SARS-CoV-2, ¿reinfección o diseminación viral persistente? Translated title: SARS-CoV-2, reinfection or persistent viral shedding?

Abstract Background Waning immunity occurs in patients who have recovered from COVID-19. However, it remains unclear whether true re-infection occurs. Methods Whole genome sequencing was performed directly on respiratory specimens collected during two episodes of COVID-19 in a patient. Comparative genome analysis was conducted to differentiate re-infection from persistent viral shedding. Laboratory results, including RT-PCR Ct values and serum SARS-CoV-2 IgG, were analyzed. Results The second episode of asymptomatic infection occurred 142 days after the first symptomatic episode in an apparently immunocompetent patient. During the second episode, there was serological evidence of elevated C-reactive protein and SARS-CoV-2 IgG seroconversion. Viral genomes from first and second episodes belong to different clades/lineages. Compared to viral genomes in GISAID, the first virus genome has a stop codon at position 64 of orf8 leading to a truncation of 58 amino acids, and was phylogenetically closely related to strains collected in March/April 2020, while the second virus genome was closely related to strains collected in July/August 2020. Another 23 nucleotide and 13 amino acid differences located in 9 different proteins, including positions of B and T cell epitopes, were found between viruses from the first and second episodes. Conclusions Epidemiological, clinical, serological and genomic analyses confirmed that the patient had re-infection instead of persistent viral shedding from first infection. Our results suggest SARS-CoV-2 may continue to circulate among the human populations despite herd immunity due to natural infection or vaccination. Further studies of patients with re-infection will shed light on protective correlates important for vaccine design.

Fei Zhou and colleagues 1 estimated mean duration of viral shedding by assessing the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA in patient samples. Assessing potential infectivity is a labour-intensive process, but the presence of nucleic acid alone cannot be used to define viral shedding or infection potential, as the authors state is possible within their methods. For many viral diseases (SARS-CoV, Middle East respiratory syndrome coronavirus, influenza virus, Ebola virus, and Zika virus) it is well known that viral RNA can be detected long after the disappearance of infectious virus.2, 3, 4, 5, 6, 7 With measles virus, viral RNA can still be detected 6–8 weeks after the clearance of infectious virus. 8 The immune system can neutralise viruses by lysing their envelope or aggregating virus particles; these processes prevent subsequent infection but do not eliminate nucleic acid, which degrades slowly over time. We were surprised to note the absence of viral load data in this study. 1 Although the use of sensitive PCR methods offers value from a diagnostic viewpoint, caution is required when applying such data to assess the duration of viral shedding and infection potential because PCR does not distinguish between infectious virus and non-infectious nucleic acid. The timely publication of insightful data is paramount in responding to outbreaks of novel pathogens. However, the findings in this study should not be used to conclude prolonged viral shedding or provide rationale to amend isolation policies, as concluded by the authors; infectivity data are required to demonstrate these specific aspects.