March 09, 2023

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Clinical Reports

Community-onset bacterial coinfection in children critically ill with SARS-CoV-2 infection
Researchers evaluated children and adolescents aged <19 years admitted to a pediatric intensive care or high-acuity unit for COVID-19 between March and December 2020. Community-onset bacterial coinfection in children with critical COVID-19 is infrequent, but empiric antibiotics are commonly prescribed. These findings inform antimicrobial use and support rapid de-escalation when evaluation shows coinfection is unlikely.
Risk of Coronavirus Disease 2019–Associated Pulmonary Aspergillosis Based on Corticosteroid Duration in Intensive Care Patients
Coronavirus disease 2019 (COVID-19)–associated pulmonary aspergillosis (CAPA) is a potential complication in critically ill COVID-19 patients. Corticosteroids are standard of care for hospitalized COVID-19 patients but carry an increased risk of secondary infections including CAPA. The objective of this study was to evaluate if duration of corticosteroid therapy ≤10 days versus >10 days affects the risk of developing CAPA. This was a retrospective cohort study of adult patients with severe COVID-19 pneumonia requiring mechanical ventilation who received at least 3 days of corticosteroid treatment. Corticosteroid treatment >10 days in critically ill COVID-19 patients is associated with an increased risk of CAPA. Patients may require corticosteroids for reasons beyond COVID-19 and clinicians should be cognizant of risk of CAPA with prolonged courses.
Cardiac abnormalities in Long COVID 1-year post-SARS-CoV-2 infection
Long COVID is associated with multiple symptoms and impairment in multiple organs. Cross-sectional studies have reported cardiac impairment to varying degrees by varying methodologies. Using cardiac MR (CMR), researchers investigated a 12-month trajectory of abnormalities in Long COVID. 534 individuals with Long COVID underwent CMR (T1/T2 mapping, cardiac mass, volumes, function and strain) and multiorgan MRI at 6 months (IQR 4.3–7.3) since first post-COVID-19 symptoms. 330 were rescanned at 12.6 (IQR 11.4–14.2) months if abnormal baseline findings were reported. Symptoms, questionnaires and blood samples were collected at both time points. CMR abnormalities were defined as ≥1 of low left or right ventricular ejection fraction (LVEF), high left or right ventricular end diastolic volume, low 3D left ventricular global longitudinal strain (GLS), or elevated native T1 in ≥3 cardiac segments. Significant change over time was reported by comparison with 92 healthy controls. CMR abnormalities (left entricular or right ventricular dysfunction/dilatation and/or abnormal T1mapping), occurred in one in five individuals with Long COVID at 6 months, persisting in over half of those at 12 months. Cardiac-related blood biomarkers could not identify CMR abnormalities in Long COVID.
Long-term gastrointestinal outcomes of COVID-19
A comprehensive evaluation of the risks and 1-year burdens of gastrointestinal disorders in the post-acute phase of COVID-19 is needed but is not yet available. Here rresearchers use the US Department of Veterans Affairs national health care databases to build a cohort of 154,068 people with COVID-19, 5,638,795 contemporary controls, and 5,859,621 historical controls to estimate the risks and 1-year burdens of a set of pre-specified incident gastrointestinal outcomes. Researchers show that beyond the first 30 days of infection, people with COVID-19 exhibited increased risks and 1-year burdens of incident gastrointestinal disorders spanning several disease categories including motility disorders, acid related disorders (dyspepsia, gastroesophageal reflux disease, peptic ulcer disease), functional intestinal disorders, acute pancreatitis, hepatic and biliary disease. The risks were evident in people who were not hospitalized during the acute phase of COVID-19 and increased in a graded fashion across the severity spectrum of the acute phase of COVID-19 (non-hospitalized, hospitalized, and admitted to intensive care). The risks were consistent in comparisons including the COVID-19 vs the contemporary control group and COVID-19 vs the historical control group as the referent category. Altogether, our results show that people with SARS-CoV-2 infection are at increased risk of gastrointestinal disorders in the post-acute phase of COVID-19. Post-covid care should involve attention to gastrointestinal health and disease.

Antiviral Therapeutics and Vaccines

Confronting the evolution and expansion of anti-vaccine activism in the USA in the COVID-19 era
Over the past two decades, anti-vaccine activism in the USA has evolved from a fringe subculture into an increasingly well organized, networked movement with important repercussions for public health. The COVID-19 pandemic has exacerbated this evolution and magnified the reach of vaccine misinformation. Anti-vaccine activists, who for many years spoke primarily to niche communities hesitant about childhood vaccinations, have used traditional and social media to amplify vaccine-related mistruths about COVID-19 vaccines while also targeting historically marginalized racial and ethnic communities. These efforts contributed to COVID-19 vaccine hesitancy and expanded the movement, with early indications suggesting that this hesitancy could now also be increasing hesitancy that existed pre-pandemic towards other vaccines. It is important to understand the implications of this recent evolution of anti-vaccine activism on vaccination uptake and the promotion of sound public health strategies. In this Viewpoint, researchers summarize the latest developments in US-based anti-vaccine activism and propose strategies for confronting them.
Effectiveness of Maternal Influenza Vaccination in Peru PRIME Cohort
Few studies have examined influenza vaccine effectiveness (VE) among women during pregnancy in middle-income countries. Researchers used data from a prospective cohort of women who were pregnant in Peru to estimate effectiveness of the 2018 Southern Hemisphere influenza vaccine. Women at <28 weeks gestation were enrolled from 4 tertiary level hospitals in Lima, Peru at the start of the 2018 influenza season and followed until the end of their pregnancies. Participants had mid-turbinate nasal swabs collected and tested for influenza by reverse-transcription polymerase chain reaction (RT-PCR) with onset of ≥1 of myalgia, cough, runny nose or nasal congestion, sore throat, or difficulty breathing. Time-varying Cox proportional hazard regression models were used to estimate the risk of RT-PCR-confirmed influenza infection after adjusting for inverse probability treatment weight. Researchers followed 1896 women for a median of 127 days (interquartile range [IQR], 86–174). Participants had a median age of 29 years (IQR, 24–34). Among the 1896 women, 49% were vaccinated with the 2018 influenza vaccine and 1039 (55%) developed influenza-like illness, 76 (7%) of whom had RT-PCR-confirmed influenza. Incidence rates of RT-PCR-confirmed influenza were 36.6 and 15.3 per 100 000 person-days among women who were unvaccinated and vaccinated, respectively. Adjusted influenza VE was 22% (95% confidence interval, −64.1% to 62.9%).Participants vaccinated against influenza had more than 50% lower incidence of RT-PCR-confirmed influenza illness. Although the VE estimated through propensity weight-adjusted time-varying Cox regression did not reach statistical significance, our findings provide additional evidence about the value of maternal influenza vaccination in middle-income countries.
Bivalent booster effectiveness against severe COVID-19 outcomes in Finland, September 2022 – January 2023
Bivalent COVID-19 vaccines were introduced in 2022 but knowledge of how their effectiveness against severe COVID-19 outcomes is sustained over time is currently limited. In Finnish register-based cohort analyses, researchers compared the risk of severe COVID-19 outcomes among those who received bivalent vaccination (exposed) between 1 September 2022 and 31 January 2023 to those who did not (unexposed). Among elderly aged 65–120 years, bivalent vaccination reduced the risk of hospitalization and death due to COVID-19. Among the elderly the hazard ratios comparing exposed and unexposed ranged from 0.36 to 0.43 during the first 14–30 days since bivalent vaccination but signs of waning were observed as soon as two months after vaccination. Among the chronically ill aged 18–64 years bivalent vaccination did not reduce the risk of severe COVID-19 outcomes. These results are crucial for further developing COVID-19 vaccination program worldwide.
Immunomodulators for severe coronavirus disease-2019 in transplant patients: Do they increase the risk of secondary infection?
The use of immunomodulators in transplant patients with severe COVID-19 was not significantly associated with an increased risk of secondary infections. Secondary infections were associated with higher risk of all-cause mortality. Future studies of larger cohorts are needed to explore the effect of immunomodulators on survival among transplant patients with COVID-19.

Epidemiology

Characteristics and predictors of persistent symptoms post-COVID-19 in children and young people: a large community cross-sectional study in England
4.4% (95% CI 3.7 to 5.1) of 3173 5–11 year-olds and 13.3% (95% CI 12.5 to 14.1) of 6886 12–17 year-olds with prior symptomatic infection reported at least one symptom lasting ≥3 months post-COVID-19, of whom 13.5% (95% CI 8.4 to 20.9) and 10.9% (95% CI 9.0 to 13.2), respectively, reported their ability to carry out day-to-day activities was reduced ‘a lot’ due to their symptoms. The most common symptoms among participants with persistent symptoms were persistent coughing (27.4%) and headaches (25.4%) in children aged 5–11 years and loss or change of sense of smell (52.2%) and taste (40.7%) in participants aged 12–17 years. Higher age and having a pre-existing health condition were associated with higher odds of reporting persistent symptoms. One in 23 5–11 year-olds and one in eight 12–17 year-olds post-COVID-19 report persistent symptoms lasting ≥3 months, of which one in nine report a large impact on performing day-to-day activities.
Parental Nonadherence to Health Policy Recommendations for Prevention of COVID-19 Transmission Among Children
In this survey study of US parents, one-quarter engaged in misrepresentation or nonadherence regarding PHMs for their children. The most common reason was to preserve parental autonomy. Additional reasons included wanting to resume a normal life for their child and the inability to miss work or other responsibilities, among other reasons. These results suggest that some PHMs implemented to limit the spread of COVID-19 may have been compromised due to misrepresentation and nonadherence by parents on behalf of their children, contributing to COVID-19–related morbidity and mortality. In addition, some children appear to have received a vaccine that was not fully tested and approved in their age group.These findings suggest a serious public health challenge in the immediate context of the COVID-19 pandemic, including future waves affecting weary parents, as well as future infectious disease outbreaks. Further work is needed to identify groups at highest risk of misrepresentation and nonadherence, to address parents’ concerns that were identified as reasons for these behaviors (eg, desire for autonomy), and to implement better support mechanisms for parents (eg, paid sick leave for family illness) during such crises so that misrepresentation and nonadherence feel less necessary.
Viral kinetics of sequential SARS-CoV-2 infections
The impact of a prior SARS-CoV-2 infection on the progression of subsequent infections has been unclear. Using a convenience sample of 94,812 longitudinal RT-qPCR measurements from anterior nares and oropharyngeal swabs, researchers compared the SARS-CoV-2 viral kinetics of first vs. second infections, adjusting for viral variant, vaccination status, and age. Relative to first infections, second infections usually featured a lower peak viral concentration and faster clearance time, especially in individuals who received a vaccine dose between their first and second infection. Furthermore, a person’s relative (rank-order) viral clearance time, compared to others infected with the same variant, was similar across first and second infections; that is, individuals who had a relatively fast clearance time in their first infection tended to also have a relatively fast clearance time in their second infection. These findings provide evidence that, like vaccination, immunity from a prior SARS-CoV-2 infection shortens the duration of subsequent acute SARS-CoV-2 infections principally by reducing viral clearance time. Additionally, there appears to be an inherent element of the immune response, or some other host factor, that shapes a person’s relative ability to clear SARS-CoV-2 infection that persists across sequential infections.
Long-term cardiovascular outcomes in COVID-19 survivors among non-vaccinated population: A retrospective cohort study from the TriNetX US collaborative networks
The long-term cardiovascular outcomes in COVID-19 survivors remain largely unclear. The aim of this study was to investigate the long-term cardiovascular outcomes in COVID-19 survivors. This study used the data from the US Collaborative Network in TriNetX. From a cohort of more than 42 million records between 1 January 2019 and 31 March 2022, a total of 4,131,717 participants who underwent SARS-CoV-2 testing were recruited. Study population then divided into two groups based on COVID-19 test results. The COVID-19 survivors were associated with increased risks of cerebrovascular diseases, such as stroke (HR [95% CI] = 1.618 [1.545-1.694]), arrhythmia related disorders, such as atrial fibrillation (HR [95% CI] = 2.407 [2.296-2.523]), inflammatory heart disease, such as myocarditis (HR [95% CI] =4.406 [2.890-6.716]), ischemic heart disease(IHD), like ischemic cardiomyopathy (HR [95% CI] = 2.811 [2.477-3.190]), other cardiac disorders, such as heart failure (HR [95% CI] =2.296 [2.200-2.396]) and thromboembolic disorders (e.g. pulmonary embolism: HR [95% CI] =2.648 [2.443-2.870]). The risks of two composite endpoints, major adverse cardiovascular event (HR [95% CI] = 1.871 [1.816–1.927]) and any cardiovascular outcome (HR [95% CI] = 1.552 [1.526–1.578]), were also higher in the COVID-19 survivors than in the controls. Moreover, the survival probability of the COVID-19 survivors dramatically decreased in all the cardiovascular outcomes. The risks of cardiovascular outcomes were evident in both male and female COVID-19 survivors. Furthermore, the risk of mortality was higher in the elderly COVID-19 survivors (age ≥ 65 years) than in the young ones. Sensitivity analyses presented roughly similar results globally. Furthermore, the impact of COVID-19 on cardio-related outcomes appeared to be more pronounced in inpatients than in outpatients. The 12-month risk of incidental cardiovascular diseases is substantially higher in the COVID-19 survivors than the non-COVID-19 controls. Clinicians and patients with a history of COVID-19 should pay attention to their cardiovascular health in long term.
One-Year Adverse Outcomes Among US Adults With Post–COVID-19 Condition vs Those Without COVID-19 in a Large Commercial Insurance Database
In this case-control study of 13 435 US adults with post–COVID-19 condition (PCC) and 26 870 matched adults without COVID-19, the adults with PCC experienced increased risks for a number of cardiovascular outcomes, such as ischemic stroke. During the 12-month follow-up period, 2.8% of the individuals with PCC vs 1.2% of the individuals without COVID-19 died, implying an excess death rate of 16.4 per 1000 individuals. Individuals with PCC may be at increased risk for adverse outcomes in the year following initial infection.