COVID-19 patient assessment system, COVID-19 patient assessment method, and computer program

Abstract

Numerical values ​​based on tryptophan metabolism in the kynurenine pathway suggest the possibility of olfactory / gustatory abnormalities (impairments). [Solution] The COVID-19 patient assessment system 1 comprises an acquisition means 10 that obtains a numerical value based on the metabolism of tryptophan in the kynurenine pathway obtained by analyzing serum S in the acute phase of a COVID-19 patient, and an evaluation means 30 that indicates the possibility that a COVID-19 patient has olfactory / gustatory abnormalities (impairments) based on this numerical value (e.g., KTR value, blood concentration value of quinolinic acid).

Description

Technical Field

[0001] The present invention relates to a COVID-19 patient evaluation system, a COVID-19 patient evaluation method, and a computer program.

Background Art

[0002] COVID-19 is a systemic disease presenting various clinical symptoms caused by SARS-CoV-2, but many aspects of its pathological conditions remain unclear. At the beginning of its emergence, the frequency of severe deterioration of acute respiratory failure, which was a problem, decreased. Instead, in recent years, the long-term persistence of post-illness symptoms (so-called sequelae) mainly characterized by neurological abnormalities such as olfactory and gustatory disorders, severe general malaise, and decline in cognitive function (so-called Long-COVID) has become a serious global problem.

[0003] For example, Patent Document 1 proposes a method for obtaining data for predicting the prognosis of coronavirus infectious diseases, which includes a step of detecting any one or more of the expression level of PRL, the expression level of TLR3, and the ratio of the expression level of PRL to the expression level of TLR3 in a biological sample collected from a living body.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0005] By the way, the post-illness symptoms of COVID-19 patients are observed in a very large number of patients and the pathological conditions are diverse, but there are many symptoms suggesting some neurological abnormalities (for example, olfactory / gustatory abnormalities).

[0006] Neurological post-symptomatic symptoms such as olfactory / gustatory abnormalities are thought to be caused by a decrease in the responsiveness of serotonin (5-HT) receptors and related signaling pathways produced by the metabolism of tryptophan (Trp) in the bodies of COVID-19 patients following SARS-CoV-2 infection.

[0007] Here, the metabolism of tryptophan involves the serotonin pathway, which produces serotonin (5-HT), and the kynurenine pathway, which produces kynurenine (Kyn), etc.

[0008] The inventors discovered that while there was little difference in serotonin blood levels between COVID-19 patients with post-symptoms and those without complaints of olfactory / gustatory abnormalities (impairments), which are an example of post-symptoms, there was a significant difference in the values ​​based on tryptophan metabolism in the kynurenine pathway.

[0009] The present invention aims to suggest the possibility of olfactory / gustatory abnormalities (impairments) based on numerical values ​​derived from tryptophan metabolism in the kynurenine pathway. [Means for solving the problem]

[0010] (1) A method for evaluating olfactory / gustatory abnormalities (impairments) in COVID-19 patients, Using a blood analyzer that analyzes components in blood, values ​​based on tryptophan metabolism in the kynurenine pathway, obtained by analyzing serum from patients in the acute phase of COVID-19, are displayed. A COVID-19 patient assessment method that evaluates the likelihood of a COVID-19 patient having olfactory / gustatory abnormalities (impairments) based on the displayed numerical values.

[0011] Here, it is hypothesized that in COVID-19 patients with olfactory / gustatory abnormalities (impairments), the kynurenine pathway is activated to such an extent that the responsiveness of serotonin (5-HT) receptors and related signaling pathways is reduced due to SARS-CoV-2 infection.

[0012] Therefore, if the values ​​based on tryptophan metabolism in the kynurenine pathway, which indicate activation of the kynurenine pathway, are relatively high, it can be assessed that there is a high possibility of having olfactory / gustatory abnormalities (impairments).

[0013] In invention (1), the method for evaluating olfactory / gustatory abnormalities (impairments) in COVID-19 patients first uses a blood analyzer to analyze the serum of COVID-19 patients in the acute phase and displays a value based on the metabolism of tryptophan in the kynurenine pathway. Then, based on values ​​derived from tryptophan metabolism, the likelihood of COVID-19 patients having olfactory / gustatory abnormalities (impairments) is assessed.

[0014] Therefore, according to invention (1), it is possible to suggest the possibility of having olfactory / gustatory abnormalities (impairments) based on numerical values ​​derived from the metabolism of tryptophan in the kynurenine pathway.

[0015] Furthermore, according to invention (1), the likelihood of having olfactory / gustatory abnormalities (impairments) is evaluated based on the value derived from the metabolism of serum tryptophan in the acute phase, which suggests the possibility of olfactory / gustatory abnormalities (impairments) occurring at a relatively early stage after contracting COVID-19.

[0016] (2) A COVID-19 patient assessment system for evaluating olfactory / gustatory abnormalities (impairments) in patients with COVID-19, A means for obtaining numerical values ​​based on tryptophan metabolism in the kynurenine pathway obtained from serum analysis of patients with COVID-19 in the acute phase, A COVID-19 patient assessment system characterized by comprising an assessment means that indicates the possibility that a COVID-19 patient has olfactory / gustatory abnormalities (impairments) based on the aforementioned numerical values.

[0017] In the invention of (2), a COVID-19 patient evaluation system for evaluating olfactory / gustatory abnormalities (disorders) in COVID-19 patients includes an acquisition means and an evaluation means. The acquisition means acquires a numerical value based on the metabolism of tryptophan in the kynurenine pathway obtained by analyzing the serum of COVID-19 patients in the acute phase. The evaluation means indicates, based on the numerical value, the possibility that a COVID-19 patient has olfactory / gustatory abnormalities (disorders).

[0018] According to the invention of (2), the same operational effects as those of the invention of (1) are achieved.

[0019] (3) The acquisition means acquires a KTR value, which is the ratio of the blood concentration of kynurenine to the blood concentration of tryptophan, as the numerical value based on the metabolism of tryptophan, The evaluation means indicates, based on the KTR value, the possibility that a COVID-19 patient has olfactory / gustatory abnormalities (disorders). The COVID-19 patient evaluation system according to (2) is characterized in this regard.

[0020] Here, the KTR (kynurenine-to-tryptophan ratio) value is one of the biomarkers indicating the activation of the kynurenine pathway and is the value obtained by dividing the blood concentration of kynurenine by the blood concentration of tryptophan. That is, when the KTR value is relatively high, it is presumed that the kynurenine pathway is activated, and as a result, the reactivity of the serotonin (5-HT) receptor and the signal transduction pathway related thereto is decreased.

[0021] In the invention of (3), based on the KTR value as the numerical value based on the metabolism of tryptophan in the kynurenine pathway, it is possible to indicate the possibility that a COVID-19 patient has olfactory / gustatory abnormalities (disorders).

[0022] Therefore, according to the invention of (3), it becomes possible to suggest the possibility of having olfactory / gustatory abnormalities (disorders) based on the KTR value.

[0023] (4) The acquisition means acquires the blood concentration value of quinolinic acid as the numerical value based on the metabolism of tryptophan, The evaluation means is characterized in that based on the blood concentration value of quinolinic acid, it indicates the possibility that a COVID-19 patient has olfactory / gustatory abnormality (disorder). The COVID-19 patient evaluation system according to (2) or (3).

[0024] Here, quinolinic acid is a metabolite produced in the kynurenine pathway in the metabolism of tryptophan. That is, when the blood concentration value of quinolinic acid is relatively high, it is presumed that the kynurenine pathway is activated, and as a result, the reactivity of the serotonin (5-HT) receptor and the signal transduction pathway related thereto is decreased.

[0025] In the invention of (4), based on the blood concentration value of quinolinic acid as the numerical value based on the metabolism of tryptophan in the kynurenine pathway, it is possible to indicate the possibility that a COVID-19 patient has olfactory / gustatory abnormality (disorder).

[0026] Therefore, according to the invention of (4), it becomes possible to suggest the possibility of having olfactory / gustatory abnormality (disorder) based on the blood concentration value of quinolinic acid.

[0027] (5) A method executed by a COVID-19 patient evaluation system for evaluating olfactory / gustatory abnormality (disorder) in COVID-19 patients, A step of acquiring a numerical value based on the metabolism of tryptophan in the kynurenine pathway obtained by analyzing the serum in the acute phase of COVID-19 patients, A step of indicating the possibility that a COVID-19 patient has olfactory / gustatory abnormality (disorder) based on the numerical value. A COVID-19 patient evaluation method characterized by including.

[0028] (6) A COVID-19 patient evaluation system for evaluating olfactory / gustatory abnormality (disorder) in COVID-19 patients, A means for obtaining numerical values ​​based on tryptophan metabolism in the kynurenine pathway, obtained by analyzing serum from patients with COVID-19 during the acute phase. A computer program characterized by functioning as an evaluation means to indicate the possibility that a person infected with COVID-19 may have olfactory / gustatory abnormalities (impairments) based on the aforementioned numerical values.

[0029] The inventions of (5) and (6) described herein produce the same effects as the COVID-19 patient assessment system described in (2). [Effects of the Invention]

[0030] According to the present invention, it is possible to suggest the possibility of having olfactory / gustatory abnormalities (impairments) based on numerical values ​​derived from tryptophan metabolism. [Brief explanation of the drawing]

[0031] [Figure 1] This figure illustrates an overview of a COVID-19 patient assessment system according to an embodiment of the present invention. [Figure 2] This diagram illustrates the metabolism of tryptophan (Trp) in the human body. [Figure 3] This is a block diagram showing the functional configuration of a COVID-19 patient assessment system according to an embodiment of the present invention. [Figure 4] This graph compares the distribution of tryptophan metabolism-based values ​​(blood concentration of tryptophan (Trp)) in COVID-19 patients who experienced olfactory / gustatory abnormalities (impairment), COVID-19 patients who did not report olfactory / gustatory abnormalities (impairment), and healthy individuals. [Figure 5] This graph compares the distribution of tryptophan metabolism-based values ​​(blood serotonin (5-HT) levels) among COVID-19 patients who experienced olfactory / gustatory abnormalities (impairment), COVID-19 patients who did not report olfactory / gustatory abnormalities (impairment), and healthy individuals. [Figure 6]This graph compares the distribution of tryptophan metabolism-based values ​​(blood concentration of kynurenine (Kyn)) in COVID-19 patients who experienced olfactory / gustatory abnormalities (impairment), COVID-19 patients who did not report olfactory / gustatory abnormalities (impairment), and healthy individuals. [Figure 7] This graph compares the distribution of tryptophan metabolism-based values ​​(KTR values) among COVID-19 patients who experienced olfactory / gustatory abnormalities (impairments), COVID-19 patients who did not report olfactory / gustatory abnormalities (impairments), and healthy individuals. [Figure 8] This graph compares the distribution of tryptophan metabolism-based values ​​(blood concentration of quinolinic acid (QUIN)) in COVID-19 patients who experienced olfactory / gustatory abnormalities (impairment), COVID-19 patients who did not report olfactory / gustatory abnormalities (impairment), and healthy individuals. [Figure 9] This graph compares the distribution of tryptophan metabolism-based values ​​(blood concentration of kynurenic acid (KYNA)) in COVID-19 patients who experienced olfactory / gustatory abnormalities (impairment), COVID-19 patients who did not report olfactory / gustatory abnormalities (impairment), and healthy individuals. [Figure 10] This flowchart shows the COVID-19 patient assessment process performed in the COVID-19 patient assessment system according to an embodiment of the present invention. [Modes for carrying out the invention]

[0032] Hereinafter, embodiments for carrying out the present invention will be described in detail with reference to the attached drawings.

[0033] [Overview of the COVID-19 Patient Assessment System] Figure 1 is a diagram illustrating an overview of a COVID-19 patient assessment system according to an embodiment of the present invention.

[0034] The COVID-19 patient assessment system 1 includes at least a blood analyzer to analyze serum S in patients with COVID-19 during the acute phase and obtain values ​​based on the metabolism of tryptophan (Trp) in serum S. Furthermore, the COVID-19 patient assessment system 1 uses numerical values ​​based on tryptophan (Trp) metabolism to indicate the likelihood that a COVID-19 patient may have post-symptoms (such as olfactory / gustatory abnormalities, memory impairment, and cognitive decline).

[0035] Figure 2 illustrates the metabolism of tryptophan (Trp) in the human body. In the human body, tryptophan (Trp) is converted into serotonin (5-HT) via the serotonin pathway, and into kynurenine (Kyn), quinolinic acid (QUIN), NAD+ (nicotinamide adenine dinucleotide), etc. via the kynurenine pathway (KP).

[0036] In Figure 2, IDO (Indoleamine 2,3-Dioxygenase) and TDO (Tryptophan 2,3-Dioxygenase) are enzymes that convert Trp to Kyn.

[0037] The activity level of IDO / TDO is generally difficult to measure directly, so it is assessed using "KTR". In other words, when infected with COVID-19, IDO / TDO is activated, Kyn increases and Trp decreases, so the KTR (Kyn / Trp) value increases.

[0038] Furthermore, the virus that causes COVID-19 (SARS-CoV-2) infects nerve cells called astrocytes and microglia, as well as immune system cells called macrophages, hijacking these cells and causing them to malfunction.

[0039] The inventors then discovered that while there was little difference in serotonin blood levels between COVID-19 patients with olfactory / gustatory abnormalities (impairments) and those without complaints of olfactory / gustatory abnormalities (impairments), there were differences in the values ​​based on tryptophan metabolism in the kynurenine pathway.

[0040] In this embodiment, it is possible to suggest the possibility of olfactory / gustatory abnormalities (impairments) by showing numerical values ​​based on the metabolism of tryptophan in the kynurenine pathway of a COVID-19 patient (e.g., KTR value or the blood concentration value of quinolinic acid). For example, if the numerical values ​​based on the metabolism of tryptophan in the kynurenine pathway of a COVID-19 patient (e.g., KTR value or the blood concentration value of quinolinic acid) are higher than those of COVID-19 patients without olfactory / gustatory abnormalities (impairments) or healthy individuals, the likelihood of having olfactory / gustatory abnormalities (impairments) increases.

[0041] [Functional Configuration of the COVID-19 Patient Assessment System] Next, we will describe the functional configuration of the COVID-19 patient assessment system. Figure 3 is a block diagram showing the functional configuration of a COVID-19 patient assessment system according to an embodiment of the present invention.

[0042] The COVID-19 patient assessment system 1 comprises an acquisition means 10, an analysis result information generation means 20, and an evaluation means 30, and can be connected via a network to an external storage device or a terminal operated by a physician (such as a personal computer or tablet).

[0043] Furthermore, the COVID-19 patient assessment system 1 may implement all of its functional configurations using a computer installed in a blood analyzer that analyzes components contained in blood, or it may implement some or all of its functional configurations using a separate device (for example, a terminal operated by a physician (such as a personal computer or tablet)) that obtains numerical values ​​based on the metabolism of tryptophan in the kynurenine pathway output from the blood analyzer, and based on those numerical values.

[0044] The acquisition means 10 acquires numerical values ​​based on the metabolism of tryptophan in the kynurenine pathway obtained by analyzing serum from COVID-19 patients in the acute phase (for example, values ​​indicating the amounts of tryptophan, kynurenine, quinolinic acid, etc.). Specifically, if the COVID-19 patient assessment system 1 includes a blood analyzer, the acquisition means 10 acquires numerical values ​​based on the metabolism of tryptophan in the kynurenine pathway obtained by analyzing serum from COVID-19 patients in the acute phase using the blood analyzer. If the COVID-19 patient assessment system 1 does not include a blood analyzer, the acquisition means 10 acquires numerical values ​​based on the metabolism of tryptophan in the kynurenine pathway output from the blood analyzer.

[0045] The analysis result information generation means 20 calculates the amount of a predetermined substance produced in the kynurenine pathway of tryptophan based on the numerical values ​​obtained by the acquisition means 10 based on the metabolism of tryptophan. Specifically, the analysis result information generation means 20 calculates (generates) the amount of a predetermined substance (analysis result information) per predetermined amount of serum (e.g., 1 mL) based on the numerical values ​​based on the metabolism of tryptophan.

[0046] In detail, the analysis result information generation means 20 calculates, for example, the KTR value per 1 mL of serum, the blood concentration value of quinolinic acid, etc., based on numerical values ​​derived from the metabolism of tryptophan in this embodiment.

[0047] Figures 4 to 9 compare the distribution of tryptophan metabolism-based values ​​among COVID-19 patients who experienced olfactory / gustatory abnormalities (impairments), COVID-19 patients who did not report olfactory / gustatory abnormalities (impairments), and healthy individuals.

[0048] In the examples shown in Figures 4 to 9, the COVID-19 patients are those who were hospitalized at the medical institution to which the inventor belongs and who were excluded from the following: patients who were difficult to interview due to severe respiratory failure, cognitive impairment, cancer progression, etc.; minors under the age of 20; pregnant women; patients who do not understand Japanese; smokers; patients who had olfactory / gustatory disorders before COVID-19 infection; patients who received anticancer drugs within three weeks prior to COVID-19 infection; and patients who had not completed treatment for brain metastases / central nervous system invasion.

[0049] In the examples shown in Figures 4 to 9, COVID-19 patients were classified as follows: "Group A" shows the distribution of values ​​based on tryptophan metabolism in patients (26 people in the examples shown in Figures 4 to 9) who had olfactory / gustatory abnormalities (impairments). "Group B" shows the distribution of tryptophan metabolism values ​​in patients who did not complain of olfactory / gustatory abnormalities (impairments) (26 patients in the examples shown in Figures 4 to 9). Furthermore, "Group C" shows the distribution of values ​​based on tryptophan metabolism in healthy individuals (26 people in the examples shown in Figures 4 to 9).

[0050] Figure 4 shows the distribution of tryptophan (Trp) blood concentration values ​​(μg / mL). As shown in Figure 4, tryptophan blood levels are significantly higher in the order of "Group A" < "Group B" < "Group C". In other words, tryptophan blood levels are lower in COVID-19 patients compared to healthy individuals, and even lower in patients with olfactory / gustatory disorders compared to patients without complaints.

[0051] Figure 5 shows the distribution of blood serotonin (5-HT) concentration values ​​(μg / mL). As shown in Figure 5, there were no significant differences in serotonin blood levels between the groups. From these results, it can be concluded that serotonin blood levels are unlikely to be involved in the development of "olfactory / gustatory disorders in the acute phase of COVID-19."

[0052] Figure 6 shows the distribution of blood concentrations (μg / mL) of kynurenine (Kyn). As shown in Figure 6, blood kynurenine levels were significantly higher in COVID-19 patients ("Group A" and "Group B") compared to healthy individuals ("Group C"). However, no significant correlation was found between blood kynurenine levels in patients with olfactory / gustatory disorders ("Group A") and in patients without complaints ("Group B").

[0053] Figure 7 shows the distribution of KTR (Kyn / Trp ratio) values. As shown in Figure 7, the KTR value decreases significantly in the order of "Group A" > "Group B" > "Group C". In other words, the KTR value is higher in COVID-19 patients compared to healthy individuals, and even higher in patients with olfactory / gustatory disorders compared to patients without complaints.

[0054] Based on these results, it can be seen that the decrease in tryptophan blood concentration in COVID-19 is due to the activation of the enzyme IDO / TDO, which in turn activates the kynurenine pathway and leads to "degradation" of tryptophan, as indicated by the KTR status. Furthermore, the higher KTR levels in patients with olfactory / gustatory disorders compared to patients without complaints indicate higher IDO / TDO enzyme activity.

[0055] Next, we will explain kynurenic acid (KYNA) and quinolinic acid (QUIN), which are produced when kynurenine is further metabolized.

[0056] Figure 8 shows the distribution of blood concentration values ​​(nM) of quinolinic acid (QUIN). Here, it is widely known that quinolinic acid is a "neurotoxin" that causes damage to the nervous system.

[0057] As shown in Figure 8, blood quinolinic acid levels decrease significantly in the order of "Group A" > "Group B" > "Group C". In other words, blood quinolinic acid levels are higher in COVID-19 patients compared to healthy individuals, and even higher in patients with olfactory / gustatory disorders compared to patients without complaints.

[0058] Figure 9 shows the distribution of blood concentration values ​​(nM) of kynurenic acid (KYNA). Here, it is widely known that quinolinic acid is a "neurotoxin," while kynurenic acid (KYNA) has a "neuroprotective effect." Therefore, it is thought that in healthy individuals, a balance is maintained between the "neurotoxin" quinolinic acid and the "neuroprotective" kynurenic acid.

[0059] As shown in Figure 9, blood levels of kynurenic acid were significantly higher in patients without complaints of olfactory / gustatory dysfunction ("Group B") than in healthy individuals ("Group C"), but no significant difference was observed between patients with olfactory / gustatory dysfunction ("Group A") and healthy individuals ("Group C"). Furthermore, there was no significant difference between COVID-19 patients ("Group A" and "Group B") based on the presence or absence of olfactory / gustatory dysfunction, suggesting that the "neuroprotective effect" may not be working effectively.

[0060] Based on the examples shown in Figures 4 to 9, we can draw the following conclusions. (Conclusion 1) There was no significant difference in serotonin (5-HT) blood levels between patients with olfactory / gustatory dysfunction during the acute phase of COVID-19, patients without complaints of olfactory / gustatory dysfunction, and healthy controls.

[0061] (Conclusion 2) In long-term COVID-19 (so-called post-COVID symptoms, also known as "post-infection symptoms" in the medical community), the activation of the kynurenine pathway (KP) depletes tryptophan (Trp), leading to a gradual depletion of stored serotonin. This serotonin depletion is then thought to contribute to the complexity of neurological symptoms.

[0062] (Conclusion 3) SARS-CoV-2 has a preference for infecting macrophages / microglia. This suggests IDO / TDO activation due to functional changes after infection. In other words, the kynurenine pathway (KP) is activated.

[0063] (Conclusion 4) Activation of the kynurenine pathway (KP) significantly increases the production of neurotoxins such as quinolinic acid (QUIN) from macrophages. Conversely, the production of the neuroprotector kynurenic acid (KYNA) in astrocytes is limited. This suggests that an imbalance between quinolinic acid (QUIN) and kynurenic acid (KYNA) correlates with olfactory and gustatory disorders, at least in the acute phase of COVID-19.

[0064] Based on the examples shown in Figures 4 to 9, the following points have become clear. (Item 1) KTR levels and blood quinolinic acid (QUIN) levels are promising biomarkers (markers for predicting disease onset and for post-treatment follow-up) for the onset of olfactory / gustatory disorders in the acute phase of COVID-19 (generally within one week of symptom onset).

[0065] (Item 2) If the mechanisms of onset are similar to those in long-term COVID-19, then (1) it may be equally useful.

[0066] (Item 3) KTR levels and blood quinolinic acid (QUIN) levels may be useful not only as biomarkers for COVID-19, but also as biomarkers for olfactory / gustatory disorders during the side effects of anticancer drugs and during pregnancy (both of which are widely known to involve IDO / TDO activation).

[0067] (Item 4) This could potentially lead to the development of treatments for neurological symptoms related to COVID-19.

[0068] Returning to Figure 3, the evaluation means 30 indicates the possibility that a COVID-19 patient has olfactory / gustatory abnormalities (impairments) based on the numerical value based on tryptophan metabolism calculated by the analysis result information generation means 20. More specifically, the evaluation means 30 indicates the possibility that a COVID-19 patient has olfactory / gustatory abnormalities (impairments) based on the KTR value calculated by the analysis result information generation means 20. In addition, the evaluation means 30 indicates the possibility that a COVID-19 patient has olfactory / gustatory abnormalities (impairments) based on the blood concentration value of quinolinic acid calculated by the analysis result information generation means 20.

[0069] Specifically, the evaluation means 30 displays the numerical values ​​based on tryptophan metabolism calculated by the analysis result information generation means 20 on a display means (e.g., a display) provided by the COVID-19 patient assessment system 1, or on a display means of a terminal connected to the COVID-19 patient assessment system 1 (e.g., a monitor, PC, tablet, smartphone, etc.), or outputs them as printed material or as audio to an output means (e.g., a printer, speaker, etc.).

[0070] Furthermore, the evaluation means 30 may determine the likelihood that a COVID-19 patient has olfactory / gustatory abnormalities (impairments) based on the numerical value calculated by the analysis result information generation means 20 based on tryptophan metabolism, and display this determination result.

[0071] In this case, the evaluation means 30 may determine, for example, that there is a possibility of having an olfactory / gustatory abnormality (impairment) if the KTR value (KTR value of a COVID-19 patient in the acute phase) calculated by the analysis result information generation means 20 is 40,000 or more, and this determination result may be shown as the possibility of having an olfactory / gustatory abnormality (impairment).

[0072] Furthermore, the evaluation means 30 may determine, for example, that there is a possibility of olfactory / gustatory abnormalities (impairments) if the blood concentration value of quinolinic acid (QUIN) calculated by the analysis result information generation means 20 (blood concentration value of quinolinic acid in a COVID-19 patient in the acute phase) is 400 nM (nanomoles) or higher, and this determination result may be shown as the possibility of olfactory / gustatory abnormalities (impairments).

[0073] In this embodiment, KTR values ​​and blood quinolinic acid (QUIN) levels are used as examples of values ​​based on tryptophan metabolism. However, the embodiment is not limited to these, and any values ​​that show a significant difference between patients with olfactory / gustatory abnormalities (impairments), patients without complaints of olfactory / gustatory abnormalities (impairments), and healthy individuals can be used.

[0074] The functional configuration of this system described above is merely an example, and a single functional block (database and functional processing unit) may be divided, or multiple functional blocks may be combined into a single functional block. Each functional processing unit is realized by a computer program (for example, core software or an application that causes the CPU to execute the various processes described above) stored in a storage device (storage means) such as ROM (Read Only Memory), flash memory, SSD (Solid State Drive), or hard disk, which is read by the CPU (Central Processing Unit) built into the device or terminal, and executed by the computer program. In other words, each functional processing unit is realized by this computer program reading and writing necessary data such as tables from a database (DB) stored in the storage device or from a storage area in memory, and, if necessary, controlling related hardware (for example, input / output devices, display devices, communication interface devices). Furthermore, the database (DB) in the embodiments of the present invention may be a commercial database, but it also means a mere collection of tables and files, and the internal structure of the database itself is not specified.

[0075] [COVID-19 patient assessment process] Next, we will describe the COVID-19 patient assessment process performed by this system. In the following processing flow chart, the order of processing steps may be changed as long as the relationship between the inputs and outputs of each step is not compromised. Figure 10 is a flowchart showing the COVID-19 patient assessment process performed by the COVID-19 patient assessment system according to an embodiment of the present invention.

[0076] In step S1, the acquisition means 10 obtains a numerical value (for example, a value indicating the amount of tryptophan, kynurenine, quinolinic acid, etc.) based on the metabolism of tryptophan in the kynurenine pathway obtained by analyzing the serum of a COVID-19 patient in the acute phase.

[0077] In step S2, the analysis result information generation means 20 calculates the amount of a predetermined substance produced in the kynurenine pathway of tryptophan (for example, the KTR value per 1 mL of serum and the blood concentration value of quinolinic acid) based on the numerical values ​​obtained by the acquisition means 10 in step S1 based on the metabolism of tryptophan.

[0078] In step S3, the evaluation means 30 indicates the possibility that a person infected with COVID-19 has olfactory / gustatory abnormalities (impairments) based on the numerical value based on tryptophan metabolism calculated by the analysis result information generation means 20 in step S2.

[0079] According to the COVID-19 patient assessment system 1, the likelihood of a COVID-19 patient having olfactory / gustatory abnormalities (impairments) is assessed based on values ​​derived from the metabolism of tryptophan in the kynurenine pathway, obtained by analyzing serum from COVID-19 patients during the acute phase. This makes it possible to suggest the possibility of olfactory / gustatory abnormalities (impairments) based on the values ​​derived from tryptophan metabolism in the kynurenine pathway.

[0080] Furthermore, according to the COVID-19 patient assessment system 1, the likelihood of having olfactory / gustatory abnormalities (impairments) is assessed based on the metabolic level of serum tryptophan during the acute phase. Therefore, it can suggest that olfactory / gustatory abnormalities (impairments) may occur at a relatively early stage after contracting COVID-19.

[0081] Furthermore, according to the COVID-19 patient assessment system 1, it is possible to indicate the possibility that COVID-19 patients have olfactory / gustatory abnormalities (impairments) based on the KTR value, which is a numerical value based on the metabolism of tryptophan in the kynurenine pathway. This makes it possible to suggest the possibility of olfactory / gustatory abnormalities (impairments) based on the KTR value.

[0082] Furthermore, according to the COVID-19 patient assessment system 1, it is possible to indicate the possibility of olfactory / gustatory abnormalities (impairments) in COVID-19 patients based on blood quinolinic acid levels, which are values ​​derived from the metabolism of tryptophan in the kynurenine pathway. This makes it possible to suggest the possibility of olfactory / gustatory abnormalities (impairments) based on blood quinolinic acid levels.

[0083] Although embodiments of the present invention have been described above, it goes without saying that the technical scope of the present invention is not limited to the contents of the above embodiments. It will be obvious to those skilled in the art that various modifications or improvements can be made to the above embodiments. Furthermore, it is clear from the claims that such modified or improved forms are also included in the technical scope of the present invention. [Explanation of Symbols]

[0084] 1. COVID-19 Patient Assessment System 10 Acquisition method 20 Analysis result information generation means 30 Evaluation methods

Claims

1. A method for evaluating olfactory / gustatory abnormalities (impairments) in COVID-19 patients, Using a blood analyzer that analyzes components in blood, values ​​based on tryptophan metabolism in the kynurenine pathway, obtained by analyzing serum from patients in the acute phase of COVID-19, are displayed. A COVID-19 patient assessment method that evaluates the likelihood of a COVID-19 patient having olfactory / gustatory abnormalities (impairments) based on the displayed numerical values.

2. A COVID-19 patient assessment system for evaluating olfactory / gustatory abnormalities (impairments) in COVID-19 patients, A means for obtaining numerical values ​​based on tryptophan metabolism in the kynurenine pathway obtained by analyzing serum from patients with COVID-19 in the acute phase, A COVID-19 patient assessment system characterized by comprising an evaluation means that indicates the possibility that a COVID-19 patient has olfactory / gustatory abnormalities (impairments) based on the aforementioned numerical values.

3. The acquisition means acquires the KTR value, which is the ratio of the blood concentration of kynurenine to the blood concentration of tryptophan, as the numerical value based on the metabolism of tryptophan. The COVID-19 patient evaluation system according to claim 2, characterized in that the evaluation means indicates the possibility that a COVID-19 patient has olfactory / gustatory abnormalities (impairments) based on the KTR value.

4. The acquisition means acquires the blood concentration value of quinolinic acid as the numerical value based on the metabolism of tryptophan, The COVID-19 patient evaluation system according to claim 2 or 3, characterized in that the evaluation means indicates the possibility that a COVID-19 patient has olfactory / gustatory abnormalities (impairments) based on the blood concentration value of quinolinic acid.

5. A method for a COVID-19 patient assessment system to evaluate olfactory / gustatory abnormalities (impairments) in COVID-19 patients, The steps include: obtaining numerical values ​​based on tryptophan metabolism in the kynurenine pathway by analyzing serum from patients with COVID-19 during the acute phase; A method for evaluating COVID-19 patients, characterized by including the step of indicating the possibility that a COVID-19 patient has olfactory / gustatory abnormalities (impairments) based on the aforementioned numerical values.

6. A COVID-19 patient assessment system to evaluate olfactory / gustatory abnormalities (impairments) in COVID-19 patients. A means for obtaining numerical values ​​based on tryptophan metabolism in the kynurenine pathway, obtained by analyzing serum from patients in the acute phase of COVID-19. A computer program characterized by functioning as an evaluation means to indicate the possibility that a person infected with COVID-19 may have olfactory / gustatory abnormalities (impairments) based on the aforementioned numerical values.

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