Immunogenicity, reactogenicity and breakthrough infections after two doses of the inactivated CoronaVac vaccine among patients on dialysis: phase 4 study.

Coronavirus disease 2019 (COVID-19)-associated lethality among patients with end-stage renal disease on dialysis is higher than in the general population [1]. Reported seroconversion rates after messenger RNA and viral-vector vaccines range between 77 and 97% [2-5]. Recently we demonstrated a seroconversion rate of 44% after the first dose of the World Health Organization–validated CoronaVac inactivated virus vaccine (Sinovac Biotech) [6, 7]. Here we report antibody response, breakthrough infections and 28-day lethality after the second dose.

Patients, on dialysis, ages 20–75 years, were asked to receive the two-dose schedule of CoronaVac between 29 April 2021 and 1 June 2021. The characteristics of the global cohort were described previously [7]. The humoral response was assessed 28 days after the first dose (D1) and 28 days after the second dose (D2) using the AdviseDx SARS-CoV-2 IgG II assay [Abbott Laboratories, Abbott Park, IL, USA; lower limit for positivity 50 arbitrary units (AUs)/mL]. A value ≥840 AU/mL was used to define ‘high-responders’, based on the US Food and Drug Administration guideline criterion for the therapeutic use convalescent plasma [8]. For this analysis, the final follow-up date for the occurrence of new confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was 18 September 2021. The study was approved by the local ethics committee and registered at ClinicalTrials.gov (NCT04801667); all patients signed an informed consent form.

There were 198 patients vaccinated with one dose and 195 fully vaccinated. Two patients died from COVID-19 and one patient was vaccinated against hepatitis B before the second dose. The most common adverse reactions after the second dose were local pain and tenderness (11%). Fever, myalgia, headache or diarrhea occurred in ≤5% of the patients and no severe adverse reactions were observed.

From the 198 initial subjects, 138 were included in the immunogenicity cohort (56 individuals had been previously exposed to SARS-CoV-2 and 4 had no sequential serological tests available). The seroconversion rate 28 days after the first dose was 44% (n = 62), increasing to 91% (n = 126) 28 days after the second dose. The median immunoglobulin G (IgG) value among patients with a positive test showed a 6-fold increase, from 103 AU/mL [interquartile range (IQR) 82–202)] after the first dose to 626 AU/mL (IQR 389–1751) after the second dose. A similar trend was observed in the proportion of high responders, increasing from 3 to 40%. Of 76 patients with a negative test after the first dose, 64 (84%) developed antibody response [17 high responders (22%)] after the second dose, showing a median IgG value of 411 AU/mL (IQR 216–907) (Figure 1). The 12 patients with no antibody response after the two doses were significantly older [median age 56 years (IQR 50–61) versus 46 (IQR 36–56); P = 0.02] and were more frequently on maintenance steroid doses (45% versus 8%; P < 0.001) than those showing seroconversion after the first dose (Supplementary Table 1).

FIGURE 1:

Abbott AdviseDx SARS-CoV-2 IgG II immunoassay for total IgG antibodies against the receptor binding domain of the S1 subunit of the SARS-CoV-2 spike protein, in logarithmic scale. The lowest limit of detection by the manufacturer is 6.8 AU/mL (0.83 log) and the analytical measuring interval is 21 [1.32 log, limit of quantification (LoQ)] to 40 000 AU/mL (4.60 log). The threshold for considering the test as positive is 50 AU/mL, or 1.69 log (black line). The value considered in this analysis for classifying the patient as a high responder is 840 AU/mL (2.92 log). Before the first dose of the vaccine, all 138 patients had negative serology; 117 (85%) had undetectable values (blue dots) and 21 (15%) had detectable values below the lowest analytical level (yellow dots). At D1 (28 days after the first dose), 18 (13%) patients remained with undetectable titers, 58 (43%) had detectable but lower than LoQ values and 62 (44%) seroconverted, with 4 (3%) considered as high responders. Twenty-eight days after the second dose of the vaccine (D2), 3 (2%) patients remained with undetectable titers, 9 (7%) had detectable but lower than LoQ values and 126 (91%) had positive titers, with 55 (40%) considered as high responders.

After the second vaccine dose, five (2.6%) patients developed COVID-19, four of them after 15 days. The median IgG titers of these five patients were 60 AU/mL (IQR 40–75). Three required hospitalization and one died 70 days after the second dose. The five patients who developed COVID-19 after the second dose had antibody titers at the threshold of positivity, suggesting a relationship between the magnitude of the humoral response and protection against infection.

This prospective study suggests that the use of the traditional two-dose regimen of the inactivated whole-virion CoronaVac vaccine in dialysis patients is safe and achieved seroconversion rates of 91.3%, similar to that observed in the general population [9, 10]. Additional strategies deserve to be explored in seronegative patients after the first dose.

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