TABLE 1.
Descriptive statistics and outcomes (Table 1A) and multivariable regression analysis (Table 1B) on outcomes for kidney transplant recipients with COVID‐19 infection treated with Sotrovimab
| Table 1A: Demographics, clinical characteristics, infection‐related parameters, and outcomes for study population, stratified by period of infection a | |||
|---|---|---|---|
| Period of infection c | |||
| Study population administered Sotrovimab b | Period 1: September–November 2021 | Period 2: December 2021–February 2022 | |
| Demographics | |||
| Number | 51 | 25 (49%) | 26 (51%) |
| Male gender | 27 (52.9%) | 18/25 (72%) | 9/26 (34.6%) |
| Ethnicity | |||
| ‐ Chinese | 31 (60.8%) | 16/25 (64%) | 15/26 (57.7%) |
| ‐ Malay | 13 (25.5%) | 6/25 (24%) | 7/26 (26.9%) |
| ‐ Indian | 6 (11.8%) | 3/25 (12%) | 3/26(11.5%) |
| ‐ Others | 1 (2%) | 0/25 (0%) | 1/26 (3.8%) |
| Age, years | 55.2 (12.1) | 57.7 (10.7) | 52.7 (13) |
| ‐ ≥65 years | 10 (19.6%) | 7 (28%) | 3 (11.5%) |
| Deceased donor transplant | 33 (64.7%) | 19/25 (76%) | 14/26 (53.8%) |
| Characteristics at time of admission with COVID‐19 | |||
| Interval posttransplant, years | 10.1 (7.2) | 11.5 (7.5) | 8.8 (6.8) |
| Diabetes | 26 (51%) | 16/25 (64%) | 10/26 (38.5%) |
|
Body mass index, kg/m2 (BMI, median, IQR) |
24.2 (6.1) | 24.8 (4.5) |
|
| ‐ BMI >30 | 6 (11.8%) | 4/25 (16%) | 2/26 (7.7%) |
| Baseline serum creatinine, μmol/L (median, IQR) | 118 (64) | 118 (62) | 122 (88) |
| Baseline estimated glomerular filtration rate (eGFR), d ml/min/1.73 m2 | 53.7 (23.4) | 57.3 (22.2) | 50.2 (24.5) |
| ‐ eGFR ≤ 30 ml/min/1.73 m2 | 9 (17.6%) | 3 (12%) | 6 (23.1%) |
| Charlson co‐morbidity score e | 2.7 (2.1) | 3.0 (2.4) | 2.5 (1.8) |
| ‐ ≥5 | 10 (19.6%) | 7/25 (28%) | 3/26 (11.5%) |
| Immunosuppression: | |||
| ‐ Tacrolimus‐mycophenolate‐prednisolone | 22 (43.1%) | 14/25 (56%) | 8/26 (30.8%) |
| ‐ Cyclosporine‐mycophenolate‐prednisolone | 20 (39.2%) | 7/25 (28%) | 13/26 (50%) |
| ‐ Other regimens | 9 (17.6%) | 4/25 (16%) | 5/26 (19.2%) |
| Vaccination status at infection: | |||
| ‐ Nil vaccination | 5 (9.8%) | 4/25 (16%) | 1/26 (3.8%) |
| ‐ 1 dose or ≤14 days after 2nd Dose | 5 (9.8%) | 5/25 (20%) | 0/26 (0%) |
| ‐ >14 days after 2nd dose and ≤14 days after 3rd dose | 19 (37.3%) | 15/25 (60%) | 4/26 (15.4%) |
| ‐ >14 days after 3rd dose | 22 (43.1%) | 1/25 (4%) | 21/26 (80.8%) |
| Type of 1st and 2nd dose vaccination among those receiving at least 2 doses | |||
| ‐ Number of KTR >14 days after 2nd dose of SARS‐CoV‐2 vaccination | 41 | 16 | 25 |
| ‐ BNT162b2, Pfizer‐BioNTech | 40 (97.6%) | 15/16 (93.8%) | 25/25 (100%) |
| ‐ mRNA‐1273, Moderna | 1 (2.4%) | 1/16 (6.3%) | 0/25 (0%) |
| ‐ Sinovac | ‐ | ‐ | |
| COVID‐19‐related parameters | |||
| Interval from symptom onset to admission, days | 2.3 (1.2) | 2.5 (1.4) | 2.0 (1.0) |
| Symptoms and signs of COVID‐19 infection at admission | |||
| ‐ Fever, without respiratory tract symptoms, other, or no symptoms | 6 (11.8%) | 4/25 (16%) | 2/26 (7.7%) |
| ‐ Upper respiratory tract symptoms | 36 (70.6%) | 14/25 (56%) | 22/26 (84.6%) |
| ‐ Lung infiltrates on chest radiograph | 9 (17.6%) | 7/25 (28%) | 2/26 (7.7%) |
| Spike antibody | |||
| ‐ Not vaccinated or nonreactive | 32 (62.7%) | 21/25 (84%) | 11/26 (42.3%) |
| ‐ 0–100 U/ml | 19 (37.3%) | 4/29 (16%) | 15/26 (57.7%) |
| ‐ >100 U/ml | ‐ | ‐ | ‐ |
| Cycle threshold, (median, IQR) | 16.6 (3.1) | 16 (2.8) | 17.2 (3.0) |
| ISARIC‐4C score at admission f | 5.2 (3.0) | 6.0 (3.1) | 4.5 (2.9) |
| ‐ Score ≥ 9 | 8 (15.7%) | 6/21 (24%) | 2/26 (7.7%) |
| Interval to Sotrovimab from symptom onset, days | 2.3 (1.2) | 2.5 (1.4) | 2.0 (1.0) |
| ‐ ≥4 Days | 9 (17.6%) | 7/25 (28%) | 2/26 (7.7%) |
| Additional therapies for COVID‐19 infection g | |||
| ‐ Nil | 42 (82.4%) | 19/25 (76%) | 23/26 (88.5%) |
| ‐ Dexamethasone | 9 (17.6%) | 6/25 (24%) | 3/26 (11.5%) |
| ‐ Remdesivir | 9 (17.6%) | 6/25 (24%) | 3/26 (11.5%) |
| ‐ Baricitinib | 6 (11.8%) | 4/25 (16%) | 2/26 (7.7%) |
| ‐ Tocilizumab | 2 (3.9%) | 1/25 (4%) | 1/26 (3.8%) |
| Outcomes h | |||
| Acute kidney injury i | 15 (29.4%) | 6/25 (24%) | 9/26 (34.6%) |
| Required supplemental oxygen | 11 (21.6%) | 8/25 (32%) | 3/26 (11.5%) |
| Required intensive care stay | 9 (17.6%) | 6/25 (24%) | 3/26 (11.5%) |
| Mortality | 5 (9.8%) | 4/25 (16%) | 1/26 (3.8%) |
| Table 1B: Multivariable regression analysis of association of clinical characteristics and infection‐related parameters on outcomes after COVID‐19 infection j | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Acute kidney injury i | Required supplemental oxygen | Required ICU stay | Mortality | |||||||||
| Dependent variable | OR k | 95% CI | p‐Value | OR k | (95% CI) | p‐Value | OR k | (95% CI) | p‐Value | OR k | (95% CI) | p‐Value |
| Age ≥ 65 Years | ‐ | ‐ | ‐ | 6.81 | (.48–95.81) | .155 | ‐ | ‐ | ‐ | 6.99 | (.44–112.23) | .17 |
| Body mass index >30 kg/m2 | 6.11 | (.80–46.67) | .081 | 48.89 | (2.47–967.88) | .011 | 19.80 | (1.03–380.44) | .048 | ‐ | ‐ | ‐ |
| Baseline estimated glomerular filtration rate (eGFR) ≤30 ml/min/1.73 m2 | 14.79 | (2.43–90.15) | .003 | ‐ | ‐ | ‐ | 18.53 | (1.28–268.59) | .032 | 32.52 | (1.98–532.84) | .015 |
| Lung infiltrates on chest radiograph at admission | ‐ | ‐ | ‐ | 36.24 | (2.40–547.92) | .010 | 82.48 | (4.57–1489.39) | .003 | 7.71 | (.48–124.79) | .15 |
| Interval to Sotrovimab from symptom onset, ≥4 Days | ‐ | ‐ | ‐ | 26.79 | (1.74–411.96) | .018 | ‐ | ‐ | ‐ | ‐ | ‐ | ‐ |
All data in Table 1A are means and standard deviations (SD) as for normally distributed parameters unless otherwise specified; medians and interquartile range (IQR) are indicated for parameters not normally distributed. Numbers and proportions (%) are shown. Demographics, characteristics at time of COVID‐19 infection, COVID‐19‐related parameters, and outcomes, stratified by period of infection, are shown.
Of 102 presenting to our hospital with SARS‐CoV‐2 infection, 45 KTR were not treated with Sotrovimab due to spike antibody levels >100 U/ml in 34, presentation at greater than 5th day of illness in 6, requirement for oxygen therapy at presentation in 2, patient refusal in 3. In addition, 6 KTR received Sotrovimab prior to result availability and had Spike Antibody levels >100 U/ml. These patients were hence excluded from the Sotrovimab study population.
The study population was stratified by period of infection. SARS‐CoV‐2 viral strains during these two periods of community surges in Singapore were predominately Delta between July 2021 to mid‐December 2021 with the Omicron BA.1 surge beginning in mid‐December 2021, waning from March 2022 onwards. There was a lower proportion of males (p = .007), a higher proportion of those having received SARS‐CoV‐2 vaccination (p < .001), and hence a higher proportion with reactive spike antibody levels 0–100 U/ml (p = .003) and higher cycle threshold values (p < .008) among patients infected during Period 2. There were no other differences for the other parameters between the two periods.
eGFR calculated by the chronic kidney disease epidemiology collaboration (CKD‐EPI) equation.
For calculation of the Charlson comorbidity score, chronic kidney disease was attributed a score of zero if eGFR was >45 ml/min/1.73 m2.
The ISARIC‐4C mortality score is a risk stratification tool that has been developed to predict mortality for hospitalized COVID‐19 patients. The score includes eight variables derived from initial hospital evaluation, including age, sex, number of comorbidities, respiratory rate, peripheral oxygen saturation, level of consciousness, urea level (Blood Urea Nitrogen, mg/dL), and C reactive protein, for a total score of 0–21 points.
KTR with disease progression were treated with therapeutic agents as per National Institute of Health recommendations as shown. As KTR with severe COVID‐19 infection received more than one additional therapeutic agent, the percentages will not add up to 100%. There was no significant difference in proportions requiring additional therapies in the two periods.
Outcomes were compared for the Sotrovimab‐treated study population in the two periods, by Pearson chi‐square analysis. There was no association of period of infection with any of the outcomes.
Acute kidney injury was defined by increase in serum creatinine by at least ≥26.5 μmol/L or increase by ≥150 to 200% of baseline values.
Binary Logistic multivariable regression analysis (Table 1B) was performed to determine the association of independent variables on the outcomes of acute kidney injury (AKI), requirement for supplemental oxygen (SuppO2), ICU stay (ICU), and Mortality. Independent variables were included in the multivariable analysis if deemed clinically significant (age, diabetes, BMI, baseline eGFR, interval posttransplant, presence of spike antibody, presence of lung infiltrates on admission chest radiograph) or if demonstrating significance with a p‐value <.05 on univariate analysis. On univariate analysis, baseline eGFR ≤30 ml/min/1.73 m2 was associated with all adverse outcomes‐ (odds ratio [OR] and 95% confidence interval [95% CI]: 14.88 [2.59–85.6], p = .002) for AKI; 7.5 (95% CI: [1.56–36.17], p = .012) for SuppO2; 11.88 (95% CI: [2.24–63.11], p = .004) for ICUStay and 32.8 (95% CI: [3.04–354.36], p = .004) for mortality. Lung infiltrates at presentation were associated with an OR of 14.8 (95% CI: [2.78–78.71], p = .002) for requiring SuppO2; 26 (95% CI: [4.23–159.91], p < .001) for requiring ICU stay; and 10 (95% CI: [1.38–72.74], p < .023) for mortality. Interval to Sotrovimab ≥4 days from symptom onset was associated with an OR of 7.5 (95% CI: [1.56–36.17], p = .012) for requiring SuppO2: 55.6% required SuppO2 if interval to Sotrovimab was ≥4 (versus 14.3% if <4 days). Finally, age ≥65 years and BMI >30 kg/m2 were associated with mortality (OR 8.36 (95% CI: [1.18–59.44], p = .034) and 1.14 (95% CI: [1.01–1.29], p = .037), respectively. While multiple models were tested, the best fit model that demonstrated the lowest Akaike information criterion on a generalized linear model for that outcome is shown. Variables not included in that model for a dependent variable are identified by dashes. All analyses were performed using SPSS version 27. The ISARIC‐4C score was not included in this multivariable regression model given the incorporation of blood urea nitrogen in the score and hence its collinearity with eGFR.
Odds ratio (OR), the nonstandardized regression coefficient, the 95% confidence intervals (CIs), and p‐values are shown.