Outcomes and Effects of Vaccination on Sars-Cov-2 Omicron Infection in Kidney Transplant Recipients

Abstract

Background

Kidney transplant recipients (KTRs) are at high risk of COVID-19. Vaccination is significantly effective at preventing infection and reducing infection severity. Omicron infections are less severe than infections by previous strains, but breakthrough disease is more common. Thus, we conducted this study to observe the vaccine efficacy in our KTRs.

Methods

During the surge in the Omicron variant, beginning in May 2022, we retrieved data from 365 KTRs who had received at least one dose of various COVID vaccines until June 30, 2022. Outcomes of the KTRs (n = 168) after at least the 2nd vaccination were assessed until September 30, 2022, before the border was opened for tourism.

Results

The antibody response in KTRs after the 1st and 2nd doses of SARS-CoV-2 vaccines demonstrated a significant increase from the 1st dose (median: 0.4; IQR: 0.4–8.4 U/mL, P < .001) to the 2nd dose (median: 57.5; IQR: 0.4–799.2 U/mL), and the response rate rose from 32% to 65% (P < .001). SARS-CoV-2 infection was identified in 14/365 (3.8%) patients after at least the 1st dose and 7/187 (3.7%) patients at least 7 days beyond the 2nd dose. Most KTRs had a mild course, but 3 (17%) were hospitalized due to pneumonia.

Conclusions

Our data demonstrate a lower response rate and anti-S titers after 2nd dose vaccination in KTRs than in the general population, but a lower incidence of SARS-CoV-2 infection after vaccination was observed during the Omicron outbreak. Owing to the breakthrough infections found in ordinarily vaccinated KTRs, we must emphasize the importance of vaccination and boosters to prevent severe illness, hospitalizations, and death among those developing infections.

Mortality rates of COVID-19 in kidney transplant recipients (KTRs) (20%-40%) were higher than those amongst admitted patients (10%-15%) [1,2]. Four variants (α, γ, β, δ) of SARS-CoV-2 have predominantly undergone a stepwise, sequential replacement of preexisting strains by strains more transmissible than the predecessor lineage [3]. The unique changes in several spike glycoprotein mutations of the Omicron genome separate Omicron from previous lineages and are associated with increased transmissibility and higher viral binding affinity for human angiotensin-converting enzyme 2 [4]. Omicron infections are significantly less severe than infections by previous strains, but the breakthrough disease is significantly more common [3].

The health authorities of most countries have prioritized vulnerable KTRs for COVID vaccination, as it has significant efficacy in preventing and reducing the severity of infection. However, there are concerns regarding the protective effects of vaccines in KTRs, due to accumulating reports of low response rates [5] and COVID-19 infections in vaccinated patients [6,7] due to chronic use of immunosuppressive agents. In Taiwan, 71.1% of the general population has received at least 3 doses of COVID vaccines. The wave of Omicron continues to cause significant increases in hospitalization and death rates; therefore, we conducted this study to observe vaccine efficacy in our KTRs.

Materials and Methods

Since the epidemic caused by the Omicron variant in Taiwan began in May 2022, we retrieved data from 365 KTRs who had received at least their 1st dose of various COVID vaccines until June 30, 2022. In KTRs (n = 168) who had received at least the 2nd vaccination, we assessed the relationship between kidney function and SCOV-2 antibody response. Outcomes were analyzed according to various vaccination statuses until September 30, 2022, which was the time before the border was opened for tourism. The study was approved by the Institutional Review Board of Taichung Veterans General Hospital (CE21377A). Antibody tests for SCOV-2 were performed using the quantitative Elecsys Anti-SARS-CoV-2 S assay (Anti-S; Roche Diagnostics, Mannheim, Germany) with a Cobas 8000 e801 unit (Roche Diagnostics) according to the manufacturer's protocol, with a range of 0.4 to 250 U/mL. The value ≥0.8 U/mL was considered positive if values above the measuring range were diluted 10-fold. The statistical significance was set at P ≤ 0.05. Statistical analyses were conducted using IBM SPSS Statistics for Windows, Version 24.0 (IBM SPSS, Inc, Armonk, NY, United States).

Results

The antibody response in KTRs after the 1st and 2nd doses of COVID vaccines is demonstrated in Fig 1 . The anti-S titer after the 2nd dose (median: 57.5; IQR: 0.4-799.2 U/mL) was significantly higher than that after the 1st dose (median: 0.4; IQR: 0.4-8.4 U/mL, P < .001), and the response rate significantly increased from 32% to 65% (P < .001). The individual COVID vaccine response rates of the 1st and 2nd doses gradually tapered from the mRNA1273 (Moderna [Cambridge, Mass, United States]; n = 93; 40% to 71%) to BNT162b2 (Pfizer–BioNTech [New York City, NY, United States/Mainz, Germany]; n = 44; 25% to 50%), to ChAdOx1 (Oxford–AstraZeneca [Oxford, UK/Wilmington, Del, United States]; n = 27; 22% to 70%), to MVC-COV1901 (Medigen [Frederick, Md, United States]; n = 7; 14% to 71%). There were no significant differences in transplant duration between groups.

Figure 1.

The antibody response in KTRs after the first and second dose SARS-CoV-2 vaccines (A) (A) Antibody responses in different brands of sars-cov-2 vaccine of KTRs after their 1^st and 2^nd vaccination; (B) Percentage of kidney transplant patients with antibody responses after the first and second doses. Elecsys Anti-SARS-CoV-2 S (anti-S) (Roche Diagnostics, Mannheim, Germany).

COVID-19 was identified in 14/365 patients (3.8%) after at least the 1st dose and 7/187 patients (3.7%) at least 7 days post 2nd dose. Most patients had a mild course, but 3 (17%) were hospitalized for pneumonia. The infection probability associated with various COVID vaccines according to their 1st dose is 10.5% (mRNA1273), 20% (BNT162b2), 40% (ChAdOx1), and 0% (MVC-COV1901). There were no significant differences in age, sex, dose, brand of vaccine, or even laboratory data between patients with COVID-19 and those without (data not shown). Patients with a higher estimated glomerular filtration rate and the mRNA1273 vaccine had a better vaccine response (P = .019) (Table 1 ). However, we found 4 patients (2.2%) with reversible renal dysfunction; 1 received a renal graft biopsy, which was unremarkable. They all exhibited systemic vaccine-associated symptoms (VASs) after vaccination with mRNA1273.

Table 1.

Assessment of the Relationship Between Vaccination and Anti-S Response in Patients After At Least 2 Vaccine Doses

	The scov-2 response state post 2nd dose vaccination (%)
	Dose 1–	Dose 1–	Dose 1+	Dose 1+
	Dose 2–	Dose 2+	Dose 2+	Dose 2–
	(n = 57)	(n = 56)	(n = 53)	(n = 2)	P value
Age, y (IQR)	50 (48-65)	59 (49.5-67.25)	57 (45-63)	46.5 (44.75-48.25)	0.447‡
Male sex (n = 103)	37 (35.9)	36 (35)	29 (28.2)	1 (1)	0.616§
Duration after KTx, y	13.1 ± 7.1	11.2 ± 5.7	13.2 ± 7.2	13.3 ± 7.5	0.603
COVID-19 infection					0.081§
Positive (n = 6)	5 (83.3)	0 (0)	1 (16.7)	0 (0)
Negative (n = 162)	52 (32.1)	56 (34.6)	52 (32.1)	2 (1.2)
Brand of the 1st dose					0.041§
Moderna (n = 92)	27 (29.3)	28 (30.4)	37 (40.2)	0 (0)
BNT (n = 42)	20 (47.6)	11 (26.2)	9 (21.4)	2 (4.8)
AZ (n = 27)	8 (29.6)	13 (48.1)	6 (22.2)	0 (0)
MVC (n = 7)	2 (28.6)	4 (57.1)	1 (14.3)	0 (0)
Biochemistry
Cr (mg/dL)	1.35 (1.17-1.91)	1.22 (1-1.66)	1.21 (1.07-1.45)	NA	0.092‡
eGFR (mL/min/1.73 m2)	49.19 (35.47-57.7)†	60.3 (40.04-69.98)⁎	56.92 (47.14-65.19)⁎†	NA	0.019‡
UPCR	110 (93.91-225.3)	138.4 (68.82-375.8)	181.1 (83.13-273.5)	NA	0.817‡

AZ: AstraZeneca; BNT: Pfizer-BioNTech; MVC: Medigen; UPCR: Urine protein to creatinine ratio.

^⁎†Means with the same letter are not significantly different from each other by the Mann-Whitney U test (P < 0.05).

^‡Kruskal-Wallis test.

^§Fisher's exact test.

Discussion

The KTRs receiving long-term immunosuppressants must maintain optimal humoral and cellular immunity to preserve graft function [8]. The weak immune response to different vaccines is well established. Novel mRNA vaccinations for SARS-CoV-2 form a brand-new research field. The mRNA1273 vaccine had the best and highest anti-S response; surprisingly, BNT162b2 was inferior to MVC-COV1901 after the 2nd dose. mRNA vaccines, especially mRNA1273, had higher immunogenicity than vector and subunit vaccines; however, after the 2nd dose of BNT162b2, antibodies gradually waned with time, especially among older, male, and immunocompromised patients [9]. In a post hoc analysis, MVC-COV1901, a protein subunit vaccine, elicits a comparable or superior immune response to that of AZD1222 [10]. An in vitro study demonstrated that the mRNA1273 booster after 2 doses of MVC-COV1901 and AZD1222 has favorable immunogenicity against the Omicron variant, including the BA.4 and BA.5 subvariants [11]. The consistent difference in immunogenicity between BNT162b2 and mRNA1273 is caused by the amount of mRNA, with 30 μg in BNT162b2 and 100 μg in mRNA1273; thus, mRNA1273 induces significantly higher levels of anti-S receptor-binding domain IgG [12]. These results support our finding of lower titers of anti-S after the 2nd dose of BNT162b2 than those observed after the 2nd dose of other vaccines.

Some KTRs suffered from VASs (without data collection); 4 reported VASs with deteriorating renal function after mRNA1273. Fortunately, they recovered after supportive care. Particularly, some patients presented with deteriorating renal function after vaccination, particularly with mRNA1273 and ChAdOx1. Vaccines contain a component of the pathogen (eg, SARS-CoV-2), inducing the immune system to generate interferons. Interferons can enhance vaccine efficacy and immune responses to infectious diseases; however, they can accelerate the cellular and humoral immune response to increase VASs and even cause acute rejection. Most reports revealed that the humoral and cellular responses to SARS-CoV-2 mRNA vaccination in KTRs were safe and not associated with significant alloimmune risks or a decline in allograft function [8,12]. Notably, Omicron variants, which change their major spike glycoprotein, may partially escape natural immunity or reduce vaccine efficacy against COVID-19 [8,11]. Taiwan had success in many waves of the COVID-19 pandemic with strict regulation; however, the Omicron variant is too contagious, and >99.7% of cases exhibited mild or no symptoms, making it impossible to achieve the goal of zero COVID-19 cases since May 2022. During this 4-month study period, the eased restrictions kept outbreaks at bay. Our KTRs maintained significantly lower rates of COVID-19 (3.8% after the 1st dose; 3.7% after the 2nd dose) than the general population, in which rates increased from 1% in May to 27.9% in September 2022. Our data indicated that KTRs practiced good self-protection and expressed high motivation for COVID vaccination during the Omicron wave.

The limitation of this study was that it was a short-term and retrospective study that only demonstrated a lower response rate (65%) and low anti-S titers after the 2nd dose. The prospective cellular and humoral immunity response to COVID vaccination should be analyzed in another study. Regardless of vaccination status or symptoms, Omicron can spread much more easily and earlier than other strains. Our data was limited to only 4 months in the early Omicron period; however, breakthrough infections in vaccinated KTRs are expected, despite efforts to prevent severe illness, hospitalizations, and death. Nowadays, there are more Omicron infections in KTRs after the border was opened for tourism; COVID-19 infections were reported in 41.4% population. The anti-viral medications paxlovid and molnupiravir are at-home COVID-19 treatment options for patients at high risk of Omicron infection.

In conclusion, our data demonstrate a lower response rate and low anti-S titers after the 2nd dose of vaccines. However, we also observed a lower incidence of COVID-19 infection after vaccination in KTRs than in the general population during the Omicron pandemic. Because of the breakthrough infections found in ordinary vaccinated KTRs, we must emphasize the importance of vaccination and boosters to prevent severe illness, hospitalizations, and death among those developing infections.

Declaration of Competing Interest

This work is supported by Taichung Veterans General Hospital (TCVGH-1113603C), Taichung Veterans General Hospital's Chia-Yi Branch (TCVGH-VHCY1108602, TCVGH-VHCY1118602), and the VGH, TSGH, AS Joint Research Program (VTA111-V2-2-1, VTA112-V2-1-1).