Methods of predicting susceptibility to infectious disease and related methods of treatment

Abstract

Disclosed herein are methods for predicting susceptibility to an infection based on the observation of specific mutations in blood cells, as well as methods for treating or reducing susceptibility to an infection in a subject.

1 . A method of treating a subject at risk of developing a severe complication from Coronavirus disease 2019 (COVID-19) infection, the method comprising
 determining whether the subject has clonal hematopoiesis of indeterminate potential (CHIP), wherein the step of determining whether the subject has CHIP comprises sequencing at least part of the genome of one or more cells in a blood sample of the subject to identify a mutation in one or more genes selected from the group consisting of DNMT3A, TET2, ASXL1, PPM1D, JAK2, TP53, SRSF2, KRAS and SF3B1, wherein the presence of said mutation indicates that the subject is at risk of developing a severe complication from COVID-19 infection; and   treating the subject identified as being at risk of developing a severe complication from COVID-19, wherein treating the subject comprises administering to the subject a treatment selected from the group consisting of an antiviral medication, monoclonal antibodies, and combinations thereof to reduce the subject's likelihood of contracting a severe complication from COVD-19 infection.   
     
     
         2 . The method of  claim 1 , wherein treating the subject further comprises administering to the subject one or more agents or vaccines to reduce the subject's likelihood of contracting COVD-19 infection. 
     
     
         3 . The method of  claim 1 , wherein the subject is under the age of 40. 
     
     
         4 . The method of  claim 1 , wherein the one or more cells in the blood sample are nucleated cells. 
     
     
         5 . The method of  claim 1 , wherein the one or more cells in the blood sample are somatic cells. 
     
     
         6 . The method of  claim 1 , wherein the mutation is a somatic mutation in DNMT3A and/or TET2. 
     
     
         7 . The method of  claim 1 , wherein the mutation is in DNMT3A in exons 7 to 23. 
     
     
         8 . The method of  claim 1 , wherein the mutation is a mis-sense mutation in DNMT3A selected from the group consisting of G543C, S714C, F732C, Y735C, R736C, R749C, F751C, W753C, and L889C. 
     
     
         9 . A method of treating a subject at risk of developing a severe coronavirus infection comprising determining whether the subject has clonal hematopoiesis of indeterminate potential (CHIP), wherein the step of determining whether the subject has CHIP comprises sequencing at least part of the genome of one or more cells in a blood sample of the subject to identify a mutation in one or more genes selected from the group consisting of DNMT3A, TET2, ASXL1, PPM1D, JAK2, TP53, SRSF2, KRAS and SF3B1, wherein the presence of said mutation indicates that the subject has CHIP and is at risk of developing a severe coronavirus infection; and
 treating the subject having CHIP by administering a treatment selected from the group consisting of an antiviral medication, monoclonal antibodies, and combinations thereof, to reduce the subject's risk of developing a severe coronavirus infection.   
     
     
         10 . The method of  claim 9 , wherein the coronavirus is selected from the group consisting of severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 
     
     
         11 . The method of  claim 9 , wherein the coronavirus comprises severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or COVID-19. 
     
     
         12 . The method of  claim 11 , wherein treating the subject further comprises administering to the subject one or more agents or vaccines to reduce the subject's likelihood of contracting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or COVID-19 infection. 
     
     
         13 . The method of  claim 9 , wherein the subject is under the age of 40. 
     
     
         14 . The method of  claim 9 , wherein the one or more cells in the blood sample are nucleated cells. 
     
     
         15 . The method of  claim 9 , wherein the one or more cells in the blood sample are somatic cells. 
     
     
         16 . The method of  claim 9 , wherein the mutation is a somatic mutation in DNMT3A and/or TET2. 
     
     
         17 . The method of  claim 9 , wherein the mutation is in DNMT3A in exons 7 to 23. 
     
     
         18 . The method of  claim 9 , wherein the mutation is a mis-sense mutation in DNMT3A selected from the group consisting of G543C, S714C, F732C, Y735C, R736C, R749C, F751C, W753C, and L889C. 
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . A method of selecting hematopoietic cells for transplantation, the method comprising the steps of:
 (a) obtaining a sample comprising hematopoietic cells from a human subject;   (b) sequencing at least part of the genome of one or more cells in the sample to identify a mutation in one or more genes selected from the group consisting of DNMT3A, TET2, ASXL1, PPM1D, JAK2, TP53, SRSF2, KRAS and SF3B1; and   (c) collecting the remaining hematopoietic cells in the sample for transplantation.