COVID-19: a challenge for the innovative community

Nikolay Suetin, Vice-President on Science & Education at the Skolkovo Foundation, has explained what he believes to be the most relevant issues in science and technologies, responding to which is critical not only to further combat COVID-19 outbreak, but also to overcome some other highly contagious infectious diseases with airborne or non-percutaneous channel of transmission.

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This article has been written exclusively for Sk.ru

Several months ago only few people had heard about SARS-CoV-2, and today this contagious respiratory disease, commonly known as COVID-19, has expanded to become a global pandemic, and mankind has to engage almost all available resources in terms of science and technologies, to combat this outbreak. It didn’t take long to identify the causal virus and determine its RNA-structure; testing and diagnostics methods have emerged, and proactive development of anti-COVID medications and vaccines is being in progress. However, development and testing vaccines and new medications take a lot of time and resources. This is the reason why the major focus of front-end health care effort is on delivering medical treatment for those who are already ill, and on outbreak containment.      

The most effective way to reduce the COVID-19 spread rate is to introduce the isolation of the population and to reduce possible contacts causing the virus transmission. It may be surprising, but despite all science and technical progress, throughout the world this approach has become the major way to combat spreading the virus, the same as centuries back. This approach has not only proven to be practically effective, but has led to far-reaching economic and social consequences.

Another most efficient alternative in combating the major outbreaks we know about, is total vaccination. Fortunately, to overcome many highly-spread viruses we have vaccines. However, in case any other, previously unknown pathogens emerge (according to some experts, they are likely to emerge more and more often), this approach (as we see with SARS-CoV-2) is not feasible, at least until the publicly available vaccine has been developed. Development, testing and serial production may take many months, or even years. On top of that, it is not quite clear how quickly the virus can morph into new forms, and whether such a vaccine will be effective against the new strains. It is even more alarming to hear the reports on the cases of repeated infestation and lack of immunity with those who had previously recovered after the COVID infection.

The question arises: which methods and measures are possible to reduce, or even better, to completely prevent this kind of epidemics? What we need is to identify and develop them, as it is believed that the current outbreak will go through the second wave in the autumn, and that COVID-19 outbreaks can become regular due to continuous virus mutations. It is important to emphasize that, in contrast to the other coronavirus infections we know, some people do not have any manifestation of COVID-19, but together with prolonged latent period this makes it increasingly difficult to identify and monitor the virus, and to prevent it from spreading. Proposed methods and measures are required to be effective both in terms of epidemiologic conditions, and in terms of economic impact - they should be better than isolation and quarantine, socially friendly and deliver minimum environmental consequences.              

This is a very complex (and for COVID-19 mainly unsolved) task which requires the involvement of a wide range of specialists in addition to doctors, virologists, geneticists: among them are engineers, physicists, chemists, aerosol specialists, and materials scientists… That is why several professors, on April 8, 2020 chose one of the leading journals of the American chemical society as a way to address a wide range of scientists and engineers with their article COVID-19: A Call for Physical Scientists and Engineers).

We shall use the major statements and propositions from this article to describe the most relevant issues in science and technologies, responding to which is critical not only to further combat COVID-19 outbreak, but also to overcome some other highly contagious infectious diseases with airborne or non-percutaneous channel of transmission. At the same time we’ll put aside the issues related to the development of vaccines, tests and medications, which is already in progress and which will hopefully bring its results in the nearest future.

Here is some general information about the epidemiologic nature of COVID-19

The main source and carriers of acute infectious diseases such as influenza, SARS, MERS, and COVID-19 are infected humans and possibly animals (although there is no direct evidence yet). Viruses enter the environment through liquid droplets (<1 to 200 μm in diameter) released by an infected person when sneezing, coughing, and, as recent studies have shown, during conversation. Moreover, the quantity and size of droplets varies greatly and depends both on the sound tone and amplitude.

Respiratory channel of transmission of the SARS-CoV-19 virus has not yet been proven, which, however, does not exclude this channel of new infections transmission. 

In the ambient air with the usual humidity below 100%, the moisture from microdroplets begins to evaporate quite quickly, while the droplets significantly decrease in diameter. This factor should be taken into account, because the filtration efficiency for the particles < 1 μm falls dramatically with most of the commonly available masks and respirators. Moreover, even virions captured by a modern mask or respirator filter are viable for a long time.

Further on, depending on the humidity and temperature of the ambient air, the droplets may remain liquid or dry out, turning into solid or viscous particles.

Many of larger droplets and dried particles quickly settle on various surrounding items (such as countertops, buttons, handrails, and touch screens), turning them into potential sources of infection. Usually droplets sized a few microns or smaller can remain in the air for hours and are transported by air streams at a distance of many metres.

Direct infestation can occur when other people inhale virions. This is likely to happen if you are in close proximity to an infected person, for example, in a crowd, or in a relatively confined space where the droplet aerosol persists for a long time. Another channel of infection transmission may occur when virions released by infected people, settle on their hands and clothing, and are then passed to others through close contact, such as a handshake. Infestation also occurs if virions from contaminated items and surfaces get (for example, through touching) into the mouth, nose, or eyes.

It is necessary to consider and apply all available methods to block the virion seeding, de-activate most virions already released into the environment, and prevent their penetration into the body of a non-infected person. 

Many measures have been implemented today, such as wearing PPEs, identification and isolation of infected patients, decontamination and sanitation of surfaces and items, filtration of contaminated air, frequent hand washing etc. The task is to improve the existing methods, and develop new ones to create extra barriers for virus outspread. At the same time we will have to accept that the main goal is not to completely eliminate the probability of infection transmission (these attempts are made by specialized clinics and research centres), but to reduce as much as possible the probability of virus transmission from carriers to non-infected people, below the reproduction index R0<1; this means less than one person will be infected by one infected patient, on average.

Additional barriers to stop the virus outspread are also possible.

Generally speaking, viruses are essentially metastable nanoparticles described as a ‘core-shell’ that are biologically produced inside the cells during self-assembly process. The virus core is a genomic polymer, which is tightly packed inside a protective protein called ‘capsid’. They can get damaged by a number of physical impacts, such as UV-radiation, heating and drying, by chemical de-contamination using acids, oxidizers, alcohols or some specialized surfactants. These approaches can seem too simple, however, they can prove highly effective for slowing down the virus, or even preventing virus outspread and transmission. However, it is necessary to refine their application methodology specifically for SARS-CoV-2.

The first barrier for infection transmission is to be put in the starting point - directly on the virus source. Various masks and respirators are commonly used for that purpose. Their function goes beyond simply capturing most of the droplets, since due to higher gas dynamic resistance they are able to reduce the range of ‘droplets shooting’ when coughing or sneezing. Given a large number of symptom-free patients, in some countries wearing masks in public places is mandatory for EVERYONE.

Studies by A British Journal of Medicine  back in 2008 demonstrated that combination of frequent hand washing and wearing masks and medical overalls results in 91% reduction of possibility of virus outspread. Important role of wearing masks for reducing the COVID-19 spread rate was confirmed by a Lancet’s publication.  

Special emphasize was put on the fact that “this measure shifts the focus from self-protection to altruistic attitude, gets each citizen actively involved and symbolizes social responsibility in global response to pandemics.” I believe that we, as an innovative centre, should demonstrate the example of such social responsibility.

Masks cannot capture a significant portion of fine droplets, so some of them go out. To make it less likely for these droplets to get onto the mucous membranes of non-infected people, it is proposed to maintain “social distance”. It appears that the recommended distance of 2 meters is a reasonable compromise, but according to recent studies, the virion outspread distance depends on the humidity and temperature of the ambient air, on the ventilation, wind speed and direction, and other factors that should be studied in more detail.    

To build the next effective barrier it is necessary to better understand the pattern of droplet structure changes, and molecular tools for de-activation of virions in the ambient environment, as well as developing methods for their detection.

Droplets of respiratory fluid contain many other components, usually several percent by weight, including insoluble particles such as proteins, enzymes, substances from the respiratory mucosa; surfactants, cholesterol; and salts and lactates. Therefore, in volatile droplets or dried particles, viruses are always surrounded by these materials, whose amount varies depending on the condition of patients.

When developing physical and chemical approaches for virion de-activation, it is necessary to take into account the surrounding “respiratory” mass. On the one hand, these non-infectious components can act as a protective matrix for virions, and, on the other hand, they can be used for accelerated de-activation, for example, by destroying the virus shell during their crystallization. It looks likely that virion viability mainly depends on the concentration of water which remains inside the droplet, and its evaporation rate. And this, in turn, depends on the temperature and humidity of ambient environment.

Several alternatives should be studied. Under high humidity (>90%) and relatively cool temperature (about 10 ° C), droplets evaporate quite slowly and are more likely to simply fall down. On the other hand, under relatively low humidity (<20%) and high temperature water will quickly evaporate leaving a solid particle which may result in the virion de-activation. Depending on the outdoor parameters and the droplet composition, the remaining particle may have more complicated structure - a combination of solid and liquid phases. Under relatively high humidity (50-60%) the droplet first evaporates and gets smaller, but it does not dry out completely due to high concentration of dissolved salts. Such a droplet can persist quite long in the ambient air as aerosol, and penetrate through the masks and eye mucous membranes. Frequent indoor airing is the most efficient method to dissipate these aerosols.   

The analysis of the aerodynamic spread of SARS-CoV-2 viruses in two hospitals in Wuhan was conducted in a recent publication in Nature . A special role of submicron particles less than 0.25 - 0.5 microns in the spread of infection was emphasized. The highest concentration of viral material was found in poorly ventilated confined spaces (corners of rooms, bathroom stalls, etc.). Apparently, these conclusions should be taken into account when designing ventilation systems not only for hospitals, but also for offices and shopping centres, as well as for public transport.     

The necessity is obvious to develop materials and designs for masks and respirators to meet the following requirements: high filtration efficiency for submicron particles and droplets, and disinfection properties, but at affordable price and with acceptable ergonomic features. To illustrate this statement we refer to a recently published study by scientists from the Aragon National Laboratory which demonstrated that placing several layers of common materials one after another significantly increases filtration efficiency for submicron droplets and particles. 

Another surprising result was recently reported by Canadian researchers - that was the increased barrier properties of masks with outer layer impregnated with salt: according by the researches, interaction with salt leads to de-activation of virions. 

It is also important to develop a method for deactivating virions captured by the surface of the filter material, as well as introducing various devices and impregnations with additional disinfecting effect on the droplets passing through the mask. Another alternative under consideration is to use UV LEDs inside the respirator.

Let us have a look at another potential infestation channel - via droplets settled on the surrounding surfaces or clothing.

The structure and wettability of the surface do matter for the droplets which settled on this surface. It was reported that both SARS-CoV-1 and SARS-CoV-2 virion remain viable during several days on smooth surfaces, such as glass, plastic and stainless steel. However, on porous hygroscopic surfaces, textiles and paper materials, they remain infectious for several hours only. This appears critically important, as stainless steel is commonly used for manufacturing medical accessories and equipment, as well as for most engineering structures and instruments.

As far as we are concerned, the influence of porous surfaces on the virus has not yet been studied well enough. One hypothesis is that on porous surfaces a faster loss of water around virions occurs, which can affect their deactivation by a number of mechanisms. Thus, it is necessary to develop new anti-virus coatings for both existing and new equipment and products, which should dramatically reduce the lifetime of the virus on the surface.

The idea to make self-cleaning surfaces which would slowly release disinfectant chemicals looks rather attractive.

Active antiviral coatings based on photocatalytic, photothermal or electrothermal stimulation also look promising.

However, while such materials and coatings are being under development, the most reliable method to kill the virus is the constant disinfection of surfaces using various anti-virus fluids or aerosols. Such disinfectants are already being developed and put into mass production, also with the participation of Skolkovo residents.

Another “conventional” method of disinfection is the use of various types of UV emitters, including those installed on mobile robotic platforms, which can be used to disinfect both air and surfaces.

 

Model systems for virions

One of the major obstacles preventing the academic and engineer communities from making their contribution into combating the outbreak is the lack of so-called “model virions”. Since only specialized laboratories are authorized to work with real viruses that cause infectious diseases, it is practically impossible for other researchers to investigate into many of the above issues.

At the same time, many physical and engineering approaches to virion deactivation are based on mechanisms of a fairly wide range, and model systems for such studies, at least at the initial stages, should not be virus-specific or contain any genomic material. For example, a model virion would be useful for studying how the virion particles interact with the ambient environment in droplets and on surfaces. Availability of this model yet common (“standardized”) system would be very useful and would help accelerate the development of many scientific and technical solutions to prevent the outspread of virus infections. 

Conclusion

COVID-19 outbreak is a global issue going beyond all existing boundaries, and a wide range of specialists need to be engaged and work together to find a solution thereof. Many science publishing houses have offered free access to all their publications covering this issue, and some universities and companies have made their patents publicly available.

Skolkovo Foundation and Skolkovo Innovation Center have a special regulatory status and host a large number of hi-tech companies, Moscow Medical Cluster and Skotech, so they could act as a driving force in the development of the above technologies and support finding solutions for the above issues by announcing special contests and providing support in cooperation between different developers and scientists, as well as allocating grants to the projects aimed at the development of technologies to reduce the probability of virus infections outspread.