Vaccine Effectiveness of Primary Series and Booster Doses against Omicron Variant COVID-19-Associated Hospitalization in the United States

Objectives: To compare the effectiveness of a primary COVID-19 vaccine series plus a booster dose with a primary series alone for the prevention of Omicron variant COVID-19 hospitalization. Design: Multicenter observational case-control study using the test-negative design to evaluate vaccine effectiveness (VE). Setting: Twenty-one hospitals in the United States (US). Participants: 3,181 adults hospitalized with an acute respiratory illness between December 26, 2021 and April 30, 2022, a period of SARS-CoV-2 Omicron variant (BA.1, BA.2) predominance. Participants included 1,572 (49%) case-patients with laboratory confirmed COVID-19 and 1,609 (51%) control patients who tested negative for SARS-CoV-2. Median age was 64 years, 48% were female, and 21% were immunocompromised; 798 (25%) were vaccinated with a primary series plus booster, 1,326 (42%) were vaccinated with a primary series alone, and 1,057 (33%) were unvaccinated. Main Outcome Measures: VE against COVID-19 hospitalization was calculated for a primary series plus a booster and a primary series alone by comparing the odds of being vaccinated with each of these regimens versus being unvaccinated among cases versus controls. VE analyses were stratified by immune status (immunocompetent; immunocompromised) because the recommended vaccine schedules are different for these groups. The primary analysis evaluated all COVID-19 vaccine types combined and secondary analyses evaluated specific vaccine products. Results: Among immunocompetent patients, VE against Omicron COVID-19 hospitalization for a primary series plus one booster of any vaccine product dose was 77% (95% CI: 71-82%), and for a primary series alone was 44% (95% CI: 31-54%) (p<0.001). VE was higher for a boosted regimen than a primary series alone for both mRNA vaccines used in the US (BNT162b2: primary series plus booster VE 80% (95% CI: 73-85%), primary series alone VE 46% (95% CI: 30-58%) [p<0.001]; mRNA-1273: primary series plus booster VE 77% (95% CI: 67-83%), primary series alone VE 47% (95% CI: 30-60%) [p<0.001]). Among immunocompromised patients, VE for a primary series of any vaccine product against Omicron COVID-19 hospitalization was 60% (95% CI: 41-73%). Insufficient sample size has accumulated to calculate effectiveness of boosted regimens for immunocompromised patients. Conclusions: Among immunocompetent people, a booster dose of COVID-19 vaccine provided additional benefit beyond a primary vaccine series alone for preventing COVID-19 hospitalization due to the Omicron variant.

SARS-CoV-2 virus dynamics in recently infected people - data from a household transmission study

We used daily real-time reverse-transcription polymerase chain reaction (rRT-PCR) results from 67 cases of SARS-CoV-2 infection in a household transmission study to examine the trajectory of cycle threshold (Ct) values, an inverse correlate of viral RNA concentration, from nasal specimens collected between April 2020 and May 2021. Ct values varied over the course of infection, across RT-PCR platforms, and by participant age. Specimens collected from children and adolescents showed higher Ct values and adults aged [≥]50 years showed lower Ct values than adults aged 18-49 years. Ct values were lower on days when participants reported experiencing symptoms.

Comparison of influenza and COVID-19-associated hospitalizations among children < 18 years old in the United States - FluSurv-NET (October-April 2017-2021) and COVID-NET (October 2020-September 2021)

BackgroundInfluenza virus and SARS-CoV-2 are significant causes of respiratory illness in children. MethodsInfluenza and COVID-19-associated hospitalizations among children <18 years old were analyzed from FluSurv-NET and COVID-NET, two population-based surveillance systems with similar catchment areas and methodology. The annual COVID-19-associated hospitalization rate per 100 000 during the ongoing COVID-19 pandemic (October 1, 2020-September 30, 2021) was compared to influenza-associated hospitalization rates during the 2017-18 through 2019-20 influenza seasons. In-hospital outcomes, including intensive care unit (ICU) admission and death, were compared. ResultsAmong children <18 years old, the COVID-19-associated hospitalization rate (48.2) was higher than influenza-associated hospitalization rates: 2017-18 (33.5), 2018-19 (33.8), and 2019-20 (41.7). The COVID-19-associated hospitalization rate was higher among adolescents 12-17 years old (COVID-19: 59.9; influenza range: 12.2-14.1), but similar or lower among children 5-11 (COVID-19: 25.0; influenza range: 24.3-31.7) and 0-4 (COVID-19: 66.8; influenza range: 70.9-91.5) years old. Among children <18 years old, a higher proportion with COVID-19 required ICU admission compared with influenza (26.4% vs 21.6%; p<0.01). Pediatric deaths were uncommon during both COVID-19- and influenza-associated hospitalizations (0.7% vs 0.5%; p=0.28). ConclusionsIn the setting of extensive mitigation measures during the COVID-19 pandemic, the annual COVID-19-associated hospitalization rate during 2020-2021 was higher among adolescents and similar or lower among children <12 years old compared with influenza during the three seasons before the COVID-19 pandemic. COVID-19 adds substantially to the existing burden of pediatric hospitalizations and severe outcomes caused by influenza and other respiratory viruses. SummaryAnnual hospitalization rates and proportions of hospitalized children experiencing severe outcomes were as high or higher for COVID-19 during October 2020-September 2021 compared with influenza during the three seasons before the COVID-19 pandemic, based on U.S. population-based surveillance data.

Surveillance and correlation of SARS-CoV-2 viral RNA, antigen, virus isolation, and self-reported symptoms in a longitudinal study with daily sampling

The novel coronavirus pandemic incited unprecedented demand for assays that detect viral nucleic acids, viral proteins, and corresponding antibodies. The 320 molecular diagnostics in receipt of FDA emergency use authorization mainly focus on viral detection; however, no currently approved test can be used to infer infectiousness, i.e., the presence of replicable virus. As the number of tests conducted increased, persistent SARS-CoV-2 RNA positivity by RT-PCR in some individuals led to concerns over quarantine guidelines. To this end, we attempted to design an assay that reduces the frequency of positive test results from individuals who do not shed culturable virus. We describe multiplex quantitative RT-PCR (qRT-PCR) assays that detect genomic RNA (gRNA) and subgenomic RNA (sgRNA) species of SARS-CoV-2, including spike (S), nucleocapsid (N), membrane (M), envelope (E), and ORF8. The absolute copy number of each RNA target was determined in longitudinal specimens from a household transmission study. Calculated viral RNA levels over the 14-day follow up period were compared with antigen testing and self-reported symptoms to characterize the clinical and molecular dynamics of infection and infer predictive values of these qRT-PCR assays relative to culture isolation. When detection of sgS RNA was added to the CDC 2019-Novel Coronavirus Real-Time RT-PCR Diagnostic Panel, we found a qRT-PCR positive result was 98% predictive of a positive culture (negative predictive value was 94%). Our findings suggest sgRNA presence correlates with active infection, may help identify individuals shedding culturable virus, and that similar multiplex assays can be adapted to current and future variants.

COVID-19-associated hospitalizations among vaccinated and unvaccinated adults >=18 years - COVID-NET, 13 states, January 1 - July 24, 2021

BackgroundAs of August 21, 2021, >60% of the U.S. population aged [≥]18 years were fully vaccinated with vaccines highly effective in preventing hospitalization due to Coronavirus Disease-2019 (COVID-19). Infection despite full vaccination (vaccine breakthrough) has been reported, but characteristics of those with vaccine breakthrough resulting in hospitalization and relative rates of hospitalization in unvaccinated and vaccinated persons are not well described, including during late June and July 2021 when the highly transmissible Delta variant predominated. MethodsFrom January 1-June 30, 2021, cases defined as adults aged [≥]18 years with laboratory-confirmed Severe Acute Respiratory Coronavirus-2 (SARS-CoV-2) infection were identified from >250 acute care hospitals in the population-based COVID-19-Associated Hospitalization Surveillance Network (COVID-NET). Through chart review for sampled cases, we examine characteristics associated with vaccination breakthrough. From January 24-July 24, 2021, state immunization information system data linked to both >37,000 cases representative cases and the defined surveillance catchment area population were used to compare weekly hospitalization rates in vaccinated and unvaccinated individuals. Unweighted case counts and weighted percentages are presented. ResultsFrom January 1 - June 30, 2021, fully vaccinated cases increased from 1 (0.01%) to 321 (16.1%) per month. Among 4,732 sampled cases, fully vaccinated persons admitted with COVID-19 were older compared with unvaccinated persons (median age 73 years [Interquartile Range (IQR) 65-80] v. 59 years [IQR 48-70]; p<0.001), more likely to have 3 or more underlying medical conditions (201 (70.8%) v. 2,305 (56.1%), respectively; p<0.001) and be residents of long-term care facilities [37 (14.5%) v. 146 (5.5%), respectively; p<0.001]. From January 24 - July 24, 2021, cumulative hospitalization rates were 17 times higher in unvaccinated persons compared with vaccinated persons (423 cases per 100,000 population v. 26 per 100,000 population, respectively); rate ratios were 23, 22 and 13 for those aged 18-49, 50-64, and [≥]65 years respectively. For June 27 - July 24, hospitalization rates were [≥]10 times higher in unvaccinated persons compared with vaccinated persons for all age groups across all weeks. ConclusionPopulation-based hospitalization rates show that unvaccinated adults aged [≥]18 years are 17 times more likely to be hospitalized compared with vaccinated adults. Rates are far higher in unvaccinated persons in all adult age groups, including during a period when the Delta variant was the predominant strain of the SARS-CoV-2 virus. Vaccines continue to play a critical role in preventing serious COVID-19 illness and remain highly effective in preventing COVID-19 hospitalizations.

Household Transmission and Clinical Features of SARS-CoV-2 Infections by Age in 2 US Communities

OBJECTIVESExamine age differences in SARS-CoV-2 transmission risk from primary cases and infection risk among household contacts, and symptoms among those with SARS-CoV-2 infection. METHODSPeople with SARS-CoV-2 infection in Nashville, Tennessee and central and western Wisconsin and their household contacts were followed daily for 14 days to ascertain symptoms and secondary transmission events. Households were enrolled between April 2020 and April 2021. Secondary infection risks (SIR) by age of the primary case and contacts were estimated using generalized estimating equations. RESULTSThe 226 primary cases were followed by 198 (49%) secondary SARS-CoV-2 infections among 404 household contacts. Age group-specific SIR among contacts ranged from 36% to 53%, with no differences by age. SIR was lower from primary cases aged 12-17 years than from primary cases 18-49 years (risk ratio [RR] 0.42; 95% confidence interval [CI] 0.19-0.91). SIR was 55% and 45%, respectively, among primary case-contact pairs in the same versus different age group (RR 1.47; 95% CI 0.98-2.22). SIR was highest among primary case-contacts pairs aged [≥]65 years (76%) and 5-11 years (69%). Among secondary SARS-CoV-2 infections, 19% were asymptomatic; there was no difference in the frequency of asymptomatic infections by age group. CONCLUSIONSBoth children and adults can transmit and are susceptible to SARS-CoV-2 infection. SIR did not vary by age, but further research is needed to understand age-related differences in probability of transmission from primary cases by age.

Effectiveness of SARS-CoV-2 mRNA Vaccines for Preventing Covid-19 Hospitalizations in the United States

BackgroundAs SARS-CoV-2 vaccination coverage increases in the United States (US), there is a need to understand the real-world effectiveness against severe Covid-19 and among people at increased risk for poor outcomes. MethodsIn a multicenter case-control analysis of US adults hospitalized March 11 - May 5, 2021, we evaluated vaccine effectiveness to prevent Covid-19 hospitalizations by comparing odds of prior vaccination with an mRNA vaccine (Pfizer-BioNTech or Moderna) between cases hospitalized with Covid-19 and hospital-based controls who tested negative for SARS-CoV-2. ResultsAmong 1210 participants, median age was 58 years, 22.8% were Black, 13.8% were Hispanic, and 20.6% had immunosuppression. SARS-CoV-2 lineage B.1.1.7 was most common variant (59.7% of sequenced viruses). Full vaccination (receipt of two vaccine doses [≥]14 days before illness onset) had been received by 45/590 (7.6%) cases and 215/620 (34.7%) controls. Overall vaccine effectiveness was 86.9% (95% CI: 80.4 to 91.2%). Vaccine effectiveness was similar for Pfizer-BioNTech and Moderna vaccines, and highest in adults aged 18-49 years (97.3%; 95% CI: 78.9 to 99.7%). Among 45 patients with vaccine-breakthrough Covid hospitalizations, 44 (97.8%) were [≥]50 years old and 20 (44.4%) had immunosuppression. Vaccine effectiveness was lower among patients with immunosuppression (59.2%; 95% CI: 11.9 to 81.1%) than without immunosuppression (91.3%; 95% CI: 85.5 to 94.7%). ConclusionDuring March-May 2021, SARS-CoV-2 mRNA vaccines were highly effective for preventing Covid-19 hospitalizations among US adults. SARS-CoV-2 vaccination was beneficial for patients with immunosuppression, but effectiveness was lower in the immunosuppressed population.

Clinical Trends Among U.S. Adults Hospitalized with COVID-19, March-December 2020

BackgroundThe COVID-19 pandemic has caused substantial morbidity and mortality. ObjectivesTo describe monthly demographic and clinical trends among adults hospitalized with COVID-19. DesignPooled cross-sectional. Setting99 counties within 14 states participating in the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET). PatientsU.S. adults (aged [≥]18 years) hospitalized with laboratory-confirmed COVID-19 during March 1-December 31, 2020. MeasurementsMonthly trends in weighted percentages of interventions and outcomes including length of stay (LOS), intensive care unit admissions (ICU), invasive mechanical ventilation (IMV), vasopressor use and in-hospital death (death). Monthly hospitalization, ICU and death rates per 100,000 population. ResultsAmong 116,743 hospitalized adults, median age was 62 years. Among 18,508 sampled adults, median LOS decreased from 6.4 (March) to 4.6 days (December). Remdesivir and systemic corticosteroid use increased from 1.7% and 18.9% (March) to 53.8% and 74.2% (December), respectively. Frequency of ICU decreased from 37.8% (March) to 20.5% (December). IMV (27.8% to 8.7%), vasopressors (22.7% to 8.8%) and deaths (13.9% to 8.7%) decreased from March to October; however, percentages of these interventions and outcomes remained stable or increased in November and December. Percentage of deaths significantly decreased over time for non-Hispanic White patients (p-value <0.01) but not non-Hispanic Black or Hispanic patients. Rates of hospitalization (105.3 per 100,000), ICU (20.2) and death (11.7) were highest during December. LimitationsCOVID-NET covers approximately 10% of the U.S. population; findings may not be generalizable to the entire country. ConclusionsAfter initial improvement during April-October 2020, trends in interventions and outcomes worsened during November-December, corresponding with the 3rd peak of the U.S. pandemic. These data provide a longitudinal assessment of trends in COVID-19-associated outcomes prior to widespread COVID-19 vaccine implementation.

Risk Factors for COVID-19-associated hospitalization: COVID-19-Associated Hospitalization Surveillance Network and Behavioral Risk Factor Surveillance System

BackgroundIdentification of risk factors for COVID-19-associated hospitalization is needed to guide prevention and clinical care. ObjectiveTo examine if age, sex, race/ethnicity, and underlying medical conditions is independently associated with COVID-19-associated hospitalizations. DesignCross-sectional. Setting70 counties within 12 states participating in the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET) and a population-based sample of non-hospitalized adults residing in the COVID-NET catchment area from the Behavioral Risk Factor Surveillance System. ParticipantsU.S. community-dwelling adults ([≥]18 years) with laboratory-confirmed COVID-19-associated hospitalizations, March 1- June 23, 2020. MeasurementsAdjusted rate ratios (aRR) of hospitalization by age, sex, race/ethnicity and underlying medical conditions (hypertension, coronary artery disease, history of stroke, diabetes, obesity [BMI [≥]30 kg/m2], severe obesity [BMI[≥]40 kg/m2], chronic kidney disease, asthma, and chronic obstructive pulmonary disease). ResultsOur sample included 5,416 adults with COVID-19-associated hospitalizations. Adults with (versus without) severe obesity (aRR:4.4; 95%CI: 3.4, 5.7), chronic kidney disease (aRR:4.0; 95%CI: 3.0, 5.2), diabetes (aRR:3.2; 95%CI: 2.5, 4.1), obesity (aRR:2.9; 95%CI: 2.3, 3.5), hypertension (aRR:2.8; 95%CI: 2.3, 3.4), and asthma (aRR:1.4; 95%CI: 1.1, 1.7) had higher rates of hospitalization, after adjusting for age, sex, and race/ethnicity. In models adjusting for the presence of an individual underlying medical condition, higher hospitalization rates were observed for adults [≥]65 years, 45-64 years (versus 18-44 years), males (versus females), and non-Hispanic black and other race/ethnicities (versus non-Hispanic whites). LimitationsInterim analysis limited to hospitalizations with underlying medical condition data. ConclusionOur findings elucidate groups with higher hospitalization risk that may benefit from targeted preventive and therapeutic interventions.

Interim Analysis of Risk Factors for Severe Outcomes among a Cohort of Hospitalized Adults Identified through the U.S. Coronavirus Disease 2019 (COVID-19)-Associated Hospitalization Surveillance Network (COVID-NET)

BackgroundAs of May 15, 2020, the United States has reported the greatest number of coronavirus disease 2019 (COVID-19) cases and deaths globally. ObjectiveTo describe risk factors for severe outcomes among adults hospitalized with COVID-19. DesignCohort study of patients identified through the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network. Setting154 acute care hospitals in 74 counties in 13 states. Patients2491 patients hospitalized with laboratory-confirmed COVID-19 during March 1-May 2, 2020. MeasurementsAge, sex, race/ethnicity, and underlying medical conditions. ResultsNinety-two percent of patients had [≥]1 underlying condition; 32% required intensive care unit (ICU) admission; 19% invasive mechanical ventilation; 15% vasopressors; and 17% died during hospitalization. Independent factors associated with ICU admission included ages 50-64, 65-74, 75-84 and [≥]85 years versus 18-39 years (adjusted risk ratio (aRR) 1.53, 1.65, 1.84 and 1.43, respectively); male sex (aRR 1.34); obesity (aRR 1.31); immunosuppression (aRR 1.29); and diabetes (aRR 1.13). Independent factors associated with in-hospital mortality included ages 50-64, 65-74, 75-84 and [≥]85 years versus 18-39 years (aRR 3.11, 5.77, 7.67 and 10.98, respectively); male sex (aRR 1.30); immunosuppression (aRR 1.39); renal disease (aRR 1.33); chronic lung disease (aRR 1.31); cardiovascular disease (aRR 1.28); neurologic disorders (aRR 1.25); and diabetes (aRR 1.19). Race/ethnicity was not associated with either ICU admission or death. LimitationData were limited to patients who were discharged or died in-hospital and had complete chart abstractions; patients who were still hospitalized or did not have accessible medical records were excluded. ConclusionIn-hospital mortality for COVID-19 increased markedly with increasing age. These data help to characterize persons at highest risk for severe COVID-19-associated outcomes and define target groups for prevention and treatment strategies. Funding SourceThis work was supported by grant CK17-1701 from the Centers of Disease Control and Prevention through an Emerging Infections Program cooperative agreement and by Cooperative Agreement Number NU38OT000297-02-00 awarded to the Council of State and Territorial Epidemiologists from the Centers for Disease Control and Prevention.