ERS 2021: COVID-19 Takes Spotlight, With Climate Change Another Focus

Throughout the European Respiratory Society International Congress 2021, which will be held September 5-8, 2021, The American Journal of Managed Care^® will cover topics such as patient outcomes in chronic obstructive pulmonary disease, management and treatment of chronic cough, the impact of climate change on lung health, and gender and respiratory health.

However, as a fully virtual meeting for the second year in a row, COVID-19 is impossible to avoid. In the pre-meeting sessions, year in review presentations included a focus on COVID-19 in children, prevention of severe symptoms after infection, and scientific findings, such as immune response to COVID-19 and the use of mRNA vaccines.

Elizabeth Whittaker, MBBAOBCh, DTM&H, MRCPCH, PhD, a consultant in pediatric infectious diseases for the Imperial College Healthcare NHS Trust, noted that the pandemic “has been completely different in children and young people compared with adults.”

She reviewed 3 papers in preprint analyzing severe disease and death in children and young people (CYP) who acquire a SARS-CoV-2 infection.

One paper was a meta-analysis of 57 studies from 19 countries, including 21,549 children. The paper found that the risk of severe disease and death increased in patients with 2 to 3 comorbidities vs no comorbidities. As in adults, obesity was associated with an increased risk of severe disease and death. However, other common conditions, such as asthma, were not.

Children with pediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS) or multisystem inflammatory syndrome in children (MIS-C) were more likely to be admitted to critical care than children with COVID-19, she noted.

Age, as with adults, played a role. Infants and teenagers had the greatest risk of severe disease in the CYP population.

A second paper reviewed 11 million CYP in England. Of the 3.6 million who had COVID-19, hospital and pediatric intensive care unit (PICU) admissions were rare. A total of 5830 CYP were hospitalized and only 4% of those went to PICU. In comparison, there were 690 patients with PIMS-TS, and 44% of them went to PICU.

The CYP patients more likely to go to intensive care were those from non-White ethnic groups or with comorbidities.

Finally, the third paper reviewed real-time data collected through the National Child Mortality Database in England from February 2020 to March 2021. A total of 61 CYP died with a positive COVID-19 test, but only 25 died due to COVID-19.

While the patients who died were evenly split along gender (12 male vs 13 female), Asians were overrepresented (n = 9). The majority (n = 18) were between the ages of 10 and 18 years and 19 had a comorbidity vs 6 who had no comorbidity. There were no deaths among patients with asthma or epilepsy.

“…the risk of severe illness or death in COVID-19 is extremely low in children and young people,” Whittaker said. “And although vulnerable groups have a slightly higher risk, it’s still very low.”

She added that the children who were at the highest risk for COVID-19 were also at risk from any winter virus or infection.

Treatments in children are a challenge:

• Dexamethasone has been recommended for adults, it has not been evaluated in children, but it is being used in children with severe disease and hypoxia.
• Tocilizumab has also been shown to be useful in adults within 24 to 48 hours of entering intensive care, but it has not been assessed in CYP patients.
• Anticoagulation is standard of care in adults, but not in children and should be used on a case-by-case basis depending on risk factors.
• Monoclonal antibodies are authorized for use in hospitalized patients and recommended in the United States within 72 hours of a positive test, but there is no evidence of safety or efficacy in children. While they should not be used routinely, they may be used on a case-by-case basis depending on age or risk factors.

In a separate session, Mona Bafadhel, MBChB, PhD, FRCP, associate professor of respiratory medicine and consultant respiratory physician, Nuffield Department of Medicine at the University of Oxford, reviewed treatments being used to prevent serious disease in adults with COVID-19.

Early observations from Wuhan, China, revealed that certain comorbidities, such as hypertension, diabetes, COPD, and asthma, were associated with hospitalization, but further research showed asthma and COPD are underrepresented compared with current knowledge of endemic influenza, she said.

In the first 3 to 6 months of the first identified COVID-19 case, there were almost 2000 registered clinical trials for treatments. In the beginning of the pandemic, few studies examined the effect of treatments on early infection. Instead, they focused on treating patients who had already been hospitalized.

Bafadhel reviewed 3 studies analyzing treatments for early infection:

1. STOIC,¹ a phase 2, open-label randomized controlled trial (RCT) of inhaled budesonide in patients ≥ 18 years who had less than 7 days of symptoms.
2. PRINCIPLE, a phase 3, open-label platform study evaluating azithromycin,² doxycycline,³ or inhaled budesonide⁴ vs usual care. Patients included were ≥ 50 years with risk factors for severe disease or ≥ 65 years and had symptoms for less than 14 days.
3. BLAZE, a phase 2/3, placebo platform RCT evaluating LY-CoV555 (bamlanivimab)⁵ and LY-CoV555 plus LV-CoV016 (bamlanivimab plus etesivamab)⁶ in patients ≥ 18 years or ≥ 12 years with risk factors.

STOIC found that the treatment arm had 1 urgent care visit, emergency department assessment, or hospitalization compared with 10 in the usual care arm (95% CI, 0.043-0.218; P = .004) and the number needed to treat was 8. Budensonide had a relative risk reduction of 91% and the resolution of fever was quicker: ≥ 1 day of fever was 11% for the budesonide arm vs 23% for usual care.

PRINCIPLE analyzed azithromycin 500 mg once a day for 3 days, doxycycline 200 mg for 1 day then 100 mg once a day for 7 days, and inhaled budesonide for 28 days. Budesonide had a favorable outcome in early COVID-19, but while there was a trend to reduction of hospitalization, it didn’t reach statistical significance.

In BLAZE the 2800 mg dose of bamlanivimab significantly reduced viral load compared with placebo. The combination treatment reduced hospitalizations vs placebo and had a relative risk difference of 70%. The combination reduced viral load at day 11 and the median time to symptom recovery was shortened by 1 day.

Bafadhel said that it remains important to find a way to treat COVID-19 infection at the onset of symptoms to prevent it from worsening. So far, the findings are translating to clinical practice and the United States is already prescribing inhaled budesonide or monoclonal antibodies for early treatment.

She noted that this is “interesting because of how long it can take to get medications to the patients who need it.”

References

1. Ramakrishnan S, Nicolau Jr DV, Langford B, et al. Inhaled budesonide in the treatment of early COVID-19 (STOIC): a phase 2, open-label, randomised controlled trial. Lancet Respir Med. 2021;9(7):763-772. doi:10.1016/S2213-2600(21)00160-0

2. PRINCIPLE Trial Collaborative Group. Azithromycin for community treatment of suspected COVID-19 in people at increased risk of an adverse clinical course in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial. Lancet. 2021;397(10279):1063-1074. doi:10.1016/S0140-6736(21)00461-X

3. Butler CC, Yu L-M, Drward J, et al. Doxycycline for community treatment of suspected COVID-19 in people at high risk of adverse outcomes in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial. Lancet Respir Med. Published online July 27, 2021. doi:10.1016/S2213-2600(21)00310-6

4. Yu L-M, Bafadhel M, Dorward J, et al. Inhaled budesonide for COVID-19 in people at high risk of complications in the community in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial. Lancet. Published online August 10, 2021. doi:10.1016/S0140-6736(21)01744-X

5. Chen P, Nirula A, Heller B, et al. SARS-CoV-2 neutralizing antibody LY-CoV555 in outpatients with Covid-19. N Engl J Med. 2021;384(3):229-237. doi:10.1056/NEJMoa2029849

6. Dougan M, Nirula A, Azizad M, et al. Bamlanivimab plus etesevimab in mild or moderate Covid-19. N Engl J Med. Published online July 14, 2021. doi:10.1056/NEJMoa2102685