System for evaluating person suffering from covid-19, method for evaluating person suffering from covid-19, and computer program

Abstract

[Problem] To suggest the possibility of olfactory / gustatory abnormality (impairment) by means of a numerical value based on the metabolism of tryptophan in the kynurenine pathway. [Solution] A system 1 for evaluating a person suffering from COVID-19 comprises: an acquisition means 10 for acquiring a numerical value based on the metabolism of tryptophan in the kynurenine pathway obtained by analyzing serum S during an acute phase of COVID-19 in a person suffering from COVID-19; and an evaluation means 30 that indicates the possibility of olfactory / gustatory abnormality (impairment) in the person suffering from COVID-19 on the basis of the numerical value (for example, a KTR value or a blood concentration value for quinolinic acid).

Description

COVID-19 Patient Evaluation System, COVID-19 Patient Evaluation Method, and Computer Program

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

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

[0003] For example, in Patent Document 1, there is proposed a method for obtaining data for predicting the prognosis of coronavirus infection, 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.

[0004] Japanese Patent Application Laid-Open No. 2024-59492

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

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

[0007] Here, the metabolism of tryptophan includes a serotonin pathway that generates serotonin (5-HT) and a kynurenine pathway that generates kynurenine (Kyn) and the like.

[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 one 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.

[0010] (1) A method for evaluating COVID-19 patients to assess olfactory / gustatory abnormalities (impairments), comprising: using a blood analyzer that analyzes components contained in the blood to analyze the serum of COVID-19 patients in the acute phase, displaying a value based on the metabolism of tryptophan in the kynurenine pathway obtained from the analysis, and evaluating the possibility that COVID-19 patients have olfactory / gustatory abnormalities (impairments) based on the displayed value.

[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 the invention of (1), the method for evaluating COVID-19 patients to assess 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 the value based on the metabolism of tryptophan, the possibility that COVID-19 patients have olfactory / gustatory abnormalities (impairments) is evaluated.

[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 a numerical 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 COVID-19 patients, comprising: an acquisition means for obtaining a numerical value based on the metabolism of tryptophan in the kynurenine pathway obtained by analyzing the serum of a COVID-19 patient in the acute phase; and an evaluation means for indicating the possibility that a COVID-19 patient has olfactory / gustatory abnormalities (impairments) based on the numerical value.

[0017] The invention of (2) provides a COVID-19 patient assessment system for evaluating olfactory / gustatory abnormalities (impairments) in COVID-19 patients, comprising an acquisition means and an evaluation means. The acquisition means acquires numerical values ​​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 values, the possibility that COVID-19 patients have olfactory / gustatory abnormalities (impairments).

[0018] The invention of (2) produces the same effects as the invention of (1).

[0019] (3) The COVID-19 patient assessment system according to (2), characterized in that 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, and the evaluation means indicates the possibility that a COVID-19 patient has olfactory / gustatory abnormalities (impairments) based on the KTR value.

[0020] Here, the KTR (Kynurene-to-Tryptophan Ratio) value is one of the biomarkers indicating activation of the kynurenine pathway, and is the value obtained by dividing the blood kynurenine concentration by the tryptophan concentration. In other words, if the KTR value is relatively high, it is presumed that the kynurenine pathway is activated, and as a result, the responsiveness of serotonin (5-HT) receptors and related signaling pathways is reduced.

[0021] In invention (3), 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.

[0022] Therefore, according to invention (3), the KTR value can be used to suggest the possibility of having an olfactory / gustatory abnormality (impairment).

[0023] (4) The COVID-19 patient assessment system according to (2) or (3), characterized in that the acquisition means acquires the blood concentration value of quinolinic acid as the numerical value based on the metabolism of tryptophan, and 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.

[0024] Here, quinolinic acid is a metabolite produced in the kynurenine pathway during tryptophan metabolism. In other words, when blood levels of quinolinic acid are relatively high, it is presumed that the kynurenine pathway is activated, and as a result, the responsiveness of serotonin (5-HT) receptors and related signaling pathways is reduced.

[0025] In invention (4), it is possible to indicate the possibility that COVID-19 patients have olfactory / gustatory abnormalities (impairments) based on the blood concentration value of quinolinic acid, which is a numerical value based on the metabolism of tryptophan in the kynurenine pathway.

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

[0027] (5) A method for evaluating a COVID-19 patient, comprising a COVID-19 patient evaluation system for evaluating olfactory / gustatory abnormalities (impairments), the method comprising: obtaining a numerical value based on the metabolism of tryptophan in the kynurenine pathway obtained by analyzing the serum of a COVID-19 patient in the acute phase; and indicating, based on the numerical value, the possibility that the COVID-19 patient has olfactory / gustatory abnormalities (impairments).

[0028] (6) A computer program that functions as a COVID-19 patient assessment system for evaluating olfactory / gustatory abnormalities (impairments) in COVID-19 patients, comprising: an acquisition means for obtaining numerical values ​​based on the metabolism of tryptophan in the kynurenine pathway obtained by analyzing the serum of COVID-19 patients in the acute phase; and an evaluation means for indicating the possibility that COVID-19 patients have olfactory / gustatory abnormalities (impairments) based on the numerical values.

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

[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.

[0031] This figure illustrates the outline of a COVID-19 patient assessment system according to an embodiment of the present invention. This figure illustrates the metabolism of tryptophan (Trp) in the human body. This block diagram shows the functional configuration of a COVID-19 patient assessment system according to an embodiment of the present invention. This figure compares the distribution of values ​​based on tryptophan metabolism (blood concentration values ​​of tryptophan (Trp)) between COVID-19 patients who had olfactory / gustatory abnormalities (impairments), COVID-19 patients who did not complain of olfactory / gustatory abnormalities (impairments), and healthy individuals. This figure compares the distribution of values ​​based on tryptophan metabolism (blood concentration values ​​of serotonin (5-HT)) between COVID-19 patients who had olfactory / gustatory abnormalities (impairments), COVID-19 patients who did not complain of olfactory / gustatory abnormalities (impairments), and healthy individuals. This figure compares the distribution of tryptophan metabolism-based values ​​(blood concentration of kynurenine (Kyn)) among COVID-19 patients who had olfactory / gustatory abnormalities (impairment), COVID-19 patients who did not report olfactory / gustatory abnormalities (impairment), and healthy individuals. This figure compares the distribution of tryptophan metabolism-based values ​​(KTR values) among COVID-19 patients who had olfactory / gustatory abnormalities (impairment), COVID-19 patients who did not report olfactory / gustatory abnormalities (impairment), and healthy individuals. This figure compares the distribution of tryptophan metabolism-based values ​​(blood concentration of quinolinic acid (QUIN)) among COVID-19 patients who had olfactory / gustatory abnormalities (impairment), COVID-19 patients who did not report olfactory / gustatory abnormalities (impairment), and healthy individuals. This figure compares the distribution of tryptophan metabolism-based values ​​(blood concentration values ​​of kynurenic acid (KYNA)) among COVID-19 patients who had olfactory / gustatory abnormalities (impairments), COVID-19 patients who did not report olfactory / gustatory abnormalities (impairments), and healthy individuals. This is a flowchart showing the COVID-19 patient evaluation process executed in the COVID-19 patient evaluation system according to an embodiment of the present invention.

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

[0033] [Overview of 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 and analyzes serum S in COVID-19 patients during the acute phase, obtaining a value based on the metabolism of tryptophan (Trp) in serum S. Based on this value based on tryptophan (Trp) metabolism, the COVID-19 patient assessment system 1 indicates the possibility that COVID-19 patients have post-symptomatic 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 to serotonin (5-HT) via the serotonin pathway, and then to kynurenine (KP), which converts it into kynurenine (Kyn), quinolinic acid (QUIN), NAD+ (nicotinamide adenine dinucleotide), etc.

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

[0037] The activity level of IDO / TDO is generally difficult to measure directly, so it is evaluated using "KTR". In other words, when a person contracts COVID-19, IDO / TDO is activated, kyn increases and trp decreases, so the KTR (kyn / trp) value rises.

[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 inventor 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, 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), it is possible to suggest the possibility of olfactory / gustatory abnormalities (impairments). 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 possibility of having olfactory / gustatory abnormalities (impairments) increases.

[0041] [Functional Configuration of COVID-19 Patient Assessment System] Next, the functional configuration of the COVID-19 patient assessment system will be described. Figure 3 is a block diagram showing the functional configuration of the 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 equipped with a blood analyzer that analyzes components contained in blood, or it may implement some or all of its functional configurations using a device other than the blood analyzer (for example, a terminal operated by a physician (such as a personal computer or tablet)) that acquires 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 a numerical value (for example, a value indicating the amounts of tryptophan, kynurenine, quinolinic acid, etc.) based on the metabolism of tryptophan in the kynurenine pathway obtained by analyzing the serum of COVID-19 patients in the acute phase. Specifically, when the COVID-19 patient evaluation system 1 includes a blood analysis device, the acquisition means 10 acquires, by the blood analysis device, 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. Also, when the COVID-19 patient evaluation system 1 does not include a blood analysis device, the acquisition means 10 acquires a numerical value based on the metabolism of tryptophan in the kynurenine pathway output from the blood analysis device.

[0045] The analysis result information generation means 20 calculates the amount of a predetermined substance generated in the kynurenine pathway of tryptophan based on the numerical value of the metabolism of tryptophan acquired by the acquisition means 10. Specifically, the analysis result information generation means 20 calculates (generates) the amount of a predetermined substance (analysis result information) per a predetermined amount of serum (for example, 1 mL, etc.) based on the numerical value of the metabolism of tryptophan.

[0046] Specifically, in the present embodiment, the analysis result information generation means 20 calculates, based on the numerical value of the metabolism of tryptophan, for example, the KTR value per 1 mL of serum, the blood concentration value of quinolinic acid, etc.

[0047] Figures 4 to 9 are diagrams comparing the distributions of numerical values based on the metabolism of tryptophan among those COVID-19 patients who had olfactory / gustatory abnormalities (disorders), those COVID-19 patients who had no complaints of olfactory / gustatory abnormalities (disorders), and healthy individuals.

[0048] In the examples shown in FIGS. 4 to 9, the COVID-19 patients are those who were excluded from the COVID-19 patients admitted to the medical institution to which the inventor belongs, including patients who are difficult to interview due to severe respiratory failure, cognitive impairment, progression of cancer, etc., minors under 20 years old, pregnant women, patients who do not understand Japanese, smokers, patients who had olfactory / gustatory disorders before COVID-19 infection, patients who were administered anticancer drugs within 3 weeks before COVID-19 infection, and patients who had not completed treatment for brain metastasis / CNS infiltration.

[0049] In the examples shown in FIGS. 4 to 9, such COVID-19 patients were classified as follows. "Group A" shows the distribution of numerical values based on the metabolism of tryptophan in patients who had olfactory / gustatory abnormalities (disorders) (26 people in the examples shown in FIGS. 4 to 9). "Group B" shows the distribution of numerical values based on the metabolism of tryptophan in patients who had no complaints of olfactory / gustatory abnormalities (disorders) (26 people in the examples shown in FIGS. 4 to 9). Also, "Group C" shows the distribution of numerical values based on the metabolism of tryptophan in healthy subjects (26 people in the examples shown in FIGS. 4 to 9).

[0050] FIG. 4 shows the distribution of blood concentration values (μg / mL) of tryptophan (Trp). As shown in FIG. 4, the blood concentration values of tryptophan are significantly higher in the order of "Group A" < "Group B" < "Group C". That is, the blood concentration of tryptophan is lower in COVID-19 patients than in healthy subjects, and even lower in patients with olfactory / gustatory disorders than in patients without complaints.

[0051] FIG. 5 shows the distribution of blood concentration values (μg / mL) of serotonin (5-HT). As shown in FIG. 5, there is no significant difference between groups in the blood concentration values of serotonin. From this result, it can be seen that the blood concentration value of serotonin is less likely to be involved in the onset of at least "olfactory / gustatory disorders in the acute phase of COVID-19".

[0052] Figure 6 shows the distribution of blood kynurenine (Kyn) concentrations (μg / mL). As shown in Figure 6, blood kynurenine concentrations were significantly higher in COVID-19 patients ("Group A" and "Group B") compared to healthy individuals ("Group C"). However, no significant correlation was detected between blood kynurenine concentrations 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, KTR values ​​decrease significantly in the order of "Group A" > "Group B" > "Group C". In other words, KTR values ​​are higher in COVID-19 patients compared to healthy individuals, and even higher in patients with olfactory / gustatory disorders compared to patients without complaints.

[0054] From 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 fact that patients with olfactory / gustatory disorders have higher KTR values ​​compared to patients without complaints indicates that the enzyme activity of IDO / TDO is higher.

[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, quinolinic acid is widely known to be 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, while quinolinic acid is known to be a "neurotoxin," kynurenic acid (KYNA) is widely known to have a "neuroprotective effect." For this reason, it is thought that in the bodies of 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, the following conclusions can be drawn: (Conclusion 1) There is no significant difference in serotonin (5-HT) blood concentration levels between patients with olfactory / gustatory dysfunction and patients without complaints of olfactory / gustatory dysfunction during the acute phase of COVID-19, and between healthy individuals.

[0061] (Conclusion 2) In long-COVID (so-called sequelae, also called "post-illness symptoms" in the medical community), tryptophan (Trp) is depleted due to activation of the kynurenine pathway (KP), and it is thought that the stored serotonin is gradually depleted. It is then hypothesized that this serotonin depletion is involved in the complexity of neurological symptoms.

[0062] (Conclusion 3) SARS-CoV-2 exhibits a preference for macrophage / microglia infection. 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. On the other hand, the production of the neuroprotector kynurenic acid (KYNA) in astrocytes is limited. From this, it can be concluded 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: (Point 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 onset).

[0065] (Item 2) If the mechanisms of onset are the same as those for olfactory / gustatory disorders and other neurological symptoms in Long-COVID, then (1) it may be similarly useful.

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

[0067] (Item 4) It may 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 values ​​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, for example, determine 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 CPU. 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, the COVID-19 patient assessment process performed by this system will be described. In the following processing flow chart, the processing order of each step may be changed as long as the relationship between the input and output of each step is not impaired. 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 based on the metabolism of tryptophan in the kynurenine pathway obtained by analyzing the serum of COVID-19 patients in the acute phase (for example, a value indicating the amount of tryptophan, kynurenine, quinolinic acid, etc.).

[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 ​​based on the metabolism of tryptophan obtained by the acquisition means 10 in step S1.

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

[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 numerical values ​​derived from the metabolism of tryptophan in the kynurenine pathway, obtained by analyzing the serum of COVID-19 patients during the acute phase. This makes it possible to suggest the possibility of olfactory / gustatory abnormalities (impairments) based on numerical values ​​derived from the metabolism of tryptophan in the kynurenine pathway.

[0080] Furthermore, according to the COVID-19 patient assessment system 1, the likelihood of having olfactory / gustatory abnormalities (impairments) is evaluated based on the value derived from serum tryptophan metabolism 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 of olfactory / gustatory abnormalities (impairments) in COVID-19 patients based on the KTR value, which is a numerical value based on the metabolism of tryptophan in the kynurenine pathway. Thus, it is 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 the blood concentration value of quinolinic acid, which is a numerical value based on the metabolism of tryptophan in the kynurenine pathway. Thus, it is possible to suggest the possibility of olfactory / gustatory abnormalities (impairments) based on the blood concentration value of quinolinic acid.

[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.

[0084] 1. COVID-19 patient assessment system 10. Acquisition means 20. Analysis result information generation means 30. Evaluation means

Claims

1. A method for evaluating olfactory / gustatory abnormalities (impairments) in COVID-19 patients, comprising: using a blood analyzer that analyzes components contained in the blood, analyzing the serum of COVID-19 patients in the acute phase, displaying a value based on the metabolism of tryptophan in the kynurenine pathway, and evaluating the possibility that COVID-19 patients have olfactory / gustatory abnormalities (impairments) based on the displayed value.

2. A COVID-19 patient assessment system for evaluating olfactory / gustatory abnormalities (impairments) in COVID-19 patients, comprising: an acquisition means for obtaining numerical values ​​based on tryptophan metabolism in the kynurenine pathway obtained by analyzing serum in the acute phase of COVID-19 patients; and an evaluation means for indicating the possibility that COVID-19 patients have olfactory / gustatory abnormalities (impairments) based on the numerical values.

3. The COVID-19 patient evaluation system according to claim 2, characterized in that 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, and the evaluation means indicates the possibility that a COVID-19 patient has olfactory / gustatory abnormalities (impairments) based on the KTR value.

4. The COVID-19 patient evaluation system according to claim 2 or 3, characterized in that the acquisition means acquires the blood concentration value of quinolinic acid as the numerical value based on the metabolism of tryptophan, and 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 evaluating a COVID-19 patient, comprising a COVID-19 patient evaluation system for evaluating olfactory / gustatory abnormalities (impairments), comprising the steps of: obtaining a numerical value based on the metabolism of tryptophan in the kynurenine pathway obtained by analyzing the serum of a COVID-19 patient in the acute phase; and indicating, based on the numerical value, the possibility that the COVID-19 patient has olfactory / gustatory abnormalities (impairments).

6. A computer program for evaluating olfactory / gustatory abnormalities (impairments) in COVID-19 patients, characterized by functioning as: an acquisition means for obtaining numerical values ​​based on tryptophan metabolism in the kynurenine pathway obtained by analyzing serum in the acute phase of COVID-19 patients; and an evaluation means for indicating the possibility that COVID-19 patients have olfactory / gustatory abnormalities (impairments) based on the numerical values.

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