Methods for treating infections
Inventors
Natarajan, Pradeep • Genovese, Giulio • ZEKAVAT, Seyedeh Maryam • MACHIELA, Mitchell J. • Lin, Shu-Hong
Assignees
Yale University • General Hospital Corp • Broad Institute Inc • US Department of Health and Human Services
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Publication Number
US-12374435-B2
Publication Date
2025-07-29
Expiration Date
Abstract
The invention features methods that are useful for treatment of a patient at increased risk for infection and for selecting a patient for treatment for an infection. In various embodiments, the infection is coronavirus disease 2019 (COVID-19), sepsis, or other respiratory infections.
Core Innovation
The invention relates to identifying a subject at high risk of having or developing a severe respiratory infection or sepsis by detecting expanded mosaic chromosomal alterations (mCAs) in DNA derived from a blood or saliva sample. The detection is performed using single-nucleotide polymorphism (SNP) microarray genotype intensity data, and the presence of an expanded mCA identifies the subject as at high risk.
The computing devices locate a chromosomal location of each expanded mCA present and determine a copy number of each expanded mCA present. This characterization of the expanded mCAs supports risk stratification for severe respiratory infection or sepsis and links expanded mCAs to incident infections, including sepsis and pneumonia, and to COVID-19 hospitalization.
The invention further provides management decisions based on the expanded mCA finding. The subject identified as high risk is provided with aggressive treatment comprising administering a nucleoside analog, wherein the nucleoside analog is remdesivir, and the framework also supports prioritizing subjects for viral testing or vaccination.
Claims Coverage
The independent claims cover three related methods that share a common workflow: detect expanded mosaic chromosomal alterations (mCAs) in DNA from a blood or saliva sample using SNP microarray genotype intensity data, then characterize the expanded mCAs by chromosomal location and copy number to support clinical risk use cases involving severe respiratory infection or sepsis, viral testing or vaccination prioritization, and selection for aggressive treatment. The claim set includes at least three independent claims.
Risk identification from expanded mCAs for severe respiratory infection or sepsis
Detect presence or absence of expanded mosaic chromosomal alterations (mCAs) in DNA derived from a blood or saliva sample using SNP microarray genotype intensity data, where presence of an expanded mCA identifies the subject as at high risk of having or developing severe respiratory infection or sepsis; locate a chromosomal location of each expanded mCA present; determine a copy number of each expanded mCA present; provide the subject at high risk with aggressive treatment comprising administering a nucleoside analog, wherein the nucleoside analog is remdesivir.
Prioritization for viral testing or vaccination using expanded mCAs
Detect presence or absence of expanded mosaic chromosomal alterations (mCAs) in DNA derived from a blood or saliva sample using SNP microarray genotype intensity data, where presence of an expanded mCA identifies the subject as at high risk of having or developing severe respiratory infection or sepsis thereby indicating that the subject should be prioritized for viral testing or vaccination; locate a chromosomal location of each expanded mCA present; determine a copy number of each expanded mCA present; provide the subject at high risk with aggressive treatment comprising administering a nucleoside analog, wherein the nucleoside analog is remdesivir.
Selection for aggressive treatment using expanded mCAs
Detect presence or absence of expanded mosaic chromosomal alterations (mCAs) in DNA derived from a blood or saliva sample using SNP microarray genotype intensity data, where presence of an expanded mCA identifies the subject as in need of aggressive treatment for the respiratory infection or sepsis; locate a chromosomal location of each expanded mCA present; determine a copy number of each expanded mCA present; where the aggressive treatment comprises administering a nucleoside analog, wherein the nucleoside analog is remdesivir.
Across the independent claims, the inventive coverage centers on using SNP microarray genotype intensity data to detect expanded mCAs in blood- or saliva-derived DNA, then locating each expanded mCA and determining its copy number. The resulting expanded mCA presence is used to identify high-risk subjects and to support downstream clinical decisions that include aggressive treatment with remdesivir, as well as prioritizing viral testing or vaccination.
Stated Advantages
Identifies a subject at high risk of having or developing a severe respiratory infection or sepsis using expanded mosaic chromosomal alterations (mCAs) detected from blood or saliva DNA.
Enables prioritizing a subject for viral testing or vaccination based on expanded mCAs indicating high risk.
Supports selection of a subject for aggressive treatment for severe respiratory infection or sepsis.
Aggressive treatment includes administering a nucleoside analog, specifically remdesivir, for subjects identified as high risk.
Documented Applications
Identifying subjects at high risk for severe respiratory infection or sepsis based on expanded mCAs detected from blood or saliva DNA using SNP microarray genotype intensity data.
Prioritizing subjects for viral testing or vaccination based on expanded mCAs indicating high risk for severe respiratory infection or sepsis.
Selecting subjects for aggressive treatment for severe respiratory infection or sepsis, with aggressive treatment comprising administering a nucleoside analog wherein the nucleoside analog is remdesivir.
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