key: cord-0938672-9wyq5h78
authors: Cheng, Chung-Yi; Hsiao, Shih-Hsin; Fang, Te-Chao; Lin, Yen-Chung; Wang, Jude Chu-Chun; Hung, Ching-Sheng; Chen, Tso-Hsiao; Sue, Yuh-Mou
title: SARS-CoV2 Antibody Response After a Third Dose of Heterologous ChAdOx1 nCoV-19 and Moderna Vaccine in Chronic Dialysis Patients
date: 2022-04-07
journal: J Infect
DOI: 10.1016/j.jinf.2022.04.011
sha: 65108544e78a0edf1afde644ef870e5e788d51f0
doc_id: 938672
cord_uid: 9wyq5h78

nan

The battle against coronavirus disease 2019 (COVID-19) remains the biggest challenge in controlling the spread of the disease globally. In this Journal, the report by Li and colleagues highlighted the danger to renal dialysis patients in the COVID-19 pandemic (1) . Using the whole-genome sequencing and epidemiological data, the author demonstrated that the risk of SARS-CoV-2 transmission was present in the community and the hospital setting. Among various strategies against the spread of infection, current evidence indicates that vaccines continue to offer substantial protection against COVID-19. However, immunogenicity reports that antibody titers wane relatively rapidly after receiving two doses of vaccine. Thus, a third dose has been recommended, especially in those with severely compromised immunity, including end-stage renal disease (ESRD) patients (2, 3) . A recent systemic review has shown that dialysis patients had a significantly lower seroconversion rate following two doses of COVID-19 vaccination than in the control group (RR, 0.88; 95%CI, 0.82-0.93)(4). Moreover, a small prospective study had shown that four months following the second dose of the Pfizer-BioTech Comirnaty vaccine, 20% of dialysis patients became seronegative (SN)(5).

Cumulating evidence has been shown that heterologous vaccines have more immunogenicity than homologous prime-boost vaccination (6, 7) . The question remains to be answered whether a third heterologous vaccine offers a better immunogenicity response than a homologous regimen in dialysis patients. In the present study, we administered the third messenger RNA-based (Moderna) vaccine to the dialysis patients, the humoral response of the additional vaccine was examined.

The present study is a successive cohort of our recently published study (8) . The Abbott IgG II method was used to quantify antibodies against the spike protein's receptor-binding domain (RBD). A value  50 AU/ml was defined as seropositive (SP), < 50 AU/ml was defined as seronegative (SN). Two time points blood tests, T4 and T5, evaluated the post-vaccination anti-RBD response. T4, 20 weeks after the second vaccine (or 0-7 days before the third vaccine). T5, 14-20 days after the third vaccine. Dialysis patients' demographic details were obtained from their medical records. All data were summarized and displayed as mean  standard deviation for the continuous variables. Table 1) . The anti-RBD levels were significantly higher in the M/M group than in the AZ/M group (2990813320 vs. 2201114436 AU/ml, p = 0.023) ( Figure 1A ). At T4, 57.32% reduction of anti-RBD levels in the AZ/M group compared to 79.23% decrease in the M/M group ( Figure 1B and 1C ). At T3 (21-35 days after the second vaccine), only five patients had antibodies < 50 AU/ml. However, at T4, 30 patients became seronegative. Figure 1D shows a significant difference in the SN, SP, and M/M groups' anti-RBD levels before and after the third vaccine. Figure 1E Univariable analysis identified age, body weight (BW), serum calcium, platelet counts, and composite comorbidities as significant factors associated with reducing antibodies in the AZ group. Using multivariable logistic regression analysis, we found that age and platelet counts were significantly correlated with reducing the AZ group's anti-RBD levels (supplementary Table S1 ).

This study followed the IgG antibody response to the RBD of the spike protein in maintenance dialysis patients who received an extended primary series of Moderna vaccines. Before the third dose, the Moderna group had a higher antibody reduction rate than the AZ group (79.23% vs. 57.32%, respectively). However, the AZ group had less sustainable antibody levels than the Moderna group (30 patients seronegative). The third vaccine, Moderna, induced a dramatic humoral response in both AZ and Moderna groups (220111016 and 299083056 AU/ml, respectively).

Age is the critical factor in the humoral response to the SARS-CoV-2 vaccine. Older patients tend to wane off anti-RBD antibodies earlier than younger patients (supplementary Table S1 ). The BW of SN and SP patients was 57.6211.55kg and 63.5113.29 kg, respectively. Current evidence regarding vaccine antibodies and the body mass index (BMI) is conflicting and scanty, perhaps partly because of differences in the distribution and physiology of fatty tissue in men compared to women. Yamamoto et al. observed that a higher BMI was associated with lower titers of spike IgG antibodies against SARS-CoV-2 in men but not women (9) . We found that BW positively correlated with antibody levels but not sex. Patients with lower BW have less sustainable antibody levels than patients with greater BW.

Dialysis patients with lower platelet counts tend to have earlier wane-off anti-RBD response than the higher platelet counts counterpart. A recent study indicated that circulating platelets of rapid responders to the BNT162b2 vaccine expressed lower surface levels of the immunoreceptor tyrosine-based inhibitory motif (ITIM)-coupled receptor CD31 (PECAM-1) compared to slow responders. This result suggests that the platelet-immune crosstalk could be exploited as early biomarkers of vaccine efficacy (10) .

In summary, the present study demonstrated the beneficial effect of the third Moderna vaccine in dialysis patients. We found that 14.5% of patients became seronegative 20 weeks after the second AZ vaccine, but all patients had a positive anti-RBD response after the additional Moderna vaccine. Monologous M/M group had higher anti-RBD levels from T1 to T5 than the heterologous AZ/M group. However, these differences had become less prominent after the third dose ( Figure 1F ). Older patients with lower platelet counts and higher calcium and GPT levels tend to have less sustainable antibody responses. A third heterologous Moderna vaccine provided a comparable anti-RBD response. The sustainability of this effect would need a further longitudinal study. Table 1 Abbreviations: Alb, albumin; BMI, body mass index; BW, body weight; DM, diabetes mellitus; Hb, hemoglobin; HD, hemodialysis; HTN, hypertension; GPT, Glutamic Pyruvic Transaminase; K, potassium; Kt/V, quantifying hemodialysis and peritoneal dialysis treatment adequacy, K, dialyzer clearance of urea; t, dialysis time; V, the volume of distribution of urea; PD, peritoneal dialysis; Pi, phosphorus; TG, triglyceride; URR, urea reduction ratio; WBC, white cell count; WCC, weekly creatinine clearance. * p < 0.05. 

Genetic epidemiology of SARS-CoV-2 transmission in renal dialysis units -A high risk community-hospital interface

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