Background and Aims Polyomaviruses (PyV) are ubiquitous human viral pathogens. BKV and JCV representing this viral family are common causative agents of viral complications among kidney recipients. Viral load higher than 1×107 copies/ml in urine (viruria) or 1×104 copies/ml in serum (viremia) in posttransplantation period may lead to polyomavirus-associated nephropathy (PVAN), hemorrhagic cystitis (HC) or even kidney transplant failure. The aim of the study was to assess PyV reactivation frequency in patients during 12 months after renal transplantation (RT) and to identify molecular subtypes of BKV and JCV. Method We examined 3207 samples of biological material (serum and urine) of 763 adult (>18 years) patients who underwent renal transplantation (RT) at the State Institution "Minsk Scientific and Practical Center for Surgery, Transplantology and Hematology", Healthcare institutions "Brest Regional Clinical Hospital", "Vitebsk Regional Clinical Hospital Belarus", "Mogilev Regional Clinical Hospital". These patients were divided into 2 groups: group 1 included 394 patients examined only for BKV infection, group 2 – 356 recipients examined for both BKV and JCV infection. Serum and urine samples for regular monitoring were collected from patients before RT, every 2 weeks first 3 months, then at 6, 9, 12 months after RT. In the case of complication development samples from patients were collected later then 1-year monitoring period. PyV DNA was detected by real-time PCR. Viral DNAs from 17 BKV-positive and 11 JCV-positive patients were molecular typed by partial sequencing of VP1 genome region. Confidence intervals for the proportions were calculated using Wald's method. Results Results showed that BKV detection total frequency in the group 1 was 14.47% [11.32%; 18.3%], almost all patients developed viruria, only 2.54% [1.32%; 4.67%] had viremia. In the group 2 PyV DNA was detected in 46.07% [40.96%; 51.26%] of recipients: 19.10% [15.34%; 23.52%] had BKV infection, 19.94% [16.11%; 24.42%] – JCV, 7.02% [4.76%; 10.2%] – BKV+JCV mixed infection. Frequency of viremia was 6.74% [4.53%; 9.87%] in this group. Maximal BKV viral load levels reached 1.2×1012 copies/ml in urine and 5.9×107 copies/ml in serum. JCV loads were up to 3×109 copies/ml in urine and 1.2×108 copies/ml in serum. Then we analyzed frequency of PyV detection before RT and during the first year after RT among the 102 recipients. Results displayed on the fig.1 showed that the peak of PyV infection registration and the higher risk for patient had a place on the 1.5-2.5 months after RT. Quantitative monitoring of viral load in posttransplant period was the basis for the correction of the applied immunosuppressive therapy regimens in relation to the recipients with a high viral load (higher than 1×107 copies/ml in urine or 1×104 copies/ml in serum). The results of molecular typing showed that 17 BKV isolates belonged to subgroups Ib-2 and IVc-2 (12 and 5 isolates, respectively). Within subgroups Ib-2 isolates formed 3 clusters corresponding 3 separate genovariants. JCV isolates belonged to subtype 1A, 1B and 2A (7, 3 and 1 of isolates, respectively). The last one had 99% nucleotide sequence similarity with Greece and South Korea isolates. Conclusion Our data demonstrated an importance of PyV DNA monitoring of kidney recipients in the posttransplant period starting from the first days after RT to predict development of PyV complications as PVAN, HC or others by correcting the immunosuppressive therapy.
Background and Aims Polyomaviruses (PyV) are ubiquitous human viral pathogens. BKV and JCV representing this viral family are common causative agents of viral complications among kidney recipients. Viral load higher than 1 × 107 copies/ml in urine (viruria) or 1 × 104 copies/ml in serum (viremia) in posttransplantation period may lead to polyomavirus-associated nephropathy (PVAN), hemorrhagic cystitis (HC) or even kidney transplant failure. The aim of the study was to assess PyV reactivation frequency in patients during 12 months after renal transplantation (RT) and to identify molecular subtypes of BKV and JCV. Method We examined 3207 samples of biological material (serum and urine) of 763 adult (>18 years) patients who underwent renal transplantation (RT) at the State Institution “Minsk Scientific and Practical Center for Surgery, Transplantology and Hematology”, Healthcare institutions “Brest Regional Clinical Hospital”, “Vitebsk Regional Clinical Hospital Belarus”, “Mogilev Regional Clinical Hospital”. These patients were divided into 2 groups: group 1 included 394 patients examined only for BKV infection, group 2 – 356 recipients examined for both BKV and JCV infection. Serum and urine samples for regular monitoring were collected from patients before RT, every 2 weeks first 3 months, then at 6, 9, 12 months after RT. In the case of complication development samples from patients were collected later then 1-year monitoring period. PyV DNA was detected by real-time PCR. Viral DNAs from 17 BKV-positive and 11 JCV-positive patients were molecular typed by partial sequencing of VP1 genome region. Confidence intervals for the proportions were calculated using Wald's method. Results Results showed that BKV detection total frequency in the group 1 was 14.47% [11.32%; 18.3%], almost all patients developed viruria, only 2.54% [1.32%; 4.67%] had viremia. In the group 2 PyV DNA was detected in 46.07% [40.96%; 51.26%] of recipients: 19.10% [15.34%; 23.52%] had BKV infection, 19.94% [16.11%; 24.42%] – JCV, 7.02% [4.76%; 10.2%] – BKV+JCV mixed infection. Frequency of viremia was 6.74% [4.53%; 9.87%] in this group. Maximal BKV viral load levels reached 1.2 × 1012 copies/ml in urine and 5.9 × 107 copies/ml in serum. JCV loads were up to 3 × 109 copies/ml in urine and 1.2 × 108 copies/ml in serum. Then we analyzed frequency of PyV detection before RT and during the first year after RT among the 102 recipients. Results displayed on the Fig. 1 showed that the peak of PyV infection registration and the higher risk for patient had a place on the 1.5-2.5 months after RT. Quantitative monitoring of viral load in posttransplant period was the basis for the correction of the applied immunosuppressive therapy regimens in relation to the recipients with a high viral load (higher than 1 × 107 copies/ml in urine or 1 × 104 copies/ml in serum). The results of molecular typing showed that 17 BKV isolates belonged to subgroups Ib-2 and IVc-2 (12 and 5 isolates, respectively). Within subgroups Ib-2 isolates formed 3 clusters corresponding 3 separate genovariants. JCV isolates belonged to subtype 1A, 1B and 2A (7, 3 and 1 of isolates, respectively). The last one had 99% nucleotide sequence similarity with Greece and South Korea isolates. Conclusion Our data demonstrated an importance of PyV DNA monitoring of kidney recipients in the posttransplant period starting from the first days after RT to predict development of PyV complications as PVAN, HC or others by correcting the immunosuppressive therapy.
BACKGROUND This paper presents the results of studying the characteristics of the antibody response in kidney recipients who are at high risk of severe COVID-19. METHOD The study of features of the formation of post-infectious anti-SARS-CoV-2 IgG was carried out in the group of kidney recipients (n = 171) with PCR confirmed diagnosis of COVID-19. Studies of the characteristics of post-vaccination immunity were carried out in a group of vaccinated recipients (n = 49) with Sputnik V (Russia) or Vero Cell (China). ELISA was used to detect IgG to S and N proteins of the SARS-CoV-2. Comparative studies used a simple randomized selection of immunocompetent COVID-19 patients (n = 163). Statistical data processing was carried out using the χ2 and Wald's methods. RESULTS It was found that 30 days after the onset of clinical symptoms of COVID-19 in kidney recipients, IgG to S and/or N proteins of SARS-CoV-2 were detected in 89.5% (83.9%–93.3%) of them. The detection rate of IgG to the S protein was higher than that to the N protein [87.7% (81.9%–91.9%) and 62.0% (54.5%–68.9%), respectively). At the same time, the seroprevalence to the pathogen varied by age: in the 18–34-year-old group it was 77.7% (59.9%–88.9%), in the 50–64-year-old group it was 96.7% (88.2%–99.8%) and in the group >64 years old it was 80.0% (66.8%–89.0%). This trend of antibody production in older recipients correlated with the highest frequency of registration in them of moderate and severe forms [66.7% (56.4%–75.6%)]. Differences due to the severity of the disease were noted both in the frequency of detectable antibodies [80.3% (69.5%–88.0%) in recipients with a mild form of COVID-19 and 96.0% in recipients with a severe form of infection (P < .001)] and in the intensity of the formed anti-SARS-CoV-2 immunity. Thus, high values of PC (positivity coefficient) (>12) to S protein were recorded in 52.7% (39.8%–65.3%) and 63.2% (53.1%–72.2%) patients with mild and severe forms of COVID-19, respectively, which indicated a direct dependence of the production of antiviral antibodies on the severity of the infection. It was found that in 62.6% (55.1%–69.5%) of recovered recipients anti-SARS-CoV-2 IgG persisted for a period of 3 months from the onset of infection. In a significant proportion of recipients [42.8% (35.5%–50.2%)], antibodies were detected for up to 15 months. In general, the post-infectious antibody response in kidney recipients and immunocompetent patients had similar patterns of development. Despite the general mechanism of antibody production, in immunocompetent patients, the frequency of detection of antiviral antibodies (to N protein: 82.9% and to S protein: 91.2%), tension indicators (high values of PC to N protein: 51.0% and to S protein: 75.5%) and the duration of retention (in 50.3% at 15 months of monitoring) were slightly higher than the same parameters in recipients with COVID-19. In kidney recipients after immunization with Sputnik V and Vero Cell (n = 34), a rather low detection rate of antiviral IgG [52.9% (36.7%–68.6%) compared with a similar parameter (P < .001) in vaccinated immunocompetent individuals [96.8% (94.8%–98.1%)] was found. The seroprevalence in the group of recipients with hybrid immunity (after illness and vaccination, n = 15) was 86.7% (60.9%–97.5%). In a comparative analysis of the intensity of post-vaccination immunity, high values of PC to S protein (>12) were recorded in 44.0% (26.7%–62.9%) of recipients vaccinated with Sputnik V and 50.0% (31.4%–68.6%) of recipients vaccinated with Vero Cell. The inverse relationship was observed in immunocompetent individuals: 64.7% (58.1%–70.7%) for Sputnik V and 44.2% (36.8%–51.8%] for Vero Cell. CONCLUSION The patterns of antibody response to the causative agent in recipients with COVID-19 are comparable to those in immunocompetent patients, while for vaccinated recipients, a low frequency of detection of antiviral antibodies was shown, which indicates the need to continue research on the humoral immunity in people with vulnerable immunity in order to select the best tactics for COVID-19 immunization.
The presented work contains an analysis of seroprevalence, tension, and duration of post-vaccination immunity to the SARS-CoV-2 coronavirus in the residents of the Republic of Belarus after immunization with two vaccine preparations available in the country: Sputnik V and Vero Cell.It was found that seroconversion after the injection of the Vero Cell vaccine occurred significantly later than after the Sputnik V vaccine (p < 0.001). Nevertheless, two-stage immunization with the vaccines provided a sufficiently high efficiency of the inoculated antibodies to the S protein of the COVID-19 pathogen: the proportion of seropositive persons reached 99.19 [96.89; 99.97] % for Sputnik V and 96.03 [90.81; 98.53] % for Vero Cell. The efficiency of antibody formation after immunization with the Vero Cell vaccine was lower in older persons (in the group > 65 years). The proportion of individuals with the highest IgG score for the SARS-CoV-2 S protein was higher after the Sputnik V administration compared to that in response to the Vero Cell vaccine (p < 0.05), and gradually decreased over time. However, no significant decrease in the level of seropositive individuals after 90 days from the start of immunization with the both vaccine preparations was detected. In COVID-19 survivors immunized with the Sputnik V vaccine, the quantitative indicators of post-vaccination antibodies reached their peak values after 1 dose of the vaccine. The obtained results complement the accumulated world science and practical information on the problem of the postvaccination immunity formation in the context of the use of different drugs against COVID-19.>< 0.001). Nevertheless, two-stage immunization with the vaccines provided a sufficiently high efficiency of the inoculated antibodies to the S protein of the COVID-19 pathogen: the proportion of seropositive persons reached 99.19 [96.89; 99.97] % for Sputnik V and 96.03 [90.81; 98.53] % for Vero Cell. The efficiency of antibody formation after immunization with the Vero Cell vaccine was lower in older persons (in the group > 65 years). The proportion of individuals with the highest IgG score for the SARS-CoV-2 S protein was higher after the Sputnik V administration compared to that in response to the Vero Cell vaccine (p < 0.05), and gradually decreased over time. However, no significant decrease in the level of seropositive individuals after 90 days from the start of immunization with the both vaccine preparations was detected. In COVID-19 survivors immunized with the Sputnik V vaccine, the quantitative indicators of post-vaccination antibodies reached their peak values after 1 dose of the vaccine.The obtained results complement the accumulated world science and practical information on the problem of the postvaccination immunity formation in the context of the use of different drugs against COVID-19.
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