A cohort study of post-COVID-19 condition across the Beta, Delta, and Omicron waves in South Africa: 6-month follow-up of hospitalized and nonhospitalized participants.

OBJECTIVES: The study aimed to describe the prevalence of and risk factors for post-COVID-19 condition (PCC). METHODS: This was a prospective, longitudinal observational cohort study. Hospitalized and nonhospitalized adults were randomly selected to undergo telephone assessment at 1, 3, and 6 months. Participants were assessed using a standardized questionnaire for the evaluation of symptoms and health-related quality of life. We used negative binomial regression models to determine factors associated with the presence of ≥1 symptoms at 6 months. RESULTS: A total of 46.7% of hospitalized and 18.5% of nonhospitalized participants experienced ≥1 symptoms at 6 months (P ≤0.001). Among hospitalized people living with HIV, 40.4% had persistent symptoms compared with 47.1% among participants without HIV (P = 0.108). The risk factors for PCC included older age, female sex, non-Black race, presence of a comorbidity, greater number of acute COVID-19 symptoms, hospitalization/COVID-19 severity, and wave period (lower risk of persistent symptoms for the Omicron compared with the Beta wave). There were no associations between self-reported vaccination status with persistent symptoms. CONCLUSION: The study revealed a high prevalence of persistent symptoms among South African participants at 6 months but decreased risk for PCC among participants infected during the Omicron BA.1 wave. These findings have serious implications for countries with resource-constrained health care systems.

Household transmission of SARS-CoV-2 from adult index cases living with and without HIV in South Africa, 2020-2021: a case-ascertained, prospective observational household transmission study.

BACKGROUND: In South Africa, 19% of the adult population are living with HIV (LWH). Few data on the influence of HIV on SARS-CoV-2 household transmission are available. METHODS: We performed a case-ascertained, prospective household transmission study of symptomatic index SARS-CoV-2 cases LWH and HIV-uninfected adults and their contacts in South Africa, October 2020 to September 2021. Households were followed up thrice weekly for 6 weeks to collect nasal swabs for SARS-CoV-2 testing. We estimated household cumulative infection risk (HCIR) and duration of SARS-CoV-2 positivity (at cycle threshold value <30 as proxy for high viral load). RESULTS: We recruited 131 index cases and 457 household contacts. HCIR was 59% (220/373); not differing by index HIV status (60% [51/85] in cases LWH vs 58% [163/279] in HIV-uninfected cases, OR 1.0, 95%CI 0.4-2.3). HCIR increased with index case age (35-59 years: aOR 3.4 95%CI 1.5-7.8 and ≥60 years: aOR 3.1, 95%CI 1.0-10.1) compared to 18-34 years, and contacts' age, 13-17 years (aOR 7.1, 95%CI 1.5-33.9) and 18-34 years (aOR 4.4, 95%CI 1.0-18.4) compared to <5 years. Mean positivity duration at high viral load was 7 days (range 2-17), with longer positivity in cases LWH (aHR 0.4, 95%CI 0.1-0.9). CONCLUSIONS: Index HIV status was not associated with higher HCIR, but cases LWH had longer positivity duration at high viral load. Adults aged >35 years were more likely to transmit, individuals aged 13-34 to acquire SARS-CoV-2 in the household. As HIV infection may increase transmission, health services must maintain HIV testing and antiretroviral therapy initiation.

Rapidly shifting immunologic landscape and severity of SARS-CoV-2 in the Omicron era in South Africa.

South Africa was among the first countries to detect the SARS-CoV-2 Omicron variant. However, the size of its Omicron BA.1 and BA.2 subvariants (BA.1/2) wave remains poorly understood. We analyzed sequential serum samples collected through a prospective cohort study before, during, and after the Omicron BA.1/2 wave to infer infection rates and monitor changes in the immune histories of participants over time. We found that the Omicron BA.1/2 wave infected more than half of the cohort population, with reinfections and vaccine breakthroughs accounting for > 60% of all infections in both rural and urban sites. After the Omicron BA.1/2 wave, we found few (< 6%) remained naïve to SARS-CoV-2 and the population immunologic landscape is fragmented with diverse infection/immunization histories. Prior infection with the ancestral strain, Beta, and Delta variants provided 13%, 34%, and 51% protection against Omicron BA.1/2 infection, respectively. Hybrid immunity and repeated prior infections reduced the risks of Omicron BA.1/2 infection by 60% and 85% respectively. Our study sheds light on a rapidly shifting landscape of population immunity in the Omicron era and provides context for anticipating the long-term circulation of SARS-CoV-2 in populations no longer naïve to the virus.

Risk Factors for Severe Coronavirus Disease 2019 Among Human Immunodeficiency Virus-Infected and -Uninfected Individuals in South Africa, April 2020-March 2022: Data From Sentinel Surveillance.

Background: Data on risk factors for coronavirus disease 2019 (COVID-19)-associated hospitalization and mortality in high human immunodeficiency virus (HIV) prevalence settings are limited. Methods: Using existing syndromic surveillance programs for influenza-like-illness and severe respiratory illness at sentinel sites in South Africa, we identified factors associated with COVID-19 hospitalization and mortality. Results: From April 2020 through March 2022, severe acute respiratory syndrome coronavirus 2 was detected in 24.0% (660 of 2746) of outpatient and 32.5% (2282 of 7025) of inpatient cases. Factors associated with COVID-19-associated hospitalization included the following: older age (25-44 [adjusted odds ratio {aOR}= 1.8, 95% confidence interval (CI) = 1.1-2.9], 45-64 [aOR = 6.8, 95% CI = 4.2-11.0] and ≥65 years [aOR = 26.6, 95% CI = 14.4-49.1] vs 15-24 years); black race (aOR, 3.3; 95% CI, 2.2-5.0); obesity (aOR, 2.3; 95% CI, 1.4-3.9); asthma (aOR, 3.5; 95% CI, 1.4-8.9); diabetes mellitus (aOR, 5.3; 95% CI, 3.1-9.3); HIV with CD4 ≥200/mm3 (aOR, 1.5; 95% CI, 1.1-2.2) and CD4 <200/mm3 (aOR, 10.5; 95% CI, 5.1-21.6) or tuberculosis (aOR, 12.8; 95% CI, 2.8-58.5). Infection with Beta (aOR, 0.5; 95% CI, .3-.7) vs Delta variant and being fully vaccinated (aOR, 0.1; 95% CI, .1-.3) were less associated with COVID-19 hospitalization. In-hospital mortality was increased in older age (45-64 years [aOR, 2.2; 95% CI, 1.6-3.2] and ≥65 years [aOR, 4.0; 95% CI, 2.8-5.8] vs 25-44 years) and male sex (aOR, 1.3; 95% CI, 1.0-1.6) and was lower in Omicron-infected (aOR, 0.3; 95% CI, .2-.6) vs Delta-infected individuals. Conclusions: Active syndromic surveillance encompassing clinical, laboratory, and genomic data identified setting-specific risk factors associated with COVID-19 severity that will inform prioritization of COVID-19 vaccine distribution. Elderly people with tuberculosis or people with HIV, especially severely immunosuppressed, should be prioritized for vaccination.

Changing Epidemiology of COVID-19 in Children and Adolescents Over Four Successive Epidemic Waves in South Africa, 2020-2022.

BACKGROUND: South Africa experienced four waves of SARS-CoV-2 infection, dominated by Wuhan-Hu, Beta, Delta, and Omicron (BA.1/BA.2). We describe the trends in SARS-CoV-2 testing, cases, admissions, and deaths among children and adolescents in South Africa over successive waves. METHODS: We analyzed national SARS-CoV-2 testing, case, and admissions data from March 2020 to February 2022 and estimated cumulative rates by age group for each endpoint. The severity in the third versus the fourth wave was assessed using multivariable logistic regression. RESULTS: Individuals ≤18 years comprised 35% (21,008,060/60,142,978) of the population but only 12% (424,394/3,593,644) of cases and 6% (26,176/451,753) of admissions. Among individuals ≤18 years, infants had the highest admission (505/100,000) rates. Testing, case, and admission rates generally increased successively in the second (Beta) and third (Delta) waves among all age groups. In the fourth (Omicron BA.1/BA.2) wave, the case rate dropped among individuals ≥1 year but increased among those <1 year. Weekly admission rates for children <1 year (169/100,000) exceeded rates in adults (124/100,000) in the fourth wave. The odds of severe COVID-19 in all admitted cases were lower in the fourth wave versus the third wave in each age group, but they were twice as high in admitted cases with at least one comorbidity than those without. CONCLUSIONS: The admission rate for children <5 years was higher in the fourth wave than in previous waves, but the overall outcomes were less severe. However, children with at least one comorbidity had increased odds of severe disease, warranting consideration of prioritizing this group for vaccination.

High prevalence of SARS-CoV-2 antibodies in pregnant women after the second wave of infections in the inner-city of Johannesburg, Gauteng Province, South Africa.

OBJECTIVES: After South Africa's second wave of COVID-19, this study estimated the SARS-CoV-2 seroprevalence among pregnant women in inner-city Johannesburg, South Africa. METHODS: In this cross-sectional survey, 500 pregnant women who were non-COVID-19-vaccinated (aged ≥12 years) were enrolled, and demographic and clinical data were collected. Serum samples were tested using the Wantai SARS-CoV-2 spike antibody enzyme-linked immunosorbent assay and Roche Elecsys® anti-SARS-CoV-2 nucleocapsid antibody assays. Seropositivity was defined as SARS-CoV-2 antibodies on either (primary) or both (secondary) assays. Univariate Poisson regression assessed risk factors associated with seropositivity. RESULTS: The median age was 27.4 years, and HIV prevalence was 26.7%. SARS-CoV-2 seroprevalence was 64.0% (95% confidence interval [CI]: 59.6-68.2%) on the primary and 54% (95% CI: 49.5-58.4%) on the secondary measure. Most (96.6%) women who were SARS-CoV-2-seropositive reported no symptoms. On the Roche assay, we detected lower seroprevalence among women living with HIV than women without HIV (48.9% vs 61.7%, P-value = 0.018), and especially low levels among women living with HIV with a clusters of differentiation 4 <350 cells/ml compared with women without immune suppression (22.2% vs 56.4%, prevalence rate ratio = 0.4; 95% CI: 0.2-0.9; P-value = 0.046). CONCLUSION: Pregnant women attending routine antenatal care had a high SARS-CoV-2 seroprevalence after the second wave in South Africa, and most had asymptomatic infections. Seroprevalence surveys in pregnant women present a feasible method of monitoring the course of the pandemic over time.

Coronavirus Host Genomics Study: South Africa (COVIGen-SA).

Host genetic factors are known to modify the susceptibility, severity, and outcomes of COVID-19 and vary across populations. However, continental Africans are yet to be adequately represented in such studies despite the importance of genetic factors in understanding Africa's response to the pandemic. We describe the development of a research resource for coronavirus host genomics studies in South Africa known as COVIGen-SA-a multicollaborator strategic partnership designed to provide harmonised demographic, clinical, and genetic information specific to Black South Africans with COVID-19. Over 2,000 participants have been recruited to date. Preliminary results on 1,354 SARS-CoV-2 positive participants from four participating studies showed that 64.7% were female, 333 had severe disease, and 329 were people living with HIV. Through this resource, we aim to provide insights into host genetic factors relevant to African-ancestry populations, using both genome-wide association testing and targeted sequencing of important genomic loci. This project will promote and enhance partnerships, build skills, and develop resources needed to address the COVID-19 burden and associated risk factors in South African communities.

Seroprevalence of Severe Acute Respiratory Syndrome Coronavirus 2 After the Second Wave in South Africa in Human Immunodeficiency Virus-Infected and Uninfected Persons: A Cross-Sectional Household Survey.

BACKGROUND: Seroprevalence studies are important for quantifying the burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in resource-constrained countries. METHODS: We conducted a cross-sectional household survey spanning the second pandemic wave (November 2020 to April 2021) in 3 communities. Blood was collected for SARS-CoV-2 antibody (2 enzyme-linked immunosorbent assays targeting spike and nucleocapsid) and human immunodeficiency virus (HIV) testing. An individual was considered seropositive if testing positive on ≥1 assay. Factors associated with infection, and the age-standardized infection case detection rate, infection hospitalization rate, and infection fatality rate were calculated. RESULTS: Overall, 7959 participants were enrolled, with a median age of 34 years and an HIV prevalence of 22.7%. SARS-CoV-2 seroprevalence was 45.2% (95% confidence interval 43.7%-46.7%) and increased from 26.9% among individuals enrolled in December 2020 to 47.1% among those enrolled in April 2021. On multivariable analysis, seropositivity was associated with age, sex, race, being overweight/obese, having respiratory symptoms, and low socioeconomic status. Persons living with HIV with high viral load were less likely to be seropositive than HIV-uninfected individuals. The site-specific infection case detection rate, infection hospitalization rate, and infection fatality rate ranged across sites from 4.4% to 8.2%, 1.2% to 2.5%, and 0.3% to 0.6%, respectively. CONCLUSIONS: South Africa has experienced a large burden of SARS-CoV-2 infections, with <10% of infections diagnosed. Lower seroprevalence among persons living with HIV who are not virally suppressed, likely as a result of inadequate antibody production, highlights the need to prioritize this group for intervention.

Post-COVID-19 condition 3 months after hospitalisation with SARS-CoV-2 in South Africa: a prospective cohort study.

BACKGROUND: Post COVID-19 condition (PCC), as defined by WHO, refers to a wide range of new, returning, or ongoing health problems in people who have had COVID-19, and it represents a rapidly emerging public health priority. We aimed to establish how this developing condition has affected patients in South Africa and which population groups are at risk. METHODS: In this prospective cohort study, we used the DATCOV national hospital surveillance system to identify participants aged 18 years or older who had been hospitalised with laboratory-confirmed SARS-CoV-2 infection in South Africa. Participants underwent telephone follow-up assessment at 1 month and 3 months after hospital discharge. Participants were assessed using a standardised questionnaire for the evaluation of symptoms, functional status, health-related quality of life, and occupational status. We used negative binomial regression models to determine factors associated with PCC. FINDINGS: Of 241 159 COVID-19 admissions reported to DATCOV between Dec 1, 2020, and Aug 23, 2021, 8309 were randomly selected for enrolment. Of the 3094 patients that we were able to contact, 2410 (77·9%) consented to participate in the study at 1 month after discharge. Of these, 1873 (77·7%) were followed up at 3 months after hospital discharge. Participants had a median age of 52 years (IQR 41-62) and 960 (51·3%) were women. At 3 months of follow-up, 1249 (66·7%) of 1873 participants reported new or persistent COVID-19-related symptoms, compared with 1978 (82·1%) of 2410 at 1 month after hospital discharge. The most common symptoms reported at 3 months were fatigue (50·3%), shortness of breath (23·4%), confusion or lack of concentration (17·5%), headaches (13·8%), and problems seeing or blurred vision (10·1%). On multivariable analysis, the factors associated with persistent symptoms after acute COVID-19 were being female (adjusted incident rate ratio 1·20, 95% CI 1·04-1·38) and admission to an intensive care unit (1·17, 1·01-1·37). INTERPRETATION: Most participants in this cohort of individuals previously hospitalised with COVID-19 reported persistent symptoms 3 months after hospital discharge and a significant impact of PCC on their functional and occupational status. The large burden of PCC symptoms identified in this study emphasises the need for a national health strategy. This should include the development of clinical guidelines and training of health-care workers for identifying, assessing, and caring for patients affected by PCC; establishment of multidisciplinary health services; and provision of information and support to people who have PCC. FUNDING: Bill & Melinda Gates Foundation, UK Foreign, Commonwealth & Development Office, and Wellcome.

Costs of seasonal influenza vaccination in South Africa.

BACKGROUND: Influenza accounts for a substantial number of deaths and hospitalisations annually in South Africa. To address this disease burden, the South African National Department of Health introduced a trivalent inactivated influenza vaccination programme in 2010. METHODS: We adapted and populated the WHO Seasonal Influenza Immunization Costing Tool (WHO SIICT) with country-specific data to estimate the cost of the influenza vaccination programme in South Africa. Data were obtained through key-informant interviews at different levels of the health system and through a review of existing secondary data sources. Costs were estimated from a public provider perspective and expressed in 2018 prices. We conducted scenario analyses to assess the impact of different levels of programme expansion and the use of quadrivalent vaccines on total programme costs. RESULTS: Total financial and economic costs were estimated at approximately USD 2.93 million and USD 7.91 million, respectively, while financial and economic cost per person immunised was estimated at USD 3.29 and USD 8.88, respectively. Expanding the programme by 5% and 10% increased economic cost per person immunised to USD 9.36 and USD 9.52 in the two scenarios, respectively. Finally, replacing trivalent inactivated influenza vaccine (TIV) with quadrivalent vaccine increased financial and economic costs to USD 4.89 and USD 10.48 per person immunised, respectively. CONCLUSION: We adapted the WHO SIICT and provide estimates of the total costs of the seasonal influenza vaccination programme in South Africa. These estimates provide a basis for planning future programme expansion and may serve as inputs for cost-effectiveness analyses of seasonal influenza vaccination programmes.

Influenza activity in the Eastern Mediterranean Region (EMR) in 2020-2021 amidst the COVID-19 pandemic.

INTRODUCTION: A global reduction in influenza virus activity during the COVID-19 pandemic has been observed, including in the Eastern Mediterranean Region (EMR). However, these changes have not been thoroughly evaluated scientifically in the EMR. OBJECTIVE: We aim to present data on seasonal influenza activity during the pre-pandemic period (2016-2019) and compare it to the pandemic period (2020-2021) in EM countries. METHODS: Epidemiological and virological influenza surveillance data were retrieved from both WHO FluNet and EMFLU networks. Four pre-pandemic analytical periods were used in the comparative analysis. We compiled and calculated weekly aggregated epidemiological data on the number of enrolled patients, number of tested specimens and number of positive influenza specimens. RESULTS: 19 out of the 22 countries of the EMR have functioning sentinel influenza surveillance systems, and these countries report the influenza data to WHO through FluNet and EMFLU. The number of enrolled patients and tested specimens increased gradually from 51 384 and 50 672, respectively, in 2016-2017 analytical period to 194 049 enrolled patients and 124 697 tested specimens in 2019-2020. A decrease has been witnessed in both enrolled patients and tested specimens in 2020-2021 'pandemic period' (166 576 and 44 764, respectively). By comparing influenza activity of analytical period 2020-2021 with that of 2016-2019 analytical periods, we found that there has been a decrease in influenza positivity rate in the EMR by 89%. CONCLUSION: The implementation of non-pharmaceutical interventions to control the COVID-19 pandemic may have also impacted the spread of influenza viruses. The low circulation of influenza viruses during 2020-2021 and the associated potential immunity gap may result in increased transmission and severity of post-pandemic influenza seasons. This necessitates high vigilance to continuous data and virus sharing to monitor circulating viruses in a timely fashion to reduce the intensity and severity of future influenza epidemics.

SARS-CoV-2 transmission, persistence of immunity, and estimates of Omicron's impact in South African population cohorts.

Understanding the build-up of immunity with successive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and the epidemiological conditions that favor rapidly expanding epidemics will help facilitate future pandemic control. We analyzed high-resolution infection and serology data from two longitudinal household cohorts in South Africa to reveal high cumulative infection rates and durable cross-protective immunity conferred by prior infection in the pre-Omicron era. Building on the history of past exposures to different SARS-CoV-2 variants and vaccination in the cohort most representative of South Africa's high urbanization rate, we used mathematical models to explore the fitness advantage of the Omicron variant and its epidemic trajectory. Modeling suggests that the Omicron wave likely infected a large fraction (44 to 81%) of the population, leaving a complex landscape of population immunity primed and boosted with antigenically distinct variants. We project that future SARS-CoV-2 resurgences are likely under a range of scenarios of viral characteristics, population contacts, and residual cross-protection.

SARS-CoV-2 cases reported from long-term residential facilities (care homes) in South Africa: a retrospective cohort study.

BACKGROUND: Globally, long-term care facilities (LTCFs) experienced a large burden of deaths during the COVID-19 pandemic. The study aimed to describe the temporal trends as well as the characteristics and risk factors for mortality among residents and staff who tested positive for SARS-CoV-2 in selected LTCFs across South Africa. METHOD: We analysed data reported to the DATCOV sentinel surveillance system by 45 LTCFs. Outbreaks in LTCFs were defined as large if more than one-third of residents and staff had been infected or there were more than 20 epidemiologically linked cases. Multivariable logistic regression was used to assess risk factors for mortality amongst LTCF residents. RESULTS: A total of 2324 SARS-CoV-2 cases were reported from 5 March 2020 through 31 July 2021; 1504 (65%) were residents and 820 (35%) staff. Among LTCFs, 6 reported sporadic cases and 39 experienced outbreaks. Of those reporting outbreaks, 10 (26%) reported one and 29 (74%) reported more than one outbreak. There were 48 (66.7%) small outbreaks and 24 (33.3%) large outbreaks reported. There were 30 outbreaks reported in the first wave, 21 in the second wave and 15 in the third wave, with 6 outbreaks reporting between waves. There were 1259 cases during the first COVID-19 wave, 362 during the second wave, and 299 during the current third wave. The case fatality ratio was 9% (138/1504) among residents and 0.5% (4/820) among staff. On multivariable analysis, factors associated with SARS-CoV-2 mortality among LTCF residents were age 40-59 years, 60-79 years and ≥ 80 years compared to < 40 years and being a resident in a LTCF in Free State or Northern Cape compared to Western Cape. Compared to pre-wave 1, there was a decreased risk of mortality in wave 1, post-wave 1, wave 2, post-wave 2 and wave 3. CONCLUSION: The analysis of SARS-CoV-2 cases in sentinel LTCFs in South Africa points to an encouraging trend of decreasing numbers of outbreaks, cases and risk for mortality since the first wave. LTCFs are likely to have learnt from international experience and adopted national protocols, which include improved measures to limit transmission and administer early and appropriate clinical care.

Prolonged Shedding of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at High Viral Loads Among Hospitalized Immunocompromised Persons Living With Human Immunodeficiency Virus (HIV), South Africa.

BACKGROUND: We assessed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA shedding duration and magnitude among persons living with human immunodeficiency virus (HIV, PLHIV). METHODS: From May through December 2020, we conducted a prospective cohort study at 20 hospitals in South Africa. Adults hospitalized with symptomatic coronavirus disease 2019 (COVID-19) were enrolled and followed every 2 days with nasopharyngeal/oropharyngeal (NP/OP) swabs until documentation of cessation of SARS-CoV-2 shedding (2 consecutive negative NP/OP swabs). Real-time reverse transcription-polymerase chain reaction testing for SARS-CoV-2 was performed, and cycle-threshold (Ct) values < 30 were considered a proxy for high SARS-CoV-2 viral load. Factors associated with prolonged shedding were assessed using accelerated time-failure Weibull regression models. RESULTS: Of 2175 COVID-19 patients screened, 300 were enrolled, and 257 individuals (155 HIV-uninfected and 102 PLHIV) had > 1 swabbing visit (median 5 visits [range 2-21]). Median time to cessation of shedding was 13 days (interquartile range [IQR] 6-25) and did not differ significantly by HIV infection. Among a subset of 94 patients (41 PLHIV and 53 HIV-uninfected) with initial respiratory sample Ct-value < 30, median time of shedding at high SARS-CoV-2 viral load was 8 days (IQR 4-17). This was significantly longer in PLHIV with CD4 count < 200 cells/µL, compared to HIV-uninfected persons (median 27 days [IQR 8-43] vs 7 days [IQR 4-13]; adjusted hazard ratio [aHR] 0.14, 95% confidence interval [CI] .07-.28, P < .001), as well as in unsuppressed-HIV versus HIV-uninfected persons. CONCLUSIONS: Although SARS-CoV-2 shedding duration did not differ significantly by HIV infection, among a subset with high initial SARS-CoV-2 viral loads, immunocompromised PLHIV shed SARS-CoV-2 at high viral loads for longer than HIV-uninfected persons. Better HIV control may potentially decrease transmission time of SARS-CoV-2.

Direct and Indirect Effects of the Coronavirus Disease 2019 Pandemic on Private Healthcare Utilization in South Africa, March 2020-September 2021.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused severe disruptions to healthcare in many areas of the world, but data remain scarce for sub-Saharan Africa. METHODS: We evaluated trends in hospital admissions and outpatient emergency department (ED) and general practitioner (GP) visits to South Africa's largest private healthcare system during 2016-2021. We fit time series models to historical data and, for March 2020-September 2021, quantified changes in encounters relative to baseline. RESULTS: The nationwide lockdown on 27 March 2020 led to sharp reductions in care-seeking behavior that persisted for 18 months after initial declines. For example, total admissions dropped 59.6% (95% confidence interval [CI], 52.4-66.8) during home confinement and were 33.2% (95% CI, 29-37.4) below baseline in September 2021. We identified 3 waves of all-cause respiratory encounters consistent with COVID-19 activity. Intestinal infections and non-COVID-19 respiratory illnesses experienced the most pronounced declines, with some diagnoses reduced 80%, even as nonpharmaceutical interventions (NPIs) relaxed. Non-respiratory hospitalizations, including injuries and acute illnesses, were 20%-60% below baseline throughout the pandemic and exhibited strong temporal associations with NPIs and mobility. ED attendances exhibited trends similar to those for hospitalizations, while GP visits were less impacted and have returned to pre-pandemic levels. CONCLUSIONS: We found substantially reduced use of health services during the pandemic for a range of conditions unrelated to COVID-19. Persistent declines in hospitalizations and ED visits indicate that high-risk patients are still delaying seeking care, which could lead to morbidity or mortality increases in the future.

SARS-CoV-2 Seroprevalence after Third Wave of Infections, South Africa.

By November 2021, after the third wave of severe acute respiratory syndrome coronavirus 2 infections in South Africa, seroprevalence was 60% in a rural community and 70% in an urban community. High seroprevalence before the Omicron variant emerged may have contributed to reduced illness severity observed in the fourth wave.

The intersecting pandemics of tuberculosis and COVID-19: population-level and patient-level impact, clinical presentation, and corrective interventions.

The global tuberculosis burden remains substantial, with more than 10 million people newly ill per year. Nevertheless, tuberculosis incidence has slowly declined over the past decade, and mortality has decreased by almost a third in tandem. This positive trend was abruptly reversed by the COVID-19 pandemic, which in many parts of the world has resulted in a substantial reduction in tuberculosis testing and case notifications, with an associated increase in mortality, taking global tuberculosis control back by roughly 10 years. Here, we consider points of intersection between the tuberculosis and COVID-19 pandemics, identifying wide-ranging approaches that could be taken to reverse the devastating effects of COVID-19 on tuberculosis control. We review the impact of COVID-19 at the population level on tuberculosis case detection, morbidity and mortality, and the patient-level impact, including susceptibility to disease, clinical presentation, diagnosis, management, and prognosis. We propose strategies to reverse or mitigate the deleterious effects of COVID-19 and restore tuberculosis services. Finally, we highlight research priorities and major challenges and controversies that need to be addressed to restore and advance the global response to tuberculosis.

SARS-CoV-2 incidence, transmission, and reinfection in a rural and an urban setting: results of the PHIRST-C cohort study, South Africa, 2020-21.

BACKGROUND: By August, 2021, South Africa had been affected by three waves of SARS-CoV-2; the second associated with the beta variant and the third with the delta variant. Data on SARS-CoV-2 burden, transmission, and asymptomatic infections from Africa are scarce. We aimed to evaluate SARS-CoV-2 burden and transmission in one rural and one urban community in South Africa. METHODS: We conducted a prospective cohort study of households in Agincourt, Mpumalanga province (rural site) and Klerksdorp, North West province (urban site) from July, 2020 to August, 2021. We randomly selected households for the rural site from a health and sociodemographic surveillance system and for the urban site using GPS coordinates. Households with more than two members and where at least 75% of members consented to participate were eligible. Midturbinate nasal swabs were collected twice a week from household members irrespective of symptoms and tested for SARS-CoV-2 using real-time RT-PCR (RT-rtPCR). Serum was collected every 2 months and tested for anti-SARS-CoV-2 antibodies. Main outcomes were the cumulative incidence of SARS-CoV-2 infection, frequency of reinfection, symptomatic fraction (percent of infected individuals with ≥1 symptom), the duration of viral RNA shedding (number of days of SARS-CoV-2 RT-rtPCR positivity), and the household cumulative infection risk (HCIR; number of infected household contacts divided by the number of susceptible household members). FINDINGS: 222 households (114 at the rural site and 108 at the urban site), and 1200 household members (643 at the rural site and 557 at the urban site) were included in the analysis. For 115 759 nasal specimens from 1200 household members (follow-up 92·5%), 1976 (1·7%) were SARS-CoV-2-positive on RT-rtPCR. By RT-rtPCR and serology combined, 749 of 1200 individuals (62·4% [95% CI 58·1-66·4]) had at least one SARS-CoV-2 infection episode, and 87 of 749 (11·6% [9·4-14·2]) were reinfected. The mean infection episode duration was 11·6 days (SD 9·0; range 4-137). Of 662 RT-rtPCR-confirmed episodes (>14 days after the start of follow-up) with available data, 97 (14·7% [11·9-17·9]) were symptomatic with at least one symptom (in individuals aged <19 years, 28 [7·5%] of 373 episodes symptomatic; in individuals aged ≥19 years, 69 [23·9%] of 289 episodes symptomatic). Among 222 households, 200 (90·1% [85·3-93·7]) had at least one SARS-CoV-2-positive individual on RT-rtPCR or serology. HCIR overall was 23·9% (195 of 817 susceptible household members infected [95% CI 19·8-28·4]). HCIR was 23·3% (20 of 86) for symptomatic index cases and 23·9% (175 of 731) for asymptomatic index cases (univariate odds ratio [OR] 1·0 [95% CI 0·5-2·0]). On multivariable analysis, accounting for age and sex, low minimum cycle threshold value (≤30 vs >30) of the index case (OR 5·3 [2·3-12·4]) and beta and delta variant infection (vs Wuhan-Hu-1, OR 3·3 [1·4-8·2] and 10·4 [4·1-26·7], respectively) were associated with increased HCIR. People living with HIV who were not virally supressed (≥400 viral load copies per mL) were more likely to develop symptomatic illness when infected with SAR-CoV-2 (OR 3·3 [1·3-8·4]), and shed SARS-CoV-2 for longer (hazard ratio 0·4 [95% CI 0·3-0·6]) compared with HIV-uninfected individuals. INTERPRETATION: In this study, 565 (85·3%) SARS-CoV-2 infections were asymptomatic and index case symptom status did not affect HCIR, suggesting a limited role for control measures targeting symptomatic individuals. Increased household transmission of beta and delta variants was likely to have contributed to successive waves of SARS-CoV-2 infection, with more than 60% of individuals infected by the end of follow-up. FUNDING: US CDC, South Africa National Institute for Communicable Diseases, and Wellcome Trust.

Excess Invasive Meningococcal Disease Associated With Seasonal Influenza, South Africa, 2003-2018.

BACKGROUND: Invasive meningococcal disease (IMD) is a devastating illness with high mortality rates. Like influenza, endemic IMD is seasonal, peaking in winter. Studies suggest that circulation of influenza virus may influence the timing and magnitude of IMD winter peaks. METHODS: This ecological study used weekly data from 2 nationwide surveillance programs: Viral Watch (proportion of outpatient influenza-positive cases from throat or nasal swab samples) and GERMS-SA (laboratory-confirmed cases of IMD), occurring across South Africa from 2003 through 2018 in all age bands. A bivariate time series analysis using wavelet transform was conducted to determine cocirculation of the diseases and the time lag between the peak seasons. We modeled excess meningococcal disease cases attributable to influenza cocirculation, using univariate regression spline models. Stata and R statistical software packages were used for the analysis. RESULTS: A total of 5256 laboratory-confirmed IMD cases were reported, with an average annual incidence of 0.23 episodes per 100 000 population and a mean seasonal peak during week 32 (±3 weeks). Forty-two percent of swab samples (10 421 of 24 741) were positive for influenza during the study period. The mean peak for all influenza occurred at week 26 (±4 weeks). There was an average lag time of 5 weeks between annual influenza and IMD seasons. Overall, 5% (1%-9%) of IMD cases can be attributable to influenza cocirculation, with, on average, 17 excess IMD cases per year attributable to influenza. CONCLUSIONS: A quantifiable proportion of IMD in South Africa is associated with influenza cocirculation; therefore, seasonal influenza vaccination may have an effect on preventing a small portion of IMD in addition to preventing influenza.