Clinical characteristics of COVID-19 in hospitalized children during the Omicron variant predominant period

IntroductionInformation regarding the clinical manifestations and outcomes of coronavirus disease 2019 (COVID-19) in children under the Omicron variant predominant period is still limited.MethodsA nationwide retrospective cohort study was conducted. Pediatric COVID-19 patients (<18 years of age) hospitalized between August 1, 2021 and March 31, 2022 were enrolled. Epidemiological and clinical characteristics between the Delta variant predominant period (August 1 to December 31, 2021) and the Omicron variant predominant period (January 1 to March 31, 2022) were compared.ResultsDuring the study period, 458 cases in the Delta predominant period and 389 cases in the Omicron predominant period were identified. Median age was younger (6.0 vs. 8.0 years, P = 0.004) and underlying diseases were more common (n = 65, 16.7% vs. n = 53, 11.6%) in the Omicron predominant period than those in the Delta variant predominant era. For clinical manifestations, fever ≥38.0 °C at 2 to <13 years old, sore throat at ≥ 13 years, and seizures at 2 to <13 years old were more commonly observed, and dysgeusia and olfactory dysfunction at ≥ 6 years old were less commonly observed in the Omicron variant predominant period. The number of patients requiring noninvasive oxygen support was higher in the Omicron predominant period than that in the Delta predominant period; however, intensive care unit admission rates were similar and no patients died in both periods.ConclusionsIn the Omicron variant predominant period, more pediatric COVID-19 patients experienced fever and seizures, although the overall outcomes were still favorable.     

Effectiveness of Monoclonal Antibodies in Preventing Severe COVID-19 With Emergence of the Delta Variant

Anti-spike monoclonal antibodies have proven invaluable in preventing severe outcomes from COVID-19, including hospitalization and death. The rise of the SARS-CoV-2 delta variant begs the question of whether monoclonal antibodies maintain similar efficacy now as they had when the alpha and beta variants predominated, when they were first assessed and approved. We used a retrospective cohort to compare rates of severe outcomes in an epoch in which alpha and beta were predominant compared with delta. A total of 5356 patients were infused during the alpha/beta variant–predominant (n=4874) and delta variant–predominant (n=482) era. Overall, odds of severe infection were 3.0% of patients in the alpha/beta-predominant era compared with 4.9% in the delta-predominant cohort. The unadjusted odds ratio (OR) was higher for severe disease in the delta era (OR, 1.67; 95% CI, 0.96 to 2.89), particularly when adjusted for Charlson Comorbidity Index (adjusted OR, 2.04; 95% CI, 1.30 to 3.08). The higher odds of severe infection could be due to a more virulent delta variant, although the possibility of decreased anti-spike monoclonal antibody effectiveness in the clinical setting cannot be excluded. Research into the most effective strategies for using and improving anti-spike monoclonals for the treatment of emerging variants is warranted.     

Clinical characteristics and prognosis of immunosuppressed inpatients with COVID-19 in Japan

IntroductionWe aimed to analyze the clinical characteristics and outcomes of immunosuppressed inpatients with coronavirus disease 2019 (COVID-19).MethodsIn this observational study, we utilized a large nationwide registry of hospitalized patients with COVID-19 in Japan. Patients’ baseline characteristics and outcomes were compared according to the immunosuppressed states of the patients. The impact of different therapeutic agents on the clinical courses of the patients was evaluated.ResultsData of 14,760 patients were included, and 887 (5.9%) were immunosuppressed. The immunosuppressed state of the patient resulted from solid tumor (43.3%, n = 384), chemotherapy within 3 months (15.6%, n = 138), collagen disease (16.9%, n = 150), use of immunosuppressive agents (16.0%, n = 142), and metastatic solid tumor (13.5%, n = 120). Immunosuppressed patients were older and had a higher severity of illness at admission and during hospitalization than non-immunosuppressed patients. The mortality rates for major diseases causing immunosuppression were as follows: solid tumor, 12.5% (48/384; P < 0.001; relative risk [RR], 3.41); metastatic solid tumor, 31.7% (38/120; P < 0.001; RR, 8.43); leukemia, 23.1% (9/39; P < 0.001; RR, 5.87); lymphoma, 33.3% (20/60; P < 0.001; RR, 8.63); and collagen disease, 15.3% (23/150; P < 0.001; RR 3.97). Underlying diseases with high mortality rates were not necessarily associated with high rates of invasive supportive care.ConclusionsThe prognosis of immunosuppressed COVID-19 inpatients varied according to the different immunosuppressed states. Multiple factors, including the severity of the underlying diseases, might have affected their invasive supportive care indications.     

Immunochromatography and chemiluminescent enzyme immunoassay for COVID-19 diagnosis

IntroductionThe rapid and accurate detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is required to prevent the spread of COVID-19. This study evaluated the utility of two SARS-CoV-2 antigen detection methods.MethodsWe evaluated two types of antigen detection methods using immunochromatography (Espline) and quantitative chemiluminescent enzyme immunoassay (Lumipulse). RT-PCR was performed as a standard procedure for COVID-19 diagnosis. Lumipulse and RT-PCR were performed for all 486 nasopharyngeal swabs and 136 saliva samples, and the Espline test was performed for 271 nasopharyngeal swabs and 93 saliva samples.ResultsThe sensitivity and specificity of the Espline test were 10/11 and 260/260 (100%), respectively for the nasopharyngeal swabs and 3/9 and 84/84 (100%), respectively for the saliva samples. High sensitivities for both saliva (8/9) and nasopharyngeal swabs (22/24) were observed in the Lumipulse test. The specificities of the Lumipulse test for nasopharyngeal swabs and saliva samples were 460/462 (99.6%) and 123/127 (96.9%), respectively.ConclusionThe Espline test is not effective for saliva samples but is useful for simple and rapid COVID-19 tests using nasopharyngeal swabs because it does not require special devices. The Lumipulse test is a powerful high-throughput tool for COVID-19 diagnosis because it has high detection performance for nasopharyngeal swabs and saliva samples.     

Evidence-Based Strategies for Clinical Organizations to Address COVID-19 Vaccine Hesitancy

The success of vaccination programs is contingent upon irrefutable scientific safety data combined with high rates of public acceptance and population coverage. Vaccine hesitancy, characterized by lack of confidence in vaccination and/or complacency about vaccination that may lead to delay or refusal of vaccination despite the availability of services, threatens to undermine the success of coronavirus disease 2019 (COVID-19) vaccination programs. The rapid pace of vaccine development, misinformation in popular and social media, the polarized sociopolitical environment, and the inherent complexities of large-scale vaccination efforts may undermine vaccination confidence and increase complacency about COVID-19 vaccination. Although the experience of recent lethal surges of COVID-19 infections has underscored the value of COVID-19 vaccines, ensuring population uptake of COVID-19 vaccination will require application of multilevel, evidence-based strategies to influence behavior change and address vaccine hesitancy. Recent survey research evaluating public attitudes in the United States toward the COVID-19 vaccine reveals substantial vaccine hesitancy. Building upon efforts at the policy and community level to ensure population access to COVID-19 vaccination, a strong health care system response is critical to address vaccine hesitancy. Drawing on the evidence base in social, behavioral, communication, and implementation science, we review, summarize, and encourage use of interpersonal, individual-level, and organizational interventions within clinical organizations to address this critical gap and improve population adoption of COVID-19 vaccination.     

Socioeconomic Disparities in Community Mobility Reduction and COVID-19 Growth

ObjectiveTo examine differences in community mobility reduction and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outcomes across counties with differing levels of socioeconomic disadvantage.MethodsThe sample included counties in the United States with at least one SARS-CoV-2 case between April 1 and May 15, 2020. Outcomes were growth in SARS-CoV-2 cases, SARS-CoV-2–related deaths, and mobility reduction across three settings: retail/recreation, grocery/pharmacy, and workplace. The main explanatory variable was the social deprivation index (SDI), a composite socioeconomic disadvantage measure.ResultsAdjusted differences in outcomes between low-, medium-, and high-SDI counties (defined by tertile) were calculated using linear regression with state-fixed effects. Workplace mobility reduction was 1.75 (95% CI, -2.36 to -1.14; P<.001) and 3.48 percentage points (95% CI, -4.21 to -2.75; P<.001) lower for medium- and high-SDI counties relative to low-SDI counties, respectively. Mobility reductions in the other settings were also significantly lower for higher-SDI counties. In analyses adjusted for SARS-CoV-2 prevalence on April 1, medium- and high-SDI counties had 1.39 (95% CI, 0.85 to 1.93; P<.001) and 2.56 (95% CI, 1.77 to 3.34; P<.001) more SARS-CoV-2 cases/1000 population on May 15 compared with low-SDI counties, respectively. Deaths per capita were also significantly higher for higher-SDI counties.ConclusionCounties with higher social deprivation scores experienced greater growth in SARS-CoV-2 cases and deaths, but reduced mobility at lower rates. These findings are consistent with evidence demonstrating that economically disadvantaged communities have been disproportionately impacted by the coronavirus disease 2019 pandemic. Efforts to socially distance may be more burdensome for these communities, potentially exacerbating disparities in SARS-CoV-2–related outcomes.     

Clinical characteristics of Japanese patients with moderate to severe COVID-19

IntroductionAlthough several reports on the risk factors for severe disease of COVID-19 already exist, reports on effective early indicators are still limited, especially from Japan. This study was conducted to clarify the patient’s characteristics whose disease progressed to severe status.MethodsThe medical records of all consecutive 300 Japanese patients hospitalized at our institution between February and November 2020 were retrospectively reviewed. The clinical characteristics were evaluated to compare between mild (no oxygen needed), moderate (oxygen needs of 1–4 L/min), and severe diseases (oxygen needs of 5 L/min or more).ResultsThe median age was 68 years old, with 123 (41.0%) males and 177 (59.0%) females. Of these, 199 patients (66.3%), 55 patients (18.3%), 46 patients (15.3%) patients were in the mild disease, moderate disease, severe disease groups, respectively. Patients with severe disease were more likely to be older, have more comorbidities, and tended to have higher body mass index. In laboratory data, lymphocyte count, levels of C-reactive protein (CRP), LDH, and AST on admission were significantly associated with the severity. In multivariate analysis, age and CRP were the independent risk factors for severe disease (OR = 1.050, 1.130, respectively). The optimal cut-off value for age was 74 years old and that for CRP was 3.15 mg/dL.ConclusionsAge and CRP were independently associated with disease severity of COVID-19 in multivariate analysis. Additionally, the numbers of underlying disease, lymphocyte count, and inflammatory markers such as LDH and D-dimer may also be related to disease severity.     

Effectiveness of COVID-19 Booster on the Risk of Hospitalization Among Medicare Beneficiaries

ObjectiveTo determine the effectiveness of booster vaccinations on the risk of hospitalization with coronavirus disease 2019 (COVID-19) and how it varies by enrollee characteristics and interval from the initial vaccination to receipt of a booster.Patients and MethodsThis cohort study used 100% Medicare claims from January 1, 2020, through December 31, 2021, and matched 3,940,475 individuals who received boosters to 3,940,475 controls based on week and type of original COVID-19 vaccine and demographic and clinical characteristics. We compared the association of booster vs no booster with COVID-19 hospitalization using Cox proportional hazards regression models controlling for patient characteristics. We also determined the association of time from original vaccine to booster with COVID-19 hospitalization.ResultsOver a maximum of 130 days of follow-up, boosted enrollees had 8.20 (95% CI, 7.81 to 8.60) COVID-19 hospitalizations per million days vs 43.70 (95% CI, 42.79 to 44.64) for controls (81% effectiveness). Effectiveness varied by race, prior hospitalizations, and certain comorbidities, for example, leukemia/lymphoma (53% effectiveness), autoimmune disease (73%), and dementia (73%). Boosters received between 6 and 9 months after original vaccination varied between 81% and 85% effectiveness, while boosters received at 5 to 6 months (62%) or less than 5 months (58%) were less effective.ConclusionBoosters are highly effective in the Medicare population. Approximately 69,225 hospitalizations would be prevented by boosters in the 15 million individuals aged 65 years or older currently not boosted in a period similar to the September 2020 through January 2021 period studied. Boosters provided the greatest benefits if they were received between 6 and 9 months following original vaccinations. However, boosters were associated with substantial decreases in COVID-19 hospitalizations in all categories of enrollees.     

Viral Endothelial Dysfunction: A Unifying Mechanism for COVID-19

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible virus with significant global impact, morbidity, and mortality. The SARS-CoV-2 virus may result in widespread organ manifestations including acute respiratory distress syndrome, acute renal failure, thromboembolism, and myocarditis. Virus-induced endothelial injury may cause endothelial activation, increased permeability, inflammation, and immune response and cytokine storm. Endothelial dysfunction is a systemic disorder that is a precursor of atherosclerotic vascular disease that is associated with cardiovascular risk factors and is highly prevalent in patients with atherosclerotic cardiovascular and peripheral disease. Several studies have associated various viral infections including SARS-CoV-2 infection with inflammation, endothelial dysfunction, and subsequent innate immune response and cytokine storm. Noninvasive monitoring of endothelial function and identification of high-risk patients who may require specific therapies may have the potential to improve morbidity and mortality associated with subsequent inflammation, cytokine storm, and multiorgan involvement.     

Leveraging the Electronic Health Record to Address the COVID-19 Pandemic

The coronavirus disease 2019 (COVID-19) pandemic continues its global spread. Coordinated effort on a vast scale is required to halt its progression and to save lives. Electronic health record (EHR) data are a valuable resource to mitigate the COVID-19 pandemic. We review how the EHR could be used for disease surveillance and contact tracing. When linked to “omics” data, the EHR could facilitate identification of genetic susceptibility variants, leading to insights into risk factors, disease complications, and drug repurposing. Real-time monitoring of patients could enable early detection of potential complications, informing appropriate interventions and therapy. We reviewed relevant articles from PubMed, MEDLINE, and Google Scholar searches as well as preprint servers, given the rapidly evolving understanding of the COVID-19 pandemic.     

Year 3 of COVID-19: Harsh Truths,Brutal Realities,and Glimmers of Hope

Severe acute respiratory syndrome coronavirus 2, the virus causing coronavirus disease 2019 (COVID-19), has now killed 1 of every 303 Americans. Whereas 4 vaccines are approved in the United States and masks are widely available, too few are fully immunized and most of the population has stopped wearing protective masks. The ongoing consequences of this include continued excess morbidity and mortality and the generation of immune-evading variants and subvariants, which in toto are injurious and ultimately self-defeating. Herein we briefly update and review COVID-19 vaccines, waning immunity, and new variants.     

Therapeutic potential of ciclesonide inhalation for COVID-19 pneumonia: Report of three cases

No specific and effective anti-viral treatment has been approved for COVID-19 so far. Systemic corticosteroid has been sometimes administered to severe infectious diseases combined with the specific treatment. However, as lack of the specific anti-SARS-CoV-2 drug, systemic steroid treatment has not been recommended for COVID-19. We report here three cases of the COVID-19 pneumonia successfully treated with ciclesonide inhalation. Rationale of the treatment is to mitigate the local inflammation with inhaled steroid that stays in the lung and to inhibit proliferation of the virus by antiviral activity. Larger and further studies are warranted to confirm the result of these cases.     

Do Patients With COVID-19 Benefit from Rehabilitation? Functional Outcomes of the First 100 Patients in a COVID-19 Rehabilitation Unit

ObjectiveTo determine the benefits associated with brief inpatient rehabilitation for coronavirus 2019 (COVID-19) patients.DesignRetrospective chart review.SettingA newly created specialized rehabilitation unit in a tertiary care medical center.ParticipantsConsecutive sample of patients (N=100) with COVID-19 infection admitted to rehabilitation.InterventionInpatient rehabilitation for postacute care COVID-19 patients.Main Outcome MeasuresMeasurements at admission and discharge comprised a Barthel Activities of Daily Living Index (including baseline value before COVID-19 infection), time to perform 10 sit-to-stands with associated cardiorespiratory changes, and grip strength (dynamometry). Correlations between these outcomes and the time spent in the intensive care unit (ICU) were explored.ResultsUpon admission to rehabilitation, 66% of the patients were men, the age was 66±22 years, mean delay from symptom onset was 20.4±10.0 days, body mass index was 26.0±5.4 kg/m², 49% had hypertension, 29% had diabetes, and 26% had more than 50% pulmonary damage on computed tomographic scans. The mean length of rehabilitation stay was 9.8±5.6 days. From admission to discharge, the Barthel index increased from 77.3±26.7 to 88.8±24.5 (P<.001), without recovering baseline values (94.5±16.2; P<.001). There was a 37% improvement in sit-to-stand frequency (0.27±0.16 to 0.37±0.16 Hz; P<.001), a 13% decrease in post-test respiratory rate (30.7±12.6 to 26.6±6.1; P=.03), and a 15% increase in grip strength (18.1±9.2 to 20.9±8.9 kg; P<.001). At both admission and discharge, Barthel score correlated with grip strength (ρ=0.39-0.66; P<.01), which negatively correlated with time spent in the ICU (ρ=–0.57 to –0.49; P<.05).ConclusionsInpatient rehabilitation for COVID-19 patients was associated with substantial motor, respiratory, and functional improvement, especially in severe cases, although there remained mild persistent autonomy loss upon discharge. After acute stages, COVID-19, primarily a respiratory disease, might convert into a motor impairment correlated with the time spent in intensive care.     

Safety of and antibody response to the BNT162b2 COVID-19 vaccine in adolescents and young adults with underlying disease

BackgroundData are limited regarding the safety of and antibody response to the BNT162b2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger ribonucleic acid vaccine in adolescents and young adults with underlying disease.MethodsThis prospective observational study enrolled patients age 12–25 years with chronic underlying disease who received 2 doses of BNT162b2. A 18-item questionnaire was used to assess adverse events within 7 days post-vaccination, and data regarding severe adverse events were collected from electronic medical records. An antibody titer for the receptor-binding domain of the spike protein in SARS-CoV-2 was used to assess antibody response after the second vaccine dose.ResultsStudy participants were 429 patients (241 [56.2%] age 12–15 years; 188 [43.8%] age 16–25 years). The most common underlying diseases were genetic or chromosomal abnormalities and/or congenital anomalies, followed by endocrine or metabolic diseases; 32% of participants were immunocompromised. Severe adverse events were observed after the second dose in 1 (0.4%) patient age 12–15 years and in 2 (1.1%) patients age 16–25 years; all patients recovered. Seropositivity after the second vaccine dose was 99.0%. The geometric mean antibody titer was higher in patients age 12–15 years versus 16–25 years (1603.3 [1321.8–1944.7] U/mL vs. 949.4 [744.2–1211.0] U/mL). Compared with immunocompetent patients, immunocompromised patients had a lower antibody titer (2106.8 [1917.5–2314.7] U/mL vs. 467.9 [324.4–674.8] U/mL).ConclusionsVaccination with BNT162b2 was acceptably safe and immunogenic for adolescents and young adults with underlying disease.     

Clinical efficacy of remdesivir for COVID-19 in children: A propensity-score-matched analysis

Clinical efficacy of remdesivir in children with COVID-19 is unclear. This propensity-score-matched retrospective cohort study of children with COVID-19 showed that the rate of patients achieving defervescence on Day 4 was higher in the remdesivir group than in the non-remdesivir group, but was not statistically different (86.7% vs 73.3%, P = 0.333).     

Identification of Functional Limitations and Discharge Destination in Patients With COVID-19

ObjectivesThe objectives of this study were to identify functional limitations in patients with coronavirus 2019 (COVID-19) admitted to acute care hospitals; to evaluate functional limitations by demographic, medical, and encounter characteristics; and to examine functional limitations in relation to discharge destination.Designand Setting:This is a cross-sectional, retrospective study of adult patients with COVID-19 who were discharged from 2 different types of hospitals (academic medical center and a community hospital) within 1 health care system from January 1 to April 30, 2020.ParticipantsPatients were identified from the Cedars-Sinai COVID-19 data registry who had a new-onset positive test for severe acute respiratory syndrome coronavirus 2. A total of 273 patients were identified, which included 230 patients who were discharged alive and 43 patients who died and were excluded from the study sample.InterventionsNot applicable.Main Outcome MeasuresFunctional limitations in patients with COVID-19 in acute care hospitals and the predictors for discharge disposition.ResultsA total of 230 records were analyzed including demographic, encounter, medical, and functional variables. In a propensity score–matched cohort based on age and comorbidity, 88.2% had functional physical health deficits, 72.5% had functional mental health deficits, and 17.6% experienced sensory deficits. In the matched cohort, individuals discharged to an institution experienced greater physical (62.7% vs 25.5%, P<.001) and mental health (49.0% vs 23.5%, P=.006) deficits than patients discharged home. Marital status (odds ratio, 3.17; P=.011) and physical function deficits (odds ratio, 3.63; P=.025) were associated with an increase odds ratio of discharge to an institution.ConclusionsThis research highlights that functional status is a strong predictor for discharge destination to an institution for patients with COVID-19. Patients who were older, in the acute care hospital longer, and with comorbidities were more likely to be discharged to an institution. Rehabilitation is a significant aspect of the health care system for these vulnerable patients. The challenges of adjusting the role of rehabilitation providers and systems during the pandemic needs further exploration. Moreover, additional research is needed to look more closely at the many facets and timing of functional status needs, to shed light in use of interdisciplinary rehabilitation services, and to guide providers and health care systems in facilitating optimal recovery and patient outcomes.     

Arterial Thrombotic Events in Adult Inpatients With COVID-19

ObjectiveTo evaluate the clinical course of and risk factors for arterial thrombotic events in adult inpatients with coronavirus disease 2019 (COVID-19).MethodsAll consecutive adult patients admitted for COVID-19 infection in a referral center in France and discharged from the hospital between April 1 and April 30, 2020, were included. All arterial thrombotic events that occurred through discharge were considered for analysis. Epidemiologic, demographic, clinical, laboratory, treatment, and outcome data were extracted from electronic medical records with use of a standardized data collection form.ResultsOverall, 531 COVID-19+ patients were analyzed. Among them, 30 (5.6%) experienced arterial thrombotic events. Arterial thrombotic events in the setting of COVID-19 infection happened at a median of 11 (5-20) days after the first symptoms of infection; occurred in high-risk patients according to traditional cardiovascular risk factors; had an atypical pattern, such as thrombosis of the aorta, upper limb, or renal arteries or cerebral microvasculopathy in 7 (23.3%) cases; and were associated with an in-hospital mortality rate of 40%. Arterial thrombotic events increased the risk of death by 3-fold in COVID-19+ patients (hazard ratio, 2.96; 95% CI, 1.4 to 4.7; P=.002). A subdistribution survival hazard model showed that a concentration of D-dimer above 1250 ng/mL increased the risk of arterial thrombotic events in COVID-19+ patients by more than 7 (subdistribution hazard ratio, 7.68; 95% CI, 2.9 to 20.6; P<.001).ConclusionA dramatically high rate of in-hospital death was observed in patients who suffered arterial thrombotic events in the setting of COVID-19 infection. A D-dimer level above 1250 ng/mL at entry may identify COVID-19+ patients at risk for arterial thrombotic events.