Coronavirus Disease 2019 (COVID-19) Re-infection by a Phylogenetically Distinct Severe Acute Respiratory Syndrome Coronavirus 2 Strain Confirmed by Whole Genome Sequencing

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.

Recurrence of Positive SARS-CoV-2 RNA in a COVID-19 Patient: Two Case Reports from Saudi Arabia

“…To and his colleagues demonstrated that second episode of asymptomatic infection occurred after the rst symptomatic episode in an apparently immunocompetent patient [4]. In addition, they con rmed SARS-CoV-2 reinfection by performing whole genome sequencing for the rst and second episodes indicating different clades [4]. We assume that the recurrence of COVID-19 is possible due to the presence of nonprotective IgG and recovered patients might be carriers and actively transmitting the virus even after their two negative tests [10,11].…”

“…A similar case presenting recurrence of SARS-CoV-2 has been reported in Hong Kong, bringing more attention lately. To and his colleagues demonstrated that second episode of asymptomatic infection occurred after the rst symptomatic episode in an apparently immunocompetent patient [4]. In addition, they con rmed SARS-CoV-2 reinfection by performing whole genome sequencing for the rst and second episodes indicating different clades [4].…”

“…When the pandemic rst started, it was thought to be an immunizing, non-relapsing disease [3]. However, in some countries, there have been reports of rare suspected cases of COVID-19 reinfection [4]. Herein, we reported two COVID-19 cases registered in Saudi Arabia with recurrence of positive SARS-CoV-2 ribonucleic acid (RNA).…”

A Minimalist Strategy Towards Temporarily Defining Protection for COVID-19

“…The latter could be the prelude to neutralization escape mutants should they occur [53]. The latter may also be the prelude to emerging reports of possible SARS-CoV-2 repeat infections [54].…”

“…Reports of repeat SARS-CoV-2 infections have already begun to emerge as the pandemic continues [54,[90][91][92]. Undoubtedly, much more similar information will be collated anecdotally or in larger series and observations.…”