Seroconversion and dynamics of the anti-SARS-CoV-2 antibody response related to a hospital COVID-19 outbreak among pediatric oncology patients

Abstract

Two recent reports published in Leukemia have described the antibody response to SARS-CoV-2 infection in adult patients with chronic lymphocytic leukemia (CLL) [1] and acute leukemia [2] in conjunction with PCR-confirmed COVID-19. These studies have demonstrated that 14/21 (67%) of the examined CLL patients and 7/8 (88%) of the examined acute leukemia patients produced anti-SARSCoV-2 IgG antibodies. Importantly, 6 out of 7 IgG-positive acute leukemia patients developed virus-neutralizing antibodies [2], assuming a protective immune response. Here we describe the anti-SARS-CoV-2 antibody response in a cohort of pediatric oncology patients with PCR-confirmed COVID-19, who became infected during an outbreak at the hemato-oncology department of the Russian children clinical hospital, Pirogov Russian National Research Medical University, at the end of April, 2020. This study enrolled 18 patients with neoplasms (16 patients with acute lymphoblastic leukemia (ALL) in remission and two patients with a brain tumor) receiving multidrug chemotherapy. The median age was 8.2 years (IQR 7.8). All patients with ALL received consolidation chemotherapy based on the local protocol ALL-MB-2015, which included daunorubicin, L-asparaginase, and methotrexate. All patients were tested SARS-CoV-2 PCR-positive on April 28 or 29, 2020. Clinical characteristics are shown in Supplementary Table 1. The majority of patients demonstrated a mild course of COVID-19 with minimal symptoms. Fever was the most common symptom (14/18); anosmia was reported in 4 (22%) patients. Among 12 patients with a lung CT scan performed, in 6 (50%) no lung involvement was found, in 5 (42%) and 1 (8%) lung involvement of CT grade 1 and 2, respectively, was observed (Supplementary Table 1). In total, we collected 113 residual serum specimens from these patients at different time points and detected serum IgM and IgG against the receptor binding domain (RBD) of the S protein (anti-RBD) and the nucleocapsid protein (antiN) of SARS-CoV-2 (Fig. 1A, Supplementary Table 2) using ELISA kits developed by XEMA Company (Moscow, Russia) (see Supplementary information). In four patients, specimens obtained prior to PCR testing were available, which contained no detectable anti-SARS-CoV-2 antibodies. Seroconversion was observed in 92% patients by week 3 and in 100% patients by week 6 post-exposure (Fig. 1A, Supplementary Table 2). The seropositive rate was maintained at around 80% for at least three consecutive weeks declining to 54% by week 18 post-exposure (Fig. 1A, Supplementary Table 2). Anti-RBD IgG were the most prevalent antibodies detected in 92% patients by week 6 (Fig. 1A, Supplementary Table 2). The highest seroprevalence rate for anti-N IgG was around 70–75%. The rate of anti-RBD IgM was 23–44% by weeks 3 to 4; IgM antibodies vanished at the end of the 9-week follow-up period. Anti-N IgM were detected in two patients (in one patient simultaneously with anti-RBD IgM). To assess the anti-SARS-CoV-2 antibody profile distribution at the specimen level, we selected virus-specific Ig-positive serum specimens, where both anti-SARS-CoV-2 IgG and IgM antibodies were measured (n= 85). The majority of specimens (71/85; 84%) contained anti-RBD * Nikolay Mayanskiy [email protected]