Intra-host SARS-CoV-2 composition varies over time, hinting at viral evolution during infection

Since the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen behind the coronavirus disease (COVID-19) pandemic, new viral variants have been continuously identified with enhanced transmissibility or virulence.

Since the SARS-CoV-2 is an RNA virus, it has a high mutation rate due to the low fidelity of the RNA polymerase. The absence of post-replication nucleotide repair mechanisms. Also, RNA viruses exist in populations of viral variants that contain various mutations between hosts, termed as inter-host, and within an individual host, called intra-host. Intra-host is also called quasispecies, a strategy of viral evolution.

Researchers at the Southern University of Science and Technology in China revealed rapid and dramatic changes in quasispecies diversity upon evaluating the SARS-CoV-2 populations present in the upper and lower respiratory tracts of patients with varying COVID-19 severity.

The study findings, published in the journal Virulence, provided new insights into the intra-host evolution of SARS-CoV-2. The intra-host quasispecies' composition differs with time during the early symptom onset, hinting at viral evolution during infection.

RNA viruses and evolution

RNA viruses proliferate as quasispecies through the dynamic distribution of divergent but closely related genomes. These species are faced with the ongoing process of genetic variation, competition, and selection. The genomic heterogeneity confers an advantage onto the viral population, allowing for rapid adaptation to a changing environment.

During SARS-CoV-2 infection, the immune system plays an imperative role in defending the body. Since there are still no available drugs to clear the virus, the immune system is a vital factor in determining the virus's evolution.

The body's humoral and cellular response work as a team to inhibit viral replication and prevent damage due to an overactive immune system. Further, virus-specific serum antibodies help ward off infection. In line with this, the B cells produce protection-specific antibodies, including immunoglobulin G (IgG) and neutralizing antibodies (Nabs), to block the virus from entering and infecting host cells. However, the virus interacts with the body's immune system, and the virus may evolve, causing mutations.

It is also essential to determine whether a viral quasispecies infects the host or the virus evolves in the cells to form quasispecies. Meanwhile, it is known that genetic diversity in the pathogen's quasispecies is affected by the pathogen-host interaction to adapt to various hosts and tissues.

The study

In the current study, the investigators aimed to reveal the genetic diversity in SARS-CoV-2 quasispecies in human specimens to shed light on the impact of distinct environments on viral evolution.

To arrive at the study findings, the researchers performed a comparative analysis of genomic diversity of SARS-CoV-2 using the meta-transcriptomic sequencing

The team enrolled 48 COVID-19 patients from the Shenzhen Third People's Hospital in China between January 20 and January 30, 2020. They also classified disease severity as mild or severe based on the Diagnosis and Treatment Scheme of SARS-CoV-2, recommended by the National Health Commission of China. Single nucleotide variants (SNVs) were identified in the SARS-CoV-2 population.

The researchers collected samples at various time points during the onset of symptoms in patients' upper and lower respiratory tracts. They obtained samples through sputum, swabs, nasal swabs, and supernatant of bronchoalveolar lavage fluid (BALF).

The team also identified fewer SNVs in SARS-CoV-2 positive samples, contributing to the lower sequencing depth and reflecting some actual loss of diversity. Further, analyses revealed the microevolution profile of SARS-CoV-2 during infection, indicating mutations viral for viral adaptation.

The positive selection analysis of the SARS-CoV-2 genome showed the positive selected amino acid G251V on ORF3a. Also, the alternative allele frequency spectrum (AAFS) of all variants noted that ORF8 could tolerate alternate alleles with high frequency.

Overall, the results show the quasispecies' profile of SARS-CoV-2 in the respiratory tract in the first two months after the outbreak," the team noted.

The team also noted that the current study has limitations, including the small sample size. The group recommends that more samples are needed to assess the intra-host genomic diversity of SARS-CoV-2.

Furthermore, more experiments should be carried out to explore the host immune system's influence on virus evolution," the team added.

Journal reference:
Angela Betsaida B. Laguipo

Written by

Angela Betsaida B. Laguipo

Angela is a nurse by profession and a writer by heart. She graduated with honors (Cum Laude) for her Bachelor of Nursing degree at the University of Baguio, Philippines. She is currently completing her Master's Degree where she specialized in Maternal and Child Nursing and worked as a clinical instructor and educator in the School of Nursing at the University of Baguio.

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