Read on for our highlighted selection of miscellaneous Covid-related studies from the scientific press for February 2022:
- Early assessment of the clinical severity of the SARS-CoV-2 omicron variant in South Africa: a data linkage study
- Attenuated replication and pathogenicity of SARS-CoV-2 B.1.1.529 Omicron
- SARS-CoV-2 Omicron virus causes attenuated disease in mice and hamsters
- Recovery of anosmia in hamsters infected with SARS-CoV-2 is correlated with repair of the olfactory epithelium
- Rapid epidemic expansion of the SARS-CoV-2 Omicron variant in southern Africa
- Structural and functional characterizations of infectivity and immune evasion of SARS-CoV-2 Omicron
Early assessment of the clinical severity of the SARS-CoV-2 omicron variant in South Africa: a data linkage study
The SARS-CoV-2 omicron variant of concern was identified in South Africa in November, 2021, and was associated with an increase in COVID-19 cases. In this article the authors aimed to assess the clinical severity of infections with the omicron variant using S gene target failure (SGTF) on the Thermo Fisher Scientific TaqPath COVID-19 PCR test as a proxy. They did data linkages for national, South African COVID-19 case data, SARS-CoV-2 laboratory test data, SARS-CoV-2 genome data, and COVID-19 hospital admissions data. For individuals diagnosed with COVID-19 via TaqPath PCR tests, infections were designated as either SGTF or non-SGTF. The delta variant was identified by genome sequencing. Using multivariable logistic regression models, the authors assessed disease severity and hospitalizations by comparing individuals with SGTF versus non-SGTF infections diagnosed between Oct 1 and Nov 30, 2021, and we further assessed disease severity by comparing SGTF-infected individuals diagnosed between Oct 1 and Nov 30, 2021, with delta variant-infected individuals diagnosed between April 1 and Nov 9, 2021. From Oct 1 (week 39), 2021, to Dec 6 (week 49), 2021, 161 328 cases of COVID-19 were reported in South Africa. 38 282 people were diagnosed via TaqPath PCR tests and 29 721 SGTF infections and 1412 non-SGTF infections were identified. The proportion of SGTF infections increased from two (3·2%) of 63 in week 39 to 21 978 (97·9%) of 22 455 in week 48. After controlling for factors associated with hospitalisation, individuals with SGTF infections had significantly lower odds of admission than did those with non-SGTF infections (256 [2·4%] of 10 547 vs 121 [12·8%] of 948; adjusted odds ratio [aOR] 0·2, 95% CI 0·1–0·3). After controlling for factors associated with disease severity, the odds of severe disease were similar between hospitalised individuals with SGTF versus non-SGTF infections (42 [21%] of 204 vs 45 [40%] of 113; aOR 0·7, 95% CI 0·3–1·4). Compared with individuals with earlier delta variant infections, SGTF-infected individuals had a significantly lower odds of severe disease (496 [62·5%] of 793 vs 57 [23·4%] of 244; aOR 0·3, 95% CI 0·2–0·5), after controlling for factors associated with disease severity. The authors concluded that their early analyses suggest a significantly reduced odds of hospitalisation among individuals with SGTF versus non-SGTF infections diagnosed during the same time period. SGTF-infected individuals had a significantly reduced odds of severe disease compared with individuals infected earlier with the delta variant. Some of this reduced severity is probably a result of previous immunity.
Wolter N, Jassat W, Walaza S, Welch R, Moultrie H, Groome M, Amoako DG, Everatt J, Bhiman JN, Scheepers C, Tebeila N, Chiwandire N, du Plessis M, Govender N, Ismail A, Glass A, Mlisana K, Stevens W, Treurnicht FK, Makatini Z, Hsiao NY, Parboosing R, Wadula J, Hussey H, Davies MA, Boulle A, von Gottberg A, Cohen C. Early assessment of the clinical severity of the SARS-CoV-2 omicron variant in South Africa: a data linkage study. Lancet. 2022 Jan 19:S0140-6736(22)00017-4. doi: 10.1016/S0140-6736(22)00017-4.
Attenuated replication and pathogenicity of SARS-CoV-2 B.1.1.529 Omicron
SARS-CoV-2 Omicron emerged in November 2021 and is rapidly spreading among the human population. While recent reports reveal that the Omicron variant robustly escapes from vaccine and therapeutic neutralization antibodies, the pathogenicity of the virus remains unknown. Here the authors show that the replication of the Omicron variant is dramatically attenuated in Calu3 and Caco2 cells. Further mechanistic investigations reveal that the Omicron variant is inefficient in transmembrane serine protease 2 (TMPRSS2) usage in comparison to that of WT and previous variants, which may explain its reduced replication in Calu3 and Caco2 cells. Omicron replication is markedly attenuated in both the upper and lower respiratory tract of infected K18-hACE2 mice in comparison to that of WT and Delta variant, which results in its dramatically ameliorated lung pathology. When compared with SARS-CoV-2 WT, Alpha, Beta, and Delta variant, infection by the Omicron variant causes the least body weight loss and mortality rate. The authors concluded that overall, their study demonstrates that the Omicron variant is attenuated In virus replication and pathogenicity in mice In comparison with WT and previous variants.
Shuai H, Chan JF, Hu B, Chai Y, Yuen TT, Yin F, Huang X, Yoon C, Hu JC, Liu H, Shi J, Liu Y, Zhu T, Zhang J, Hou Y, Wang Y, Lu L, Cai JP, Zhang AJ, Zhou J, Yuan S, Brindley MA, Zhang BZ, Huang JD, To KK, Yuen KY, Chu H. Attenuated replication and pathogenicity of SARS-CoV-2 B.1.1.529 Omicron. Nature. 2022 Jan 21. Doi: 10.1038/s41586-022-04442-5.
SARS-CoV-2 Omicron virus causes attenuated disease in mice and hamsters
The recent emergence of B.1.1.529, the Omicron variant has raised concerns for escape from protection by vaccines and therapeutic antibodies. A key test for potential countermeasures against B.1.1.529 is their activity in pre-clinical rodent models of respiratory tract disease. Here, using the collaborative network of the SARS-CoV-2 Assessment of Viral Evolution (SAVE) program of the National Institute of Allergy and Infectious Diseases (NIAID), the authors evaluated the ability of multiple B.1.1.529 Omicron isolates to cause infection and disease in immunocompetent and human ACE2 (hACE2) expressing mice and hamsters. Despite modeling data suggesting that B.1.1.529 spike can bind more avidly to murine ACE2, the authors observed less infection in 129, C57BL/6, BALB/c, and K18-hACE2 transgenic mice as compared with previous SARS-CoV-2 variants, with limited weight loss and lower viral burden in the upper and lower respiratory tracts. In wild-type and hACE2 transgenic hamsters, lung infection, clinical disease, and pathology with B.1.1.529 also were milder compared to historical isolates or other SARS-CoV-2 variants of concern. Overall, experiments from the SAVE/NIAID network with several B.1.1.529 isolates demonstrate attenuated lung disease in rodents, which parallels preliminary human clinical data.
Halfmann PJ, Iida S, Iwatsuki-Horimoto K, Maemura T, Kiso M, Scheaffer SM, Darling TL, Joshi A, Loeber S, Singh G, Foster SL, Ying B, Case JB, Chong Z, Whitener B, Moliva J, Floyd K, Ujie M, Nakajima N, Ito M, Wright R, Uraki R, Warang P, Gagne M, Li R, Sakai-Tagawa Y, Liu Y, Larson D, Osorio JE, Hernandez-Ortiz JP, Henry AR, Ciouderis K, Florek KR, Patel M, Odle A, Wong LR, Bateman AC, Wang Z, Edara VV, Chong Z, Franks J, Jeevan T, Fabrizio T, DeBeauchamp J, Kercher L, Seiler P, Gonzalez-Reiche AS, Sordillo EM, Chang LA, van Bakel H, Simon V; Consortium Mount Sinai Pathogen Surveillance (PSP) study group, Douek DC, Sullivan NJ, Thackray LB, Ueki H, Yamayoshi S, Imai M, Perlman S, Webby RJ, Seder RA, Suthar MS, García-Sastre A, Schotsaert M, Suzuki T, Boon ACM, Diamond MS, Kawaoka Y. SARS-CoV-2 Omicron virus causes attenuated disease in mice and hamsters. Nature. 2022 Jan 21. doi: 10.1038/s41586-022-04441-6.
Recovery of anosmia in hamsters infected with SARS-CoV-2 is correlated with repair of the olfactory epithelium
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for a pandemic affecting billions of people worldwide. Apart from the extreme global economic impact, the pandemic will likely have a lasting impact through long-term sequelae not yet fully understood. Fully understanding the mechanisms driving the various symptoms and sequelae of SARS-CoV-2 infection will allow for the eventual development of therapeutics to prevent or treat such life-altering symptoms. In this study, the authors developed a behavioral test of anosmia in SARS-CoV-2-infected hamsters. They find a moderately strong correlation between the level of anosmia and the score of histological damage within the olfactory epithelium. They also find a moderately strong correlation between the level of anosmia and the thickness of the olfactory epithelium, previously demonstrated to be severely damaged upon infection. Thus, this food-searching behavioral test can act as a simple and effective screening method in a hamster model for various therapeutics for SARS-CoV-2-related anosmia.
Reyna, R.A., Kishimoto-Urata, M., Urata, S. et al. Recovery of anosmia in hamsters infected with SARS-CoV-2 is correlated with repair of the olfactory epithelium. Sci Rep 12, 628 (2022). https://doi.org/10.1038/s41598-021-04622-9.
Rapid epidemic expansion of the SARS-CoV-2 Omicron variant in southern Africa
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in southern Africa has been characterized by three distinct waves. The first was associated with a mix of SARS-CoV-2 lineages, whilst the second and third waves were driven by the Beta and Delta variants, respectively. In November 2021, genomic surveillance teams in South Africa and Botswana detected a new SARS-CoV-2 variant associated with a rapid resurgence of infections in Gauteng Province, South Africa. Within three days of the first genome being uploaded, it was designated a variant of concern (Omicron) by the World Health Organization and, within three weeks, had been identified in 87 countries. The Omicron variant is exceptional for carrying over 30 mutations in the spike glycoprotein, predicted to influence antibody neutralization and spike function4. Here, the authors describe the genomic profile and early transmission dynamics of Omicron, highlighting the rapid spread in regions with high levels of population immunity.
Viana, R., Moyo, S., Amoako, D.G. et al. Rapid epidemic expansion of the SARS-CoV-2 Omicron variant in southern Africa. Nature (2022). https://doi.org/10.1038/s41586-022-04411-y.
Structural and functional characterizations of infectivity and immune evasion of SARS-CoV-2 Omicron
The SARS-CoV-2 Omicron with increased fitness is spreading rapidly worldwide. Analysis of cryo-EM structures of the Spike (S) from Omicron reveals amino acid substitutions forging interactions that stably maintain an active conformation for receptor recognition. The relatively more compact domain organization confers improved stability and enhances attachment but compromises the efficiency of the viral fusion step. Alterations in local conformation, charge and hydrophobic microenvironments underpin the modulation of the epitopes such that they are not recognized by most NTD- and RBD-antibodies, facilitating viral immune escape. Structure of the Omicron S bound with human ACE2, together with the analysis of sequence conservation in ACE2 binding region of 25 sarbecovirus members as well as heatmaps of the immunogenic sites and their corresponding mutational frequencies sheds light on conserved and structurally restrained regions that can be used for the development of broad-spectrum vaccines and therapeutics.
Cui, Z., Liu, P., Wang, N., Wang, L., Fan, K., Zhu, Q., Wang, K., Chen, R., Feng, R., Jia, Z., Yang, M., Xu, G., Zhu, B., Fu, W., Chu, T., Feng, L., Wang, Y., Pei, X., Yang, P., Xie, X.S., Cao, L., Cao, Y., Wang, X., Structural and functional characterizations of infectivity and immune evasion of SARS-CoV-2 Omicron, Cell (2022), doi: https://doi.org/10.1016/j.cell.2022.01.019.