key: cord-0725174-18t1ufhc authors: Medina-Pestana, José; Teixeira, Cinthia Montenegro; Viana, Laila Almeida; Manfredi, Silvia Regina; Nakamura, Monica Rika; Lucena, Elizabeth França; Amiratti, Adriano Luiz; Tedesco-Silva, Helio; Covas, Dimas Tadeu; Cristelli, Marina Pontello title: Immunogenicity, reactogenicity and breakthrough infections after two doses of the inactivated CoronaVac vaccine among patients on dialysis: phase 4 study date: 2021-12-11 journal: Clin Kidney J DOI: 10.1093/ckj/sfab258 sha: 7e6492a1d1126721dca49af9f7991042ccafd17c doc_id: 725174 cord_uid: 18t1ufhc nan 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] [3] [4] [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 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. 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) . 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 Coro-naVac 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. Results from the ERA-EDTA registry indicate a high mortality due to COVID-19 in dialysis patients and kidney transplant recipients across Europe Antibody response to mRNA SARS-CoV-2 vaccines in haemodialysis patients Seroprevalence of antibody to S1 spike protein following vaccination against COVID-19 in patients receiving hemodialysis: a call to arms Humoral response to mRNA versus an adenovirus vector-based SARS-CoV-2 vaccine in dialysis patients Spike and neutralizing antibodies response to COVID-19 vaccination in haemodialysis patients World Health Organization. Immunization, Vaccines and Biologicals Clinical impact, reactogenicity and immunogenicity after the first coronavac dose in dialysis patients: a Phase IV prospective study Emergency Use Authorization Declaration. Washington, DC: U.S. Food and Drug Administration Dynamic IgG seropositivity after rollout of CoronaVac and BNT162b2 COVID-19 vaccines in Chile: a sentinel surveillance study Quantitation of antibodies against SARS-CoV-2 spike protein after two doses of CoronaVac in healthcare workers Supplementary data are available at ckj online. C.M.T. has been working as a medical manager at AstraZeneca since September 2021. The other authors have no conflicts of interests to declare.