The authors of this case study evaluated the possibility of true COVID-19 reinfection.
Study design
Whole genome sequencing was performed directly on respiratory specimens collected during 2 episodes of COVID-19 in a 33-year-old male patient who was apparently immunocompetent. Comparative genome analysis was conducted to differentiate reinfection from persistent viral shedding. Laboratory results, including RT-PCR values and serum SARS-CoV-2 IgG, were analyzed. The patient was discharged from the first episode of COVID-19 on April 14, 2020, after 2 negative SARS-COV-2 RT-PCR assays on nasopharyngeal and throat swabs taken 24 hours apart.
Outcomes
The second episode of asymptomatic infection occurred on August 15, 2020, approximately 4.5 months after the first symptomatic episode. Viral genomes from first and second episodes belonged to different clades/lineages with 24 nucleotide differences. During the second episode, there was serological evidence of elevated C-reactive protein, relatively high viral load with gradual decline and SARS-CoV-2 IgG seroconversion.
The authors performed a blast search for the first and second genome. The first viral genome is most closely related to strains from the United States or England collected in March and April 2020. The second viral genome is most closely related to strains from Switzerland and England collected in July and August 2020.
Limitations
It is possible that the second infection related to prolonged viral shedding rather than reinfection. However, it is unlikely given the difference in 24 nucleotides suggests that the virus strain detected in the second episode is completely different from the strain found in the first episode. The elevated CRP, IgG seroconversion and high viral load also suggest that this is a genuine episode of acute infection.
In addition, there was an interval of 142 days between the first and second episodes. Previous studies have shown that viral RNA is undetectable 1 month after symptom onset for most patients. Prolonged viral shedding for over 1 month is rare. Finally, the patient had recently traveled to Europe, where resurgence of COVID-19 cases has occurred since late July 2020. Since patients may not mount antibody response within 10 days, the negative antibody test does not exclude the possibility that the patient indeed developed antibody response during the early convalescent phase for the first episode. The virus culture using upper respiratory tract specimens from both episodes are still ongoing, and therefore the neutralizing antibody titer against the virus from the first and second episode cannot be compared. Further studies of patients with reinfection are necessary to shed light on protective correlates important for vaccine design.
Clinical significance
Epidemiological, clinical, serological and genomic analyses confirmed that the patient had reinfection instead of persistent viral shedding from first infection. The results suggest SARS-CoV-2 may continue to circulate among the human populations despite herd immunity due to natural infection or vaccination and true reinfection can occur. It is crucial for even those who have been infected with COVID-19 to take the same prophylactic precautions as those who have not been infected with COVID-19.