Relative COVID-19 viral persistence and antibody kinetics

Importance The COVID-19 antibody response is a critical indicator for evaluating immunity and also serves as the knowledge base for vaccine development. The picture is still not clear because of many limitations including testing tools, time of sampling, and the unclear impact of varying clinical status. In addition to these problems, antibody levels may not be equivalent to protective capacity. Objective To define the key factor for the different patterns of COVID-19 antibody response. Design We elucidated the antibody response with time-series throat and serum samples for viral loads and antibody levels, then used a neutralization test to evaluate protectiveness. Setting A medical center that typically cares for patients with moderate to severe diseases. Because of the low prevalence of COVID-19 in Taiwan and local government policy, however, we also admit COVID-19 patients with mild disease or even those without symptoms for inpatient care. Participants RT-PCR-confirmed COVID-19 patients. Results We found that only patients with relative persistence of virus at pharynx displayed strong antibody responses that were proportional to the pharyngeal viral load. They also had proportional neutralization titers per unit of serum. Although antibody levels decreased around 2 weeks after symptom onset, the neutralization efficacy per unit antibody remained steady and even continued to increase over time. The antibody response in patients with rapid virus clearance was weak, but the neutralization efficacy per unit antibody in these patients was comparable to those with persistent presence of virus. The deceased were with higher viral load, higher level of antibody, and higher neutralization titers in the serum, but the neutralization capacity per unit antibody is relatively low. Conclusions and Relevance Strong antibody response depends on the relative persistence of the virus, instead of the absolute virus amount. The antibody response is still weak if large amount of virus is cleared quickly. The neutralization efficacy per unit antibody is comparable between high and low antibody patterns. Strong antibody response contains more inefficient and maybe even harmful antibodies. Low antibody response is also equipped with a capable B cell pool of efficient antibodies, which may expand with next virus encounter and confer protection. Key points Question The key factor for the different “patterns” of COVID-19 antibody response. Findings Strong antibody response depends on the relative persistence of the virus, instead of the absolute virus amount. The antibody response is still weak if large amount of virus is cleared quickly. The neutralization efficacy per unit antibody is comparable between high and low antibody patterns. High antibody level contains more inefficient antibodies. Meaning Strong response contains inefficient and maybe harmful antibodies. Low antibody response is also equipped with a capable B cell pool of efficient antibodies, which may expand with next virus encounter and confer protection.