METHOD FOR THE RAPID IDENTIFICATION OF COVID-19 INFECTION

An embodiment provides a method for identifying Covid-19 in a body fluid of a patient, including: removing the body fluid from a patient; applying a treatment to the body fluid, wherein the treatment comprises an antibody that joins with a Covid-19 targeted antigen (TA) in the body fluid to form an antibody-TA complex, wherein the antibody comprises a light functional antibody; identifying the antibody-TA complex, using a spectroscopic technique, from the body fluid using a light source; and returning the body fluid to the patient. Other aspects are described and claimed.

FIELD

This application relates generally to a method for the rapid identification of COVID-19, and, more particularly, to a fluorescent or luminous virion-antibody complex for the rapid identification of COVID-19.

BACKGROUND

Coronaviruses are a family of viruses that can cause illnesses such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). A new coronavirus (Covid-19) was identified as the cause of a disease outbreak in China. The virus is presently known as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease it causes is called coronavirus disease 2019 (COVID-19).

Cases of COVID-19 have been reported in multiple countries, where it has caused a great deal of morbidity and mortality, in a worldwide pandemic. The disorder is characterized by shortness of breath, increased mucus production, sore throat, cough, and fever. This may necessitate admission to a hospital, with subsequent admission to an intensive care unit for the respiratory support of the infected patient.

There is a need for the rapid identification of Covid-19 from a patient's body fluid or sample (mucus, saliva, blood, cerebrospinal fluid), due to the worldwide pandemic of this infection.

BRIEF SUMMARY

In summary, one embodiment provides a method for identifying Covid-19 in a body fluid of a patient, comprising: removing the body fluid from a patient; applying a treatment to the body fluid, wherein the treatment comprises an antibody that joins with a Covid-19 targeted antigen (TA) in the body fluid to form an antibody-TA complex, wherein the antibody comprises a light functional antibody; identifying the antibody-TA complex, using a spectroscopic technique, from the body fluid using a light source; and returning the body fluid to the patient.

Another embodiment provides a device for identifying Covid-19 in a body fluid of a patient, comprising: a transparent first stage including an inlet for the body fluid and at least one exterior wall defining a treatment chamber; a transparent second stage,  fluidly connected to the first stage, comprising a removal module and an outlet for the body fluid, wherein the treatment chamber comprises a delivery tube for introducing an antibody into the treatment chamber, wherein the delivery tube comprises a hollow tube including at least one interior wall defining a plurality of holes through which the antibody can be added to the treatment chamber, wherein the treatment is delivered through the hollow tube in counter-current mode with reference to the body fluid; and at least one sensor to identify the light functional antibody; the device being configured to: remove the body fluid from a patient; apply a treatment to the body fluid, wherein the treatment comprises an antibody that joins with a Covid-19 targeted antigen (TA) in the body fluid to form an antibody-TA complex, wherein the antibody comprises a light functional antibody; identify the antibody-TA complex, using a spectroscopic technique, from the body fluid using a light source; and return the body fluid to the patient.

A further embodiment provides a method for identifying Covid-19 in a body fluid of a patient, comprising: removing the body fluid from a patient; applying a treatment to the body fluid, wherein the treatment comprises an antibody that joins with a Covid-19 targeted antigen (TA) in the body fluid to form an antibody-TA complex, wherein the antibody comprises a light functional antibody; identifying the antibody-TA complex, using a spectroscopic technique, from the body fluid using a light source; capturing, using an antibody microarray, the antibody-TA complex, wherein the  microarray comprises a plurality of the antibody on a transparent solid surface; and returning the body fluid to the patient.

DETAILED DESCRIPTION

COVID-19 has spread worldwide and become a global pandemic. The loss of life, suffering, and economic struggles have reached all corners of the globe. Symptoms may manifest about 2-14 days after exposure. The symptoms may include fever, chills, cough, shortness of breath, difficulty breathing, fatigue, muscle/body aches, new loss of taste/smell, sore throat, congestion, runny nose, nausea, vomiting, or diarrhea. More severe symptoms may include trouble breathing, persistent pain/pressure in the chest, confusion, inability to wake or stay awake, or bluish lips/face. Some cases may require hospitalization and even intensive care unit healthcare. Because of the novelty of the virus, very few tests exist that are specific for COVID-19. What is needed is a method for rapid identification of COVID-19 in a patient.

Coronaviruses are a family of viruses that can cause illnesses such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). A new coronavirus (Covid-19) was identified as the cause of a disease outbreak in China. The virus is known as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease it causes is called coronavirus disease 2019 (COVID-19).

In a phylogenetic analysis of 103 strains of SARS-CoV-2 from China, two different types of SARS-CoV-2 were identified, designated type L (accounting for 70  percent of the strains) and type S (accounting for 30 percent). The strains in L type, derived from S type, are evolutionarily more aggressive and contagious.

Cases of COVID-19 have been reported in multiple countries, where it has caused a great deal of morbidity and mortality, in a worldwide pandemic. The disorder is characterized by shortness of breath, increased mucus production, sore throat, cough, and fever. This may necessitate admission to a hospital, with subsequent admission to an intensive care unit for the respiratory support of the infected patient. There is therefore a need for rapid identification of Covid-19.

Accordingly, described herein is a method for the rapid identification of Covid-19 from a patient's body fluid or sample, for example, blood, CSF (cerebrospinal fluid), mucus, or saliva. The method includes removing the body fluid from a patient which may contain Covid-19 virions, exposing the body fluid to at least one binding antibody so that any Covid-19 virions present in the body fluid form a virion antibody complex with the binding antibody, and then determining the presence or absence of the virion binding antibody complex. The binding antibody can include, for example, a fluorescent antibody, a luminous antibody, or combinations thereof. The binding antibody may be referred to as a light functional antibody. The concentration of binding antibody may be made as high as necessary for the identification of extremely small, e.g., picogram/microliter, concentrations of the final virion binding antibody complex. The  signal from the virion binding antibody complex can be amplified as needed to identify a signal

A method comprises treating a patient's body fluid with at least one binding antibody that reacts with and binds at least one antigen/target antigen (TA) of Covid-19. The body fluid can include any body tissue capable of containing the Covid-19 virus but is preferably selected from the group consisting of saliva, mucus, blood, and CSF. The binding antibody can include an antibody capable of detection using a spectroscopic technique, such as but not limited to, a fluorescent antibody, a luminous antibody, or combinations thereof. The Covid-19 antigen/TA can include, but is not limited to: Covid-19 spike glycoprotein, Covid-19 M-Protein, Covid-19 Hemoglutinesterase dimer, Covid-19 Envelope, Covid-19 E-Protein, Covid-19 N-Protein, nsp (non-structural protein) 12 RNA-dependent RNA polymerase (nsp 12), nsp (non-structural protein) 7, nsp 8, nsp 14, nsp 12-nsp 7-nsp 8 complex, nsp7-nsp8 complex, nsp10-nsp14 complex, nsp10-nsp16 complex forming virion antibody complexes, and combinations thereof. Identification of Covid-19 positivity is then made by a standard technique well known by laboratory personnel.

Referring toFIG. 1, the first stage can include an exterior wall2defining a treatment chamber5. The treatment can be applied in the treatment chamber5. Residence times of the blood to be treated can be altered by changing the dimensions of the treatment chamber or the flow rate of the body fluid through the treatment chamber5. body fluid to be treated enters the inlet3, passes through the treatment chamber5, and exits the outlet4. In embodiments, the treatment or antibodies can be applied from a delivery tube6located within the treatment chamber5. An interior wall9defines the delivery tube6. The delivery tube6can include at least one lead7,8. The lead7,8can deliver the treatment to the treatment chamber5. Conveniently, the delivery tubes6will have a high contact surface area with the body fluid. As shown, the delivery tube6comprises a helical coil.

Referring toFIG. 2, the delivery tube6can be hollow and the interior wall9can define a plurality of holes21. In this design for example, designer antibodies can be pumped through the delivery tube6to affect a desired concentration of antibodies in the body fluid (blood and/or CSF). The antibodies can perfuse through the holes21. The delivery tube6can include any suitable material including, for example, metal, plastic, ceramic or combinations thereof. The delivery tube6can also be rigid or flexible. In one embodiment, the delivery tube6is a metal tube perforated with a plurality of holes. Alternatively, the delivery tube6can be plastic and/or transparent.

The antibody, targeting the antigen: can be delivered in a concurrent or counter-current mode with reference to the blood and/or CSF. In counter-current mode, the body fluid enters the treatment chamber5at the inlet3. The designer antibody can enter through a first lead8near the outlet4of the treatment chamber5. The body fluid then passes to the outlet4and the designer antibodies pass to the second lead7near the inlet3. The removal module of the second stage substantially removes the designer antibodies-antigen molecular compound from the blood and/or CSF.

In the first stage, a body fluid may be withdrawn from a patient using standard medical techniques, such as, but not limited to a sterile cotton swab, blood draw, or lumbar puncture. Other techniques known to those skilled in the art are contemplated by this disclosure.

In the second stage a treatment may be applied to the body fluid. The treatment comprises exposing the body fluid to a binding antibody, such as F/LT Ab, that binds to an antigen specific to Covid-19. The Covid-19 specific antigen can include at least one antigen selected from the group consisting of Covid-19 spike glycoprotein, Covid-19 M-Protein, Covid-19 Hemoglutinesterase dimer, Covid-19 Envelope, Covid-19 E-Protein, Covid-19 N-Protein, nsp (non-structural protein) 12 RNA-dependent RNA polymerase (nsp 12), nsp (non-structural protein) 7, nsp 8, nsp 14, nsp 12-nsp 7-nsp 8 complex, nsp?-nsp8 complex, nsp10-nsp14 complex, nsp10-nsp16 complex, and  combinations thereof. The binding antibody and Covid-19 specific antigen form a virion antibody complex (F/LT Ab-TPA complex).

The virion antibody complex can be detected by standard laboratory techniques, such as spectroscopy. The amplified signal from the laboratory technique created by the virion antibody complex can be transmitted to a control unit which identifies the Covid-19 positivity or negativity. The entire system may be monitored and controlled utilizing a computer. Persons having ordinary skill in art will recognize that the steps described above can be performed on various devices/machines.

As an alternative to using a type of device as described above, the Covid-19 virions may be captured using antibody microarrays containing a binding antibody in a microarray. In one embodiment, the binding antibody comprises a fluorescent antibody (Fl). In a second embodiment, the binding antibody comprise a luminescent (Lu) antibody. The binding antibody can be organized in a microarray. The microarray is a plurality of antibodies fixed on a solid surface. The solid surface can be any suitable material but is conveniently transparent and selected from a group consisting of glass, plastic, silicon, and combinations thereof. The microarray allows detection of the virion antibody complex.

The microarray may comprise a plurality of monoclonal antibodies attached at high density on the solid surface. Typically, the microarray will contain  millions of antibodies, and the solid surface is transparent to facilitate detection. Any microarrays known by those skilled in the art sufficient to perform the described technique and are anticipated by this disclosure.

Exposure of the virion to the binding antibodies on the microarray may create the virion antibody complex. The complex can be tracked using an appropriate sensor. All steps in the process can be monitored and controlled by a computer in real time. Persons having ordinary skill in art will recognize that the steps described above can be performed on various devices/machines. This disclosure contemplates all known devices/machine that can perform the steps described in the above illustrative example.

To identify the virion antibody complex after exposure in the microarrays, the body fluid may then be forced through a container preferably constructed from a transparent material, which exposes the virion antibody complex to a light-sensing device. The sensing device also creates an enlarged, magnified visual image of virion antibody complex.

A concentrated and focused intense energy beam, such as light, may then be used to properly illuminate the virion antibody complex within the body fluid. Each virion antibody complex may be rapidly identified. The virion antibody complex may also be identified and tracked using optical or digital enhancement or magnification. Location and tracking of the virion antibody complex may also be achieved using  computer graphics and computer programs well known in the art. Latency times can be less than one microsecond. An alternative methodology would use optical pattern recognition of the virion antibody complex. Persons having ordinary skill in art will recognize that the steps described above can be performed on various devices/machines. This disclosure recognizes all known devices/machine that can perform the steps of the method.

Referring toFIG. 3, an example method is illustrated. A method for treating a body fluid comprising: a first stage including removing the body fluid from a patient at301; a second stage including applying a treatment to the body fluid wherein the treatment comprises an antibody that joins with an Covid-19 targeted antigen (TA) in the body fluid to form an antibody-TA complex, wherein the treatment comprises an antibody that joins with a Covid-19 targeted antigen (TA) in the body fluid to form an antibody-TA complex, wherein the antibody comprises a light functional antibody at302, and identifying the antibody-TA complex, using a spectroscopic technique, from the body fluid using a light source at303; and, as an optional step a third stage including returning the body fluid to the patient at304.

An exemplar embodiment has been described above. However, it will be apparent to those skilled in the art that numerous variations of the type described could be made to the present invention without departing from the spirit of the invention. The  scope of the present invention is defined by the broad general meaning of the terms in which the claims are expressed.

Unless otherwise indicated, all numbers expressing quantities of ingredients, properties such as molecular weight, reaction conditions, and so forth used in the specification and claims are to be understood as being modified in all instances by the term “about.”

While the invention has been particularly shown and described with reference to a preferred embodiment, it will be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the spirit and scope of the invention. All documents, books, manuals, papers, patents, published patent applications, guides, abstracts, and other references cited herein are incorporated by reference in their entirety.

It can be appreciated from the foregoing that electronic components of one or more systems or devices may include, but are not limited to, at least one processing unit, a memory, and a communication bus or communication means that couples various components including the memory to the processing unit(s). A system or device may include or have access to a variety of device readable media. System memory may include device readable storage media in the form of volatile and/or nonvolatile memory such as read only memory (ROM) and/or random access memory (RAM). By way of example, and not limitation, system memory may also include an operating system, application programs, other program modules, and program data.

Embodiments may be implemented as an instrument, system, method or program product. Accordingly, an embodiment may take the form of an entirely hardware embodiment, or an embodiment including software (including firmware, resident software, micro-code, etc.) that may all generally be referred to herein as a “circuit,” “module” or “system.” Furthermore, embodiments may take the form of a program  product embodied in at least one device readable medium having device readable program code embodied thereon.

A combination of device readable storage medium(s) may be utilized. In the context of this document, a device readable storage medium (“storage medium”) may be any tangible, non-signal medium that can contain or store a program comprised of program code configured for use by or in connection with an instruction execution system, apparatus, or device. For the purpose of this disclosure, a storage medium or device is to be construed as non-transitory, i.e., not inclusive of signals or propagating media.

Example embodiments are described herein with reference to the figures, which illustrate example methods, devices and products according to various example embodiments. It will be understood that the actions and functionality may be implemented at least in part by program instructions. These program instructions may be provided to a processor of a device, e.g., a hand-held measurement device, or other programmable data processing device to produce a machine, such that the instructions, which execute via a processor of the device, implement the functions/acts specified.

It is noted that the values provided herein are to be construed to include equivalent values as indicated by use of the term “about.” The equivalent values will be evident to those having ordinary skill in the art, but at the least include values obtained by ordinary rounding of the last significant digit.