Neutralizing Antibodies Correlate with Protection from SARS-CoV-2 in Humans during a Fishery Vessel Outbreak with a High Attack Rate

Abstract

The development of vaccines against SARS-CoV-2 would be greatly facilitated by the identification of immunological correlates of protection in humans. However, to date, studies on protective immunity have been performed only in animal models and correlates of protection have not been established in humans. Here, we describe an outbreak of SARS-CoV-2 on a fishing vessel associated with a high attack rate. Predeparture serological and viral reverse transcription-PCR (RT-PCR) testing along with repeat testing after return to shore was available for 120 of the 122 persons on board over a median follow-up of 32.5 days (range, 18.8 to 50.5 days). A total of 104 individuals had an RT-PCR-positive viral test with a cycle threshold (C_T ) of <35 or seroconverted during the follow-up period, yielding an attack rate on board of 85.2% (104/122 individuals). Metagenomic sequencing of 39 viral genomes suggested that the outbreak originated largely from a single viral clade. Only three crew members tested seropositive prior to the boat's departure in initial serological screening and also had neutralizing and spike-reactive antibodies in follow-up assays. None of the crew members with neutralizing antibody titers showed evidence of bona fide viral infection or experienced any symptoms during the viral outbreak. Therefore, the presence of neutralizing antibodies from prior infection was significantly associated with protection against reinfection (Fisher's exact test, P = 0.002).

Keywords: COVID-19; SARS-CoV-2; attack rate; boat; correlates; fishing; neutralizing antibodies; protection; vessel.

FIG 1

Predeparture serological assays. (A) Abbott Architect index values for all 120 individuals assayed. The gray line indicates the cutoff for a positive Abbott reading (≥1.40). Individuals with negative Abbott index values are further classified by whether they subsequently became infected on the ship. Individuals with positive Abbott index values are further characterized by whether their preboarding serum was neutralizing. (B) Neutralization curves for all six preboarding samples that were positive in the Abbott Architect assay. (C) Titers of RBD- or spike-binding IgG antibodies in all six Abbott assay-positive preboarding samples as measured by ELISA. The negative-control sample is pooled sera collected in 2017 to 2018 from 75 individuals (Gemini Biosciences, item 100-110, lot H86W03J).

FIG 2

(A) Abbott Architect SARS-CoV-2 index values over time (pre- and postdeparture) are depicted for each individual with at least two serum draws. The dashed line denotes the seropositivity cutoff of the assay (1.40). Individuals who had a positive RT-PCR with a C_T of <35 or who seroconverted during the follow-up period are shown in light blue. Individuals who were not infected by the above case definition criteria are shown in green. Individuals who screened positive by the Abbott Architect SARS-CoV-2 IgG assay but lacked neutralizing antibodies and were infected are shown in brown. Individuals who had preexisting neutralizing antibodies and were not infected are shown in dark blue. (B) SARS-CoV-2 whole-genome sequencing of cases from the fishery vessel confirms an outbreak. SARS-CoV-2 genomes from 39 cases with C_T values of <26 were recovered, and a phylogenetic tree was made using FastTree along with 109 other isolates reflective of global diversity. Thirty-eight cases are highlighted in red with a median pairwise difference of 1 single nucleotide variation, while one outlier case from the boat is indicated by a red dot. Clade A strains associated with early trans-Pacific transmission are shown in purple.