In some embodiments, methods of inhibiting, ameliorating, reducing the severity of, treating, reducing the likelihood of, or preventing social isolation stress or symptoms thereof in a subject in need thereof are described. In some embodiments, methods of determining a risk of social isolation stress in a subject are described.

Provided herein are, in various embodiments, methods of detecting an acute inflammatory response associated with a viral infection in a patient, methods of predicting a likelihood of developing an acute inflammatory response (e.g., an acute respiratory distress syndrome) in a patient having a viral infection, such as a SARS-CoV2 infection, and methods of preparing a bodily fluid sample that is useful for performing the disclosed methods. The present invention also provides methods of treating a patient having a viral infection with a therapy that inhibits acute inflammation, such as acute inflammation mediated by the kinin-kallikrein system and/or the renin-angiotensin system (RAS).

In some embodiments, methods of inhibiting, ameliorating, reducing the severity of, treating, reducing the likelihood of, or preventing social isolation stress or symptoms thereof in a subject in need thereof are described. In some embodiments, methods of determining a risk of social isolation stress in a subject are described.

The invention discloses a method for measurement of peptidic degradation products of a proteolytic cascade in biological samples, especially blood samples, wherein the sample is incubated until a steady state equilibrium is reached for at least one peptidic degradation product involved in said proteolytic cascade and wherein said at least one peptidic degradation product in steady state equilibrium of the proteolytic cascade is quantified in the sample.

A recombinant protein drug includes a parent protein drug coupled with a modified kininogen-1 peptide. The modified kininogen-1 peptide has the sequence of SEQ ID NO:2 or a homolog having a sequence identity of 80% or higher. The parent protein drug is a bispecific antibody having a first targeting domain linked by a bridging domain with a second targeting domain. The modified kininogen-1 peptide is fused between the first targeting domain and the bridging domain, or between the bridging domain and the second targeting domain. A method for increasing the serum half-life of a protein drug includes constructing a fusion protein comprising the protein drug coupled with a modified kininogen-1 peptide.

In certain embodiments, the present invention provides a method of detecting hypoxia status in a tumor cell by detecting a level of hydroxyprolyl BK (Hyp-BK) peptides in a patient sample, and detecting a level of bradykinin (BK) peptides the patient sample, wherein a change in the Hyp-BK/BK ratio as compared to the Hyp-BK/BK ratio in a comparable normal cell is a marker for tumor hypoxia.

In some embodiments, methods of inhibiting, ameliorating, reducing the severity of, treating, reducing the likelihood of, or preventing social isolation stress or symptoms thereof in a subject in need thereof are described. In some embodiments, methods of determining a risk of social isolation stress in a subject are described.

In some embodiments, methods of inhibiting, ameliorating, reducing the severity of, treating, reducing the likelihood of, or preventing social isolation stress or symptoms thereof in a subject in need thereof are described. In some embodiments, methods of determining a risk of social isolation stress in a subject are described.

The invention discloses a method for measurement of peptidic degradation products of a proteolytic cascade in biological samples, especially blood samples, wherein the sample is incubated until a steady state equilibrium is reached for at least one peptidic degradation product involved in said proteolytic cascade and wherein said at least one peptidic degradation product in steady state equilibrium of the proteolytic cascade is quantified in the sample.

The invention discloses a method for measurement of peptidic degradation products of a proteolytic cascade (for example, the renin-angiotensin system (RAS) and the bradykinin system) in biological samples, especially blood samples, wherein the sample is incubated until a steady state equilibrium is reached for at least one peptidic degradation product involved in said proteolytic cascade and wherein said at least one peptidic degradation product in steady state equilibrium of the proteolytic cascade is quantified in the sample.