Changing Severity and Epidemiology of Adults Hospitalized With Coronavirus Disease 2019 (COVID-19) in the United States After Introduction of COVID-19 Vaccines, March 2021-August 2022.

INTRODUCTION: Understanding the changing epidemiology of adults hospitalized with coronavirus disease 2019 (COVID-19) informs research priorities and public health policies. METHODS: Among adults (≥18 years) hospitalized with laboratory-confirmed, acute COVID-19 between 11 March 2021, and 31 August 2022 at 21 hospitals in 18 states, those hospitalized during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron-predominant period (BA.1, BA.2, BA.4/BA.5) were compared to those from earlier Alpha- and Delta-predominant periods. Demographic characteristics, biomarkers within 24 hours of admission, and outcomes, including oxygen support and death, were assessed. RESULTS: Among 9825 patients, median (interquartile range [IQR]) age was 60 years (47-72), 47% were women, and 21% non-Hispanic Black. From the Alpha-predominant period (Mar-Jul 2021; N = 1312) to the Omicron BA.4/BA.5 sublineage-predominant period (Jun-Aug 2022; N = 1307): the percentage of patients who had ≥4 categories of underlying medical conditions increased from 11% to 21%; those vaccinated with at least a primary COVID-19 vaccine series increased from 7% to 67%; those ≥75 years old increased from 11% to 33%; those who did not receive any supplemental oxygen increased from 18% to 42%. Median (IQR) highest C-reactive protein and D-dimer concentration decreased from 42.0 mg/L (9.9-122.0) to 11.5 mg/L (2.7-42.8) and 3.1 mcg/mL (0.8-640.0) to 1.0 mcg/mL (0.5-2.2), respectively. In-hospital death peaked at 12% in the Delta-predominant period and declined to 4% during the BA.4/BA.5-predominant period. CONCLUSIONS: Compared to adults hospitalized during early COVID-19 variant periods, those hospitalized during Omicron-variant COVID-19 were older, had multiple co-morbidities, were more likely to be vaccinated, and less likely to experience severe respiratory disease, systemic inflammation, coagulopathy, and death.

Comparison of mRNA vaccine effectiveness against COVID-19-associated hospitalization by vaccination source: Immunization information systems, electronic medical records, and self-report-IVY Network, February 1-August 31, 2022.

BACKGROUND: Accurate determination of COVID-19 vaccination status is necessary to produce reliable COVID-19 vaccine effectiveness (VE) estimates. Data comparing differences in COVID-19 VE by vaccination sources (i.e., immunization information systems [IIS], electronic medical records [EMR], and self-report) are limited. We compared the number of mRNA COVID-19 vaccine doses identified by each of these sources to assess agreement as well as differences in VE estimates using vaccination data from each individual source and vaccination data adjudicated from all sources combined. METHODS: Adults aged ≥18 years who were hospitalized with COVID-like illness at 21 hospitals in 18 U.S. states participating in the IVY Network during February 1-August 31, 2022, were enrolled. Numbers of COVID-19 vaccine doses identified by IIS, EMR, and self-report were compared in kappa agreement analyses. Effectiveness of mRNA COVID-19 vaccines against COVID-19-associated hospitalization was estimated using multivariable logistic regression models to compare the odds of COVID-19 vaccination between SARS-CoV-2-positive case-patients and SARS-CoV-2-negative control-patients. VE was estimated using each source of vaccination data separately and all sources combined. RESULTS: A total of 4499 patients were included. Patients with ≥1 mRNA COVID-19 vaccine dose were identified most frequently by self-report (n = 3570, 79 %), followed by IIS (n = 3272, 73 %) and EMR (n = 3057, 68 %). Agreement was highest between IIS and self-report for 4 doses with a kappa of 0.77 (95 % CI = 0.73-0.81). VE point estimates of 3 doses against COVID-19 hospitalization were substantially lower when using vaccination data from EMR only (VE = 31 %, 95 % CI = 16 %-43 %) than when using all sources combined (VE = 53 %, 95 % CI = 41 %-62%). CONCLUSION: Vaccination data from EMR only may substantially underestimate COVID-19 VE.

Total and subgenomic RNA viral load in patients infected with SARS-CoV-2 Alpha, Delta, and Omicron variants.

BACKGROUND: SARS-CoV-2 genomic and subgenomic RNA levels are frequently used as a correlate of infectiousness. The impact of host factors and SARS-CoV-2 lineage on RNA viral load is unclear. METHODS: Total nucleocapsid (N) and subgenomic N (sgN) RNA levels were measured by RT-qPCR in specimens from 3,204 individuals hospitalized with COVID-19 at 21 hospitals. RT-qPCR cycle threshold (Ct) values were used to estimate RNA viral load. The impact of time of sampling, SARS-CoV-2 variant, age, comorbidities, vaccination, and immune status on N and sgN Ct values were evaluated using multiple linear regression. RESULTS: Ct values at presentation for N (mean ±standard deviation) were 24.14±4.53 for non-variants of concern, 25.15±4.33 for Alpha, 25.31±4.50 for Delta, and 26.26±4.42 for Omicron. N and sgN RNA levels varied with time since symptom onset and infecting variant but not with age, comorbidity, immune status, or vaccination. When normalized to total N RNA, sgN levels were similar across all variants. CONCLUSIONS: RNA viral loads were similar among hospitalized adults, irrespective of infecting variant and known risk factors for severe COVID-19. Total N and subgenomic RNA N viral loads were highly correlated, suggesting that subgenomic RNA measurements adds little information for the purposes of estimating infectivity.

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.

Early Estimates of Bivalent mRNA Vaccine Effectiveness in Preventing COVID-19-Associated Hospitalization Among Immunocompetent Adults Aged ≥65 Years - IVY Network, 18 States, September 8-November 30, 2022.

Monovalent COVID-19 mRNA vaccines, designed against the ancestral strain of SARS-CoV-2, successfully reduced COVID-19-related morbidity and mortality in the United States and globally (1,2). However, vaccine effectiveness (VE) against COVID-19-associated hospitalization has declined over time, likely related to a combination of factors, including waning immunity and, with the emergence of the Omicron variant and its sublineages, immune evasion (3). To address these factors, on September 1, 2022, the Advisory Committee on Immunization Practices recommended a bivalent COVID-19 mRNA booster (bivalent booster) dose, developed against the spike protein from ancestral SARS-CoV-2 and Omicron BA.4/BA.5 sublineages, for persons who had completed at least a primary COVID-19 vaccination series (with or without monovalent booster doses) ≥2 months earlier (4). Data on the effectiveness of a bivalent booster dose against COVID-19 hospitalization in the United States are lacking, including among older adults, who are at highest risk for severe COVID-19-associated illness. During September 8-November 30, 2022, the Investigating Respiratory Viruses in the Acutely Ill (IVY) Network§ assessed effectiveness of a bivalent booster dose received after ≥2 doses of monovalent mRNA vaccine against COVID-19-associated hospitalization among immunocompetent adults aged ≥65 years. When compared with unvaccinated persons, VE of a bivalent booster dose received ≥7 days before illness onset (median = 29 days) against COVID-19-associated hospitalization was 84%. Compared with persons who received ≥2 monovalent-only mRNA vaccine doses, relative VE of a bivalent booster dose was 73%. These early findings show that a bivalent booster dose provided strong protection against COVID-19-associated hospitalization in older adults and additional protection among persons with previous monovalent-only mRNA vaccination. All eligible persons, especially adults aged ≥65 years, should receive a bivalent booster dose to maximize protection against COVID-19 hospitalization this winter season. Additional strategies to prevent respiratory illness, such as masking in indoor public spaces, should also be considered, especially in areas where COVID-19 community levels are high (4,5).

Vaccine effectiveness of primary series and booster doses against covid-19 associated hospital admissions in the United States: living test negative design study.

OBJECTIVE: To compare the effectiveness of a primary covid-19 vaccine series plus booster doses with a primary series alone for the prevention of hospital admission with omicron related covid-19 in the United States. DESIGN: Multicenter observational case-control study with a test negative design. SETTING: Hospitals in 18 US states. PARTICIPANTS: 4760 adults admitted to one of 21 hospitals with acute respiratory symptoms between 26 December 2021 and 30 June 2022, a period when the omicron variant was dominant. Participants included 2385 (50.1%) patients with laboratory confirmed covid-19 (cases) and 2375 (49.9%) patients who tested negative for SARS-CoV-2 (controls). MAIN OUTCOME MEASURES: The main outcome was vaccine effectiveness against hospital admission with covid-19 for a primary series plus booster doses and a primary series alone by comparing the odds of being vaccinated with each of these regimens versus being unvaccinated among cases versus controls. Vaccine effectiveness analyses were stratified by immunosuppression status (immunocompetent, immunocompromised). The primary analysis evaluated all covid-19 vaccine types combined, and secondary analyses evaluated specific vaccine products. RESULTS: Overall, median age of participants was 64 years (interquartile range 52-75 years), 994 (20.8%) were immunocompromised, 85 (1.8%) were vaccinated with a primary series plus two boosters, 1367 (28.7%) with a primary series plus one booster, and 1875 (39.3%) with a primary series alone, and 1433 (30.1%) were unvaccinated. Among immunocompetent participants, vaccine effectiveness for prevention of hospital admission with omicron related covid-19 for a primary series plus two boosters was 63% (95% confidence interval 37% to 78%), a primary series plus one booster was 65% (58% to 71%), and for a primary series alone was 37% (25% to 47%) (P<0.001 for the pooled boosted regimens compared with a primary series alone). Vaccine effectiveness was higher for a boosted regimen than for a primary series alone for both mRNA vaccines (BNT162b2 (Pfizer-BioNTech): 73% (44% to 87%) for primary series plus two boosters, 64% (55% to 72%) for primary series plus one booster, and 36% (21% to 48%) for primary series alone (P<0.001); mRNA-1273 (Moderna): 68% (17% to 88%) for primary series plus two boosters, 65% (55% to 73%) for primary series plus one booster, and 41% (25% to 54%) for primary series alone (P=0.001)). Among immunocompromised patients, vaccine effectiveness for a primary series plus one booster was 69% (31% to 86%) and for a primary series alone was 49% (30% to 63%) (P=0.04). CONCLUSION: During the first six months of 2022 in the US, booster doses of a covid-19 vaccine provided additional benefit beyond a primary vaccine series alone for preventing hospital admissions with omicron related covid-19. READERS' NOTE: This article is a living test negative design study that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.

Increase in Acute Respiratory Illnesses Among Children and Adolescents Associated with Rhinoviruses and Enteroviruses, Including Enterovirus D68 - United States, July-September 2022.

Increases in severe respiratory illness and acute flaccid myelitis (AFM) among children and adolescents resulting from enterovirus D68 (EV-D68) infections occurred biennially in the United States during 2014, 2016, and 2018, primarily in late summer and fall. Although EV-D68 annual trends are not fully understood, EV-D68 levels were lower than expected in 2020, potentially because of implementation of COVID-19 mitigation measures (e.g., wearing face masks, enhanced hand hygiene, and physical distancing) (1). In August 2022, clinicians in several geographic areas notified CDC of an increase in hospitalizations of pediatric patients with severe respiratory illness and positive rhinovirus/enterovirus (RV/EV) test results.* Surveillance data were analyzed from multiple national data sources to characterize reported trends in acute respiratory illness (ARI), asthma/reactive airway disease (RAD) exacerbations, and the percentage of positive RV/EV and EV-D68 test results during 2022 compared with previous years. These data demonstrated an increase in emergency department (ED) visits by children and adolescents with ARI and asthma/RAD in late summer 2022. The percentage of positive RV/EV test results in national laboratory-based surveillance and the percentage of positive EV-D68 test results in pediatric sentinel surveillance also increased during this time. Previous increases in EV-D68 respiratory illness have led to substantial resource demands in some hospitals and have also coincided with increases in cases of AFM (2), a rare but serious neurologic disease affecting the spinal cord. Therefore, clinicians should consider AFM in patients with acute flaccid limb weakness, especially after respiratory illness or fever, and ensure prompt hospitalization and referral to specialty care for such cases. Clinicians should also test for poliovirus infection in patients suspected of having AFM because of the clinical similarity to acute flaccid paralysis caused by poliovirus. Ongoing surveillance for EV-D68 is critical to ensuring preparedness for possible future increases in ARI and AFM.

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.

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 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.

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.

Hospitalizations of Children and Adolescents with Laboratory-Confirmed COVID-19 - COVID-NET, 14 States, July 2021-January 2022.

The first U.S. case of COVID-19 attributed to the Omicron variant of SARS-CoV-2 (the virus that causes COVID-19) was reported on December 1, 2021 (1), and by the week ending December 25, 2021, Omicron was the predominant circulating variant in the United States.* Although COVID-19-associated hospitalizations are more frequent among adults,† COVID-19 can lead to severe outcomes in children and adolescents (2). This report analyzes data from the Coronavirus Disease 19-Associated Hospitalization Surveillance Network (COVID-NET)§ to describe COVID-19-associated hospitalizations among U.S. children (aged 0-11 years) and adolescents (aged 12-17 years) during periods of Delta (July 1-December 18, 2021) and Omicron (December 19, 2021-January 22, 2022) predominance. During the Delta- and Omicron-predominant periods, rates of weekly COVID-19-associated hospitalizations per 100,000 children and adolescents peaked during the weeks ending September 11, 2021, and January 8, 2022, respectively. The Omicron variant peak (7.1 per 100,000) was four times that of the Delta variant peak (1.8), with the largest increase observed among children aged 0-4 years.¶ During December 2021, the monthly hospitalization rate among unvaccinated adolescents aged 12-17 years (23.5) was six times that among fully vaccinated adolescents (3.8). Strategies to prevent COVID-19 among children and adolescents, including vaccination of eligible persons, are critical.*.

SARS-CoV-2 Seroprevalence in a Rural and Urban Household Cohort during First and Second Waves of Infections, South Africa, July 2020-March 2021.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections may be underestimated because of limited access to testing. We measured SARS-CoV-2 seroprevalence in South Africa every 2 months during July 2020-March 2021 in randomly selected household cohorts in 2 communities. We compared seroprevalence to reported laboratory-confirmed infections, hospitalizations, and deaths to calculate infection-case, infection-hospitalization, and infection-fatality ratios in 2 waves of infection. Post-second wave seroprevalence ranged from 18% in the rural community children <5 years of age, to 59% in urban community adults 35-59 years of age. The second wave saw a shift in age distribution of case-patients in the urban community (from persons 35-59 years of age to persons at the extremes of age), higher attack rates in the rural community, and a higher infection-fatality ratio in the urban community. Approximately 95% of SARS-CoV-2 infections were not reported to national surveillance.

Enterovirus D68-Associated Acute Respiratory Illness ─ New Vaccine Surveillance Network, United States, July-November 2018-2020.

Enterovirus D68 (EV-D68) is associated with a broad spectrum of illnesses, including mild to severe acute respiratory illness (ARI) and acute flaccid myelitis (AFM). Enteroviruses, including EV-D68, are typically detected in the United States during late summer through fall, with year-to-year fluctuations. Before 2014, EV-D68 was infrequently reported to CDC (1). However, numbers of EV-D68 detection have increased in recent years, with a biennial pattern observed during 2014-2018 in the United States, after the expansion of surveillance and wider availability of molecular testing. In 2014, a national outbreak of EV-D68 was detected (2). EV-D68 was also reported in 2016 via local (3) and passive national (4) surveillance. EV-D68 detections were limited in 2017, but substantial circulation was observed in 2018 (5). To assess recent levels of circulation, EV-D68 detections in respiratory specimens collected from patients aged <18 years* with ARI evaluated in emergency departments (EDs) or admitted to one of seven U.S. medical centers† within the New Vaccine Surveillance Network (NVSN) were summarized. This report provides a provisional description of EV-D68 detections during July-November in 2018, 2019 and 2020, and describes the demographic and clinical characteristics of these patients. In 2018, a total of 382 EV-D68 detections in respiratory specimens obtained from patients aged <18 years with ARI were reported by NVSN; the number decreased to six detections in 2019 and 30 in 2020. Among patients aged <18 years with EV-D68 in 2020, 22 (73%) were non-Hispanic Black (Black) persons. EV-D68 detections in 2020 were lower than anticipated based on the biennial circulation pattern observed since 2014. The circulation of EV-D68 in 2020 might have been limited by widespread COVID-19 mitigation measures; how these changes in behavior might influence the timing and levels of circulation in future years is unknown. Ongoing monitoring of EV-D68 detections is warranted for preparedness for EV-D68-associated ARI and AFM.

Influenza economic burden among potential target risk groups for immunization in South Africa, 2013-2015.

BACKGROUND: Data on influenza economic burden in risk groups for severe influenza are important to guide targeted influenza immunization, especially in resource-limited settings. However, this information is limited in low- and middle-income countries. METHODS: We estimated the cost (from a health system and societal perspective) and years of life lost (YLL) for influenza-associated illness in South Africa during 2013-2015 among (i) children aged 6-59 months, (ii) individuals aged 5-64 years with HIV, pulmonary tuberculosis (PTB) and selected underlying medical conditions (UMC), separately, (iii) pregnant women and (iv) individuals aged ≥65 years, using publicly available data and data collected through laboratory-confirmed influenza surveillance and costing studies. All costs were expressed in 2015 prices using the South Africa all-items Consumer Price Index. RESULTS: During 2013-2015, the mean annual cost of influenza-associated illness among the selected risk groups accounted for 52.1% ($140.9/$270.5 million) of the total influenza-associated illness cost (for the entire population of South Africa), 45.2% ($52.2/$115.5 million) of non-medically attended illness costs, 43.3% ($46.7/$107.9 million) of medically-attended mild illness costs and 89.3% ($42.0/$47.1 million) of medically-attended severe illness costs. The YLL among the selected risk groups accounted for 86.0% (262,069 /304,867 years) of the total YLL due to influenza-associated death. CONCLUSION: In South Africa, individuals in risk groups for severe influenza accounted for approximately half of the total influenza-associated illness cost but most of the cost of influenza-associated medically attended severe illness and YLL. This study provides the foundation for future studies on the cost-effectiveness of influenza immunization among risk groups.

Decline of influenza and respiratory syncytial virus detection in facility-based surveillance during the COVID-19 pandemic, South Africa, January to October 2020.

BackgroundIn South Africa, COVID-19 control measures to prevent SARS-CoV-2 spread were initiated on 16 March 2020. Such measures may also impact the spread of other pathogens, including influenza virus and respiratory syncytial virus (RSV) with implications for future annual epidemics and expectations for the subsequent northern hemisphere winter.MethodsWe assessed the detection of influenza and RSV through facility-based syndromic surveillance of adults and children with mild or severe respiratory illness in South Africa from January to October 2020, and compared this with surveillance data from 2013 to 2019.ResultsFacility-based surveillance revealed a decline in influenza virus detection during the regular season compared with previous years. This was observed throughout the implementation of COVID-19 control measures. RSV detection decreased soon after the most stringent COVID-19 control measures commenced; however, an increase in RSV detection was observed after the typical season, following the re-opening of schools and the easing of measures.ConclusionCOVID-19 non-pharmaceutical interventions led to reduced circulation of influenza and RSV in South Africa. This has limited the country's ability to provide influenza virus strains for the selection of the annual influenza vaccine. Delayed increases in RSV case numbers may reflect the easing of COVID-19 control measures. An increase in influenza virus detection was not observed, suggesting that the measures may have impacted the two pathogens differently. The impact that lowered and/or delayed influenza and RSV circulation in 2020 will have on the intensity and severity of subsequent annual epidemics is unknown and warrants close monitoring.

Cohort profile: A Prospective Household cohort study of Influenza, Respiratory syncytial virus and other respiratory pathogens community burden and Transmission dynamics in South Africa, 2016-2018.

PURPOSE: The PHIRST study (Prospective Household cohort study of Influenza, Respiratory Syncytial virus, and other respiratory pathogens community burden and Transmission dynamics in South Africa) aimed to estimate the community burden of influenza and respiratory syncytial virus (RSV) including the incidence of infection, symptomatic fraction, and to assess household transmission. PARTICIPANTS: We enrolled 1684 individuals in 327 randomly selected households in a rural and an urban site over three consecutive influenza and two RSV seasons. A new cohort of households was enrolled each year. Participants were sampled with nasopharyngeal swabs twice-weekly during the RSV and influenza seasons of the year of enrolment. Serology samples were collected at enrolment and before and after the influenza season annually. FINDINGS TO DATE: There were 122 113 potential individual follow-up visits over the 3 years, and participants were interviewed for 105 783 (87%) of these. Out of 105 683 nasopharyngeal swabs, 1258 (1%) and 1026 (1%) tested positive on polymerase chain reaction (PCR) for influenza viruses and RSV, respectively. Over one third of individuals had PCR-confirmed influenza each year. Overall, there was influenza transmission to 10% of household contacts of an index case. FUTURE PLANS: Future planned analyses include analysis of influenza serology results and RSV burden and transmission. Households enrolled in the PHIRST study during 2016-2018 were eligible for inclusion in a study of SARS-CoV-2 transmission initiated in July 2020. This study uses similar testing frequency to assess the community burden of SARS-CoV-2 infection and the role of asymptomatic infection in virus transmission.