Long-Term Symptoms Associated With SARS-CoV-2 Infection Among Blood Donors.

Importance: Long-term symptoms, lasting more than 4 consecutive weeks after acute COVID-19 disease, are an important consequence of SARS-CoV-2 infection. Many prior studies have lacked a non-SARS-CoV-2-infected control population to distinguish background prevalence of symptoms from the direct impact of COVID-19 disease. Objective: To examine the prevalence of long-term physical and mental health symptoms associated with SARS-CoV-2 infection in a large population of blood donors based on self-report and serologic test results. Design, Setting, and Participants: This cross-sectional study included American Red Cross blood donors (aged ≥18 years) who were surveyed between February 22 and April 21, 2022, about new long-term symptoms arising after March 2020 and their SARS-CoV-2 infection status. All participants underwent at least 1 serologic test for antinucleocapsid antibodies between June 15, 2020, and December 31, 2021. Exposures: SARS-CoV-2 infection as defined by a self-reported, confirmed acute infection or antinucleocapsid antibody positivity. Main Outcomes and Measures: New long-term symptoms since March 2020, including 5 symptom categories (neurologic, gastrointestinal, respiratory and cardiac, mental health, and other). Results: Among 818 361 individuals who received the survey, 272 965 (33.4%) responded, with 238 828 meeting the inclusion criteria (138 576 [58.0%] female; median [IQR] age, 59.0 [47.0-67.0] years). Of the 83 015 individuals with a history of SARS-CoV-2 infection, 43.3% reported new long-term symptoms compared with 22.1% of those without a history of SARS-CoV-2 infection. After controlling for age, sex, race and ethnicity, and number of underlying conditions, those with a history of SARS-CoV-2 infection had an increased odds of new long-term symptoms compared with those without (adjusted odds ratio [AOR], 2.55; 95% CI, 2.51-2.61). Female sex and a history of chronic conditions were associated with new long-term symptoms. Long-term symptoms in the other category (AOR, 4.14; 95% CI, 4.03-4.25), which included changes in taste or smell, and the respiratory and cardiac symptom categories (AOR, 3.21; 95% CI, 3.12-3.31) were most associated with prior SARS-CoV-2 infection. Mental health long-term symptoms were also associated with prior SARS-CoV-2 infection (AOR, 1.05; 95%, CI, 1.02-1.08). Conclusions and Relevance: This study's findings suggest that long-term symptoms lasting more than 4 weeks are common in the adult population, but there is a significantly higher prevalence among those with SARS-CoV-2 infection. Continued efforts to define and track long-term sequelae of SARS-CoV-2 using a control group without infection and serologic information to include those who had asymptomatic or unidentified infections are needed.

Combined protection of vaccination and nirmatrelvir-ritonavir against hospitalization in adults with COVID-19.

Among U.S. adults at risk for severe COVID-19 in Epic Cosmos, the lowest rate of hospitalization was among those receiving three or more mRNA vaccine doses and nirmatrelvir-ritonavir (aHR 0.22, 95%CI: 0.19-0.24). Adults who are at high-risk of severe COVID-19 disease, including vaccinated persons, should be considered for antiviral treatment.

Use of Updated COVID-19 Vaccines 2023-2024 Formula for Persons Aged ≥6 Months: Recommendations of the Advisory Committee on Immunization Practices - United States, September 2023.

COVID-19 vaccines protect against severe COVID-19-associated outcomes, including hospitalization and death. As SARS-CoV-2 has evolved, and waning vaccine effectiveness has been noted, vaccine formulations and policies have been updated to provide continued protection against severe illness and death from COVID-19. Since September 2022, bivalent mRNA COVID-19 vaccines have been recommended in the United States, but the variants these vaccines protect against are no longer circulating widely. On September 11, 2023, the Food and Drug Administration (FDA) approved the updated (2023-2024 Formula) COVID-19 mRNA vaccines by Moderna and Pfizer-BioNTech for persons aged ≥12 years and authorized these vaccines for persons aged 6 months-11 years under Emergency Use Authorization (EUA). On October 3, 2023, FDA authorized the updated COVID-19 vaccine by Novavax for use in persons aged ≥12 years under EUA. The updated COVID-19 vaccines include a monovalent XBB.1.5 component, which is meant to broaden vaccine-induced immunity and provide protection against currently circulating SARS-CoV-2 XBB-sublineage variants including against severe COVID-19-associated illness and death. On September 12, 2023, the Advisory Committee on Immunization Practices recommended vaccination with updated COVID-19 vaccines for all persons aged ≥6 months. These recommendations will be reviewed as new evidence becomes available or new vaccines are approved and might be updated.

Bacterial and viral infections among adults hospitalized with COVID-19, COVID-NET, 14 states, March 2020-April 2022.

Background: Bacterial and viral infections can occur with SARS-CoV-2 infection, but prevalence, risk factors, and associated clinical outcomes are not fully understood. Methods: We used the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET), a population-based surveillance system, to investigate the occurrence of bacterial and viral infections among hospitalized adults with laboratory-confirmed SARS-CoV-2 infection between March 2020 and April 2022. Clinician-driven testing for bacterial pathogens from sputum, deep respiratory, and sterile sites were included. The demographic and clinical features of those with and without bacterial infections were compared. We also describe the prevalence of viral pathogens including respiratory syncytial virus, rhinovirus/enterovirus, influenza, adenovirus, human metapneumovirus, parainfluenza viruses, and non-SARS-CoV-2 endemic coronaviruses. Results: Among 36 490 hospitalized adults with COVID-19, 53.3% had bacterial cultures taken within 7 days of admission and 6.0% of these had a clinically relevant bacterial pathogen. After adjustment for demographic factors and co-morbidities, bacterial infections in patients with COVID-19 within 7 days of admission were associated with an adjusted relative risk of death 2.3 times that of patients with negative bacterial testing. Staphylococcus aureus and Gram-negative rods were the most frequently isolated bacterial pathogens. Among hospitalized adults with COVID-19, 2766 (7.6%) were tested for seven virus groups. A non-SARS-CoV-2 virus was identified in 0.9% of tested patients. Conclusions: Among patients with clinician-driven testing, 6.0% of adults hospitalized with COVID-19 were identified to have bacterial coinfections and 0.9% were identified to have viral coinfections; identification of a bacterial coinfection within 7 days of admission was associated with increased mortality.

Occupations Associated With Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Vaccination, US Blood Donors, May 2021-December 2021.

BACKGROUND: There are limited data on the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the United States by occupation. We identified occupations at higher risk for prior SARS-CoV-2 infection as defined by the presence of infection-induced antibodies among US blood donors. METHODS: Using a nested case-control study design, blood donors during May-December 2021 with anti-nucleocapsid (anti-N) testing were sent an electronic survey on employment status, vaccination, and occupation. The association between previous SARS-CoV-2 infection and occupation-specific in-person work was estimated using multivariable logistic regression adjusting for sex, age, month of donation, race and ethnicity, education, vaccination, and telework. RESULTS: Among 85 986 included survey respondents, 9504 (11.1%) were anti-N reactive. Healthcare support (20.3%), protective service (19.9%), and food preparation and serving related occupations (19.7%) had the highest proportion of prior infection. After adjustment, prior SARS-CoV-2 infection was associated with healthcare practitioners (adjusted odds ratio [aOR], 2.10; 95% confidence interval [CI], 1.74-2.54) and healthcare support (aOR, 1.82; 95% CI, 1.39-2.40) occupations compared with computer and mathematical occupations as the referent group. Lack of coronavirus disease 2019 vaccination (aOR, 16.13; 95% CI, 15.01-17.34) and never teleworking (aOR, 1.17; 95% CI, 1.05-1.30) were also independently associated with prior SARS-CoV-2 infection. Construction and extraction occupations had the highest proportion of unvaccinated workers (30.5%). CONCLUSIONS: Workers in healthcare, protective services, and food preparation had the highest prevalence of prior SARS-CoV-2 infection. Occupational risks for SARS-CoV-2 infection remained after adjusting for vaccination, telework, and demographic factors. These findings underscore the need for mitigation measures and personal protection in healthcare settings and other workplaces.

Paxlovid Associated with Decreased Hospitalization Rate Among Adults with COVID-19 - United States, April-September 2022.

Nirmatrelvir-ritonavir (Paxlovid), an oral antiviral treatment, is authorized for adults with mild-to-moderate COVID-19 who are at increased risk for progression to severe illness. However, real-world evidence on the benefit of Paxlovid, according to vaccination status, age group, and underlying health conditions, is limited. To examine the benefit of Paxlovid in adults aged ≥18 years in the United States, a large electronic health record (EHR) data set (Cosmos†) was analyzed to assess the association between receiving a prescription for Paxlovid and hospitalization with a COVID-19 diagnosis in the ensuing 30 days. A Cox proportional hazards model was used to estimate this association, adjusted for demographic characteristics, geographic location, vaccination, previous infection, and number of underlying health conditions. Among 699,848 adults aged ≥18 years eligible for Paxlovid during April-August 2022, 28.4% received a Paxlovid prescription within 5 days of COVID-19 diagnosis. Being prescribed Paxlovid was associated with a lower hospitalization rate among the overall study population (adjusted hazard ratio [aHR] = 0.49), among those who had received ≥3 mRNA COVID-19 vaccines (aHR = 0.50), and across age groups (18-49 years: aHR = 0.59; 50-64 years: aHR = 0.40; and ≥65 years: aHR = 0.53). Paxlovid should be prescribed to eligible adults to reduce the risk of COVID-19-associated hospitalization.

Seasonality of Common Human Coronaviruses, United States, 2014-20211.

The 4 common types of human coronaviruses (HCoVs)-2 alpha (HCoV-NL63 and HCoV-229E) and 2 beta (HCoV-HKU1 and HCoV-OC43)-generally cause mild upper respiratory illness. Seasonal patterns and annual variation in predominant types of HCoVs are known, but parameters of expected seasonality have not been defined. We defined seasonality of HCoVs during July 2014-November 2021 in the United States by using a retrospective method applied to National Respiratory and Enteric Virus Surveillance System data. In the 6 HCoV seasons before 2020-21, season onsets occurred October 21-November 12, peaks January 6-February 13, and offsets April 18-June 27; most (>93%) HCoV detection was within the defined seasonal onsets and offsets. The 2020-21 HCoV season onset was 11 weeks later than in prior seasons, probably associated with COVID-19 mitigation efforts. Better definitions of HCoV seasonality can be used for clinical preparedness and for determining expected patterns of emerging coronaviruses.

Primary and Secondary Attack Rates by Vaccination Status after a SARS-CoV-2 B.1.617.2 (Delta) Variant Outbreak at a Youth Summer Camp-Texas, June 2021.

Children are capable of initiating COVID-19 transmission into households, but many questions remain about the impact of vaccination on transmission. Data from a COVID-19 Delta variant outbreak at an overnight camp in Texas during June 23-27, 2021, were analyzed. The camp had 451 attendees, including 364 youths aged  < 18 years and 87 adults. Detailed interviews were conducted with 92 (20.4%) of consenting attendees and 117 household members of interviewed attendees with COVID-19. Among 450 attendees with known case status, the attack rate was 41%, including 42% among youths; attack rates were lower among vaccinated (13%) than among unvaccinated youths (48%). The secondary attack rate was 51% among 115 household contacts of 55 interviewed index patients. Secondary infections occurred in 67% of unvaccinated household members and 33% of fully or partially vaccinated household members. Analyses suggested that household member vaccination and camp attendee masking at home protected against household transmission.

Twelve-Month Follow-up of Early COVID-19 Cases in the United States: Cellular and Humoral Immune Longevity.

We quantify antibody and memory B-cell responses to severe acute respiratory syndrome coronavirus 2 at 6 and 12 months postinfection among 7 unvaccinated US coronavirus disease 2019 cases. All had detectable S-specific memory B cells and immunoglobulin G at both time points, with geometric mean titers of 117.2 BAU/mL and 84.0 BAU/mL at 6 and 12 months, respectively.

Relationship of SARS-CoV-2 Antigen and Reverse Transcription PCR Positivity for Viral Cultures.

We assessed the relationship between antigen and reverse transcription PCR (RT-PCR) test positivity and successful virus isolation. We found that antigen test results were more predictive of virus recovery than RT-PCR results. However, virus was isolated from some antigen-negative and RT-PCR‒positive paired specimens, providing support for the Centers for Disease Control and Prevention antigen testing algorithm.

Quantitative comparison of SARS-CoV-2 nucleic acid amplification test and antigen testing algorithms: a decision analysis simulation model.

BACKGROUND: Antigen tests for SARS-CoV-2 offer advantages over nucleic acid amplification tests (NAATs, such as RT-PCR), including lower cost and rapid return of results, but show reduced sensitivity. Public health organizations recommend different strategies for utilizing NAATs and antigen tests. We sought to create a framework for the quantitative comparison of these recommended strategies based on their expected performance. METHODS: We utilized a decision analysis approach to simulate the expected outcomes of six testing algorithms analogous to strategies recommended by public health organizations. Each algorithm was simulated 50,000 times in a population of 100,000 persons seeking testing. Primary outcomes were number of missed cases, number of false-positive diagnoses, and total test volumes. Outcome medians and 95% uncertainty ranges (URs) were reported. RESULTS: Algorithms that use NAATs to confirm all negative antigen results minimized missed cases but required high NAAT capacity: 92,200 (95% UR: 91,200-93,200) tests (in addition to 100,000 antigen tests) at 10% prevalence. Selective use of NAATs to confirm antigen results when discordant with symptom status (e.g., symptomatic persons with negative antigen results) resulted in the most efficient use of NAATs, with 25 NAATs (95% UR: 13-57) needed to detect one additional case compared to exclusive use of antigen tests. CONCLUSIONS: No single SARS-CoV-2 testing algorithm is likely to be optimal across settings with different levels of prevalence and for all programmatic priorities. This analysis provides a framework for selecting setting-specific strategies to achieve acceptable balances and trade-offs between programmatic priorities and resource constraints.

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.

Antigen Test Performance Among Children and Adults at a SARS-CoV-2 Community Testing Site.

BACKGROUND: Performance characteristics of SARS-CoV-2 antigen tests among children are limited despite the need for point-of-care testing in school and childcare settings. We describe children seeking SARS-CoV-2 testing at a community site and compare antigen test performance to real-time reverse transcription-polymerase chain reaction (RT-PCR) and viral culture. METHODS: Two anterior nasal specimens were self-collected for BinaxNOW antigen and RT-PCR testing, along with demographics, symptoms, and exposure information from individuals ≥5 years at a community testing site. Viral culture was attempted on residual antigen or RT-PCR-positive specimens. Demographic and clinical characteristics, and the performance of SARS-CoV-2 antigen tests, were compared among children (<18 years) and adults. RESULTS: About 1 in 10 included specimens were from children (225/2110); 16.4% (37/225) were RT-PCR-positive. Cycle threshold values were similar among RT-PCR-positive specimens from children and adults (22.5 vs 21.3, P = .46) and among specimens from symptomatic and asymptomatic children (22.5 vs 23.2, P = .39). Sensitivity of antigen test compared to RT-PCR was 73.0% (27/37) among specimens from children and 80.8% (240/297) among specimens from adults; among specimens from children, specificity was 100% (188/188), positive and negative predictive values were 100% (27/27) and 94.9% (188/198), respectively. Virus was isolated from 51.4% (19/37) of RT-PCR-positive pediatric specimens; all 19 had positive antigen test results. CONCLUSIONS: With lower sensitivity relative to RT-PCR, antigen tests may not diagnose all positive COVID-19 cases; however, antigen testing identified children with live SARS-CoV-2 virus.

Performance of Repeat BinaxNOW Severe Acute Respiratory Syndrome Coronavirus 2 Antigen Testing in a Community Setting, Wisconsin, November 2020-December 2020.

Repeating the BinaxNOW antigen test for severe acute respiratory syndrome coronavirus 2 using 2 groups of readers within 30 minutes resulted in high concordance (98.9%) in 2110 encounters. Same-day repeat antigen testing did not significantly improve test sensitivity (77.2% to 81.4%) while specificity remained high (99.6%).

Shedding of Culturable Virus, Seroconversion, and 6-Month Follow-up Antibody Responses in the First 14 Confirmed Cases of Coronavirus Disease 2019 in the United States.

We aimed to characterize presence of culturable virus in clinical specimens during acute illness, and antibody kinetics up to 6 months after symptom onset, among 14 early patients with coronavirus disease 2019 in the United States. We isolated viable severe acute respiratory syndrome coronavirus 2 from real-time reverse-transcription polymerase chain reaction-positive respiratory specimens collected during days 0-8 after onset, but not after. All 13 patients with 2 or more serum specimens developed anti-spike antibodies; 12 developed detectable neutralizing antibodies. We did not isolate virus after detection of neutralizing antibodies. Eight participants provided serum at 6 months after onset; all retained detectable anti-spike immunoglobulin G, and half had detectable neutralizing antibodies. Two participants reported not feeling fully recovered at 6 months.

Climate predicts geographic and temporal variation in mosquito-borne disease dynamics on two continents.

Climate drives population dynamics through multiple mechanisms, which can lead to seemingly context-dependent effects of climate on natural populations. For climate-sensitive diseases, such as dengue, chikungunya, and Zika, climate appears to have opposing effects in different contexts. Here we show that a model, parameterized with laboratory measured climate-driven mosquito physiology, captures three key epidemic characteristics across ecologically and culturally distinct settings in Ecuador and Kenya: the number, timing, and duration of outbreaks. The model generates a range of disease dynamics consistent with observed Aedes aegypti abundances and laboratory-confirmed arboviral incidence with variable accuracy (28-85% for vectors, 44-88% for incidence). The model predicted vector dynamics better in sites with a smaller proportion of young children in the population, lower mean temperature, and homes with piped water and made of cement. Models with limited calibration that robustly capture climate-virus relationships can help guide intervention efforts and climate change disease projections.

No Evidence of O'nyong-nyong Viremia among Children with Febrile Illness in Kenya (2015-2018).

O'nyong-nyong virus (ONNV) is a little-known arbovirus causing intermittent, yet explosive, outbreaks in Africa. It is closely related to chikungunya virus, an emerging infectious disease. O'nyong-nyong virus causes a self-limited illness characterized by bilateral polyarthritis, rash, low-grade fever, and lymphadenopathy. In 1959, an extensive outbreak of ONNV occurred in East Africa, and decades later, another large outbreak was documented in Uganda in 1996. Limited evidence for interepidemic transmission is available, although serologic studies indicate a high prevalence of exposure. 1,045 febrile child participants in western and coastal Kenya were tested for the presence of ONNV using a multiplexed real-time reverse transcriptase-PCR assay. More than half of the participants had malaria parasitemia, and there was no evidence of active ONNV viremia in these participants. Further work is required to better understand the interepidemic circulation of ONNV and to reconcile evidence of high serologic exposure to ONNV among individuals in East Africa.

High Dengue Burden and Circulation of 4 Virus Serotypes among Children with Undifferentiated Fever, Kenya, 2014-2017.

Little is known about the extent and serotypes of dengue viruses circulating in Africa. We evaluated the presence of dengue viremia during 4 years of surveillance (2014-2017) among children with febrile illness in Kenya. Acutely ill febrile children were recruited from 4 clinical sites in western and coastal Kenya, and 1,022 participant samples were tested by using a highly sensitive real-time reverse transcription PCR. A complete case analysis with genomic sequencing and phylogenetic analyses was conducted to characterize the presence of dengue viremia among participants during 2014-2017. Dengue viremia was detected in 41.9% (361/862) of outpatient children who had undifferentiated febrile illness in Kenya. Of children with confirmed dengue viremia, 51.5% (150/291) had malaria parasitemia. All 4 dengue virus serotypes were detected, and phylogenetic analyses showed several viruses from novel lineages. Our results suggests high levels of dengue virus infection among children with undifferentiated febrile illness in Kenya.

Climate change could shift disease burden from malaria to arboviruses in Africa.

Malaria is a long-standing public health problem in sub-Saharan Africa, whereas arthropod-borne viruses (arboviruses) such as dengue and chikungunya cause an under-recognised burden of disease. Many human and environmental drivers affect the dynamics of vector-borne diseases. In this Personal View, we argue that the direct effects of warming temperatures are likely to promote greater environmental suitability for dengue and other arbovirus transmission by Aedes aegypti and reduce suitability for malaria transmission by Anopheles gambiae. Environmentally driven changes in disease dynamics will be complex and multifaceted, but given that current public efforts are targeted to malaria control, we highlight Ae aegypti and dengue, chikungunya, and other arboviruses as potential emerging public health threats in sub-Saharan Africa.