COVID-19 Primer Weekly Briefing

Posted by Primer

April 14, 2020
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Exponential Growth of Covid-19 Research

There have been 960 new research papers and scientific articles published in the 7 days from April 6th to April 12th bringing the total number of papers to 3993 papers. The growth of research into COVID-19/ SARS-CoV-2 continues to increase exponentially with a doubling time of 14.5 days. This growth in research is discussed in this Quartz article published last week.

Cumulative Growth Curve

Face Masks and Personal Protective Equipment

26% of the papers in this topic were published in the past 7 days making it one of the fastest growing emerging topics of research in the field. There was a key research paper published on Friday, Face masks for the public during the covid-19 crisis, this paper was published in BMJ by Greenhalgh et al.

This research received a lot of mainstream news coverage including in the article Time to encourage people to wear face masks as a precaution, say experts. Professor Trisha Greenhalgh (the author of the BMJ study) at the University of Oxford say that despite limited evidence, masks "could have a substantial impact on transmission with a relatively small impact on social and economic life."

Speaking might play a bigger role in transmission than previously thought. Could SARS-CoV-2 be transmitted via speech droplets?: "Speaking may be a primary mode of transmission of SARS-CoV-2... We found that saying the words 'Stay Healthy' generates thousands of droplets that are otherwise invisible to the naked eye. A damp homemade cloth face mask... reduced droplet excretion."

Reusing N95 masks can be done in hospital settings – good news. See the paper here N95 Mask Decontamination using Standard Hospital Sterilization Technologies. Anand Kumar from the University of Manitoba, found that one cycle of treatment with all modalities was effective in decontamination (of the masks) and was associated with no structural or functional deterioration in the masks.

Transmission of the Virus

Presymptomatic Transmission

Presymptomatic Transmission is being recorded from contact tracing studies in Singapore. Read the paper that was published on the CDC site here. "Investigation of all 243 cases of COVID-19 reported in Singapore during January 23–March 16 identified seven clusters of cases in which presymptomatic transmission is the most likely explanation for the occurrence of secondary cases." The researchers find that "presymptomatic transmission occurred 1–3 days before symptom onset in the presymptomatic source patient."

The relatively good news is that presymptomatic transmission doesn’t seem to be the major transmission vehicle. The researchers found: "10 of the 157 (6.4%) locally acquired cases are included in these clusters and were attributed to presymptomatic transmission. These findings are supported by other studies that suggest that presymptomatic transmission of COVID-19 can occur (1–3). An examination of transmission events among cases in Chinese patients outside of Hubei province, China, suggested that 12.6% of transmissions could have occurred before symptom onset in the source patient."

80% of Outbreaks Were Found to Occur at Home

Indoor transmission of SARS-CoV-2 by Qian et al. “Case reports were extracted from the local Municipal Health Commissions of 320 prefectural cities (municipalities) in China, not including Hubei province, between 4 January and 11 February 2020. [...] Home outbreaks were the dominant category (254 of 318 outbreaks; 79.9%), followed by transport (108; 34.0%; note that many outbreaks involved more than one venue category). Most home outbreaks involved three to five cases. We identified only a single outbreak in an outdoor environment, which involved two cases. Conclusions: All identified outbreaks of three or more cases occurred in an indoor environment, which confirms that sharing indoor space is a major SARS-CoV-2 infection risk.”

Toilets are a Hotspot for Transmission

Toilets dominate environmental detection of SARS-CoV-2 virus in a hospital. The researchers found that “the faecal-derived aerosols in patients' toilets contained most of the detected SARS-CoV-2 virus in the hospital, highlighting the importance of surface and hand hygiene for intervention.”

In light of this research, this tiktok challenge was even more stupid (if that’s possible) than anyone originally thought.

HCQ & Azithromycin

The Debate About HCQ Continues

A number of new papers were published this week including this research from Chen et al.: Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial. Chen and his team found that: “Among patients with COVID-19, the use of HCQ could significantly shorten TTCR and promote the absorption of pneumonia.”

Broader Commentary of this research has been critical. “People take these tiny studies, and quote them as gospel,” Lyn-Kew said. “We need real science behind this disease,” adding physicians are "desperate for something to help people.”

While in the field anecdotal feedback from Physicians has also been mixed. “‘We've been using it,’ said Dr. Hugh Cassiere, a pulmonologist and medical director of Respiratory Care Services at North Shore University Hospital in Long Island, New York, a hot spot for the pandemic in the United States. ‘But we really haven't seen any efficacy.’”

Potential Dangers of HCQ

There were several research papers looking into the dangers associated with HCQ treatment protocols. Including this paper published in the The Canadian Medical Association Journal. Safety considerations with chloroquine, hydroxychloroquine and azithromycin in the management of SARS-CoV-2 infection.

“Despite optimism (in some, even enthusiasm) for the potential of chloroquine or hydroxychloroquine in the treatment of COVID-19, little consideration has been given to the possibility that the drugs might negatively influence the course of disease,” said Dr Juurlink the lead author of the research.

There was a second highly shared paper on this topic from a team led by researcher Patrick Ryan: Safety of hydroxychloroquine, alone and in combination with azithromycin, in light of rapid wide-spread use for COVID-19: a multinational, network cohort and self-controlled case series study. “The paper concludes that short-term HCQ monotherapy does appear to be safe, but notes that long-term HCQ dosing is indeed tied to increased cardiovascular mortality.”

But the researchers go onto to say that “Worryingly, significant risks are identified for combination users of HCQ+AZM even in the short-term as proposed for COVID19 management, with a 15-20% increased risk of angina/chest pain and heart failure, and a two-fold risk of cardiovascular mortality in the first month of treatment.”

Getting Back to "Normal"

Mass Testing

LAMP-Seq: Population-Scale COVID-19 Diagnostics Using a Compressed Barcode Space. Where the authors propose LAMP-Seq, a barcoded Reverse-Transcription Loop-mediated Isothermal Amplification (RT-LAMP) protocol that could dramatically reduce the cost and complexity of population-scale testing.

This paper had the 2nd highest social media sharing of all the research over the past 7 days and also received a significant amount of mainstream media coverage including an article by Vox: “The alternative to mass surveillance is mass testing….on a scale no one else is contemplating — 22 million tests per day — so that the entire country is being tested every 14 days, and anyone who tests positive can be quickly quarantined. Most experts I’ve spoken to doubt that’s realistic anytime soon. Some believe it’s possible - eventually."

Mobile Phone Contact Tracing

PACT: Privacy Sensitive Protocols and Mechanisms for Mobile Contact Tracing. The research team advocates for "a third-party free approach to assisted mobile contact tracing, because such an approach mitigates the security and privacy risks of requiring a trusted third party. We also explicitly consider the inferential risks involved in any contract tracing system, where any alert to a user could itself give rise to de-anonymizing information."

The EFF put together a very detailed and thoughtful response looking at the potential impacts this technology will have if it is to be rolled out across the society.

The Atlantic drew on this research as it put together it’s piece, "The Technology That Could Free America From Quarantine."

A New Type of Lockdown

Adaptive cyclic exit strategies from lockdown to suppress COVID-19 and allow economic activity, by Karin et al., a research team out of Israel. The research received 84 shares on social media. Researchers propose (and then model) a solution for cycling people in and out of lockdown to create a "new normal" that would keep deaths from COVID to a minimum while allowing people to work in person (in some capacity).

The researchers say: "cyclic schedule of 4-day work and 10-day lockdown....can in certain conditions suppress the epidemic while providing part-time employment [...] The cycle reduces the reproduction number R by a combination of reduced exposure time and a resonance effect where those infected during work days reach peak infectiousness during lockdown days."

New Kinds of Surveillance Technology

Portable Health Screening Device of Respiratory Infections. "In this system, the thermal video of human faces is first captured through a portable thermal imaging camera. Then, body temperature and respiration state are extracted from the video and are imported into the following health assessment module. Finally, the screening result can be obtained. The results of preliminary experiments show that this system can give an accurate screening result within 15 seconds."

Overview - portable health screening

Frontline Healthcare Workers Are Suffering

Now we are starting to be able to measure how bad it is. This research into the Impact of viral epidemic outbreaks on mental health of healthcare workers should give us all pause for thought. The researchers from Spain state: "The prevalence of anxiety, depression, acute and post-traumatic stress disorder, and burnout, was high both during and after the outbreaks. These problems not only have a long-lasting effect on the mental health of HCWs, but also hinder the urgent response to the current COVID-19 pandemic, by jeopardising attention and decision-making. Governments and healthcare authorities should take urgent actions to protect the mental health of HCWs."

Forecasting and Modelling

Predicting the Covid-19 Activity

A machine learning methodology for real-time forecasting of the 2019-2020 COVID-19 outbreak using Internet searches, news alerts, and estimates from mechanistic models. Authors claim: “We present a…methodology that combines disease estimates from mechanistic models with digital traces… to reliably forecast COVID-19 activity in Chinese provinces in real-time. Specifically, our method is able to produce stable and accurate forecasts 2 days ahead of current time.”

Network Analysis of the Virus

Phylogenetic network analysis of SARS-CoV-2 genomes. The study was published in the high impact journal the Proceedings of the National Academy of Sciences. “We find three central variants distinguished by amino acid changes, which we have named A, B, and C, with A being the ancestral type according to the bat outgroup coronavirus. The A and C types are found in significant proportions outside East Asia, that is, in Europeans and Americans. In contrast, the B type is the most common type in East Asia, and its ancestral genome appears not to have spread outside East Asia without first mutating into derived B types, pointing to founder effects or immunological or environmental resistance against this type outside Asia.”

Lead author Dr. Peter Forster, a geneticist at the University of Cambridge: “These techniques are mostly known for mapping the movements of prehistoric human populations through DNA. We think this is the first time they have been used to trace the infection routes of a coronavirus like SARS-CoV-2.”

Mapping movements

This research received 41 news articles including this piece. “The viral network we have detailed is a snapshot of the early stages of an epidemic, before the evolutionary paths of COVID-19 become obscured by vast numbers of mutations. It’s like catching an incipient supernova in the act.”

Covid-19 Propaganda and the News

Pandemic Populism: Facebook Pages of Alternative News Media and the Corona Crisis -- A Computational Content Analysis. “While they do not spread obvious lies, they are predominantly sharing overly critical, even anti-systemic messages, opposing the view of the mainstream news media and the political establishment. With this pandemic populism, they contribute to a contradictory, menacing, and distrusting worldview, as portrayed in detail in this analysis.”

“Go eat a bat, Chang!”: An Early Look on the Emergence of Sinophobic Behavior on Web Communities in the Face of COVID-19. “We find that COVID-19 indeed drives the rise of Sinophobia on the Web and that the dissemination of Sinophobic content is a cross-platform phenomenon…..on Twitter we observe a shift towards blaming China for the situation, while on /pol/ we find a shift towards using more (and new) Sinophobic slurs.”

Predicting Respiratory Failure

Level of IL-6 predicts respiratory failure in hospitalized symptomatic COVID-19 patients. “Owing to the highly variable course and lack of reliable predictors for deterioration, we aimed to identify variables that allow the prediction of patients with a high risk of respiratory failure and need of mechanical ventilation [...] elevated interleukin-6 (IL-6) was strongly associated with the need for mechanical ventilation [...] Our study shows that IL-6 is an effective marker that might be able to predict upcoming respiratory failure with high accuracy and help physicians correctly allocate patients at an early stage.”

Read more about the research here in this informative article by Science Magazine.

Interesting Novel Research

Fancang Shelter Hospitals

Fangcang shelter hospitals: a novel concept for responding to public health emergencies. This work was published in the Lancet by Chen et al. “The term Fangcang, which sounds similar to Noah’s Ark in Chinese, was borrowed from military field hospitals, but it refers to a novel concept: large, temporary hospitals built by converting public venues, such as stadiums and exhibition centres, into health-care facilities to isolate patients with mild to moderate symptoms of an infectious disease from their families and communities, while providing medical care, disease monitoring, food, shelter, and social activities.”

Authors found that “Fangcang shelter hospitals could be powerful components of national responses to the COVID-19 pandemic, as well as future epidemics and public health emergencies.”

Interesting novel research

The research received relatively little social media coverage with only 4 shares - and no mainstream media articles linked to this research.

Second Order Impact of Covid-19 As It Begins to Hit Africa

Why measles deaths are surging — and coronavirus could make it worse. "23 countries have suspended measles vaccination campaigns as they cope with SARS-CoV-2 [...] Already, 23 countries have suspended scheduled measles campaigns, and others will probably follow suit, says Linkins. This means that 78 million children will not be vaccinated as planned, he says. The DRC, however, is continuing its outbreak response.

‘We must protect vulnerable populations from the spread of COVID-19,’ Linkins says, but limiting measles-immunization activities will create ‘dangerous immunity gaps’. Modellers are just beginning work to estimate the impact of COVID-19 on measles control, but it is clear that countries must be able to resume their campaigns quickly after the pandemic subsides, he says."

Measles cases graph

17 News Articles to Read

Debate about where the virus originated. How did coronavirus break out? Theories abound as researchers race to solve genetic detective story and Most New York Coronavirus Cases Came From Europe, Genomes Show. "'If there was a so-called intermediate host, an animal that the bat virus got into and then allowed it to get into people, the virus might still be in that host,’ said Daszak, the virus hunter working in China."

The Latest Hydroxychloroquine Data, As of April 11. As the Hydroxychloroquine debate continues and new studies are coming online, this is a good summary from Science Magazine of where it all stands today.

We are making good progress towards understanding the structure of the virus: Scientists chart weak spots in coronavirus protein that antiviral drugs can target.

"Designed to be slow": Why these coronavirus vaccines in the pipeline won't be ready this year. We may be able to produce a vaccine to defeat COVID-19 – but this will not be a quick process.

Getting back to "normal" – from contact tracing to social distancing, many different groups are trying to figure out how we can remove ourselves from lockdown: Google and Apple Plan to Turn Phones into COVID-19 Contact-Tracking Devices, Coronavirus economy plans are clear: No return to normal in 2020 and How Do COVID-19 Tests Work Science.

What Can COVID-19 Forecasters Learn from Pascal's Wager. Modeling the outbreak – we’ve never seen so much focus and attention on epidemiological models – but everyone creating these models would do well to learn about Pascal’s Wager.

916,000 In Iran Have Coronavirus: Expert. Estimating the numbers of people that have actually been infected in a country (as opposed to the number that test positive) continues to be an active area of research. Researchers suggest that the number infected in Iran may be 10x higher than those reported by the Government there. The model showed that 916,000 people in Iran had likely been infected—with 15,485 dead and 407,515 recovered—by March 20th 2020.

How can AI help in the COVID-19 fight – it turns out there’s a lot that machine learning can do here: How to fight COVID-19 with machine learning and Fighting COVID-19 with Data and AI: A Review of Active Research Groups and Datasets.

Hospitals and Diagnosis: New algorithm aims to protect surgical team members against infection with COVID-19 virus and Cytokine Storm: The Sudden Crash in Patients with COVID-19

COVID-19 Risk Factors: Smoking, age, other factors raise risk of COVID-19 death and Covid-19 death rate rises in counties with high air pollution.

Thinking about what the world will look like after the fight with COVID-19 is over: Can We Reimagine Global Health In The Post-Pandemic World?