WO2021182989A2

WO2021182989A2 - A method of coronavirus infection diagnosis

Info

Publication number: WO2021182989A2
Application number: PCT/RU2020/000265
Authority: WO
Inventors: Evgeny Aleksandrovich PETRISCHEV
Original assignee: Petrischev Evgeny Aleksandrovich
Priority date: 2020-03-11
Filing date: 2020-06-03
Publication date: 2021-09-16
Also published as: RU2020110229A3; RU2020110229A

Description

A method of coronavirus infection diagnosis

Field of the invention

Invention belongs to the field of analytical chemistry and can be used to create an operational method for diagnosing patient's infection with coronavirus and fastacting portable devices for detecting and/or identifying chemicals in the air.

The sense of smell is a valuable diagnostic tool of medicine. Infectious diseases and neoplasms are often associated with metabolic changes that can be detected by the sense of smell.

It is known that infectious diseases and neoplasms are often associated with metabolic changes that can be detected by the sense of smell. For example, the smell of acetone from the mouth can indicate such diseases as diabetes or thyrotoxicosis, and one can also register ammonia compounds — a sign of kidney failure. Electronic nose is also able to detect infectious agents very effectively and at early stages. For example, a modem immunoassay requires three times more flu vims envelope proteins than a "smelling" biosensor using antibodies.

Prior art

There is a method and multi-sensor device for the recognition and/or detection of odors of the Electronic Nose type, which is based on the sensor response, expressed in changes in their physical parameters, containing an aspiration pump, a pneumatic switch, a filter and a sensor unit pneumatically connected to each other, as well as a registration and management unit that includes the software for pattern recognition, while the touch unit comprises at least two sensors, consisting of polymer semi-conducting thin-film materials that are different from each other in sensitivity and selectivity, and to determine the response of sensors to odors, the measurement of DC electrical conductivity and/or dielectric characteristics of sensors, namely, electrical capacitance and/or dielectric losses (RU 117007) is used.

There is a method and device for diagnosing human diseases by exhaled air, containing a means for sampling exhaled air that is connected to the inlet pipe of the gas pipeline with the output connected to the suction device, while the case of the gas pipeline contains gas sensors, each of which is designed to detect a particular gas in the exhaled air, as well as a humidity sensor, a temperature sensor and an air flow speed sensor installed in such a way that their sensitive elements are arranged in the inner cavity of the pipe of the gas pipeline. The outside of the gas pipeline case features a thermostatic element fixed thereon with its thermoactive part and with the input connected to the first output of the signal conversion unit of the temperature sensor with an input coupled with the output of the temperature sensor, while the second output is connected to the first input of the digital controller with the first output connected to the input of the suction device control unit with the output connected to the input of the suction device, while the humidity sensor output is connected to the input of the humidity sensor signal conversion unit with the output coupled to the second input of the digital controller with the second output connected to the switching unit control unit, wherein outputs of gas sensors are connected to respective inputs of the unit of gas sensor conversion signals, while its N outputs are connected to respective N inputs of the gas sensor signal correction unit with the N+l input connected to the output of the airflow speed sensor. The N+2 input is connected to the third output of the digital controller, while N outputs of the gas sensor signal correction unit connected to respective N inputs of the switching unit with the output connected to the input of the analog-digital conversion unit and its output connected to the fourth input of the digital controller, while M outputs of physiological state sensors are connected to corresponding M inputs of the conversion unit of physiological state signal sensors with M outputs connected to corresponding M inputs of the switching unit (EN 51849).

There is a gas multi sensor that includes an array of N organic field-effect transistors, each of which includes at least electrodes - "drain", "source", separated by a layer of organic semiconductor, an electrode "gate", a dielectric layer and an additional receptor layer based on metalloporphyrin of general formula 1 or 2, completely or partially covering the layer of organic semiconductor in the structure of the N-th organic field-effect transistor (RU 2676860):

The disadvantage of known devices is the relatively low sensitivity and selectivity of multi-sensor systems for detecting odors, as well as narrow functionality.

The closest one to the proposed is a method of obtaining diagnostic information by the smell of the skin. It uses a gas analyzer of the "electronic nose" type with a set of four sensors based on quartz crystal resonators (QCR) with bulk acoustic waves with a base frequency of 10.0 MHz with electrodes treated with sorbents from acetone suspensions of multi-layer carbon nanotubes, potassium fluoride, zirconyl nitrate, hydroxyapatite. To do this fat-free quartz crystal resonators are immersed in acetone suspensions for 5 sec, then free solvent is removed for 10 min at 100°C. Specialists place resonators with sorbents in device hubs, put a cylindrical cap with an open entrance, keep the system for 5 min to establish the stability of the original oscillation frequency of each sensor, turn on the measurement program with a duration of 200 sec and tightly clamp the inner side of the forearm to the cap for 80 sec, and then they gently take the hand away and continue to record changes in signals of all sensors before the time set; the program converts stored signals into "visual prints" of sensor responses at discrete moments of measurement and compares them with data from the database corresponding to the normal state of a particular person. The deviation of these data sets by more than 35% according to the automatic evaluation in the program indicates a change in normal metabolism (RU 2679409, prototype).

The disadvantage of the prototype is the narrowness of functionality, insufficient efficiency and reliability of results.

Summary of the Inventions

A technical issue solved with this invention is to improve the efficiency, modify and enhance the method to expand the range of methods for diagnosing diseases using odors.

The technical result that provides a solution to this issue is to expand the functionality for testing coronavirus in the "incubation" period, which is 14-20 days from the moment of hypothetical infection, for rapid and reliable diagnosis of coronavirus infection in the incubation period.

The essence of the invention is that the method for diagnosing viral infection involves determining the composition of diagnostic enzymes that are secretion products produced by the human body, highlighting their changes and features, as well as fixing a set of characteristics of such patient's enzymes to determine the presence or absence of infection, while the composition and properties of external secretion enzymes (pheromones) are analyzed as diagnostic enzymes. Specialists also fix a set of their characteristics in terms of changes and features typical of the coronavirus COVID-19 disease, and following the results of pheromone analysis they establish the presence or absence of infection with the specified coronavirus. If all characteristics typical of the coronavirus infection are established, the diagnosis is considered to be determined.

Preferably, the diagnosis of viral infection is carried out before the appearance of its clinical signs during the incubation period.

Preferably, infection is detected based on the analysis of a set of isolated enzymes by the presence of a set of characteristics inherent in coronavirus infection using such equipment as an "electronic nose".

Preferably, viral infection is diagnosed by determining the spatial and temporal distribution of pheromone activity.

In particular cases of method implementation, additional characteristics from the group are used for diagnosis: a set of micro expressions of the face, heart rate and sweating, pupil dilation, observed reflex movements, body temperature increase, and subjective sensations.

Detailed Description of the Invention

The method for diagnosing a virus infection is implemented as follows.

Initially, the patient is authenticated by at least one, and preferably several different methods.

After receiving confirmation of successful authentication of the patient, the electronic nose device initiates the procedure for diagnosing coronavirus infection that has the official Latin abbreviation of the COVID-19 virus.

The claimed solution is based on the fact that the bodies of those infected with coronavirus produce specific enzymes (external secretion products), which can technically be isolated and determined using medical equipment already available on the market (the "electronic nose" line of devices).

The patient is placed in a room where, after a temporary exposure with the help of electronic nose devices, specialists analyze the composition and properties of external secretion enzymes (pheromones) as diagnostic enzymes, as well as fix a set of their characteristics in terms of changes and features inherent in coronavirus disease. Following the results of pheromone analysis, the presence or absence of coronavirus infection is determined, and specialists analyze the composition and properties of external secretion enzymes (pheromones) as diagnostic enzymes. Specialists also fix a set of their characteristics in terms of changes and features typical of the coronavirus COVID-19 disease, and following the results of pheromone analysis they establish the presence or absence of infection with the specified coronavirus. If all characteristics typical of the coronavirus infection are established, the diagnosis is considered to be determined.

In this case, specific enzymes - the diagnostic profile of pheromones can be detected using such equipment as an "electronic nose" using machine learning methods based on statistical classifiers, where measured levels of pheromone features are used as inputs. If a set of features: {xl, x2, x3, xn} is a vector, then the general form of the statistical classifier of emotion detection can be described by the function f - decision tree, neural network, logistic regressor, or other statistical classifier described in the literature on machine learning. The function minimizes an empirical error (an error found when training the classifier), as well as minimizes the complexity - for example, Occam's razor, searching for the simplest function, and a set of parameters for such function that allows obtaining the desired result. In addition, an active learning criterion can be added in order to determine which pheromones and other features, taking into account various biochemical pathways of pheromones, are the most valuable for determining the presence of a set of characteristics inherent in the coronavirus infection.

Human exhalation is a complex mixture of about 750 volatile compounds that are formed in the body as a result of metabolic processes. They pass through the bloodstream, participate in alveolar exchange and subsequently appear when exhaling.

When using a portable small-sized version of the "electronic nose" device (a gas analyzer diagnosing the light-volatile part of the human metabolome), the result of diagnostics on the person's exhalation can be established in a few minutes.

Due to the need to monitor coronavirus, the proposed method can be used for mass diagnostics of people in places of congestion.

Preferably, using this method, the diagnosis of viral infection is carried out before the appearance of its clinical signs during the incubation period. Preferably, using this method, infection is detected based on the analysis of a set of isolated enzymes based on the presence of a set of characteristics inherent in coronavirus infection using such equipment as an "electronic nose" with a self- learning computer electronic medical information program (artificial intelligence) installed.

The device of the "electronic nose" type, for example, consists of a microcontroller and a power unit. The first output of the power unit is connected to the input of the microcontroller, however the following devices can be additionally introduced: sample selection and provision unit, analytical unit, control and primary processing unit, while the second output of the power unit is connected to the first input of the sample selection and provision unit with the second input connected to the first output of the control and primary processing unit; the output of the sample selection and provision unit is connected to the first input of the analytical unit with the output and the second input connected to the input and the second output of the control and primary processing unit, including a microcontroller with a pulse-length modulator, data exchange shaper, parameter shaper, control unit of external devices, while inputs and outputs of the data exchange driver and parameter driver, as well as control unit of external devices are connected to the corresponding inputs and outputs of the microcontroller.

Preferably, using this method, viral infection is diagnosed by determining the spatial and temporal distribution of pheromone activity.

Preferably, using this method, additional characteristics from the group are used for diagnosis: a set of micro expressions of the face, heart rate and sweating, pupil dilation, observed reflex movements, increased body temperature, and subjective sensations.

For the presentation of electronic medical information, an electronic medical information program installed on the "electronic nose" equipment can function as an input tool for entering electronic card information; a means for generating an electronic card from the information entered, a storage tool for storing the generated electronic card in an electronic card file; a reader for setting / displaying buttons for links associated with an e-map file in the list and a reader for clicking on any of the buttons for an e-map link from an e-map file and a display tool for displaying an e- map that has been read for viewing.

For the presentation of electronic medical information, an electronic medical information program installed on the "electronic nose" equipment can provide the operation of a computer as a reader for reading from an electronic card file of one or more types of information in relation to the examination, an accumulation means for the accumulation of information that has been read; a list generation tool to arrange the change in time of accumulated information in a time sequence, and for reading the relevant information when clicking on any of the link buttons; and a display tool for displaying information that has been read for viewing.

For the presentation of electronic medical information, an electronic medical information program installed on the "electronic nose" equipment can provide a computer as a storage tool for storing in a file of an ordinary card of an ordinary card converted into an electronic document format that accurately reproduces the original image; a reading tool to read upon the query to view the file of an ordinary card of an ordinary card requested for viewing, from the file of an ordinary card and a display means for displaying the ordinary cards, which has been read for viewing.

In addition, for the purpose of presenting electronic medical information, an electronic medical information program installed on the "electronic nose" equipment can provide the functioning of such equipment as a means of accumulating information corresponding to an electronic card from the information recorded in the file of an ordinary card, as a means of accumulating and generating a list by ordering the change in time of each type of information of an accumulated ordinary card in a time sequence, so it can be compared with the change in time of the schedule.

In order to implement the above-mentioned features, the "electronic nose" equipment recording medium stores any of the electronic medical information programs.

Thus, the electronic medical information system installed on the "electronic nose" equipment allows viewing the time dependence between the initial complaint of the patient and results of diagnosing coronavirus infection. A doctor can view necessary information on a single screen without searching for cards, prescriptions and results of previous examinations during the patient's consultation, which prevents the spread of coronavirus infection and contributes to proper and rapid medical care.

As a result of using the claimed solution, the functionality for testing coronavirus in the "incubation period", which is from 14 to 20 days, is expanded from the moment of hypothetical infection for rapid and reliable diagnosis of coronavirus infection during the incubation period.

Industrial application

The invention is implemented with multipurpose equipment extensively employed by the industry.

Claims

1 . A method for diagnosing viral infection, which provides for determining the composition of diagnostic enzymes that are secretion products produced by the human body, highlighting their changes and features, as well as fixing a set of characteristics of such patient's enzymes to determine the presence or absence of infection, characterized in that specialists analyze the composition and properties of external secretion enzymes (pheromones) as diagnostic enzymes, as well as fix a set of their characteristics in terms of changes and features inherent in coronavirus COVID-19 disease. Following the results of pheromone analysis they establish the presence or absence of infection with the specified coronavirus. If all characteristics typical of the coronavirus infection are established, the diagnosis is considered to be determined.

2. The method according to Claim 1, is characterized by the following: diagnosis of viral infection is carried out before the appearance of clinical signs during the incubation period.

3. The method according to any of Claims 1,2, is characterized by the following: infection is detected based on the analysis of a set of isolated enzymes in the presence of a set of characteristics inherent in coronavirus infection, using such equipment as an "electronic nose".

4. The method according to any of Claims 1,2, is characterized by the following: viral infection is diagnosed by determining the spatial and temporal distribution of pheromone activity.

5. The method according to any of Claims 1,2, is characterized by the following: when diagnosing, additional characteristics from the group are used for diagnosis: a set of micro expressions of the face, heart rate and sweating, pupil dilation, observed reflex movements, increased body temperature, and subjective sensations.