLY-INSURED US POPULATION -

Objective: To estimate the US incidence of thrombotic events and related rare diagnoses. Design: Claims-based retrospective cohort study of incidence. Setting: US commercial health insurance administrative claims database. Participants: Adults 25-65 years of age between 2015 and 2019 with a minimum of 12 consecutive thrombosis-free months of continuous enrollment beginning 2014 were selected. Main Outcomes: Age (10 year intervals) and sex stratum specific incidence rates per 100,000 person-years were determined for: venous thromboembolism (VTE), cerebral venous thrombosis (CVT), and any major thrombosis. Incidence also was estimated for immune thrombocytopenic purpura (ITP), hemolytic-uremic syndrome (HUS), and heparin-induced thrombocytopenia (HIT). Results: Among approximately 15 million enrollees per year (half female/male), incidence of any thrombotic event (DVT, PE, CVT, or other thrombosis) was 247.89 per 100,000 person-years (95% CI: 245.96, 249.84). Incidence of VTE was 213.79 with ICD codes alone (95% CI: 211.99, 215.59) and 127.18 (95% CI: 125.80, 128.58) when also requiring a filled anticoagulation prescription. Incidence rates were 6.37 for CVT (95% CI: 6.07, 6.69), 26.06 for ITP (95% CI: 25.44, 26.78), 0.94 for HUS (95% CI: 0.82, 1.06), and 4.82 for HIT (95% CI: 4.56, 5.10). The co-occurrence of CVT with either ITP or HIT (diagnoses within 14 days of one another) was 0.090 (95% CI: 0.06, 0.13). Incidence tended to increase with age and was higher for women under 55. Incidence for CVT, HUS, and CVT with ITP or HIT was higher for women in all age groups. Conclusions: These results are the first US estimates for incidence of thrombotic and rare events in a large, commercially-insured US population. Findings provide a critically important reference for determining excess morbidity associated with COVID-19 and more generally for vaccine pharmacovigilance.

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Evaluation of saliva molecular point of care for detection of SARS-CoV-2 in ambulatory care -

Background: The rapid identification of SARS-CoV-2 infected individuals is a cornerstone in strategies for the control of virus spread. The sensitivity of SARS-CoV-2 RNA detection by RT-PCR is similar in saliva and nasopharyngeal swab. Rapid molecular point-of-care tests in saliva could facilitate, broaden and speed up the diagnosis. Objectives and methods: We conducted a prospective study in two community COVID-19 screening centers to evaluate the performances of a CE-marked RT-LAMP assay (EasyCoV) specifically designed for the detection of SARS-CoV-2 RNA from fresh saliva samples, compared to nasopharyngeal RT-PCR as reference test, saliva RT-PCR and nasopharyngeal antigen testing. Results: Overall, 117 of the 1718 participants (7%) were tested positive with nasopharyngeal RT-PCR. Sensitivities of saliva RT-PCR and nasopharyngeal antigen test were 93% (95% Confidence Interval (95%CI): 86-97) and 85% (95%CI: 77-91), respectively. The sensitivity and specificity of the RT-LAMP assay in saliva were 34% (95%CI: 26-44) and 97% (95%CI: 96-98). The performance was similar in symptomatic and asymptomatic participants and whatever the reference standard considered. Ct values of nasopharyngeal RT-PCR were significantly lower in the 40 true positive subjects with saliva RT-LAMP (Ct 25.9) than in the 48 false negative subjects with saliva RT-LAMP (Ct 28.4) (p=0.028). Conclusion: In the ambulatory setting, the detection of SARS-CoV-2 from crude saliva samples with the RT-LAMP assay had a lower sensitivity than nasopharyngeal RT-PCR, saliva RT-PCR and nasopharyngeal antigen testing.

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The Spectre of SARS-CoV-2 in the Ambient Urban Natural Water in Ahmedabad and Guwahati: A Tale of Two Cities -

COVID-19 positive patients can egest live SARS-CoV-2 virus through fecal matter and urine, raising concerns about viral transmission through the fecal-oral route and/or contaminated aerosolized water. These worries are heightened in many low and middle-income nations, where raw sewage is often dumped into surface waterways and open defecation betide. In this manuscript we attempt to discern the presence of SARS-CoV-2 genetic material (ORF-1ab, N and S genes) in two urban cities of India viz., Ahmedabad, in western India with ~12 WWTPs and Guwahati, in the northeast of the country with no such plants. 100% and 20% of the surface water samples had detectable SARSCoV-2 RNA load in Ahmedabad and Gandhinagar, respectively. N-gene>S-gene>ORF-1ab-gene were readily detected in the surface water of Ahmedabad, whereas, no such significant trend was found in the case of Guwahati. The high concentration of gene (ORF-1ab 800 copies/L for Sabarmati river, Ahmedabad and S-gene 565 copies/L for Bharalu urban river, Guwahati) found in natural waters indicates low sanitation and have various health and ecological consequences that should be investigated further.

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Solidarities, Fairness, and Economic Governance in Advanced Capitalism: The Cases of COVID-19 Responses in Germany and the United States -

This paper addresses the theoretical question of how competing models of social and economic solidarity shape patterns of economic governance in periods of economic crisis. Using the COVID-19 pandemic as a signal case, we seek to understand how changes in public opinion in response to similar social and economic shocks are informed by deeper ideational structures among citizens relating to their capacity for empathy, mutual support, and willingness to support and trust public policy interventions. Drawing on scholarly literatures related to moral economies and the social embeddedness of economic relationships, we undertake an empirical study of how the COVID-19 pandemic has shaped patterns of support for social and economic policies. We focus on Germany and the United States, countries with widely divergent modes of integration of capitalist markets and, therefore, potentially different levels of support for particular kinds of policy responses. We trace American and German policy responses since March 2020 across a number of domains, complemented by a systematic analysis of public opinion in the two countries, drawing from fifteen different sources of public-opinion data, in order to assess the pandemic’s effects on public support for individualized and collectively-oriented policy responses.

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COVID-19 prevention and control measures in workplace settings: a rapid review and meta-analysis -

Workplaces are high-risk environments for SARS-CoV-2 outbreaks and subsequent community transmission. Identifying, understanding, and implementing effective workplace SARS-CoV-2 infection prevention and control (IPC) measures is critical to protect workers, their families, and communities. A rapid review and meta-analysis were conducted to synthesize evidence assessing the effectiveness of COVID-19 IPC measures implemented in global workplace settings through April 2021. Medline, Embase, PubMed, and Cochrane Library were searched for studies that quantitatively assessed the effectiveness of workplace COVID-19 IPC measures. Included studies comprised varying empirical designs and occupational settings. Measures of interest included surveillance measures, outbreak investigations, personal protective equipment (PPE), changes in work arrangements, and worker education. Sixty-three studies from international healthcare, nursing home, meatpacking, manufacturing, and office settings were included, accounting for ~280,000 employees. Meta-analyses showed that combined measures (0.2% positivity; 95%CI 0-0.4%) were associated with lower post-intervention employee COVID-19 positivity estimates than single measures like asymptomatic PCR testing (1.7%; 95%CI 0.9-2.9%) and universal masking (24%; 95%CI 3.4-55.5%). Modelling studies showed that combinations of (i) timely and widespread contact tracing and case isolation, (ii) facilitating smaller worker cohorts, and (iii) effective use of PPE can reduce workplace transmission. Comprehensive COVID-19 IPC measures incorporating swift contact tracing and case isolation, PPE, and facility zoning, can effectively prevent workplace outbreaks. Masking alone should not be considered as sufficient protection from SARS-CoV-2 outbreaks in workplace environments at high risk of virus transmission.

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Covid-19 Sentry

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