Introduction of ORF3a-Q57H SARS-CoV-2 Variant Causing Fourth Epidemic Wave of COVID-19, Hong Kong, China

Abstract

We describe an introduction of clade GH severe acute respiratory syndrome coronavirus 2 causing a fourth wave of coronavirus disease in Hong Kong. The virus has an ORF3a-Q57H mutation, causing truncation of ORF3b. This virus evades induction of cytokine, chemokine, and interferon-stimulated gene expression in primary human respiratory cells.

Keywords: COVID-19; China; Hong Kong; SARS; SARS-CoV-2; coronavirus; coronavirus disease; respiratory infections; severe acute respiratory syndrome coronavirus 2; viruses; zoonoses.

Figure 1

Timeline of COVID-19 cases during fourth epidemic, September 9–October 19, 2020, Hong Kong, China. Asymptomatic cases occurred in patients A1–A3, B1, B2, BB4, BB12, BB13, BB15, C3, C4, C7, and C9. Symptomatic cases occurred among patients A4, BB1–BB3, BB5–BB11, BB14, C1, C2, C5, C6, and C8. COVID-19, coronavirus disease; RT-PCR, reverse transcription PCR.

Figure 2

Innate immune responses in human airway organs experimentally infected with SARS-CoV-2 viruses from COVID-19 epidemic waves 1, 3, and 4, Hong Kong, China. A) ORF1b; B) IFN-β; C) IFN-λ 1; D) IFN-λ 2/3; E) IP-10; F) ISG15; G) MX1; H) MDA5. Messenger RNA expression of viral genes in human airway air-liquid interface organoids (n = 4; multiplicity of infection = 2) from the apical side at 48 h post infection. Mock samples were not infected. The gene expression of infected cells was first normalized with β-actin and further normalized with ORF1b gene. The gene expression of mock-infected cells was presented after normalization with β-actin. The differences were compared using 1-way ANOVA followed by a Tukey multiple-comparison test. Means and SD error bars are as shown. *p<0.05; **p<0.01; ***p<0.001. COVID-19, coronavirus disease; IFN, interferon; IP-10 interferon gamma-induced protein-10; ISG15, interferon stimulated gene 15; MDA5, melanoma differentiation-associated protein 5; MX1, interferon-induced GTP binding protein 1; ORF, open reading frame; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.