Comparison of Influenza and Coronavirus Disease 2019-Associated Hospitalizations Among Children Younger Than 18 Years Old in the United States: FluSurv-NET (October-April 2017-2021) and COVID-NET (October 2020-September 2021).

BACKGROUND: Influenza virus and SARS-CoV-2 are significant causes of respiratory illness in children. METHODS: Influenza- and COVID-19-associated hospitalizations among children <18 years old were analyzed from FluSurv-NET and COVID-NET, 2 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 (1 October 2020-30 September 2021) was compared with influenza-associated hospitalization rates during the 2017-2018 through 2019-2020 influenza seasons. In-hospital outcomes, including intensive care unit (ICU) admission and death, were compared. RESULTS: Among children <18 years, the COVID-19-associated hospitalization rate (48.2) was higher than influenza-associated hospitalization rates: 2017-2018 (33.5), 2018-2019 (33.8), and 2019-2020 (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, a higher proportion with COVID-19 required ICU admission compared with influenza (26.4% vs 21.6%; P < .01). Pediatric deaths were uncommon during both COVID-19- and influenza-associated hospitalizations (0.7% vs 0.5%; P = .28). CONCLUSIONS: In 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 compared with influenza during the 3 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.

Factors Associated with Severe Outcomes Among Immunocompromised Adults Hospitalized for COVID-19 - COVID-NET, 10 States, March 2020-February 2022.

Immunocompromised persons are at increased risk for severe COVID-19-related outcomes, including intensive care unit (ICU) admission and death (1). Data on adults aged ≥18 years hospitalized with laboratory-confirmed COVID-19 from 10 U.S. states in the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) were analyzed to assess associations between immunocompromise and ICU admission and in-hospital death during March 1, 2020-February 28, 2022. Associations of COVID-19 vaccination status with ICU admission and in-hospital death were also examined during March 1, 2021-February 28, 2022. During March 1, 2020-February 28, 2022, among a sample of 22,345 adults hospitalized for COVID-19, 12.2% were immunocompromised. Among unvaccinated patients, those with immunocompromise had higher odds of ICU admission (adjusted odds ratio [aOR] = 1.26; 95% CI = 1.08-1.49) and in-hospital death (aOR = 1.34; 95% CI = 1.05-1.70) than did nonimmunocompromised patients. Among vaccinated patients,* those with immunocompromise had higher odds of ICU admission (aOR = 1.40; 95% CI = 1.01-1.92) and in-hospital death (aOR = 1.87; 95% CI = 1.28-2.75) than did nonimmunocompromised patients. During March 1, 2021-February 28, 2022, among nonimmunocompromised patients, patients who were vaccinated had lower odds of death (aOR = 0.58; 95% CI = 0.39-0.86) than did unvaccinated patients; among immunocompromised patients, odds of death between vaccinated and unvaccinated patients did not differ. Immunocompromised persons need additional protection from COVID-19 and using multiple known COVID-19 prevention strategies,† including nonpharmaceutical interventions, up-to-date vaccination of immunocompromised persons and their close contacts,§ early testing, and COVID-19 prophylactic (Evusheld) and early antiviral treatment,¶ can help prevent hospitalization and subsequent severe COVID-19 outcomes among immunocompromised persons.

Laboratory-Confirmed COVID-19-Associated Hospitalizations Among Adults During SARS-CoV-2 Omicron BA.2 Variant Predominance - COVID-19-Associated Hospitalization Surveillance Network, 14 States, June 20, 2021-May 31, 2022.

Beginning the week of March 20­26, 2022, the Omicron BA.2 variant of SARS-CoV-2, the virus that causes COVID-19, became the predominant circulating variant in the United States, accounting for >50% of sequenced isolates.* Data from the COVID-19­Associated Hospitalization Surveillance Network (COVID-NET) were analyzed to describe recent COVID-19­associated hospitalization rates among adults aged ≥18 years during the period coinciding with BA.2 predominance (BA.2 period [Omicron BA.2 and BA.2.12.1; March 20­May 31, 2022]). Weekly hospitalization rates (hospitalizations per 100,000 population) among adults aged ≥65 years increased threefold, from 6.9 (week ending April 2, 2022) to 27.6 (week ending May 28, 2022); hospitalization rates in adults aged 18­49 and 50­64 years both increased 1.7-fold during the same time interval. Hospitalization rates among unvaccinated adults were 3.4 times as high as those among vaccinated adults. Among hospitalized nonpregnant patients in this same period, 39.1% had received a primary vaccination series and 1 booster or additional dose; 5.0% had received a primary series and ≥2 boosters or additional doses. All adults should stay up to date† with COVID-19 vaccination, and multiple nonpharmaceutical and medical prevention measures should be used to protect those at high risk for severe COVID-19 illness, irrespective of vaccination status§ (1).Beginning the week of March 20­26, 2022, the Omicron BA.2 variant of SARS-CoV-2, the virus that causes COVID-19, became the predominant circulating variant in the United States, accounting for >50% of sequenced isolates.* Data from the COVID-19­Associated Hospitalization Surveillance Network (COVID-NET) were analyzed to describe recent COVID-19­associated hospitalization rates among adults aged ≥18 years during the period coinciding with BA.2 predominance (BA.2 period [Omicron BA.2 and BA.2.12.1; March 20­May 31, 2022]). Weekly hospitalization rates (hospitalizations per 100,000 population) among adults aged ≥65 years increased threefold, from 6.9 (week ending April 2, 2022) to 27.6 (week ending May 28, 2022); hospitalization rates in adults aged 18­49 and 50­64 years both increased 1.7-fold during the same time interval. Hospitalization rates among unvaccinated adults were 3.4 times as high as those among vaccinated adults. Among hospitalized nonpregnant patients in this same period, 39.1% had received a primary vaccination series and 1 booster or additional dose; 5.0% had received a primary series and ≥2 boosters or additional doses. All adults should stay up to date† with COVID-19 vaccination, and multiple nonpharmaceutical and medical prevention measures should be used to protect those at high risk for severe COVID-19 illness, irrespective of vaccination status§ (1).

Hospitalizations of Children Aged 5-11 Years with Laboratory-Confirmed COVID-19 - COVID-NET, 14 States, March 2020-February 2022.

On October 29, 2021, the Food and Drug Administration expanded the Emergency Use Authorization for Pfizer-BioNTech COVID-19 vaccine to children aged 5-11 years; CDC's Advisory Committee on Immunization Practices' recommendation followed on November 2, 2021.* In late December 2021, the B.1.1.529 (Omicron) variant of SARS-CoV-2 (the virus that causes COVID-19) became the predominant strain in the United States,† coinciding with a rapid increase in COVID-19-associated hospitalizations among all age groups, including children aged 5-11 years (1). COVID-19-Associated Hospitalization Surveillance Network (COVID-NET)§ data were analyzed to describe characteristics of COVID-19-associated hospitalizations among 1,475 U.S. children aged 5-11 years throughout the pandemic, focusing on the period of early Omicron predominance (December 19, 2021-February 28, 2022). Among 397 children hospitalized during the Omicron-predominant period, 87% were unvaccinated, 30% had no underlying medical conditions, and 19% were admitted to an intensive care unit (ICU). The cumulative hospitalization rate during the Omicron-predominant period was 2.1 times as high among unvaccinated children (19.1 per 100,000 population) as among vaccinated¶ children (9.2).** Non-Hispanic Black (Black) children accounted for the largest proportion of unvaccinated children (34%) and represented approximately one third of COVID-19-associated hospitalizations in this age group. Children with diabetes and obesity were more likely to experience severe COVID-19. The potential for serious illness among children aged 5-11 years, including those with no underlying health conditions, highlights the importance of vaccination among this age group. Increasing vaccination coverage among children, particularly among racial and ethnic minority groups disproportionately affected by COVID-19, is critical to preventing COVID-19-associated hospitalization and severe outcomes.

Hospitalization of Infants and Children Aged 0-4 Years with Laboratory-Confirmed COVID-19 - COVID-NET, 14 States, March 2020-February 2022.

The B.1.1.529 (Omicron) variant of SARS-CoV-2, the virus that causes COVID-19, has been the predominant circulating variant in the United States since late December 2021.* Coinciding with increased Omicron circulation, COVID-19-associated hospitalization rates increased rapidly among infants and children aged 0-4 years, a group not yet eligible for vaccination (1). Coronavirus Disease 19-Associated Hospitalization Surveillance Network (COVID-NET)† data were analyzed to describe COVID-19-associated hospitalizations among U.S. infants and children aged 0-4 years since March 2020. During the period of Omicron predominance (December 19, 2021-February 19, 2022), weekly COVID-19-associated hospitalization rates per 100,000 infants and children aged 0-4 years peaked at 14.5 (week ending January 8, 2022); this Omicron-predominant period peak was approximately five times that during the period of SARS-CoV-2 B.1.617.2 (Delta) predominance (June 27-December 18, 2021, which peaked the week ending September 11, 2021).§ During Omicron predominance, 63% of hospitalized infants and children had no underlying medical conditions; infants aged <6 months accounted for 44% of hospitalizations, although no differences were observed in indicators of severity by age. Strategies to prevent COVID-19 among infants and young children are important and include vaccination among currently eligible populations (2) such as pregnant women (3), family members, and caregivers of infants and young children (4).

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.*.

Hospitalizations Associated with COVID-19 Among Children and Adolescents - COVID-NET, 14 States, March 1, 2020-August 14, 2021.

Although COVID-19-associated hospitalizations and deaths have occurred more frequently in adults,† COVID-19 can also lead to severe outcomes in children and adolescents (1,2). Schools are opening for in-person learning, and many prekindergarten children are returning to early care and education programs during a time when the number of COVID-19 cases caused by the highly transmissible B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, is increasing.§ Therefore, it is important to monitor indicators of severe COVID-19 among children and adolescents. This analysis uses Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET)¶ data to describe COVID-19-associated hospitalizations among U.S. children and adolescents aged 0-17 years. During March 1, 2020-August 14, 2021, the cumulative incidence of COVID-19-associated hospitalizations was 49.7 per 100,000 children and adolescents. The weekly COVID-19-associated hospitalization rate per 100,000 children and adolescents during the week ending August 14, 2021 (1.4) was nearly five times the rate during the week ending June 26, 2021 (0.3); among children aged 0-4 years, the weekly hospitalization rate during the week ending August 14, 2021, was nearly 10 times that during the week ending June 26, 2021.** During June 20-July 31, 2021, the hospitalization rate among unvaccinated adolescents (aged 12-17 years) was 10.1 times higher than that among fully vaccinated adolescents. Among all hospitalized children and adolescents with COVID-19, the proportions with indicators of severe disease (such as intensive care unit [ICU] admission) after the Delta variant became predominant (June 20-July 31, 2021) were similar to those earlier in the pandemic (March 1, 2020-June 19, 2021). Implementation of preventive measures to reduce transmission and severe outcomes in children is critical, including vaccination of eligible persons, universal mask wearing in schools, recommended mask wearing by persons aged ≥2 years in other indoor public spaces and child care centers,†† and quarantining as recommended after exposure to persons with COVID-19.§§.

Extrapolating Sentinel Surveillance Information to Estimate National COVID Hospital Admission Rates: A Bayesian Modeling Approach.

The COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) was established in March 2020 to monitor trends in hospitalizations associated with SARS-CoV-2 infection. COVID-NET is a geographically diverse population-based surveillance system for laboratory-confirmed COVID-19-associated hospitalizations with a combined catchment area covering approximately 10% of the US population. Data collected in COVID-NET includes monthly counts of hospitalizations for persons with confirmed SARS-CoV-2 infection who reside within the defined catchment area. A Bayesian modeling approach is proposed to estimate US national COVID-associated hospital admission rates based on information reported in the COVID-NET system. A key component of the approach is the ability to estimate uncertainty resulting from extrapolation of hospitalization rates observed within COVID-NET to the US population. In addition, the proposed model enables estimation of other contributors to uncertainty including temporal dependence among reported COVID-NET admission counts, the impact of unmeasured site-specific factors, and the frequency and accuracy of testing for SARS-CoV-2 infection. Based on the proposed model, an estimated 6.3 million (95% uncertainty interval (UI) 5.4-7.3 million) COVID-19-associated hospital admissions occurred in the United States from September 2020 through December 2023. Between April 2020 and December 2023, model-based monthly admission rate estimates ranged from a minimum of 1 per 10,000 population (95% UI 0.7-1.2) in June of 2023 to a highest monthly level of 16 per 10,000 (95% UI 13-19) in January 2022.

Clinical Outcomes of US Adults Hospitalized for COVID-19 and Influenza in the Respiratory Virus Hospitalization Surveillance Network, October 2021-September 2022.

Severe outcomes were common among adults hospitalized for COVID-19 or influenza, while the percentage of COVID-19 hospitalizations involving critical care decreased from October 2021 to September 2022. During the Omicron BA.5 period, intensive care unit admission frequency was similar for COVID-19 and influenza, although patients with COVID-19 had a higher frequency of in-hospital death.

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.

Characteristics and treatment of hospitalized pregnant women with COVID-19.

BACKGROUND: Pregnant women less frequently receive COVID-19 vaccination and are at increased risk for adverse pregnancy outcomes from COVID-19. OBJECTIVE: This study aimed to first, describe the vaccination status, treatment, and outcomes of hospitalized, symptomatic pregnant women with COVID-19, and second, estimate whether treatment differs by pregnancy status among treatment-eligible (ie, requiring supplemental oxygen per National Institutes of Health guidelines at the time of the study) women. STUDY DESIGN: From January to November 2021, the COVID-19-Associated Hospitalization Surveillance Network completed medical chart abstraction for a probability sample of 2715 hospitalized women aged 15 to 49 years with laboratory-confirmed SARS-CoV-2 infection. Of these, 1950 women had symptoms of COVID-19 on admission, and 336 were pregnant. We calculated weighted prevalence estimates of demographic and clinical characteristics, vaccination status, and outcomes among pregnant women with symptoms of COVID-19 on admission. We used propensity score matching to estimate prevalence ratios and 95% confidence intervals of treatment-eligible patients who received remdesivir or systemic steroids by pregnancy status. RESULTS: Among 336 hospitalized pregnant women with symptomatic COVID-19, 39.6% were non-Hispanic Black, 24.8% were Hispanic or Latino, and 61.9% were aged 25 to 34 years. Among those with known COVID-19 vaccination status, 92.9% were unvaccinated. One-third (32.7%) were treatment-eligible. Among treatment-eligible pregnant women, 74.1% received systemic steroids and 61.4% received remdesivir. Among those that were no longer pregnant at discharge (n=180), 5.4% had spontaneous abortions and 3.5% had stillbirths. Of the 159 live births, 29.0% were preterm. Among a propensity score-matched cohort of treatment-eligible hospitalized women of reproductive age, pregnant women were less likely than nonpregnant women to receive remdesivir (prevalence ratio, 0.82; 95% confidence interval, 0.69-0.97) and systemic steroids (prevalence ratio, 0.80; 95% confidence interval, 0.73-0.87). CONCLUSION: Most hospitalized pregnant patients with symptomatic COVID-19 were unvaccinated. Hospitalized pregnant patients were less likely to receive recommended remdesivir and systemic steroids compared with similar hospitalized nonpregnant women. Our results underscore the need to identify opportunities for improving COVID-19 vaccination, implementation of treatment of pregnant women, and the inclusion of pregnant women in clinical trials.

Orthopoxvirus pan-genomic DNA assay.

A genome-spanning assay is described that enables laboratory confirmation of infections with orthopoxviruses (OPVs), particularly Vaccinia, Monkeypox, and Variola viruses, which can cause vesiculo-pustular rash illnesses in humans. The assay uses a series of polymerase chain reaction (PCR) amplicons that overlap to span the approximately 200kilobase pair linear DNA genome of OPVs. Corresponding amplicons of different viral isolates can then be compared by matching their restriction fragment length polymorphism (RFLP) gel electrophoresis patterns. The PCR step does not necessarily require viral growth to produce sufficient DNA for the RFLP comparisons. The assay would be useful as a prelude to sequencing entire or partial DNA genome regions of various OPVs, including natural or recombinant OPVs and potentially dangerous bioengineered OPVs designed to express foreign DNA or other viruses.

Identification of galectin-4 isoforms in porcine small intestine.

Lactose-binding proteins with molecular masses of 14-, 17-, 18-, 28-, and 34-kDa were identified in extracts from porcine small intestinal mucosa. Amino acid sequence analysis of peptides generated by CNBr cleavage of the 34-kDa protein, the most abundant of these proteins, identified this protein as porcine galectin-4. To determine if a porcine homolog of murine galectin-6 is expressed in small intestine, primers for a reverse transcriptase-polymerase chain reaction (RT-PCR) were developed that amplified across the linker region of galectin-4, which is the region that differs between murine galectins-4 and -6. Using these primers, this RT-PCR approach identified two galectin-4 isoforms that differed in the length of their linker region. The larger isoform, galectin-4.1, is nine amino acids longer in its linker region than the smaller isoform, galectin-4.2. Based on nucleotide sequence similarities, the two isoforms are likely splice variants of galectin-4 pre-mRNA and not products of separate genes like murine galectins-4 and -6.

Heterogeneity in Nsp2 of European-like porcine reproductive and respiratory syndrome viruses isolated in the United States.

Recently, isolates of porcine reproductive and respiratory syndrome virus (PRRSV) that possess nucleotide sequences similar to European isolates have been reported in United States herds. The origin, diversity and prevalence of European-like North American PRRSV isolates in the U.S. remain unknown. Nucleotide sequence analysis of the 12kb ORF1 of a North American isolate, SDPRRS 01-08 (01-08), showed 93.7% identity with Lelystad virus (LV), the prototypic European isolate, but only 58% identity with VR-2332, the prototypic North American isolate. Comparisons between LV and 01-08 at the peptide sequence level of the predicted non-structural proteins (Nsp) showed that Nsp9 (98.9% amino acid identity) was the most conserved and the least conserved was Nsp2 at 90.6% identity. For the purpose of comparison, GP5, the principal envelope structural protein, showed a 93.5% identity between 01-08 and LV. The most dramatic differences between the Nsp2 proteins of LV and 01-08 were a single 17 amino acid deletion between residues 734 and 750, as well as several amino acid differences. The same deletion was identified in the Nsp2 in five of seven other EuroPRRSV isolates submitted to the South Dakota Animal Disease Research and Diagnostic Laboratory. The remaining two isolates contained small deletions, but in other regions of Nsp2. Peptide sequence diversity in the form of hypervariability and deletions in Nsp2 demonstrate that European-like PRRSV isolates in the USA represent a heterogeneous group. Furthermore, areas in Nsp2 with deletions and amino acid hypervariability localize to regions that are predicted to be immunologically important.

Characterization of emerging European-like porcine reproductive and respiratory syndrome virus isolates in the United States.

European-like field isolates of porcine reproductive and respiratory syndrome virus (PRRSV) have recently emerged in North America. The full-length genomic sequence of an index isolate characterized in 1999, strain EuroPRRSV, served as the reference strain for further studies of the evolution and epidemiology of European-like isolates (type 1) in the United States. Strain EuroPRRSV shared 90.1 to 100% amino acid identity with the prototype European strain, Lelystad, within the structural and nonstructural open reading frames (ORFs) and 95.3% overall nucleotide identity. The 5' untranslated region and two nonstructural regions within ORF 1 were closely examined due to significant divergence from strain Lelystad. A 51-bp deletion in a region within ORF 1a, coding for nonstructural protein 2 (NSP2), was observed. Sequence analysis of the structural ORFs 2 to 7 of additional European-like isolates indicated that these isolates share 93% nucleotide identity with one another and 95 to 96% identity with the Lelystad strain but only 70% identity with the North American reference strain VR-2332. Phylogenetic analysis with published PRRSV ORF 3, 5, and 7 nucleotide sequences indicated that these newly emerging isolates form a clade with the Lelystad and United Kingdom PRRSV isolates. Detailed analysis of four of these isolates with a panel of 60 monoclonal antibodies directed against the structural proteins confirmed a recognition pattern that was more consistent with strain Lelystad than with other North American isolates.