Asymptomatic COVID-19 re-infection in a Japanese male by elevated half-maximal inhibitory concentration (IC50) of neutralizing antibodies

Abstract

Introduction: "Re-infection" with COVID-19 is a growing concern; re-infection cases have reported worldwide. However, the clinical characteristics of SARS-CoV-2 re-infection, including the levels and role of anti-SARS-CoV-2 Spike protein IgG antibodies and the half-maximal concentration (IC₅₀) of neutralizing antibodies remain unknown.

Methods: Both the epidemiological and clinical information has been collected during two episodes of COVID-19 in a patient. Laboratory results, including RT-PCR, Ct values, anti-SARS-CoV-2 Spike protein IgG antibodies, and the IC₅₀ of neutralizing antibodies levels were analyzed on the patient.

Results: The patient was a 58-year-old man who developed moderate COVID-19 pneumonia with oxygen demand (cannula 2 L/min) in the first episode. By day 30, he recuperated and was discharged after testing negative for SARS-CoV-2. After two and a half months, his three family members showed COVID-19 symptoms and tested positive for SARS-CoV-2. He tested positive for SARS-CoV-2 once again and was asymptomatic (the second episode). The IC₅₀ of neutralizing antibodies against SARS-CoV-2 greatly increased from 50.0 μg/mL (after the first episode) to 14.8 μg/mL (after the second episode), and remained strongly reactive (20.1 μl/mL) after 47 days of the second episode.

Conclusions: Epidemiological, clinical, and serological analyses confirmed that the patient had re-infection instead of persistent viral shedding from first infection. Our results suggest that SARS-CoV-2 re-infection may manifest as asymptomatic with increased neutralizing antibody levels. Further studies such as the virus characteristics, immunology, and epidemiology on SARS-CoV-2 re-infection are needed.

Keywords: Anti-Spike protein IgG antibody; COVID-19; Neutralizing antibody; Re-infection; SARS-CoV-2.

Fig. 1

Timeline of SARS-CoV-2 infection. The patient was admitted to the hospital after presenting symptoms related to moderate COVID-19 pneumonia between April 20 and May 17, 2020. He showed no relapse of symptoms after discharge (the first episode). On July 31, the patient, his wife, and daughter underwent a nasopharyngeal test for SARS-CoV-2 RNA after coming in close contact with his son, who was febrile and was diagnosed with COVID-19 on July 29. Quantitative reverse transcription-polymerase chain reaction showed a positive readout for SARS-CoV-2, and they were isolated in a hotel for 10 days (the second episode). The half-maximal inhibitory concentration (IC₅₀) of neutralizing antibodies was 50.0 μg/mL after first episode (July 20). However, the IC₅₀ of neutralizing antibodies after the second episode (August 21) was greater than that after the first episode (14.8 μg/mL), and that at 152 days after the onset of the first infection (September 16) remained strongly positive at 20.1 μg/mL.

Fig. 2

The results of anti-spike IgG and neutralizing antibody IC₅₀upon re-infection with COVID-19. Lower the half-maximal inhibitory concentration (IC₅₀) of neutralizing antibodies indicates a strongly active neutralizing antibody. The IC₅₀ of neutralizing antibodies was 50.0 μg/mL after first episode (July 20). However, the IC₅₀ of neutralizing antibodies after the second episode (August 21) was greater than that after the first episode (14.8 μg/mL), and that at 152 days after the onset of the first infection (September 16) remained strongly positive at 20.1 μg/mL.