key: cord-1029883-l32p80ai authors: Hirata, Marino; Fukuchi, Takahiko; Sugawara, Hitoshi title: Trajectory of SARS-CoV-2 anti-S IgG levels following transfusion and a third dose of BNT162b2 vaccine in a patient with massive postoperative bleeding: A case report date: 2022-02-24 journal: Int J Infect Dis DOI: 10.1016/j.ijid.2022.02.042 sha: 5812220f313eae7c6f14e7881cdfbff6cbe7bb53 doc_id: 1029883 cord_uid: l32p80ai Objective : Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been shown to be effective in preventing infection and severe disease. Massive bleeding and transfusion after vaccination can lead to a decrease in the antibody level. The effect of an additional dose of vaccine after blood transfusion has not been described previously. We report the SARS-CoV-2 anti-S IgG trajectory in a man who received a third dose of vaccine after a massive postoperative bleed and blood and plasma transfusion. Case presentation : A 57-year-old male physician had a SARS-CoV-2 anti-S IgG level of 44 AU/mL, measured using the Lumipulse Presto chemiluminescence assay, 3 months after receiving two doses of BNT162b2 vaccine. He underwent a hemicolectomy for colon cancer, experienced massive postoperative bleeding, and required a transfusion. His SARS-CoV-2 anti-S IgG level dropped to 9.2 AU/mL. A third dose of BNT162b2 vaccination was administered to reduce the risk of breakthrough infection. Fifteen days after receiving the third vaccine dose, the patient's SARS-CoV-2 anti-S IgG level increased to 421 AU/mL, likely to reflect protection. Conclusion : This report suggests that administering an extra dose of vaccine is useful for restoring protective antibody levels in vaccinated patients who experience massive bleeding. Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with two doses of the BNT162b2 (Pfizer-BioNTech) messenger RNA (mRNA) vaccine has been reported to produce neutralizing antibodies and be highly effective in preventing disease (Dagan et al., 2021; Walsh et al., 2020) . However, neutralizing antibodies decrease within 6 months, which may make vaccinated patients and healthcare workers susceptible to nosocomial SARS-CoV-2 infection Naaber et al., 2021; Tartof et al., 2021) . A third dose has been shown to increase neutralizing antibodies to a protective level ( Bar-On et al., 2021; Pfizer, 2021) . The neutralizing antibody level directly determines the functional capacity of the immune response. However, due to the complex procedure, it is not suitable for routine use. Measuring IgG antibody to spike surface protein has been investigated as an alternative method of assessing immune response to SARS-CoV-2 vaccination. Although it is unclear whether IgG antibody level is correlated with protection against infection and reducing disease severity, the levels are significantly correlated with neutralizing antibody levels (Michos et al., 2021; Salvagno et al., 2021) . To the best of our knowledge, there have been no previous reports of changes in antibody levels due to bleeding in patients post SARS-CoV-2 vaccination with BNT162b2 as well as other vaccinations. In this report, we describe changes in serum SARS-CoV-2 anti-S IgG levels in a man who received two doses of BNT162b2 vaccine, and was given a third dose after experiencing massive postoperative bleeding. A 57-year-old Japanese male physician was admitted for transverse colon cancer surgery. He was taking amlodipine, pemafibrate, and rosuvastatin for hypertension and dyslipidemia. Four months before admission, he had received a second dose of BNT162b2 vaccine. One month before admission, colonoscopy revealed an adenocarcinoma in the transverse colon. Five days before admission, the SARS-CoV2 PCR test was negative. He had not reported any coronavirus disease 2019 symptoms such as anosmia, dysgeusia/ageusia, anorexia, headache, fever, and fatigue. On hospital day 2, he underwent laparoscopy-assisted left hemicolectomy and D2 lymph node dissection. Next day, he developed abdominal pain, vomiting, and experienced a drop in haemoglobin level. Contrast-enhanced computed tomography showed active bleeding from left gastroduodenal artery and bloody ascites; emergency laparotomy was performed and left gastroduodenal artery was ligated. The total blood loss was 4,185 mL. He required 9 units of red blood cells and 10 units of fresh frozen plasma transfusion. On hospital day 12, he was discharged without any further complications. The patient's SARS-CoV-2 anti-S IgG levels were monitored using a commercial quantitative chemiluminescence immunoassay (Lumipulse Presto, Fujirebio, Japan). The cutoff level for a positive result was 1.0 AU/mL. The patient's SARS-CoV-2 anti-S IgG level 2 days before admission was 44 AU/mL, and decreased to 9.2 AU/mL 4 days after admission, after massive bleeding. The SARS-CoV-2 anti-S IgG level remained low (18 AU/mL) 24 days after admission ( Figure 1 ). Being a healthcare worker, he was at high risk of exposure to SARS-CoV-2 infection. A third dose had not yet been approved in Japan at the time. The patient provided written informed consent and was administered the vaccine 16 days after discharge. His SARS-CoV-2 anti-S IgG level 15 days later was 421 AU/mL. This case demonstrated a rapid, sharp decline in the SARS-CoV-2 anti-S IgG level after massive postoperative bleeding which increased after administration of a third dose of BNT162b2 vaccine has been reported to induce sustained germinal centre B-cell response, with generation of SARS-CoV-2 S-specific neutralizing antibodies, and cellular immunity of both CD4+ and CD8+ T cells after two doses of vaccine (Turner et al., 2021 ). Even if the antibody level decreases over time, antibodies are likely to rapidly generate upon re-exposure ( Bar-On et al., 2021; Pfizer, 2021) . This patient experienced mild increase in antibody level in the natural course of recovery, but the titre had previously been low. It has been reported that a low serum antibody level may increase the risk of breakthrough infection (Bergwerk et al., 2021) , so it is desirable to maintain moderate 6 serum antibody level in individuals at high risk of infection, such as healthcare workers. A third dose of vaccination has been initiated in some countries to boost serum antibody levels. According to the Pfizer report (2021), a third dose elicits neutralizing titres against the Delta variant that are more than five times and 11 times higher among individuals aged 18-55 years and 65-85 years, respectively, than after two doses of vaccine. The IgG (S-RBD) titre, measured using the Abbott Architect SARS-CoV-2 IgG Quant II assay (Abbott, Sligo, Ireland), was determined to have a threshold of 4,160 AU/mL for protection (Ebinger et al., 2021) . The Lumipulse Presto SARS-CoV2-IgG-S assay used in this study has been compared with the Abbott Architect SARS-CoV-2 IgG Quant II assay in 100 Japanese healthcare workers (n=100) and correlation has been examined (Hibino et al., 2021) . Blood samples were collected 3 times from all 100 participants after they had received both doses of the vaccine. The concordance results in all 300 samples before and after vaccination was 99.7% [299/300, 95% confidence interval (CI): 98.1%-99.9%], and the kappa coefficient was 0.99 (95% CI: 0.98-1.00). The Pearson's correlation coefficient was 0.963 (95% CI: 0.954-0.970, P<0.001). According to manufacture's report, the neutralizing capacity threshold of 4,160 AU/mL for the Abbott Architect SARS-CoV-2 IgG Quant II assay was estimated to be equivalent to 72 AU/mL measured by the Lumipulse Presto SARS-CoV2-IgG-S assay. In this patient, the SARS-CoV2-IgG-S level on the 16th day after third vaccination was 422 AU/mL, which was well above the threshold of 72 AU/mL, indicating an adequate antibody level. Because the recovery in the antibody titre post massive bleeding is only slight in the natural course, patients may be susceptible to SARS-CoV-2 infection after massive bleeding. Additional vaccination may be necessary for healthcare workers, such as this patient, and for older adults and immunocompromised individuals with weak immune 7 responses. This study evaluated only one case, and so it is desirable to accumulate further reports of similar cases and to conduct further research on antibody titres in the natural course of recovery following a massive bleed. A 57-year-old male physician who had received two doses of BNT162b2, experienced a sharp decrease in SARS-CoV-2 anti-S IgG level after massive postoperative bleeding. A third dose of BNT162b2 vaccine was administered because the low antibody level indicated that he was at risk of breakthrough infection. After receiving a third dose of BNT162b2 vaccine, his SARS-CoV-2 anti-S IgG titre increased to a level likely to reflect protection. 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Lancet Reg Health Eur Quarter 2021 Earnings Teleconference. Pfizer BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans The strength of association between pre-and post-booster BNT162b2 anti-SARS-CoV-2 antibodies levels depends on the immunoassay Effectiveness of mRNA BNT162b2 COVID-19 vaccine up to 6 months in a large integrated health system in the USA: a retrospective cohort study SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates Figure 1. Trajectory of SARS-CoV-2 anti-S IgG levels in the case patient The patient underwent surgery 2 days after admission and received 9 units of red blood cells and 10 units of fresh frozen plasma for massive postoperative bleeding 3 days after admission. The SARS-CoV-2 anti-S IgG levels decreased from 44 AU/mL before admission to 9.2 AU/mL after the transfusion. The patient received the 3rd dose of BNT162b2 vaccine 28 days after admission, and the levels of SARS-CoV-2 anti-S IgG The authors thank all the clinical staff at our hospital for their dedication to patient care.The authors would like to thank Editage (www.editage.com) for English-language editing.