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1.
Trends in Molecular Medicine ; 2022.
Article in English | ScienceDirect | ID: covidwho-1819576

ABSTRACT

Coronavirus disease 2019 (COVID-19) which is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been associated with severe illness in pregnant women. Furthermore, COVID-19 during pregnancy is associated with adverse foetal outcomes, including preterm labour. Pregnant women were largely excluded from initial clinical trials on the safety and efficacy of COVID-19 vaccines;however, they have since been included as part of the routine roll out of these vaccines. This narrative review, synthesis the evidence on the safety, immunogenicity, and effectiveness of mainly the messenger ribonucleic acid (mRNA) COVID-19 vaccines, which have been most widely used in pregnant women.

2.
The Lancet HIV ; 9(5):e309-e322, 2022.
Article in English | ScienceDirect | ID: covidwho-1805401

ABSTRACT

Summary Background There is a paucity of data on COVID-19 vaccines in people living with HIV-1, who could be at increased risk of severe illness and death from COVID-19. We evaluated the safety and immunogenicity of a Matrix-M adjuvanted recombinant spike protein nanoparticle COVID-19 vaccine (NVX-CoV2373;Novavax) in HIV-negative people and people living with HIV-1. Methods In this randomised, observer-blinded, multicentre, placebo-controlled phase 2A/B trial in South Africa, participants aged 18–84 years, with and without underlying HIV-1, were enrolled from 16 sites and randomly assigned (1:1) to receive two intramuscular injections of NVX-CoV2373 or placebo, 21 days apart. People living with HIV-1 were on stable antiretroviral therapy and had an HIV-1 viral load of less than 1000 copies per mL. Vaccine dosage was 5 μg SARS-CoV-2 recombinant spike protein with 50 μg Matrix-M adjuvant, whereas 0·9% saline was used as placebo injection (volume 0·5 mL each). All study staff and participants remained masked to study group assignment. We previously reported an interim analysis on the efficacy and safety of the NVX-CoV2373 vaccine (coprimary endpoints). In this Article, we present an expanded safety analysis for the full cohort of participants and report on the secondary objective of vaccine immunogenicity in the full cohort of people living with HIV-1 and in HIV-negative individuals overall and stratified by baseline SARS-CoV-2 serostatus. This trial is registered with ClinicalTrials.gov, NCT04533399, and the Pan-African Clinical Trials Registry, PACTR202009726132275. Findings Participants were enrolled between Aug 17 and Nov 25, 2020. The safety analysis set included 4164 HIV-negative participants (2089 in the intervention group and 2075 in the placebo group) and 244 people living with HIV-1 (122 in the intervention group and 122 in the placebo group). 1422 (34·1%) of 4164 HIV-negative people and 83 (34·0%) of 244 people living with HIV-1 were categorised as baseline SARS-CoV-2-positive (ie, anti-spike IgG reactive at enrolment or had a reactive SARS-CoV-2 nucleic acid amplification test by 14 days after the second study vaccination). In the NVX-CoV2373 group, solicited local and systemic adverse events were more common in HIV-negative participants (427 [30·6%] local and 401 [28·7%] systemic) than in people living with HIV-1 (20 [25·3%] local and 20 [25·3%] systemic) among those who were baseline SARS-CoV-2-seronegative (naive). Of the serious adverse events that occurred among HIV-negative people (of whom, two [0·1%] were baseline SARS-CoV-2-negative and four [0·6%] were baseline SARS-CoV-2-positive) and people living with HIV-1 (for whom there were no serious adverse events) in the NVX-CoV2373 group, none were assessed as related to the vaccine. Among participants who were baseline SARS-CoV-2-negative in the NVX-CoV2373 group, the anti-spike IgG geometric mean titres (GMTs) and seroconversion rates (SCRs) were lower in people living with HIV-1 (n=62) than in HIV-negative people (n=1234) following the first vaccination (GMT: 508·6 vs 1195·3 ELISA units [EU]/mL;SCR: 51·6% vs 81·3%);and similarly so 14 days after the second vaccination for GMTs (14 420·5 vs 31 631·8 EU/mL), whereas the SCR was similar at this point (100·0% vs 99·3%). In the NVX-CoV2373 group, anti-spike IgG GMTs 14 days after the second vaccination were substantially higher in those who were baseline SARS-CoV-2-positive than in those who were baseline SARS-CoV-2-seronegative for HIV-negative participants (100 666·1 vs 31 631·8 EU/mL) and for people living with HIV-1 (98 399·5 vs 14 420·5 EU/mL). This was also the case for angiotensin-converting enzyme 2 receptor-binding antibody and neutralising antibody titres. Interpretation The safety of the NVX-CoV2373 vaccine in people living with HIV-1 was similar to that in HIV-negative participants. However, people living with HIV-1 not previously exposed to SARS-CoV-2 had attenuated humoral immune responses to NVX-CoV2373 compared with their HIV-negative vaccine counterparts, but not so if they were baseline SARS-CoV-2-positive. Funding Novavax and the Bill & Melinda Gates Foundation;investigational vaccine manufacturing support was provided by the Coalition for Epidemic Preparedness Innovations.

3.
S Afr J Infect Dis ; 37(1): 339, 2022.
Article in English | MEDLINE | ID: covidwho-1786163

ABSTRACT

Effective risk communication is essential for outbreak mitigation, as recently highlighted during the coronavirus disease 2019 (COVID-19) pandemic. Hand hygiene is one of the proposed public health interventions to protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) acquisition and transmission along with social distancing, improved ventilation, environmental cleaning, and wearing of masks. Improving hand hygiene practices in the community requires an understanding of the socio-behavioural context. This cross-sectional community survey in Soweto identified gaps in hand hygiene, which can inform appropriate messaging at the community level. Only 42% of survey respondents practiced adequate hand hygiene. Tailored educational messaging should be targeted at young adults in particular, and the importance of soap for hand hygiene must be emphasised for all age groups. Risk communication should expand to focus on preventing multiple infectious diseases during and beyond the COVID-19 pandemic.

4.
Nat Commun ; 13(1): 1976, 2022 Apr 08.
Article in English | MEDLINE | ID: covidwho-1783980

ABSTRACT

Global genomic surveillance of SARS-CoV-2 has identified variants associated with increased transmissibility, neutralization resistance and disease severity. Here we report the emergence of the PANGO lineage C.1.2, detected at low prevalence in South Africa and eleven other countries. The initial C.1.2 detection is associated with a high substitution rate, and includes changes within the spike protein that have been associated with increased transmissibility or reduced neutralization sensitivity in SARS-CoV-2 variants of concern or variants of interest. Like Beta and Delta, C.1.2 shows significantly reduced neutralization sensitivity to plasma from vaccinees and individuals infected with the ancestral D614G virus. In contrast, convalescent donors infected with either Beta or Delta show high plasma neutralization against C.1.2. These functional data suggest that vaccine efficacy against C.1.2 will be equivalent to Beta and Delta, and that prior infection with either Beta or Delta will likely offer protection against C.1.2.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , Humans , Neutralization Tests , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
5.
Vaccines (Basel) ; 10(3)2022 Mar 17.
Article in English | MEDLINE | ID: covidwho-1753697

ABSTRACT

We investigated Omicron infections among healthcare workers (HCW) presenting with symptoms of SARS-CoV-2 infection and evaluated the protective effect of vaccination or prior infection. Between 24 November and 31 December 2021, HCW in Johannesburg, South Africa, were tested for SARS-CoV-2 infection by Nucleic Acid Amplification Test (NAAT). Blood samples collected either at the symptomatic visit or in the 3 months prior, were tested for spike protein immunoglobulin G (IgG). Overall, 433 symptomatic HCW were included in the analysis, with 190 (43.9%) having an Omicron infection; 69 (16.7%) were unvaccinated and 270 (62.4%) received a single dose of the Ad26.COV.2 vaccine. There was no difference in the odds of identifying Omicron between unvaccinated and Ad26.COV.2 vaccinated HCW (adjusted odds ratio (aOR) 0.81, 95% confidence interval (CI): 0.46, 1.43). One-hundred and fifty-four (35.3%) HCW had at least one SARS-CoV-2 NAAT-confirmed prior infection; these had lower odds of Omicron infection compared with those without past infection (aOR 0.55, 95%CI: 0.36, 0.84). Anti-spike IgG concentration of 1549 binding antibody unit/mL was suggestive of significant reduction in the risk of symptomatic Omicron infection. We found high reinfection and vaccine breakthrough infection rates with the Omicron variant among HCW. Prior infection and high anti-spike IgG concentration were protective against Omicron infection.

6.
N Engl J Med ; 386(9): 837-846, 2022 03 03.
Article in English | MEDLINE | ID: covidwho-1721750

ABSTRACT

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection and hospitalization in infants. Nirsevimab is a monoclonal antibody to the RSV fusion protein that has an extended half-life. The efficacy and safety of nirsevimab in healthy late-preterm and term infants are uncertain. METHODS: We randomly assigned, in a 2:1 ratio, infants who had been born at a gestational age of at least 35 weeks to receive a single intramuscular injection of nirsevimab or placebo before the start of an RSV season. The primary efficacy end point was medically attended RSV-associated lower respiratory tract infection through 150 days after the injection. The secondary efficacy end point was hospitalization for RSV-associated lower respiratory tract infection through 150 days after the injection. RESULTS: A total of 1490 infants underwent randomization: 994 were assigned to the nirsevimab group and 496 to the placebo group. Medically attended RSV-associated lower respiratory tract infection occurred in 12 infants (1.2%) in the nirsevimab group and in 25 infants (5.0%) in the placebo group; these findings correspond to an efficacy of 74.5% (95% confidence interval [CI], 49.6 to 87.1; P<0.001) for nirsevimab. Hospitalization for RSV-associated lower respiratory tract infection occurred in 6 infants (0.6%) in the nirsevimab group and in 8 infants (1.6%) in the placebo group (efficacy, 62.1%; 95% CI, -8.6 to 86.8; P = 0.07). Among infants with data available to day 361, antidrug antibodies after baseline were detected in 58 of 951 (6.1%) in the nirsevimab group and in 5 of 473 (1.1%) in the placebo group. Serious adverse events were reported in 67 of 987 infants (6.8%) who received nirsevimab and in 36 of 491 infants (7.3%) who received placebo. CONCLUSIONS: A single injection of nirsevimab administered before the RSV season protected healthy late-preterm and term infants from medically attended RSV-associated lower respiratory tract infection. (Funded by MedImmune/AstraZeneca and Sanofi; MELODY ClinicalTrials.gov number, NCT03979313.).


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antiviral Agents/therapeutic use , Infant, Premature, Diseases/prevention & control , Infant, Premature , Respiratory Syncytial Virus Infections/prevention & control , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , Drug Administration Schedule , Female , Humans , Infant , Infant, Newborn , Injections, Intramuscular , Kaplan-Meier Estimate , Male
8.
N Engl J Med ; 386(14): 1314-1326, 2022 Apr 07.
Article in English | MEDLINE | ID: covidwho-1703992

ABSTRACT

BACKGROUND: The B.1.1.529 (omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified on November 25, 2021, in Gauteng province, South Africa. Data regarding the seroprevalence of SARS-CoV-2 IgG in Gauteng before the fourth wave of coronavirus disease 2019 (Covid-19), in which the omicron variant was dominant, are needed. METHODS: We conducted a seroepidemiologic survey from October 22 to December 9, 2021, in Gauteng to determine the seroprevalence of SARS-CoV-2 IgG. Households included in a previous seroepidemiologic survey (conducted from November 2020 to January 2021) were contacted; to account for changes in the survey population, there was a 10% increase in the households contacted, with the use of the same sampling framework. Dried-blood-spot samples were tested for IgG against SARS-CoV-2 spike protein and nucleocapsid protein with the use of quantitative assays. We also evaluated Covid-19 epidemiologic trends in Gauteng, including cases, hospitalizations, recorded deaths, and excess deaths from the start of the pandemic through January 12, 2022. RESULTS: Samples were obtained from 7010 participants, of whom 1319 (18.8%) had received a Covid-19 vaccine. The seroprevalence of SARS-CoV-2 IgG ranged from 56.2% (95% confidence interval [CI], 52.6 to 59.7) among children younger than 12 years of age to 79.7% (95% CI, 77.6 to 81.5) among adults older than 50 years of age. Vaccinated participants were more likely to be seropositive for SARS-CoV-2 than unvaccinated participants (93.1% vs. 68.4%). Epidemiologic data showed that the incidence of SARS-CoV-2 infection increased and subsequently declined more rapidly during the fourth wave than it had during the three previous waves. The incidence of infection was decoupled from the incidences of hospitalization, recorded death, and excess death during the fourth wave, as compared with the proportions seen during previous waves. CONCLUSIONS: Widespread underlying SARS-CoV-2 seropositivity was observed in Gauteng before the omicron-dominant wave of Covid-19. Epidemiologic data showed a decoupling of hospitalizations and deaths from infections while omicron was circulating. (Funded by the Bill and Melinda Gates Foundation.).


Subject(s)
COVID-19 , Adult , Aged , Antibodies, Viral , COVID-19/epidemiology , COVID-19 Vaccines , Child , Humans , Immunoglobulin G , SARS-CoV-2 , Seroepidemiologic Studies , South Africa/epidemiology , Spike Glycoprotein, Coronavirus
10.
J Virol Methods ; 300: 114394, 2022 02.
Article in English | MEDLINE | ID: covidwho-1654865

ABSTRACT

We compared plasma and dried blood spots for detection of SARS-CoV-2 IgG antibodies. There was a good correlation between IgG values measured by both sampling methods, r = 0.935 and 0.965 for Receptor Binding Domain and full-length spike protein of SARS-CoV-2. Bland-Altman assessment showed good agreement between two sampling methods. Dried blood spots is a more pragmatic method for collecting samples for sero-epidemiological surveys of SARS-CoV-2 infection.


Subject(s)
Antibodies, Viral/blood , COVID-19 , Dried Blood Spot Testing , Immunoglobulin G/blood , Spike Glycoprotein, Coronavirus/immunology , COVID-19/diagnosis , Humans , SARS-CoV-2
11.
Front Immunol ; 12: 808064, 2021.
Article in English | MEDLINE | ID: covidwho-1649357

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy is associated with a higher risk for severe morbidity and mortality when compared with infection in non-pregnant women of childbearing age. An increasing number of countries recommend immunization against SARS-CoV-2 in pregnant women. Recent studies provide preliminary and supportive evidence on safety, immunogenicity and effectiveness of coronavirus disease 2019 (COVID-19) vaccines in pregnant women; however, important knowledge gaps remain which warrant further studies. This collaborative consensus paper provides a review of the current literature on COVID-19 vaccines in pregnant women, identifies knowledge gaps and outlines priorities for future research to optimize protection against SARS-CoV-2 in the pregnant women and their infants.


Subject(s)
Antibodies, Viral/immunology , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Maternal-Fetal Exchange/immunology , SARS-CoV-2/immunology , /adverse effects , /adverse effects , Adoptive Transfer , /immunology , COVID-19/immunology , Female , Humans , Infectious Disease Transmission, Vertical/prevention & control , Milk, Human/immunology , Pregnancy , Pregnancy Complications, Infectious/immunology , Pregnancy Complications, Infectious/prevention & control , Pregnancy Complications, Infectious/virology , Spike Glycoprotein, Coronavirus/immunology , Vaccination , /statistics & numerical data
12.
PLoS One ; 17(1): e0262179, 2022.
Article in English | MEDLINE | ID: covidwho-1636037

ABSTRACT

Comparisons of histopathological features and microbiological findings between decedents with respiratory symptoms due to SARS-CoV-2 infection or other causes, in settings with high prevalence of HIV and Mycobacterium tuberculosis (MTB) infections have not been reported. Deaths associated with a positive ante-mortem SARS-CoV-2 PCR test and/or respiratory disease symptoms at Chris Hani Baragwanath Academic Hospital in Soweto, South Africa from 15th April to 2nd November 2020, during the first wave of the South African COVID-19 epidemic, were investigated. Deceased adult patients had post-mortem minimally-invasive tissue sampling (MITS) performed to investigate for SARS-CoV-2 infection and molecular detection of putative pathogens on blood and lung samples, and histopathology examination of lung, liver and heart tissue. During the study period MITS were done in patients displaying symptoms of respiratory disease including 75 COVID-19-related deaths (COVID+) and 42 non-COVID-19-related deaths (COVID-). The prevalence of HIV-infection was lower in COVID+ (27%) than in the COVID- (64%), MTB detection was also less common among COVID+ (3% vs 13%). Lung histopathology findings showed differences between COVID+ and COVID- in the severity of the morphological appearance of Type-II pneumocytes, alveolar injury and repair initiated by SARS-CoV-2 infection. In the liver necrotising granulomatous inflammation was more common among COVID+. No differences were found in heart analyses. The prevalence of bacterial co-infections was higher in COVID+. Most indicators of respiratory distress syndrome were undifferentiated between COVID+ and COVID- except for Type-II pneumocytes. HIV or MTB infection does not appear in these data to have a meaningful correspondence with COVID-related deaths.


Subject(s)
Alveolar Epithelial Cells/pathology , COVID-19/epidemiology , COVID-19/mortality , Diabetes Mellitus/epidemiology , Hypertension/epidemiology , Pandemics , SARS-CoV-2/genetics , Adult , Aged , Autopsy , Biopsy, Large-Core Needle/methods , COVID-19/pathology , COVID-19/virology , COVID-19 Nucleic Acid Testing/methods , Comorbidity , Female , Humans , Length of Stay , Male , Middle Aged , Real-Time Polymerase Chain Reaction/methods , South Africa/epidemiology
14.
Ann N Y Acad Sci ; 2022 Jan 14.
Article in English | MEDLINE | ID: covidwho-1625044

ABSTRACT

The rapid development of COVID-19 vaccines was the result of decades of research to establish flexible vaccine platforms and understand pathogens with pandemic potential, as well as several novel changes to the vaccine discovery and development processes that partnered industry and governments. And while vaccines offer the potential to drastically improve global health, low-and-middle-income countries around the world often experience reduced access to vaccines and reduced vaccine efficacy. Addressing these issues will require novel vaccine approaches and platforms, deeper insight how vaccines mediate protection, and innovative trial designs and models. On June 28-30, 2021, experts in vaccine research, development, manufacturing, and deployment met virtually for the Keystone eSymposium "Innovative Vaccine Approaches" to discuss advances in vaccine research and development.

15.
Cell ; 2022.
Article in English | EuropePMC | ID: covidwho-1601904

ABSTRACT

On the 24th November 2021 the sequence of a new SARS CoV-2 viral isolate Omicron-B.1.1.529 was announced, containing far more mutations in Spike (S) than previously reported variants. Neutralization titres of Omicron by sera from vaccinees and convalescent subjects infected with early pandemic as well as Alpha, Beta, Gamma, Delta are substantially reduced or fail to neutralize. Titres against Omicron are boosted by third vaccine doses and are high in cases both vaccinated and infected by Delta. Mutations in Omicron knock out or substantially reduce neutralization by most of a large panel of potent monoclonal antibodies and antibodies under commercial development. Omicron S has structural changes from earlier viruses, combining mutations conferring tight binding to ACE2 to unleash evolution driven by immune escape, leading to a large number of mutations in the ACE2 binding site which rebalance receptor affinity to that of early pandemic viruses. A comprehensive analysis of sera from vaccinees, convalescent patients infected previously by multiple variants and potent monoclonal antibodies from early in the COVID-19 pandemic reveals a substantial overall reduction the ability to neutralize the SARS-CoV-2 Omicron variant, which a third vaccine dose seems to ameliorate. Structural analyses of the Omicron RBD suggest a selective pressure enabling the virus bind ACE2 with increased affinity that is offset by other changes in the receptor binding motif that facilitates immune escape.

17.
Influenza Other Respir Viruses ; 16(1): 34-47, 2022 01.
Article in English | MEDLINE | ID: covidwho-1526373

ABSTRACT

INTRODUCTION: We describe epidemiology and outcomes of confirmed SARS-CoV-2 infection and positive admissions among children <18 years in South Africa, an upper-middle income setting with high inequality. METHODS: Laboratory and hospital COVID-19 surveillance data, 28 January - 19 September 2020 was used. Testing rates were calculated as number of tested for SARS-CoV-2 divided by population at risk; test positivity rates were calculated as positive tests divided by total number of tests. In-hospital case fatality ratio (CFR) was calculated based on hospitalized positive admissions with outcome data who died in-hospital and whose death was judged SARS-CoV-2 related by attending physician. FINDINGS: 315 570 children aged <18 years were tested for SARS-CoV-2; representing 8.9% of all 3 548 738 tests and 1.6% of all children in the country. Of children tested, 46 137 (14.6%) were positive. Children made up 2.9% (n = 2007) of all SARS-CoV-2 positive admissions to sentinel hospitals. Among children, 47 died (2.6% case-fatality). In-hospital deaths were associated with male sex [adjusted odds ratio (aOR) 2.18 (95% confidence intervals [CI] 1.08-4.40)] vs female; age <1 year [aOR 4.11 (95% CI 1.08-15.54)], age 10-14 years [aOR 4.20 (95% CI1.07-16.44)], age 15-17 years [aOR 4.86 (95% 1.28-18.51)] vs age 1-4 years; admission to a public hospital [aOR 5.07(95% 2.01-12.76)] vs private hospital and ≥1 underlying conditions [aOR 12.09 (95% CI 4.19-34.89)] vs none. CONCLUSIONS: Children with underlying conditions were at greater risk of severe SARS-CoV-2 outcomes. Children > 10 years, those in certain provinces and those with underlying conditions should be considered for increased testing and vaccination.


Subject(s)
COVID-19 , Adolescent , Child , Child, Preschool , Female , Hospitals , Humans , Infant , Male , Risk Factors , SARS-CoV-2 , South Africa/epidemiology
18.
Clin Infect Dis ; 73(10): 1896-1900, 2021 11 16.
Article in English | MEDLINE | ID: covidwho-1522151

ABSTRACT

From April to September 2020, we investigated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in a cohort of 396 healthcare workers (HCWs) from 5 departments at Chris Hani Baragwanath Hospital, South Africa. Overall, 34.6% of HCWs had polymerase chain reaction-confirmed SARS-CoV-2 infection (132.1 [95% confidence interval, 111.8-156.2] infections per 1000 person-months); an additional 27 infections were identified by serology. HCWs in the internal medicine department had the highest rate of infection (61.7%). Among polymerase chain reaction-confirmed cases, 10.4% remained asymptomatic, 30.4% were presymptomatic, and 59.3% were symptomatic.


Subject(s)
COVID-19 , SARS-CoV-2 , Cohort Studies , Health Personnel , Humans , Longitudinal Studies , South Africa/epidemiology
19.
Int J Epidemiol ; 2021 Oct 30.
Article in English | MEDLINE | ID: covidwho-1493815

ABSTRACT

BACKGROUND: Limitations in laboratory testing capacity undermine the ability to quantify the overall burden of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. METHODS: We undertook a population-based serosurvey for SARS-CoV-2 infection in 26 subdistricts, Gauteng Province (population 15.9 million), South Africa, to estimate SARS-CoV-2 infection, infection fatality rate (IFR) triangulating seroprevalence, recorded COVID-19 deaths and excess-mortality data. We employed three-stage random household sampling with a selection probability proportional to the subdistrict size, stratifying the subdistrict census-sampling frame by housing type and then selecting households from selected clusters. The survey started on 4 November 2020, 8 weeks after the end of the first wave (SARS-CoV-2 nucleic acid amplification test positivity had declined to <10% for the first wave) and coincided with the peak of the second wave. The last sampling was performed on 22 January 2021, which was 9 weeks after the SARS-CoV-2 resurgence. Serum SARS-CoV-2 receptor-binding domain (RBD) immunoglobulin-G (IgG) was measured using a quantitative assay on the Luminex platform. RESULTS: From 6332 individuals in 3453 households, the overall RBD IgG seroprevalence was 19.1% [95% confidence interval (CI): 18.1-20.1%] and similar in children and adults. The seroprevalence varied from 5.5% to 43.2% across subdistricts. Conservatively, there were 2 897 120 (95% CI: 2 743 907-3 056 866) SARS-CoV-2 infections, yielding an infection rate of 19 090 per 100 000 until 9 January 2021, when 330 336 COVID-19 cases were recorded. The estimated IFR using recorded COVID-19 deaths (n = 8198) was 0.28% (95% CI: 0.27-0.30) and 0.67% (95% CI: 0.64-0.71) assuming 90% of modelled natural excess deaths were due to COVID-19 (n = 21 582). Notably, 53.8% (65/122) of individuals with previous self-reported confirmed SARS-CoV-2 infection were RBD IgG seronegative. CONCLUSIONS: The calculated number of SARS-CoV-2 infections was 7.8-fold greater than the recorded COVID-19 cases. The calculated SARS-CoV-2 IFR varied 2.39-fold when calculated using reported COVID-19 deaths (0.28%) compared with excess-mortality-derived COVID-19-attributable deaths (0.67%). Waning RBD IgG may have inadvertently underestimated the number of SARS-CoV-2 infections and conversely overestimated the mortality risk. Epidemic preparedness and response planning for future COVID-19 waves will need to consider the true magnitude of infections, paying close attention to excess-mortality trends rather than absolute reported COVID-19 deaths.

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