Clinical severity of SARS-CoV-2 Omicron BA.4 and BA.5 lineages in South Africa (preprint)

Omicron lineages BA.4 and BA.5 drove a fifth wave of COVID-19 cases in South Africa. We assessed the severity of BA.4/BA.5 infections using the presence/absence of the S-gene target for infections diagnosed using the TaqPath PCR assay between 1 October 2021 and 26 April 2022. We linked national COVID-19 individual-level data including case, laboratory test and hospitalisation data. We assessed severity using multivariable logistic regression comparing the risk of hospitalisation and risk of severe disease, once hospitalised, for Delta, BA.1, BA.2 and BA.4/BA.5 infections. After controlling for factors associated with hospitalisation and severe outcome respectively, BA.4/BA.5-infected individuals had a similar odds of hospitalisation (aOR1.24, 95% CI 0.98–1.55) and severe outcome (aOR 0.71, 95%CI 0.41–1.25) compared to BA.1-infected individuals. Newly emerged Omicron lineages BA.4/BA.5 continue to show reduced clinical severity compared to previous variants, as observed for Omicron BA.1.

Rapid epidemic expansion of the SARS-CoV-2 Omicron variant in southern Africa (preprint)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in southern Africa has been characterised 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, we describe the genomic profile and early transmission dynamics of Omicron, highlighting the rapid spread in regions with high levels of population immunity.

Bounding the levels of transmissibility & immune evasion of the Omicron variant in South Africa (preprint)

A new SARS-CoV-2 variant of concern, Omicron (B.1.1.529), has been identified based on genomic sequencing and epidemiological data in South Africa. Presumptive Omicron cases in South Africa have grown extremely rapidly, despite high prior exposure and moderate vaccination coverage. The available evidence suggests that Omicron spread is at least in part due to evasion of this immune protection, though Omicron may also exhibit higher intrinsic transmissibility. Using detailed laboratory and epidemiological data from South Africa, we estimate the constraints on these two characteristics of the new variant and their relationship. Our estimates and associated uncertainties provide essential information to inform projection and scenario modeling analyses, which are crucial planning tools for governments around the world. One Sentence Summary We report a region of plausibility for the relative transmissibility and immune escape characteristics of the SARS-CoV-2 Omicron variant estimated by integrating laboratory and epidemiological data from South Africa.

Early assessment of the clinical severity of the SARS-CoV-2 Omicron variant in South Africa (preprint)

ABSTRACT Background The SARS-CoV-2 Omicron variant of concern (VOC) almost completely replaced other variants in South Africa during November 2021, and was associated with a rapid increase in COVID-19 cases. We aimed to assess clinical severity of individuals infected with Omicron, using S Gene Target Failure (SGTF) on the Thermo Fisher Scientific TaqPath COVID-19 PCR test as a proxy. Methods We performed data linkages for (i) SARS-CoV-2 laboratory tests, (ii) COVID-19 case data, (iii) genome data, and (iv) the DATCOV national hospital surveillance system for the whole of South Africa. For cases identified using Thermo Fisher TaqPath COVID-19 PCR, infections were designated as SGTF or non-SGTF. Disease severity was assessed using multivariable logistic regression models comparing SGTF-infected individuals diagnosed between 1 October to 30 November to (i) non-SGTF in the same period, and (ii) Delta infections diagnosed between April and November 2021. Results From 1 October through 6 December 2021, 161,328 COVID-19 cases were reported nationally; 38,282 were tested using TaqPath PCR and 29,721 SGTF infections were identified. The proportion of SGTF infections increased from 3% in early October (week 39) to 98% in early December (week 48). On multivariable analysis, after controlling for factors associated with hospitalisation, individuals with SGTF infection had lower odds of being admitted to hospital compared to non-SGTF infections (adjusted odds ratio (aOR) 0.2, 95% confidence interval (CI) 0.1-0.3). Among hospitalised individuals, after controlling for factors associated with severe disease, the odds of severe disease did not differ between SGTF-infected individuals compared to non-SGTF individuals diagnosed during the same time period (aOR 0.7, 95% CI 0.3-1.4). Compared to earlier Delta infections, after controlling for factors associated with severe disease, SGTF-infected individuals had a lower odds of severe disease (aOR 0.3, 95% CI 0.2-0.5). Conclusion Early analyses suggest a reduced risk of hospitalisation among SGTF-infected individuals when compared to non-SGTF infected individuals in the same time period. Once hospitalised, risk of severe disease was similar for SGTF- and non-SGTF infected individuals, while SGTF-infected individuals had a reduced risk of severe disease when compared to earlier Delta-infected individuals. Some of this reducton is likely a result of high population immunity.

Comparison of three nasopharyngeal swab types and the impact of physiochemical properties for optimal SARS-CoV-2 detection (preprint)

Adequate swab specimen collection, release and detection of nucleic acids by molecular diagnostic assays is largely attributed to the physical and chemical characteristics of different swab types. We investigated properties of three types of commercial nasopharyngeal swabs (nylon flocked: Type 1-Media Merge; Type 2- Kang Jian Medical Apparatus, China and Type 3- Wuxi NEST Biotechnology Co. Ltd, China) used in clinical diagnostics with the aim to establish if different swab designs and configurations had any effect on swab performance. Properties investigated included viral absorption, release, capture, extraction and recovery efficiency from each swab for the detection of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). All swab types (n=18) were inoculated with different amounts of SARS-CoV-2 live viral cultures (1:10, 1:100 and 1:1000 copies/ml) and eluted in sterile phosphate buffer saline. RNA was extracted from all swab eluates using a fully automated system (BD MAX System) and cycle threshold (Ct) values were compared. RNA stability was also investigated after dry storage of swabs at room temperature for 72 hours. Statistically significant differences (p<0.05) were observed in the absorption and release capabilities between Type 1 and 3 as well as between Type 2 and 3 swabs, however, no significant difference was observed between Type 1 and 2. Ct values and extraction efficiency amounts of SARS-CoV-2 varied amongst the swab types. We conclude that in order to facilitate accurate SARS-CoV-2 diagnosis, assessment of NP swab characteristics is of importance before implementation for specimen collection in the clinical setting.

SARS-CoV-2 antigens expressed in plants detect antibody responses in COVID-19 patients (preprint)

BackgroundThe SARS-CoV-2 pandemic has swept the world and poses a significant global threat to lives and livelihoods, with over 16 million confirmed cases and at least 650 000 deaths from COVID-19 in the first 7 months of the pandemic. Developing tools to measure seroprevalence and understand protective immunity to SARS-CoV-2 is a priority. We aimed to develop a serological assay using plant-derived recombinant viral proteins, which represent important tools in less-resourced settings. MethodsWe established an indirect enzyme-linked immunosorbent assay (ELISA) using the S1 and receptor-binding domain (RBD) portions of the spike protein from SARS-CoV-2, expressed in Nicotiana benthamiana. We measured antibody responses in sera from South African patients (n=77) who had tested positive by PCR for SARS-CoV-2. Samples were taken a median of six weeks after the diagnosis, and the majority of participants had mild and moderate COVID-19 disease. In addition, we tested the reactivity of pre-pandemic plasma (n=58) and compared the performance of our in-house ELISA with a commercial assay. We also determined whether our assay could detect SARS-CoV-2-specific IgG and IgA in saliva. ResultsWe demonstrate that SARS-CoV-2-specific immunoglobulins are readily detectable using recombinant plant-derived viral proteins, in patients who tested positive for SARS-CoV-2 by PCR. Reactivity to S1 and RBD was detected in 51 (66%) and 48 (62%) of participants, respectively. Notably, we detected 100% of samples identified as having S1-specific antibodies by a validated, high sensitivity commercial ELISA, and OD values were strongly and significantly correlated between the two assays. For the pre-pandemic plasma, 1/58 (1.7%) of samples were positive, indicating a high specificity for SARS-CoV-2 in our ELISA. SARS-CoV-2-specific IgG correlated significantly with IgA and IgM responses. Endpoint titers of S1- and RBD-specific immunoglobulins ranged from 1:50 to 1:3200. S1-specific IgG and IgA were found in saliva samples from convalescent volunteers. ConclusionsWe demonstrate that recombinant SARS-CoV-2 proteins produced in plants enable robust detection of SARS-CoV-2 humoral responses. This assay can be used for seroepidemiological studies and to measure the strength and durability of antibody responses to SARS-CoV-2 in infected patients in our setting.