Coronavirus Disease 2019 (COVID-19)
Conditions
Keywords
COVID-19, Antibodies, viral/blood, adult, Human, Retrospective Studies, Immunization, Passive, Pandemics, Antibodies, Neutralizing, COVID-19 serotherapy, Severe acute respiratory syndrome coronavirus 2, Coronavirus Infections / therapy
Brief summary
The purpose of this study is to assess whether convalescent plasma therapy is associated with reduced 30-day all-cause mortality in a population of Veteran inpatients with non-severe coronavirus disease 2019 (COVID-19).
Detailed description
The convalescent plasma (CP) of individuals who have recovered from COVID-19 may help reduce symptoms and mortality when given to ill patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clinical trials are needed to provide definitive evidence of the benefits and harms of CP in the treatment of COVID-19. While clinical trials are underway, observational research plays a critical role in providing preliminary scientific evidence to guide clinical practice. This observational study aims to estimate the association between CP therapy and mortality after 30 days in a sample of SARS-CoV-2-positive patients with non-severe illness. Patients include those hospitalized at a facility within the Veterans Health Administration (VHA) of the Department of Veterans Affairs (VA), the largest integrated healthcare system in the United States. Using VA electronic health record data, the study is designed to emulate a target trial of convalescent plasma transfusion and mortality. The primary exposure of interest is the use or non-use of COVID-19 convalescent plasma, and the primary outcome is 30-day all-cause mortality. A nested trial design will be used, in which patients will be followed from each day in which eligibility criteria are met (while hospitalized and after date of first positive SARS-CoV-2 test) for 30 days. The association between CP therapy and mortality will be assessed using pooled logistic models to estimate 30-day cumulative incidence curves, risk differences, and hazard ratios. Inverse probability weighting derived from propensity scores will be employed to minimize confounding by indication and other biases.
Interventions
BIOLOGICALCOVID-19 convalescent plasma
Convalescent plasma collected from individuals who have recovered from COVID-19
Sponsors
Mayo Clinic
VA Office of Research and Development
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
21 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* US Veterans aged 21-80 years old * Hospitalized between May 1, 2020 and November 17, 2020 with a SARS-CoV-2 positive test, at a VA Medical Center where convalescent plasma had been administered to at least one patient and remained a current practice at that VA Medical Center * SARS-CoV-2 positive test within 7 days before or after hospital admission * Minimum oxygen saturation (measured within the past day) \>=90% * Vitals (pulse, respiration, temperature, systolic blood pressure) and acute labs (hemoglobin, platelet, white blood cells) measured within the past 2 days * Albumin, Alanine Aminotransferase (ALT), creatinine measured within the past 30 days * Weight measurement recorded in the past 2 years
Exclusion criteria
* Prior intubation, ventilation, high flow oxygen, extracorporeal membrane oxygenation (ECMO), dialysis, or vasopressors during current hospitalization * Record of prior treatment with CP * Received long-term care in a domiciliary or nursing home in the past 90 days * First CP recipient at a site * Less than 30 days of follow-up
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| All-cause Mortality | 30 days | Death at 30 days recorded in the electronic health record. Follow-up starts at the treatment date, which must be within 2 days after both hospitalization and SARS-CoV-2-positive test, and ends at 30 days or death. |
Countries
United States
Participant flow
Recruitment details
This observational study did not recruit patients but rather analyzed patients' VA electronic health record data. Eligibility was assessed through the examination of clinical and administrative data of US Veterans with non-severe COVID-19 who were hospitalized between1 May 2020 and 17 November 2020 at a VA medical center where convalescent plasma was a current practice.
Pre-assignment details
We included patients in a trial on each day of eligibility (0, 1, 2) (person-trial). Each patient could be assigned to the plasma group once and to the non-plasma group up to 3 times. Because plasma patients could contribute non-plasma person-trials on eligible days prior to treatment, the sum of patients in the 2 groups (5,044) exceeds the number of eligible patients (4,755). Of 11,269 person-trials, there were 402 plasma trials (402 patients) and 10,867 non-plasma trials (4,642 patients).
Participants by arm
| Arm | Count |
|---|---|
| Exposed-Convalescent Plasma Group Veterans who received COVID-19 convalescent plasma therapy within 2 days of eligibility
COVID-19 convalescent plasma: Convalescent plasma collected from individuals who have recovered from COVID-19 | 402 |
| Exposed-Convalescent Plasma Group Veterans who received COVID-19 convalescent plasma therapy within 2 days of eligibility
COVID-19 convalescent plasma: Convalescent plasma collected from individuals who have recovered from COVID-19 | 402 |
| Unexposed-Non-plasma Group Veterans who did not receive COVID-19 convalescent plasma therapy | 4,642 |
| Unexposed-Non-plasma Group Veterans who did not receive COVID-19 convalescent plasma therapy | 10,867 |
| Total | 16,313 |
Baseline characteristics
| Characteristic | Exposed-Convalescent Plasma Group | Unexposed-Non-plasma Group | Total |
|---|---|---|---|
| Age, Continuous | 65.0 years STANDARD_DEVIATION 11.3 | 64.1 years STANDARD_DEVIATION 12 | 64.2 years STANDARD_DEVIATION 12 |
| Body mass index | 32.2 kg/m^2 STANDARD_DEVIATION 7.1 | 31.0 kg/m^2 STANDARD_DEVIATION 7.2 | 31.0 kg/m^2 STANDARD_DEVIATION 7.2 |
| Calendar day of trial start | 249 days STANDARD_DEVIATION 52 | 231 days STANDARD_DEVIATION 52 | 232 days STANDARD_DEVIATION 52 |
| Cardiovascular disorder within past 5 years | 156 Person-trials | 4663 Person-trials | 4819 Person-trials |
| Chronic obstructive pulmonary disease | 119 Person-trials | 2463 Person-trials | 2582 Person-trials |
| Dementia | 29 Person-trials | 816 Person-trials | 845 Person-trials |
| Diabetes | 219 Person-trials | 5145 Person-trials | 5364 Person-trials |
| Estimated glomerular filtration rate within past 30 days | 75.3 ML/min/1.73m2 STANDARD_DEVIATION 27.6 | 73.5 ML/min/1.73m2 STANDARD_DEVIATION 27.8 | 73.5 ML/min/1.73m2 STANDARD_DEVIATION 27.8 |
| First oxygen saturation during hospitalization | 93.8 Percentage of oxyhemoglobin saturation STANDARD_DEVIATION 3.8 | 95.5 Percentage of oxyhemoglobin saturation STANDARD_DEVIATION 3.3 | 95.4 Percentage of oxyhemoglobin saturation STANDARD_DEVIATION 3.4 |
| Glucocorticoid use | 215 Person-trials | 2258 Person-trials | 2473 Person-trials |
| Hypertension | 307 Person-trials | 7747 Person-trials | 8054 Person-trials |
| In intensive care unit | 153 Person-trials | 2204 Person-trials | 2357 Person-trials |
| Maximum white blood cell count in past 2 days | 7.4 1000 cells/ul STANDARD_DEVIATION 4.1 | 6.8 1000 cells/ul STANDARD_DEVIATION 3.9 | 6.8 1000 cells/ul STANDARD_DEVIATION 3.9 |
| Minimum oxygen saturation in past day | 93.3 Percentage of oxyhemoglobin saturation STANDARD_DEVIATION 2.8 | 94.6 Percentage of oxyhemoglobin saturation STANDARD_DEVIATION 3.1 | 94.5 Percentage of oxyhemoglobin saturation STANDARD_DEVIATION 3.1 |
| Race/Ethnicity, Customized Race Black | 109 Person-trials | 3814 Person-trials | 3923 Person-trials |
| Race/Ethnicity, Customized Race Other | 35 Person-trials | 859 Person-trials | 894 Person-trials |
| Race/Ethnicity, Customized Race White | 258 Person-trials | 6194 Person-trials | 6452 Person-trials |
| Remdesivir use | 187 Person-trials | 1476 Person-trials | 1663 Person-trials |
| Sex: Female, Male Female | 32 Person-trials | 766 Person-trials | 798 Person-trials |
| Sex: Female, Male Male | 370 Person-trials | 10101 Person-trials | 10471 Person-trials |
| Smoking status Current | 81 Person-trials | 2836 Person-trials | 2917 Person-trials |
| Smoking status Former | 74 Person-trials | 1923 Person-trials | 1997 Person-trials |
| Smoking status Never | 109 Person-trials | 2791 Person-trials | 2900 Person-trials |
| Smoking status Unknown | 138 Person-trials | 3317 Person-trials | 3455 Person-trials |
| Supplemental non-high-flow oxygen | 9 Person-trials | 161 Person-trials | 170 Person-trials |
| Systemic inflammatory response syndrome | 243 Person-trials | 4739 Person-trials | 4982 Person-trials |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 40 / 402 | 343 / 4,642 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
All-cause Mortality
Death at 30 days recorded in the electronic health record. Follow-up starts at the treatment date, which must be within 2 days after both hospitalization and SARS-CoV-2-positive test, and ends at 30 days or death.
Time frame: 30 days
Population: Intention-to-treat analysis; per-protocol analysis with adjustment for baseline covariates via inverse probability weighting
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Convalescent Plasma Group | All-cause Mortality | 40 Person-trials |
| Non-plasma Group | All-cause Mortality | 671 Person-trials |
Comparison: The investigators estimated the 30-day mortality risk difference comparing patients assigned to each group. Adjustment for covariates would be carried out via inverse probability weighting.95% CI: [-2.3, 3.6]
Comparison: The investigators estimated the 30-day mortality hazard ratio comparing patients assigned to each group. The hazard ratio was estimated from pooled logistic models with inverse probability weighting to adjust for confounding.95% CI: [0.64, 1.62]