SARS-CoV-2 501Y.V2 (B.1.351), a novel lineage of coronavirus causing COVID-19, contains substitutions in two immunodominant domains of the spike protein. Here, we show that pseudovirus expressing ...501Y.V2 spike protein completely escapes three classes of therapeutically relevant antibodies. This pseudovirus also exhibits substantial to complete escape from neutralization, but not binding, by convalescent plasma. These data highlight the prospect of reinfection with antigenically distinct variants and foreshadows reduced efficacy of spike-based vaccines.
Invasive pneumococcal disease is an important cause of severe illness. In South Africa, a national program to vaccinate children with the conjugated pneumococcal vaccine resulted in a substantial ...decline in invasive pneumococcal disease countrywide, including in adults.
The majority of deaths associated with childhood pneumococcal disease occur in Africa.
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In randomized trials conducted in Africa,
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a pneumococcal conjugate vaccine (PCV) was given to infants when they were 6, 10, and 14 weeks of age, without a booster dose. The vaccine showed efficacy for the prevention of invasive pneumococcal disease caused by the nine serotypes contained in the vaccine among infants who were not infected with the human immunodeficiency virus (HIV) (83% efficacy; 95% confidence interval CI, 39 to 97) and among infants who were infected with HIV (65% efficacy; 95% CI, 24 to 86).
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We provide two methods for monitoring reinfection trends in routine surveillance data to identify signatures of changes in reinfection risk and apply these approaches to data from South Africa's ...severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic to date. Although we found no evidence of increased reinfection risk associated with circulation of the Beta (B.1.351) or Delta (B.1.617.2) variants, we did find clear, population-level evidence to suggest immune evasion by the Omicron (B.1.1.529) variant in previously infected individuals in South Africa. Reinfections occurring between 1 November 2021 and 31 January 2022 were detected in individuals infected in all three previous waves, and there has been an increase in the risk of having a third infection since mid-November 2021.
Up to the end of January, 2022, South Africa has had four recognisable COVID-19 pandemic waves, each predominantly dominated by one variant of concern: the ancestral strain with an Asp614Gly mutation ...during the first wave, the beta variant (B.1.351) during the second wave, the delta variant (B.1.617.2) during the third wave, and lastly, the omicron variant (B.1.1.529) during the fourth wave. We aimed to assess the clinical disease severity of patients admitted to hospital with SARS-CoV-2 infection during the omicron wave and compare the findings with those of the preceding three pandemic waves in South Africa.
We defined the start and end of each pandemic wave as the crossing of the threshold of weekly incidence of 30 laboratory-confirmed SARS-CoV-2 cases per 100 000 population. Hospital admission data were collected through an active national COVID-19-specific surveillance programme. We compared disease severity across waves by post-imputation random effect multivariable logistic regression models. Severe disease was defined as one or more of the following: acute respiratory distress, receipt of supplemental oxygen or mechanical ventilation, admission to intensive care, or death.
We analysed 335 219 laboratory-confirmed SARS-CoV-2 hospital admissions with a known outcome, constituting 10·4% of 3 216 179 cases recorded during the four waves. During the omicron wave, 52 038 (8·3%) of 629 617 cases were admitted to hospital, compared with 71 411 (12·9%) of 553 530 in the Asp614Gly wave, 91 843 (12·6%) of 726 772 in the beta wave, and 131 083 (10·0%) of 1 306 260 in the delta wave (p<0·0001). During the omicron wave, 15 421 (33·6%) of 45 927 patients admitted to hospital had severe disease, compared with 36 837 (52·3%) of 70 424 in the Asp614Gly wave, 57 247 (63·4%) of 90 310 in the beta wave, and 81 040 (63·0%) of 128 558 in the delta wave (p<0·0001). The in-hospital case-fatality ratio during the omicron wave was 10·7%, compared with 21·5% during the Asp614Gly wave, 28·8% during the beta wave, and 26·4% during the delta wave (p<0·0001). Compared with those admitted to hospital during the omicron wave, patients admitted during the other three waves had more severe clinical presentations (adjusted odds ratio 2·07 95% CI 2·01–2·13 in the Asp614Gly wave, 3·59 3·49–3·70 in the beta wave, and 3·47 3·38–3·57 in the delta wave).
The trend of increasing cases and admissions across South Africa's first three waves shifted in the omicron wave, with a higher and quicker peak but fewer patients admitted to hospital, less clinically severe illness, and a lower case-fatality ratio compared with the preceding three waves. Omicron marked a change in the SARS-CoV-2 epidemic curve, clinical profile, and deaths in South Africa. Extrapolations to other populations should factor in differing vaccination and previous infection levels.
National Institute for Communicable Diseases.
The first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in South Africa was identified on 5 March 2020, and by 26 March the country was in full lockdown (Oxford stringency ...index of 90)
. Despite the early response, by November 2020, over 785,000 people in South Africa were infected, which accounted for approximately 50% of all known African infections
. In this study, we analyzed 1,365 near whole genomes and report the identification of 16 new lineages of SARS-CoV-2 isolated between 6 March and 26 August 2020. Most of these lineages have unique mutations that have not been identified elsewhere. We also show that three lineages (B.1.1.54, B.1.1.56 and C.1) spread widely in South Africa during the first wave, comprising ~42% of all infections in the country at the time. The newly identified C lineage of SARS-CoV-2, C.1, which has 16 nucleotide mutations as compared with the original Wuhan sequence, including one amino acid change on the spike protein, D614G (ref.
), was the most geographically widespread lineage in South Africa by the end of August 2020. An early South African-specific lineage, B.1.106, which was identified in April 2020 (ref.
), became extinct after nosocomial outbreaks were controlled in KwaZulu-Natal Province. Our findings show that genomic surveillance can be implemented on a large scale in Africa to identify new lineages and inform measures to control the spread of SARS-CoV-2. Such genomic surveillance presented in this study has been shown to be crucial in the identification of the 501Y.V2 variant in South Africa in December 2020 (ref.
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Using previously described methods,1 we performed individual-level data linkage for national data from three sources: (1) national COVID-19 case data, (2) SARS-CoV-2 laboratory test data for public ...sector laboratories and one large private sector laboratory, and (3) DATCOV, which is an active surveillance system for COVID-19 hospital admissions in South Africa (including both incidental and attributable admissions). CC has received grant support from the South African Medical Research Council, UK Foreign, Commonwealth and Development Office, Wellcome Trust, US Centers for Disease Control and Prevention (CDC), and Sanofi Pasteur. AvG has received grant support from the US CDC, Africa Centres for Disease Control and Prevention, African Society for Laboratory Medicine, South African Medical Research Council, WHO Regional Office for Africa, The Fleming Fund, and Wellcome Trust. Sequencing activities for the National Institute for Communicable Diseases are supported by a conditional grant from the South African National Department of Health as part of the emergency COVID-19 response; a cooperative agreement between the National Institute for Communicable Diseases of the National Health Laboratory Service and the US CDC; the African Society of Laboratory Medicine and Africa Centers for Disease Control and Prevention through a sub-award from the Bill & Melinda Gates Foundation; the UK Foreign, Commonwealth and Development Office and the Wellcome Trust; and the UK Department of Health and Social Care, managed by the Fleming Fund and performed under the auspices of the SEQAFRICA project.
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. We 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.
We 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, we assessed disease severity and hospitalisations 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.
Our 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.
The South African Medical Research Council, the South African National Department of Health, US Centers for Disease Control and Prevention, the African Society of Laboratory Medicine, Africa Centers for Disease Control and Prevention, the Bill & Melinda Gates Foundation, the Wellcome Trust, and the Fleming Fund.
Increased morbidity and mortality from lower respiratory tract infection (LRTI) has been suggested in HIV-exposed uninfected (HEU) children; however, the contribution of respiratory viruses is ...unclear. We studied the epidemiology of LRTI hospitalization in HIV-unexposed uninfected (HUU) and HEU infants aged <6 months in South Africa.
We prospectively enrolled hospitalized infants with LRTI from 4 provinces from 2010 to 2013. Using polymerase chain reaction, nasopharyngeal aspirates were tested for 10 viruses and blood for pneumococcal DNA. Incidence for 2010-2011 was estimated at 1 site with population denominators.
We enrolled 3537 children aged <6 months. HIV infection and exposure status were determined for 2507 (71%), of whom 211 (8%) were HIV infected, 850 (34%) were HEU, and 1446 (58%) were HUU. The annual incidence of LRTI was elevated in HEU (incidence rate ratio IRR 1.4; 95% confidence interval CI 1.3-1.5) and HIV infected (IRR 3.8; 95% CI 3.3-4.5), compared with HUU infants. Relative incidence estimates were greater in HEU than HUU, for respiratory syncytial virus (RSV; IRR 1.4; 95% CI 1.3-1.6) and human metapneumovirus-associated (IRR 1.4; 95% CI 1.1-2.0) LRTI, with a similar trend observed for influenza (IRR 1.2; 95% CI 0.8-1.8). HEU infants overall, and those with RSV-associated LRTI had greater odds (odds ratio 2.1, 95% CI 1.1-3.8, and 12.2, 95% CI 1.7-infinity, respectively) of death than HUU.
HEU infants were more likely to be hospitalized and to die in-hospital than HUU, including specifically due to RSV. This group should be considered a high-risk group for LRTI.
Background. Changes in serotype prevalence among pneumococcal populations result from both serotype replacement and serotype (capsular) switching. Temporal changes in serotype distributions are well ...documented, but the contribution of capsular switching to such changes is unknown. Furthermore, it is unclear to what extent vaccine-induced selective pressures drive capsular switching. Methods. Serotype and multilocus sequence typing data for 426 pneumococci dated from 1937 through 2007 were analyzed. Whole-genome sequence data for a subset of isolates were used to investigate capsular switching events. Results. We identified 36 independent capsular switch events, 18 of which were explored in detail with wholegenome sequence data. Recombination fragment lengths were estimated for 11 events and ranged from approximately 19.0 kb to > 58.2 kb. Two events took place no later than 1960, and the imported DNA included the capsular locus and the nearby penicillin-binding protein genes pbp2x and pbpla. Conclusions. Capsular switching has been a regular occurrence among pneumococcal populations throughout the past 7 decades. Recombination of large DNA fragments (> 30 kb), sometimes including the capsular locus and penicillin-binding protein genes, predated both vaccine introduction and widespread antibiotic use. This type of recombination has likely been an intrinsic feature throughout the history of pneumococcal evolution.
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