Reactivation of multiple viruses in patients with sepsis.
A current controversy is whether patients with sepsis progress to an immunosuppressed state. We hypothesized that reactivation of latent viruses occurred with prolonged sepsis thereby providing evidence of clinically-relevant immunosuppression and potentially providing a means to serially-monitor pa...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4053360?pdf=render |
| _version_ | 1818566474427531264 |
|---|---|
| author | Andrew H Walton Jared T Muenzer David Rasche Jonathan S Boomer Bryan Sato Bernard H Brownstein Alexandre Pachot Terrence L Brooks Elena Deych William D Shannon Jonathan M Green Gregory A Storch Richard S Hotchkiss |
| author_facet | Andrew H Walton Jared T Muenzer David Rasche Jonathan S Boomer Bryan Sato Bernard H Brownstein Alexandre Pachot Terrence L Brooks Elena Deych William D Shannon Jonathan M Green Gregory A Storch Richard S Hotchkiss |
| author_sort | Andrew H Walton |
| collection | DOAJ |
| description | A current controversy is whether patients with sepsis progress to an immunosuppressed state. We hypothesized that reactivation of latent viruses occurred with prolonged sepsis thereby providing evidence of clinically-relevant immunosuppression and potentially providing a means to serially-monitor patients' immune status. Secondly, if viral loads are markedly elevated, they may contribute to morbidity and mortality. This study determined if reactivation of herpesviruses, polyomaviruses, and the anellovirus TTV occurred in sepsis and correlated with severity. Serial whole blood and plasma samples from 560 critically-ill septic, 161 critically-ill non-septic, and 164 healthy age-matched patients were analyzed by quantitative-polymerase-chain-reaction for cytomegalovirus (CMV), Epstein-Barr (EBV), herpes-simplex (HSV), human herpes virus-6 (HHV-6), and TTV. Polyomaviruses BK and JC were quantitated in urine. Detectable virus was analyzed with respect to secondary fungal and opportunistic bacterial infections, ICU duration, severity of illness, and survival. Patients with protracted sepsis had markedly increased frequency of detectable virus. Cumulative viral DNA detection rates in blood were: CMV (24.2%), EBV (53.2%), HSV (14.1%), HHV-6 (10.4%), and TTV (77.5%). 42.7% of septic patients had presence of two or more viruses. The 50% detection rate for herpesviruses was 5-8 days after sepsis onset. A small subgroup of septic patients had markedly elevated viral loads (>104-106 DNA copies/ml blood) for CMV, EBV, and HSV. Excluding TTV, DNAemia was uncommon in critically-ill non-septic patients and in age-matched healthy controls. Compared to septic patients without DNAemia, septic patients with viremia had increased fungal and opportunistic bacterial infections. Patients with detectable CMV in plasma had higher 90-day mortality compared to CMV-negative patients; p<0.05. Reactivation of latent viruses is common with prolonged sepsis, with frequencies similar to those occurring in transplant patients on immunosuppressive therapy and consistent with development of an immunosuppressive state. Whether reactivated latent viruses contribute to morbidity and mortality in sepsis remains unknown. |
| first_indexed | 2024-12-14T01:54:09Z |
| format | Article |
| id | doaj.art-75f11ecda5b64839bf9c4017521c98c5 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T01:54:09Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-75f11ecda5b64839bf9c4017521c98c52022-12-21T23:21:15ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0192e9881910.1371/journal.pone.0098819Reactivation of multiple viruses in patients with sepsis.Andrew H WaltonJared T MuenzerDavid RascheJonathan S BoomerBryan SatoBernard H BrownsteinAlexandre PachotTerrence L BrooksElena DeychWilliam D ShannonJonathan M GreenGregory A StorchRichard S HotchkissA current controversy is whether patients with sepsis progress to an immunosuppressed state. We hypothesized that reactivation of latent viruses occurred with prolonged sepsis thereby providing evidence of clinically-relevant immunosuppression and potentially providing a means to serially-monitor patients' immune status. Secondly, if viral loads are markedly elevated, they may contribute to morbidity and mortality. This study determined if reactivation of herpesviruses, polyomaviruses, and the anellovirus TTV occurred in sepsis and correlated with severity. Serial whole blood and plasma samples from 560 critically-ill septic, 161 critically-ill non-septic, and 164 healthy age-matched patients were analyzed by quantitative-polymerase-chain-reaction for cytomegalovirus (CMV), Epstein-Barr (EBV), herpes-simplex (HSV), human herpes virus-6 (HHV-6), and TTV. Polyomaviruses BK and JC were quantitated in urine. Detectable virus was analyzed with respect to secondary fungal and opportunistic bacterial infections, ICU duration, severity of illness, and survival. Patients with protracted sepsis had markedly increased frequency of detectable virus. Cumulative viral DNA detection rates in blood were: CMV (24.2%), EBV (53.2%), HSV (14.1%), HHV-6 (10.4%), and TTV (77.5%). 42.7% of septic patients had presence of two or more viruses. The 50% detection rate for herpesviruses was 5-8 days after sepsis onset. A small subgroup of septic patients had markedly elevated viral loads (>104-106 DNA copies/ml blood) for CMV, EBV, and HSV. Excluding TTV, DNAemia was uncommon in critically-ill non-septic patients and in age-matched healthy controls. Compared to septic patients without DNAemia, septic patients with viremia had increased fungal and opportunistic bacterial infections. Patients with detectable CMV in plasma had higher 90-day mortality compared to CMV-negative patients; p<0.05. Reactivation of latent viruses is common with prolonged sepsis, with frequencies similar to those occurring in transplant patients on immunosuppressive therapy and consistent with development of an immunosuppressive state. Whether reactivated latent viruses contribute to morbidity and mortality in sepsis remains unknown.http://europepmc.org/articles/PMC4053360?pdf=render |
| spellingShingle | Andrew H Walton Jared T Muenzer David Rasche Jonathan S Boomer Bryan Sato Bernard H Brownstein Alexandre Pachot Terrence L Brooks Elena Deych William D Shannon Jonathan M Green Gregory A Storch Richard S Hotchkiss Reactivation of multiple viruses in patients with sepsis. PLoS ONE |
| title | Reactivation of multiple viruses in patients with sepsis. |
| title_full | Reactivation of multiple viruses in patients with sepsis. |
| title_fullStr | Reactivation of multiple viruses in patients with sepsis. |
| title_full_unstemmed | Reactivation of multiple viruses in patients with sepsis. |
| title_short | Reactivation of multiple viruses in patients with sepsis. |
| title_sort | reactivation of multiple viruses in patients with sepsis |
| url | http://europepmc.org/articles/PMC4053360?pdf=render |
| work_keys_str_mv | AT andrewhwalton reactivationofmultiplevirusesinpatientswithsepsis AT jaredtmuenzer reactivationofmultiplevirusesinpatientswithsepsis AT davidrasche reactivationofmultiplevirusesinpatientswithsepsis AT jonathansboomer reactivationofmultiplevirusesinpatientswithsepsis AT bryansato reactivationofmultiplevirusesinpatientswithsepsis AT bernardhbrownstein reactivationofmultiplevirusesinpatientswithsepsis AT alexandrepachot reactivationofmultiplevirusesinpatientswithsepsis AT terrencelbrooks reactivationofmultiplevirusesinpatientswithsepsis AT elenadeych reactivationofmultiplevirusesinpatientswithsepsis AT williamdshannon reactivationofmultiplevirusesinpatientswithsepsis AT jonathanmgreen reactivationofmultiplevirusesinpatientswithsepsis AT gregoryastorch reactivationofmultiplevirusesinpatientswithsepsis AT richardshotchkiss reactivationofmultiplevirusesinpatientswithsepsis |