RESULTS
In the pandemic year 2020, the donation program in Slovakia dropped by 28.6% (P<0.0001) compared to 2019 which was the most successful year for organ transplants in the history of Slovakia. The number of kidney transplantations decreased by 33.5% (P<0.0001), kidney transplantations from living donors were at a comparable level (P=0.0767). Compared to 2018, kidney transplantations decreased by 10.3% (P=0.0001) during the COVID-19 crisis in Slovakia (Figure 1).
A total of 305 patients (210 men, 68.8%) with confirmed SARS-CoV-2 positivity between March 6, 2020 and March 31, 2021 were included in our analysis. Basic characteristics of the group are shown in Table 1. The median age was 54 years (52.7 ± 12), the median body mass index was 29 kg/m2 (29.6 ± 18.3), 291 recipients (95.4%) suffered from hypertension and 109 (35.7%) from diabetes mellitus. Patients who were longer after the kidney transplantation became ill more frequently, with a median of 68 months (84.8 ± 64.3). Excellent graft function (eGFR; CKD-EPI ≥ 1.5 mL/s/1.73 m2) at the time of the first positive test was found in 27 cases (8.9%), 121 patients (39.7%) were in the second stage of chronic kidney disease (eGFR; CKD-EPI 1.49 – 1.0 mL/s/1.73 m2), 120 (39.3%) in the third stage (eGFR; CKD-EPI 0.99 – 0.5 mL/s/1.73 m2), and 37 (12.1%) with advanced graft dysfunction (eGFR; CKD-EPI < 0.5 mL/s/1.73 m2).
In the first wave of COVID-19 crisis only three positively tested patients (1%) for SARS-CoV-2 were identified in Slovakia, the course of the disease was asymptomatic/moderate. During the second wave, the COVID-19 morbidity rose significantly, SARS-CoV-2 was identified in 302 KTRs (99%), of which, in the first period of the second wave, it was 147 KTRs (48.2%), followed by 155 (50.8%) positively tested KTRs in the second period of the second pandemic wave (Tab. 1).
Criteria for the asymptomatic/moderate course of the disease were met by 206 patients (67.5%), admission to the hospital was indicated in 99 KTRs (32.5%) (Tab. 1). 192 positively tested patiens (63%) called the transplant centers and consulted the symptoms and the treatment (Tab. 1), more frequently during the second period of the second wave (54.9%vs 71.6%; P=0.0028), more commonly with asymptomatic/moderate course of the disease (72.1% vs 46.9%); P<0.0001) (Tab. 2). In 92 hospitalized patients (92.9%), the physicians from the hospitals/COVID-19 departments to which the patients were admitted consulted the treatment with experienced nephrologists from the transplant centers, especially discontinuation of immunosuppressants, doses of steroids, and supportive antimicrobial treatment and prevention of thrombosis (Tab. 2). There were no deaths recorded during the first wave, thirty patients (9.8%) died during the second wave of COVID-19 pandemic, there was no significant difference between both periods of the second wave (Tab. 1). Elderly patients were hospitalized more frequently (P=0.0059); for the whole set, in both univariate and multivariate analysis (Tab. 3), the age over 59 years was a risk factor for a more severe course and death. Another risk factor for hospitalization and death in the whole set, according to the univariate analysis, was diabetes mellitus, while in the multivariate analysis (Tab. 3), diabetes mellitus was only associated with a more severe course of the disease (OR [95% CI]: 2.0433 [1.1812-3.5346]; P=0.0106). Patients with advanced graft dysfunction defined by eGFR < 0.5 mL/s (Tab. 3), OR [95% CI] had a worse prognosis associated with the risk of death: 4.8668 [1.7182-13.7849]; P=0.0029). In contrast, better graft function was more common in patients with a mild course (45.9% vs 27.6%, P=0.0028).
We did not find any effect of arterial hypertension, BMI, time since transplantation, CNI, MMF/MPA, mTOR-I and ACE-I on the incidence and clinical course of COVID-19 in KTRs during the first and second waves of the pandemic (Tab. 2). At the time of finding of the infection, patients with a more severe course and need for hospitalization (93.9 vs85.8; P=0.0419) were more frequently treated with corticosteroids at a higher mean dose than the mild course group (7.3±5.3 vs 5.9±3.1; P=0.0056). While according to a univariate analysis, a lower dose of prednisolone (<10mg) was a protective factor at the onset of infection, the protective effect of low doses of corticosteroids was not confirmed by the multivariate analysis (Tab. 3).
We focused our interest in whether the proliferation of the alpha variant of the SARS-CoV-2 virus affected the course and risk factors of COVID-19 in kidney transplant patients. By comparing subgroup 2 (09/2020 - 12/2020) and subgroup 3 (01/2021 - 03/2021), we did not find any significant differences in the screened parameters depending on the period when patients became ill or tested positive for SARS-CoV-2 virus (Tab. 2, Tab. 4, Tab. 5).
Finally, we compared COVID-19 morbidity and mortality rates between KTRs and patients on hemodialysis (HD). While among the patients after kidney transplantation, 14% tested positive, in the hemodialysis cohort, there was up to 52% positivity (P<0.0001). Mortality among the infected kidney recipients was 9.8% vs 30% (P <0.0001) in HD patients. Of the total set of KTRs in dispensary, a total of 1.4% died in Slovakia during the COVID-19 pandemic by the end of March 2021, while in the population of HD patients it was up to 15.6% (P<0.0001).