Temporal dynamics of SARS-CoV-2 genome mutations that occurred in vivo on an aircraft.

We analyzed variations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome during a flight-related cluster outbreak of coronavirus disease 2019 (COVID-19) in Shenzhen, China, to explore the characteristics of SARS-CoV-2 transmission and intra-host single nucleotide variations (iSNVs) in a confined space. Thirty-three patients with COVID-19 were sampled, and 14 were resampled 3-31 days later. All 47 nasopharyngeal swabs were deep sequenced. iSNVs and similarities in the consensus genome sequence were analyzed. Three SARS-CoV-2 variants of concern, Delta (n=31), Beta (n=1), and C.1.2 (n=1), were detected among the 33 patients. The viral genome sequences from 30 Delta-positive patients had similar SNVs; 14 of these patients provided two successive samples. Overall, the 47 sequenced genomes contained 164 iSNVs. Of the 14 paired (successive) samples, the second samples (T2) contained more iSNVs (median: 3; 95% confidence interval [95%CI]: 2.77-10.22) than did the first samples (T1; median: 2; 95%CI: 1.63-3.74; Wilcoxon test, P=0.021). 38 iSNVs were detected in T1 samples, and only seven were also detectable in T2 samples. Notably, T2 samples from two of the 14 paired samples had additional mutations than the T1 samples. The iSNVs of the SARS-CoV-2 genome exhibited rapid dynamic changes during a flight-related cluster outbreak event. Intra-host diversity increased gradually with time, and new site mutations occurred in vivo without a population transmission bottleneck. Therefore, we could not determine the generational relationship from the mutation site changes alone.

Functional mutations of SARS-CoV-2: implications to viral transmission, pathogenicity and immune escape.

ABSTRACT: The pandemic of coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to major public health challenges globally. The increasing viral lineages identified indicate that the SARS-CoV-2 genome is evolving at a rapid rate. Viral genomic mutations may cause antigenic drift or shift, which are important ways by which SARS-CoV-2 escapes the human immune system and changes its transmissibility and virulence. Herein, we summarize the functional mutations in SARS-CoV-2 genomes to characterize its adaptive evolution to inform the development of vaccination, treatment as well as control and intervention measures.

Possible recombination between two variants of concern in a COVID-19 patient.

We identified an individual who was coinfected with two SARS-CoV-2 variants of concern, the Beta and Delta variants. The ratio of the relative abundance between the two variants was maintained at 1:9 (Beta:Delta) in 14 days. Furthermore, possible evidence of recombinations in the Orf1ab and Spike genes was found.

Profiling Early Humoral Response to Diagnose Novel Coronavirus Disease (COVID-19).

BACKGROUND: The emergence of coronavirus disease 2019 (COVID-19) is a major healthcare threat. The current method of detection involves a quantitative polymerase chain reaction (qPCR)-based technique, which identifies the viral nucleic acids when present in sufficient quantity. False-negative results can be achieved and failure to quarantine the infected patient would be a major setback in containing the viral transmission. We aim to describe the time kinetics of various antibodies produced against the 2019 novel coronavirus (SARS-CoV-2) and evaluate the potential of antibody testing to diagnose COVID-19. METHODS: The host humoral response against SARS-CoV-2, including IgA, IgM, and IgG response, was examined by using an ELISA-based assay on the recombinant viral nucleocapsid protein. 208 plasma samples were collected from 82 confirmed and 58 probable cases (qPCR negative but with typical manifestation). The diagnostic value of IgM was evaluated in this cohort. RESULTS: The median duration of IgM and IgA antibody detection was 5 (IQR, 3-6) days, while IgG was detected 14 (IQR, 10-18) days after symptom onset, with a positive rate of 85.4%, 92.7%, and 77.9%, respectively. In confirmed and probable cases, the positive rates of IgM antibodies were 75.6% and 93.1%, respectively. The detection efficiency by IgM ELISA is higher than that of qPCR after 5.5 days of symptom onset. The positive detection rate is significantly increased (98.6%) when combining IgM ELISA assay with PCR for each patient compared with a single qPCR test (51.9%). CONCLUSIONS: The humoral response to SARS-CoV-2 can aid in the diagnosis of COVID-19, including subclinical cases.