Rapid evolution of SARS-CoV-2 challenges human defenses.

The race between pathogens and their hosts is a major evolutionary driver, where both reshuffle their genomes to overcome and reorganize the defenses for infection, respectively. Evolutionary theory helps formulate predictions on the future evolutionary dynamics of SARS-CoV-2, which can be monitored through unprecedented real-time tracking of SARS-CoV-2 population genomics at the global scale. Here we quantify the accelerating evolution of SARS-CoV-2 by tracking the SARS-CoV-2 mutation globally, with a focus on the Receptor Binding Domain (RBD) of the spike protein determining infection success. We estimate that the > 820 million people that had been infected by October 5, 2021, produced up to 1021 copies of the virus, with 12 new effective RBD variants appearing, on average, daily. Doubling of the number of RBD variants every 89 days, followed by selection of the most infective variants challenges our defenses and calls for a shift to anticipatory, rather than reactive tactics involving collaborative global sequencing and vaccination.

Re-infection with a different SARS-CoV-2 clade and prolonged viral shedding in a hematopoietic stem cell transplantation patient.

Immunocompromised patients who have a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection pose many clinical and public health challenges. We describe the case of a hematopoietic stem cell transplantation patient with lymphoma who had a protracted illness requiring three consecutive hospital admissions. Whole genome sequencing confirmed two different SARS-CoV-2 clades. Clinical management issues and the unanswered questions arising from this case are discussed.

Detection of SARS-CoV-2 variants requires urgent global coordination.

OBJECTIVES: To assess the efforts deployed by different nations and territories in sequencing SARS-CoV-2 isolates, thus enabling detection of variants, known and novel, of concern. METHODS: The sources of over one million full genome sequences of SARS-CoV-2 virus available in the COVID-19 virus Mutation Tracker (CovMT) were analyzed to determine the number of variants in the RBD region of the genome determining infectivity detected in the various nations and territories. RESULTS: The number of detected variants increased as the square root of sequencing effort by nations. Eight nations have contributed 79% of all SARS-CoV-2 isolates that have been sequenced, with two-thirds of all unique variants, adding to 1118 RBD variants, reported by five nations. The median number of sequenced isolates required to detect, on average, one novel RBD variant is 24.05, which is a threshold achieved by 70 nations. CONCLUSIONS: Many developing nations have not contributed any sequences due to lack of capacity. This poses a risk of dangerous virus variants in these under-sampled regions spreading globally before being detected. A collaborative program to sequence SARS-CoV-2 isolates, and other pathogens of concern, is needed to monitor, track, and control the pandemic.

No Evidence for Temperature-Dependence of the COVID-19 Epidemic.

The pandemic of the COVID-19 extended from China across the north-temperate zone, and more recently to the tropics and southern hemisphere. The hypothesis that COVID-19 spread is temperature-dependent was tested based on data derived from nations across the world and provinces in China. No evidence of a pattern between spread rates and ambient temperature was found, suggesting that the SARS-CoV-2 is unlikely to behave as a seasonal respiratory virus.

Functional Pangenome Analysis Shows Key Features of E Protein Are Preserved in SARS and SARS-CoV-2.

The spread of the novel coronavirus (SARS-CoV-2) has triggered a global emergency, that demands urgent solutions for detection and therapy to prevent escalating health, social, and economic impacts. The spike protein (S) of this virus enables binding to the human receptor ACE2, and hence presents a prime target for vaccines preventing viral entry into host cells. The S proteins from SARS and SARS-CoV-2 are similar, but structural differences in the receptor binding domain (RBD) preclude the use of SARS-specific neutralizing antibodies to inhibit SARS-CoV-2. Here we used comparative pangenomic analysis of all sequenced reference Betacoronaviruses, complemented with functional and structural analyses. This analysis reveals that, among all core gene clusters present in these viruses, the envelope protein E shows a variant cluster shared by SARS and SARS-CoV-2 with two completely-conserved key functional features, namely an ion-channel, and a PDZ-binding motif (PBM). These features play a key role in the activation of the inflammasome causing the acute respiratory distress syndrome, the leading cause of death in SARS and SARS-CoV-2 infections. Together with functional pangenomic analysis, mutation tracking, and previous evidence, on E protein as a determinant of pathogenicity in SARS, we suggest E protein as an alternative therapeutic target to be considered for further studies to reduce complications of SARS-CoV-2 infections in COVID-19.