A total of 537 patients were initially identified. After excluding patients that were deceased (n = 37), already on dialysis (n = 26), moved out of area (n = 23), or lost to follow up (n = 7), a total of 444 patients remained for analysis (Fig. 1.). A total of 84 patients elected to participate in testing for the seroconversion analysis, who were analysed as a subgroup. Baseline characteristics of the final 444 prevalent KTRs are shown in Table 1. They were predominantly male (60%), with a median age 58 years (Interquartile range [IQR]21.0) and baseline mean estimated glomerular filtration rate (eGFR) of 57 ml/min/1.73m2 (Standard Deviation [SD] 21.9). Patients were primarily deceased donor recipients (69%) due to glomerulonephritis (50%) or diabetes (15%), with a median transplant vintage of 69.0 months (IQR 111.0). The primary immunosuppression regimen consisted of prednisolone (93%), mycophenolate (80%), and tacrolimus (72%).

Flow chart of patient inclusion and COVID-19 diagnosis

Vaccination status was acquired for 440 (99%) patients. By study end, 95% (n = 423) of patients had received at least 1 vaccination. The number of patients that received 1,2,3, or 4 vaccine doses was 4 (1%), 75 (17%), 239 (54%) and 105 (24%) respectively. 17 (4%) patients remained unvaccinated throughout the study period. The vaccines administered included Pfizer BioNTech BNT162b2 (70%), AstraZeneca ChAdOx1 nCoV-19 (26%) and Moderna mRNA-1273 (3%) (Supp Table 2).

COVID-19 was reported in 142 (32%) patients, and of these 54 (38%) required admission for COVID-19 with 10 (7%) deaths due to COVID-19. 17 (4%) patients died from any cause during the study period, with COVID-19 accounting for 59% of all deaths.

Univariate factors associated with acquiring COVID-19 are shown in Table 2. On multivariable analysis, an increased risk of acquiring COVID-19 was associated with male sex (aOR 1.7, 1.093–2.701, p = 0.019), younger age (aOR, 0.98, 0.964–0.994, p = 0.006) and lower eGFR (aOR 0.99, 0.978–0.998, p = 0.020), after adjusting for significant univariate associations, body mass index (BMI) and diabetes. (Table 3). Receipt of 3 or more doses of vaccine was protective (aOR 0.48, 95% CI 0.287–0.796, p = 0.005).

Deaths from COVID-19 occurred throughout the study period, with 3 deaths in September 2021, 1 death in January 2022, 4 deaths in February 2022 and 1 death in both April and May 2022. Univariate analyses are shown in Table 2. On multivariate analysis, increased mortality due to COVID-19 was associated with older age (aOR1.1, 95%CI 1.004–1.192, p = 0.04), respiratory disease (aOR 14.2, 95%CI 1.825–110.930, p = 0.011) and current or past smoking exposure (aOR 8.2, 95% CI 1.020-65.649, p = 0.048) after adjusting for significant univariate associations, sex, BMI, diabetes, and vaccination (3 + doses). Vaccination of 3 or more doses was protective (aOR 0.6, 95% CI 0.007–0.523, p = 0.011) (Table 3).

Of those with reported COVID-19, 62 (44%) received sotrovimab and 11 (8%) received molnupiravir (Suppl Table 6.). 54 (38%) patients required hospitalisation for COVID-19, and 16 (11%) required intensive care unit (ICU) care. 33 (23%) patients required oxygen therapy. The maximum level of oxygen required was: low flow nasal prong oxygen in 13 (9%), high flow nasal prong oxygen in 4 (3%), non-invasive ventilation in 8 (6%) and invasive ventilation in 8 (6%) patients. Sotrovimab and molnupiravir were given in the community. When provided, neither were found to be protective for hospital admission (p = 0.11, p = 021 respectively). Among hospitalised patients, those who received sotrovimab had evidence of protection for ICU admission (OR 0.2, 95%CI 0.035–0.886, p = 0.030). Median length of hospital stay was 8 days (IQR ± 13). There was an association between prior sotrovimab use and shorter length of stay (5 vs. 10 days, p = 0.027). Vaccination with 3 doses did not impact hospital admission (p = 0.32), ICU admission (p = 0.14) or length of stay (0.54).

Immunosuppression alteration occurred frequently in hospitalised patients (85%), as compared to those who were not hospitalised (10%). Hospitalisation with COVID-19 increased the odds of a reduction of immunosuppression (OR 50.5, 95% CI 18.211-139.883, p < 0.001), however it was not significant for those who required an ICU admission among hospitalised patients (p = 0.41) or mortality (p = 0.64). Univariate factors associated with hospitalisation for COVID-19 are shown in Table 2.

On multivariable analysis, increased hospitalisation was associated with older age (aOR 1.0, 95% CI 1.007–1.0092, p = 0.021), lower eGFR (aOR 0.96, 95% CI 0.994 − 0.982, p < 0.001) and receipt of a deceased donor graft (aOR 4.1, 95% CI 1.128–14.747, p = 0.032), after adjusting for significant univariable associations, sex, BMI and vaccination (3 doses) (Table 3). Vaccination was not protective.

84 patients underwent serological testing, including: 71 patients who had a single test, 12 who had 2 serial tests and 1 patient who had 3 serial tests. All but one patient, had a non-reactive Eleycs assay, indicating no prior exposure to COVID-19. The single patient with a reactive Eleycs assay was not known to have had prior COVID-19, however, was transplanted overseas with limited details prior to returning to Australia before the study period. This patient had no further serological evaluation and was excluded from the seroconversion analysis, resulting in 83 patients providing 97 serological tests assessed for vaccine-induced seroconversion.

All but 2/97 tests were collected prior to documented COVID-19. These two patients participated in serial testing. Prior to known COVID-19 they were Elecsys assay and QuantiVac ELISA negative. Post COVID-19 they remained Elecsys assay negative, however seroconverted on the QuantiVac ELISA. During this interval they received additional vaccinations, incrementing from 2 to 3 doses. As it is not possible to determine if these patients seroconverted due to wild type COVID-19 infection or vaccination, the serial samples prior to known COVID-19 were analysed. Of the remaining 95 tests, 5 were excluded based on QuantiVac ELISA results: 1 patient who did not have a QuanitVac ELISA processed on initial collection 1, but undertook repeat testing which was utilised, 3 patients with serial reactive tests performed after 2 and 3 doses of vaccine with no status change, therefore sampling after the 2nd dose was included, and 1 patient with 2 serial reactive tests, both after the 4th dose of vaccine and the earlier sample was included.

This resulted in 90 analysed samples: 1, 64, 21 and 4 samples after 1,2,3 and 4 doses of vaccine respectively (Suppl Table 3). Seroconversion rates after 1, 2, 3 and 4 doses were: 0, 22%, 48%, and 75% respectively (Suppl Table 4). Overall seroconversion rate at study end was 33% (27/83).

Univariate factors associated with COVID-19 diagnosis in this subgroup are shown in Supplementary Table 5. On multivariable analysis, after adjusting for univariate associations, in addition to age and diabetes, factors associated with an increased rate of acquiring COVID-19 included Asian place of birth (aOR 9.0, 95% CI 1.803–44.888, p = 0.007) and higher dose of prednisolone (aOR 1.5, 95% CI 1.125–1.949, p = 0.005). Seroconversion was protective (aOR 0.1, 95% CI 0.025–0.627, p = 0.011), independent of vaccination of 3 + doses (p = 0.108) (Table 3).

The number of hospitalised patients in this subgroup was small (n = 6). No hospitalised patients demonstrated evidence of seroconversion, however this did not reach statistical significance (p = 0.539). No patient who died underwent serology assessment.