Highlights From COVID-19 Research Published in September 2020
DeepTech: Where Engineering Meets Deep Science
The Synergetic Convergence of AI, Data Science, & Advanced Biomedicine
Since January 2020 I’ve shared hundreds of daily summaries of COVID-19 research. This article includes highlights from my daily sumaries of COVID-19 research published in September 2020.
This is an article by Dr. Gabriel Leung, Dean of Medicine at Hong Kong University Medical Center, and Dr. Malik Peiris, Professor at the University of Hong Kong. They write that: 1) COVID vaccines are needed, even if they have minimal impact on transmission 2) COVID vaccines may not help us achieve herd immunity 3) COVID vaccine trials primarily assess prevention of virologically confirmed disease — not infection or transmission 4) an “effective” vaccine confers protection from disease but might not reduce spread 5) if COVID vaccines are effective in reducing morbidity and mortality in high-risk groups, they would have an important role, irrespective of impact on transmission and population immunity 6) if high-risk populations can be shielded by vaccination, COVID control measures could be recalibrated 7) the idea that COVID vaccine-induced population immunity will allow a return to normalcy may be based on false assumptions 8) no country will be truly safe until the entire world is vaccinated.
This new study from Dr. Akiko Iwasaki, PhD and colleagues at Yale University offers the first clear evidence that COVID can invade brain cells 1) 40–60% of hospitalized COVID patients experience neurological complications including nerve damage and stroke 2) this study suggests that COVID in the brain may be more lethal than the respiratory infection caused by COVID 3) COVID hijacks brain cells to make copies of itself then exploits the brain cells’ machinery to multiply 4) then COVID chokes off oxygen to adjacent brain cells causing them to die 5) a few days into the infection there is a dramatic decrease the number of synapses (the connections between neurons in the brain) 6) the researchers didn’t find any evidence of an immune response to remedy this problem. It’s a silent infection with evasion mechanisms 7) some people may be susceptible because of their genetic background or high viral load.
Researchers used Summit Supercomputer to analyze 2.5 billion genetic combinations from COVID; then they made the Bradykinin Hypothesis 1) it took Summit 1 week to run the numbers. this would take workstation clusters many months 2) COVID causes levels of ACE in lung cells to decrease while the levels of ACE2 increases 3) this increases the level of bradykinin molecules in the cells 4) as the production of hyaluronic acid increases, the enzymes that could degrade it decreases 5) hyaluronic acid absorbs >1,000 times its weight in water and forms a gel 6) leakage of fluid into the lungs combined with excess hyaluronic acid results in a Jello-like substance in the lungs 7) this prevents oxygen uptake and carbon dioxide is released in the lungs 8) bradykinin storm affects major organs that are regulated by angiotensin derivatives 9) COVID tricks the body into upregulating ACE2 receptors in places where they’re usually expressed at low levels 10) this includes kidney, heart, brain, muscles, lungs 11) suggests 10 FDA approved drugs as potential treatments including vitamin D, icatibant, berinert, cinryze, haegarda, hymecromone, timbetasin, ecallantide, danazol, stanasolol.
These high-powered microscopic images show very high viral loads of SARS-CoV-2 on human respiratory surfaces ready to spread the virus 1) Camille Ehre PhD and colleagues at UNC Chapel Hill School of Medicine generated these microscopic images of SARS-CoV-2. 2) in a biosafety level 3 facility, researchers inoculated the SARS-Co-V-2 virus into human bronchial epithelial cells 3) the cells were examined 96 hours later using scanning electron microscopy 4) the images show infected ciliated cells with strands of mucus (yellow) attached to cilia tips (blue) 5) higher power magnification shows the structure and high density of SARS-CoV-2 virions (red) produced by human airway epithelia 6) virions are the complete infectious form of the virus released onto respiratory surfaces by infected host cells 7) the high viral burden is a source for spread of infection to multiple organs of an infected individual and likely mediates the high frequency of COVID transmission between humans.
Viral genetic sequencing demonstrates that intensive testing and contact tracing could have prevented SARS-CoV-2 from becoming established in the US and Europe 1) scientists used viral genetic sequencing to trace the introduction of SARS-CoV-2 into the US and Europe 2) they examined the evolutionary history and relationships among people who were infected with the virus 3) they found that the entire global population of SARS-CoV-2 viruses through March 2020 differed by only 0–12 nucleotide substitutions from the inferred ancestor of the whole pandemic 4) the results suggest that rapid early interventions successfully prevented early introductions of the virus into Germany and the US from taking hold 5) later introductions of the virus from China to Italy and to Washington State founded the US and European transmission networks 6) dashed arrows show early dead-end introductions of SARS-CoV-2 to US & Europe that died out 7) solid arrows show successful dispersals of SARS-CoV-2 between late January and February that led to sustained transmission of the virus throughout the US & Europe, from China to Northern Italy, from China to Washington State, from Europe to New York City.
These are 6 key questions about COVID reinfection and long-term immunity 1) how common is reinfection? 2) who is susceptible to reinfection? 3) are reinfections more or less severe than the first? 4) what implications do reinfections have for vaccine prospects? Corollary questions that should be considered: 5) does prior infection or vaccination lead to more serious disease upon reinfection? This is known as immune enhancement or antibody dependent enhancement 6) do second infections or infections after vaccination not prevent infection, but rather cause a mild or asymptomatic infection, creating carriers who think they are immune but actually spread the virus to others?
- BERG is clinical stage biotech company that uses AI to research diseases and develop innovative treatments 2) today Berg announced the results of a COVID-19 study 3) the study was a collaboration with scientists from University of Oxford and Virginia Commonwealth University 3) the objective was to describe a biological framework associating ethnic prevalence of ACE deletion polymorphism to COVID-19 comorbidities 4) the study identified a genetic factor that might account in part for the prevalence of COVID in African Americans 5) highlights the increased frequency of an ACE deletion polymorphism in the African American population 6) this genetic aberration has a known association with risk of greater susceptibility to lung and kidney dysfunction 7) ACE DD polymorphism is also associated with hypertension, acute respiratory distress and diabetic nephropathy, all considered high risk for severe COVID 8) the study provides strong rationale for use use of existing ACE inhibitors and ARBs to manage serious clinical symptoms
- severe COVID even in young healthy people can cause potentially fatal cardiac damage 2) SARS-CoV-2 can damage the heart directly and indirectly 3) there’s a diverse spectrum of cardiovascular manifestations of COVID 4) severe COVID can cause inflammation of the heart 5) increased out-of-hospital cardiac arrest and sudden death in multiple geographic regions of high COVID spread 6) during the COVID outbreak in Italy in early 2020, there was a 77% increase in cardiac arrest in Lombardy compared with the prior year 7) cardiac involvement in athletes has elevated concerns. this demographic group — young and healthy — are the most common to lack symptoms after SARS-CoV-2 infections, which raises the question of how many athletes have occult cardiac disease 8) systematic assessment of athletes who test positive for SARS-CoV-2, irrespective of symptoms, with suitable controls through some form of cardiac imaging and arrhythmia screening seems prudent until more is understood 9) the most intriguing question is why do certain individuals have a propensity for heart involvement after SARS-CoV-2 infection?
1) CDC investigation of a cluster of cases among passengers on a 10-hour flight from London to Hanoi on March 2, 2020 2) the index case was a 27 year old woman from Vietnam returning from a trip to London, Paris, and Milan. She was symptomatic during the flight with a sore throat and cough and was seated in business class. She boarded the flight with symptoms and did not declare them before or after the flight 3) after the flight, 15 passengers on the flight were confirmed to be COVID positive via PCR testing 4) 75% of the passengers who tested positive were seated in business class with the index case (attack rate 62%) 5) seating proximity was strongly associated with increased infection risk (marked red & orange in the graphic) 6) the most likely route of transmission during the flight was aerosol or droplet transmission from the index case 7) contact with the index case might also have occurred in the pre-departure lounge area or during boarding, or after arrival during immigration or at baggage claim 8) the investigation concluded that airline flights have the potential to cause COVID clusters of substantial size.
There is growing evidence that superspreader events might be a typical feature of COVID-19. This study in Hong Kong assessed the superspreading potential of SARS-CoV-2 1) used contact tracing data from 1,038 COVID cases 2) researchers identified and characterized all local clusters of infection 3) identified 4–7 superspreader events across 51 clusters 4) est. that 19% of cases seeded 80% of all local transmission 5) observed transmission within family households most frequently (54.4%) 6) followed by social (33.1%) 7) followed by work (11.8%) 8) social settings were associated with younger cases 9) social venues such as bars, weddings, religious sites and restaurants appear at increased risk for large outbreaks and likely constitute the core behavioral risk factor for SSEs
- more than 300 vaccine candidates 2) 40 are being tested on humans 3) 9 are in phase 3 trials UK: AstraZeneca/Oxford US: Pfizer, BioNTech, Moderna, J&J China: Sinovac, CanSino, Sinopharm, Russia: Gamaleya Research Institute 4) UK has the largest and most diversified vaccine portfolio, per capita 5) UK has purchased 5 doses/citizen spread across 6 leading candidates 6) UK is followed closely by the US, Canada, Japan 7) scientists forecasts for when the first vaccine could present positive phase 3 trial results range from October 2020 mid-2021.
This is an assessment in Nature of the new $5 rapid antigen tests for COVID-19 that give results in minutes 1) in August the FDA granted EUA to a new credit-card-sized testing device for COVID that costs $5, gives results in 15 minutes and doesn’t require a lab or machine for processing 2) the US is spending $760 million on 150 million of these tests from Abbott which plans to ramp up production to 50 million/month in October 3) the tests detect antigens on the surface of the virus, and can identify people who are at the peak of infection, when virus levels in the body are likely to be high 4) antigen tests could help us contain the virus because they can be rolled out in huge numbers and can identify the people who are at greatest risk of spreading COVID 5) antigen tests are a key element in the testing strategies in some countries including India and Italy 6) antigen assays are much faster and cheaper than PCR tests which are the gold-standard tests that detect viral RNA 7) high-sensitivity PCR tests are almost 100% accurate in spotting infected people but require trained personnel and expensive machines that take hours to provide results.
Dr. Craig Spencer, Director of Global Health in Emergency Medicine at NewYork-Presbyterian Hospital Columbia University Irving Medical Center has treated 100s of COVID patients in NYC. He says that if people understood the effects of COVID they would rethink herd immunity 1) Kidney- 46% of patients admitted to a NY hospital with COVID had acute kidney injury, 19% required urgent dialysis. the next epidemic will be chronic kidney disease in the US among recovered COVID patients 2) Heart long-term cardiac problems, including inflammation of the heart muscle and disease of the heart muscle that prevents the heart from pumping effectively 3)Brain headaches, long-term disability from stroke, encephalitis, cranial neuropathies, myasthenia gravis, altered motor function.
Drug Treatments for COVID: a systematic review and network meta-analysis of 35 randomized controlled trials 1) despite huge efforts to identify effective drug interventions for COVID, evidence for effective treatment remains limited 2) this study analyzed 35 randomized controlled trials that evaluated these drug treatments for COVID favipiravir, glucocorticoids, hydroxychloroquine, hydroxychloroquine plus azithromycin, lopinavir-ritonavir, remdesivir, umifenovir 3) the objective was to compare the effects of these treatments for COVID 4) 35 trials / 16,588 participants 5) the certainty of the evidence for most interventions tested is very low 6) this data will be updated regularly as more trials are published. The current analysis suggests that: — glucocorticoids probably reduce mortality and mechanical ventilation, and duration of hospitalization (results driven almost entirely by the RECOVERY trial) — remdesivir reduces both time to symptom resolution and duration of mechanical ventilation, but it remains uncertain whether remdesivir has any effect on mortality — hydroxychloroquine may not reduce the risk of death, mechanical ventilation, or duration of hospitalization.
Evidence is emerging that COVID can cause heart damage even in people who’ve had mild symptoms or none at all especially if those people exercise while they’re infected 1) data from China and the US suggest that up to 30% of patients hospitalized with COVID show signs of cardiac injury 2) Big Ten and Pac-12 colleges postponed the 2020 fall sports season over concerns about myocarditis 3) with myocarditis the muscular walls of the heart become inflamed making it more difficult for the heart to pump blood 4) if people rest during recovery, most of the time inflammation recedes and the heart heals 5) strenuous activity while the heart is weakened can cause swelling in the legs, dizziness, shortness of breath, irregular heartbeat, cardiac arrest, and sudden death 6) extreme outcomes are seen most often in competitive athletes. that’s why cardiologists have been urging caution about sports during the pandemic 7) amateur athletes such as marathoners and triathletes might not be aware of the risks of training post COVID 8) it’s estimated that over 50 million people in the US have been infected with COVID. if only 1% of those people have a heart issue that’s 500,000 people.
This comprehensive T-cell mapping study is an important first step to identify the targets of SARS-CoV-2-specific T cells so that subsequent targeted studies can be carried out. 1) the data provided in this study and other recent T cell studies support the use of vaccine modalities designed to induce both cellular and humoral immunity 2) the resolution phase of COVID-19 (blue box), showing a broadly targeted CD4+and CD8+ T cell response 3) cell colors and numbers represent relative frequencies of indicated protein specificities 4) the total T cell response (solid blue line) is stronger and broader in severe cases (assumed to have had higher viral burden, red curve) 5) correlating with stronger antibody responses (solid gray line) 6) however, there are, proportionally, more CD8+ T cells in mild disease 7) central questions arising from this study (listed in red) 8) concern the unknown hierarchy and kinetics of T cells (dashed blue lines) 9) and antibodies (dashed grey lines) in the acute and memory phases
A wedding in Maine led to a COVID outbreak that infected more than 270 people and killed 8 people. None of the people who died attended the wedding 1) the wedding ceremony took place at the Tri-Town Baptist Church and the wedding reception took place at the Big Moose Inn on August 7th 2) only 65 close family members attended 3) the wedding party and their guests did not wear masks and ignored signs to observe social distancing guidelines 4) tables in the Inn’s restaurant were not spaced 6 feet apart and the employees did not wear masks 5) after the wedding 24 of the 65 people who attended the wedding tested positive for COVID 6) contact tracing identified more than 175 COVID cases linked to the wedding 7) 8 people who did not attend the wedding died of COVID traced back to the wedding 8) the pastor who officiated the wedding has criticized COVID restrictions. 10 COVID cases have been traced to his church 9) exposure among non-attendees multiplied exponentially and many people who had no connection to the wedding became sick with COVID10) only 10–20% of infected people are responsible for 80% of the spread of COVID 11) superspreader events like weddings, funerals, and parties have been largely responsible for the spread of COVID.
- CanSino Biologics is in talks with several countries to get emergency approval to use their experimental COVID vaccine before the completion of large-scale safety and effectiveness trials 2) Early distribution would give CanSino a head start over rivals by making its vaccine the first to go into public use internationally outside of clinical trials 3) China’s military has already approved the use of CanSino’s vaccine before the completion of Phase 3 trials, according to a filing the company made with the Hong Kong stock exchange 4) initial doses will be given to healthcare workers, the military, and the police 5) this effort shows the intensity of the race to become the first to develop a vaccine 6) public-health experts say immunizing people widely before large-scale tests are completed could present serious health risks 7) CanSino said that getting the vaccine out to millions of people before trials are finished will increase knowledge about the drug’s safety and effectiveness.
- all clinical vaccine trials are approved and adhere to FDA guidelines 2) at every step of the process data safety monitoring committees (independent of vaccine manufacturers and investigators) composed of clinicians and epidemiologists review the safety data that is generated 3) unusual or unexpected adverse events are meticulously evaluated and their rates are compared with background rates 4) all recipients of vaccines in the clinical trials will be monitored for adverse health outcomes for 1–3 years 5) vaccine scientists have reviewed the literature on adverse events associated with earlier vaccines against coronavirus and have proposed immunological conditions that should be met by candidate vaccines 6) vaccines need to be shown to be safe and consistently immunogenic in large and varied population groups 7) vaccine manufacturers are mandated to conduct safety studies.
- the world needs efficient, speedy, and reliable evaluation of many candidate vaccines against COVID 2) deployment of marginally effective vaccines could actually worsen the pandemic if vaccinated individuals incorrectly believe they are at substantially reduced risk or immune and they don’t comply with control measures 3) a weakly effective vaccine could result from a misleadingly promising result from an underpowered trial 4) a weakly effective vaccine would reduce COVID incidence by only 10–20% 5) WHO recommends that vaccines should show efficacy of greater than 30% 6) a vaccine that has 50% efficacy could appreciably reduce incidence of COVID in vaccinated people 7) reliable evidence is also needed about longer-term efficacy, vaccine safety, and protection against severe COVID 8) the WHO Solidarity Vaccines Trial aims to evaluate the efficacy of multiple vaccines in 3–6 months to help ensure that marginally effective vaccines are not deployed 9) the WHO trial will recruit in many high-incidence countries through fixed and pop-up research sites in localities where there are substantial COVID attack rates.
“From January onward, Margaretta Colangelo has been relentlessly cranking out COVID-19 news and tech updates, plus insights into the hunt for a cure; and we’ve been the recipient of some wonderful AI material that neatly intersects with our mission of robotics, automation, and people. The amount, frequency, and quality of COVID research data, papers, studies, information, and news, coming from Margaretta Colangelo is nothing short of extraordinary. Seemingly, not an hour goes by without her posting something very cool to our LinkedIn network. She’s become my go-to source for everything COVID. I told her that if there was a Nobel Prize for excellence in producing and sharing COVID knowledge, she’d win, hands down. In fact, Stockholm should probably make note of her just in case. She’s at her best when illuminating the intersection of AI and COVID. Fascinating how she takes the different threads of research to create an amazing picture of this super-deadly virus in all of its subtle, killing ways and disguises, and how science, like some great global COVID posse, is chasing it down. Robotics and automation tech have become necessary allies throughout the great chase. Collectively, her postings are like a new-age version of Paul de Kruif’s Microbe Hunters-remember that classic book? Margaretta’s, however, are not stories written in hindsight; hers are happening in the here and now, and she takes us along on the hunt. The work that pours out of her matters a helluva lot to a world scared to death of living in constant fear of plague. She’s amazing. You should check her out.” — Asian Robotics Review.
This article is part of a series on COVID-19 research by Margaretta Colangelo. You can read more articles in the series at https://www.margaretta.com
Originally published at https://www.linkedin.com.