Predictors of Mortality in Tocilizumab-Treated Severe COVID-19
Purpose: Tocilizumab is associated with positive outcomes in severe COVID-19. We wanted to describe the characteristics of nonresponders to treatment. Methods: This was a retrospective multicenter study in two respiratory departments investigating adverse outcomes at 90 days from diagnosis in subjec...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | Vaccines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-393X/10/6/978 |
| _version_ | 1797481567560400896 |
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| author | Konstantinos Pagkratis Serafeim Chrysikos Emmanouil Antonakis Aggeliki Pandi Chrysavgi Nikolaou Kosti Eleftherios Markatis Georgios Hillas Antonia Digalaki Sofia Koukidou Eleftheria Chaini Andreas Afthinos Katerina Dimakou Ilias C. Papanikolaou |
| author_facet | Konstantinos Pagkratis Serafeim Chrysikos Emmanouil Antonakis Aggeliki Pandi Chrysavgi Nikolaou Kosti Eleftherios Markatis Georgios Hillas Antonia Digalaki Sofia Koukidou Eleftheria Chaini Andreas Afthinos Katerina Dimakou Ilias C. Papanikolaou |
| author_sort | Konstantinos Pagkratis |
| collection | DOAJ |
| description | Purpose: Tocilizumab is associated with positive outcomes in severe COVID-19. We wanted to describe the characteristics of nonresponders to treatment. Methods: This was a retrospective multicenter study in two respiratory departments investigating adverse outcomes at 90 days from diagnosis in subjects treated with tocilizumab (8 mg/kg intravenously single dose) for severe progressive COVID-19. Results: Of 121 subjects, 62% were males, and 9% were fully vaccinated. Ninety-six (79.4%) survived, and 25 died (20.6%). Compared to survivors (S), nonsurvivors (NS) were older (median 57 versus 75 years of age), had more comorbidities (Charlson comorbidity index 2 versus 5) and had higher rates of intubation/mechanical ventilation (<i>p</i> < 0.05). On admission, NS had a lower PO<sub>2</sub>/FiO<sub>2</sub> ratio, higher blood ferritin, and higher troponin, and on clinical progression (day of tocilizumab treatment), NS had a lower PO<sub>2</sub>/FiO<sub>2</sub> ratio, decreased lymphocytes, increased neutrophil to lymphocyte ratio, increased ferritin and lactate dehydrogenase (LDH), disease located centrally on computed tomography scan, and increased late c-reactive protein. Cox proportional hazards regression analysis identified age and LDH on deterioration as predictors of death; admission PO<sub>2</sub>/FiO<sub>2</sub> ratio and LDH as predictors of intubation; PO<sub>2</sub>/FiO<sub>2</sub> ratios, LDH, and central lung disease on radiology as predictors of noninvasive ventilation (NIV) (a < 0.05). The log-rank test of mortality yielded the same results (<i>p</i> < 0.001). ROC analysis of the above predictors in a separate validation cohort yielded significant results. Conclusions: Older age and high serum LDH levels are predictors of mortality in tocilizumab-treated severe COVID-19 patients. Hypoxia levels, LDH, and central pulmonary involvement radiologically are associated with intubation and NIV. |
| first_indexed | 2024-03-09T22:16:28Z |
| format | Article |
| id | doaj.art-a1dacb5c449a489bbed576b4d1f99eea |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-09T22:16:28Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-a1dacb5c449a489bbed576b4d1f99eea2023-11-23T19:22:23ZengMDPI AGVaccines2076-393X2022-06-0110697810.3390/vaccines10060978Predictors of Mortality in Tocilizumab-Treated Severe COVID-19Konstantinos Pagkratis0Serafeim Chrysikos1Emmanouil Antonakis2Aggeliki Pandi3Chrysavgi Nikolaou Kosti4Eleftherios Markatis5Georgios Hillas6Antonia Digalaki7Sofia Koukidou8Eleftheria Chaini9Andreas Afthinos10Katerina Dimakou11Ilias C. Papanikolaou12Pulmonary Department, Corfu General Hospital, 49100 Corfu, Greece5th Respiratory Medicine Department, SOTIRIA Chest Hospital, 11527 Athens, GreecePulmonary Department, Corfu General Hospital, 49100 Corfu, GreecePulmonary Department, Corfu General Hospital, 49100 Corfu, Greece5th Respiratory Medicine Department, SOTIRIA Chest Hospital, 11527 Athens, GreecePulmonary Department, Corfu General Hospital, 49100 Corfu, Greece5th Respiratory Medicine Department, SOTIRIA Chest Hospital, 11527 Athens, Greece5th Respiratory Medicine Department, SOTIRIA Chest Hospital, 11527 Athens, Greece5th Respiratory Medicine Department, SOTIRIA Chest Hospital, 11527 Athens, GreecePulmonary Department, Corfu General Hospital, 49100 Corfu, GreecePulmonary Department, Corfu General Hospital, 49100 Corfu, Greece5th Respiratory Medicine Department, SOTIRIA Chest Hospital, 11527 Athens, GreecePulmonary Department, Corfu General Hospital, 49100 Corfu, GreecePurpose: Tocilizumab is associated with positive outcomes in severe COVID-19. We wanted to describe the characteristics of nonresponders to treatment. Methods: This was a retrospective multicenter study in two respiratory departments investigating adverse outcomes at 90 days from diagnosis in subjects treated with tocilizumab (8 mg/kg intravenously single dose) for severe progressive COVID-19. Results: Of 121 subjects, 62% were males, and 9% were fully vaccinated. Ninety-six (79.4%) survived, and 25 died (20.6%). Compared to survivors (S), nonsurvivors (NS) were older (median 57 versus 75 years of age), had more comorbidities (Charlson comorbidity index 2 versus 5) and had higher rates of intubation/mechanical ventilation (<i>p</i> < 0.05). On admission, NS had a lower PO<sub>2</sub>/FiO<sub>2</sub> ratio, higher blood ferritin, and higher troponin, and on clinical progression (day of tocilizumab treatment), NS had a lower PO<sub>2</sub>/FiO<sub>2</sub> ratio, decreased lymphocytes, increased neutrophil to lymphocyte ratio, increased ferritin and lactate dehydrogenase (LDH), disease located centrally on computed tomography scan, and increased late c-reactive protein. Cox proportional hazards regression analysis identified age and LDH on deterioration as predictors of death; admission PO<sub>2</sub>/FiO<sub>2</sub> ratio and LDH as predictors of intubation; PO<sub>2</sub>/FiO<sub>2</sub> ratios, LDH, and central lung disease on radiology as predictors of noninvasive ventilation (NIV) (a < 0.05). The log-rank test of mortality yielded the same results (<i>p</i> < 0.001). ROC analysis of the above predictors in a separate validation cohort yielded significant results. Conclusions: Older age and high serum LDH levels are predictors of mortality in tocilizumab-treated severe COVID-19 patients. Hypoxia levels, LDH, and central pulmonary involvement radiologically are associated with intubation and NIV.https://www.mdpi.com/2076-393X/10/6/978COVID-19tocilizumabmortalityoutcomesseverity |
| spellingShingle | Konstantinos Pagkratis Serafeim Chrysikos Emmanouil Antonakis Aggeliki Pandi Chrysavgi Nikolaou Kosti Eleftherios Markatis Georgios Hillas Antonia Digalaki Sofia Koukidou Eleftheria Chaini Andreas Afthinos Katerina Dimakou Ilias C. Papanikolaou Predictors of Mortality in Tocilizumab-Treated Severe COVID-19 Vaccines COVID-19 tocilizumab mortality outcomes severity |
| title | Predictors of Mortality in Tocilizumab-Treated Severe COVID-19 |
| title_full | Predictors of Mortality in Tocilizumab-Treated Severe COVID-19 |
| title_fullStr | Predictors of Mortality in Tocilizumab-Treated Severe COVID-19 |
| title_full_unstemmed | Predictors of Mortality in Tocilizumab-Treated Severe COVID-19 |
| title_short | Predictors of Mortality in Tocilizumab-Treated Severe COVID-19 |
| title_sort | predictors of mortality in tocilizumab treated severe covid 19 |
| topic | COVID-19 tocilizumab mortality outcomes severity |
| url | https://www.mdpi.com/2076-393X/10/6/978 |
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