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Nose vs. Lungs: Study Compares SARS-CoV-2 Concordance in Upper and Lower Respiratory Tracts

Published on July 20, 2020 in Cornerstone Blog · Last updated 1 year ago
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“Study

CHOP researchers study the concordance of SARS-CoV-2 in upper and lower respiratory tracts.

mccannn [at] email.chop.edu (By Nancy McCann)

Current standard testing for SARS-CoV-2, the virus responsible for COVID-19, involves collecting nasal secretion samples from the back of the nose and throat. The nasopharyngeal (NP) swab test reveals whether cells collected contain the virus or not. But is it possible to receive a negative result — no virus present in your upper respiratory tract — yet have virus present in your lungs or lower respiratory tract?

Audrey Odom John, MD, PhD, chief of Infectious Diseases at Children’s Hospital of Philadelphia, aims to find out as primary investigator of the study, “Concordance of Findings in Respiratory Sample Measurements (CONFIRM COVID-19).” Gaining more knowledge about the prevalence and nature of this concordance, or possible discordance, could inform infection prevention and control measures, especially for healthcare workers who are at increased risk of exposure to COVID-19 when performing lower respiratory tract procedures involving the airway.

“We think that it’s possible, although rare, for a child to have no virus in their nose but still have virus in their lungs,” Dr. Odom John said. “So to understand how risky certain procedures are for our anesthesiologists, it’s important to understand whether children can have virus in their lungs, even if their noses are negative.

“We need this information to know the right way to protect our healthcare providers with the correct personal protective equipment (PPE). We think that what we’re doing right now is as safe as can be. But truly, we need additional data to know for sure that we don’t need to modify what we’re doing, in order to make sure our healthcare providers are as safe as possible.”

Compare the Concordance

The overall objective of CONFIRM COVID-19 is to compare the concordance between NP swabs and post intubation lower respiratory samples for the presence of SARS-CoV-2 among children undergoing intubation for a clinically required procedure during the coronavirus pandemic. The lower respiratory specimens will be collected from either a tracheal aspirate (TA), a method of obtaining tracheal secretions, or a bronchoalveolar lavage (BAL), a procedure performed during a bronchoscopy that collects fluid from the lungs.

This observational study will enroll a cohort of approximately 500 patients with known negative status for SARS-CoV-2 in their noses. During the children’s scheduled endotracheal intubation or bronchoscopy procedures as part of their clinical care, samples will be taken from their lower airways and tested for the presence of the coronavirus. If a discordance is found — if the lower respiratory sample turns out to be unexpectedly positive — that information will go in the child’s medical record, and the clinical team will be informed, Dr. Odom John said.

The study investigators, including Elaina Lin, MD, attending anesthesiologist at CHOP, and faculty at the Perelman School of Medicine in the University of Pennsylvania; and Lisa Young, MD, chief of the CHOP Division of Pulmonary Medicine, and associate director of the Penn-CHOP Lung Biology Institute, will be performing intermittent interim analyses.

“We’re not going to wait until all 500 children have been studied,” Dr. Odom John said. “If we do the first 20 kids, and one or two are positive, that might change the way those procedures are done [in regard to PPE], in order to better protect our clinicians.”

Looking for Clues to Children’s Lower Susceptibility to Severe COVID-19

The other arm of this research involves children under 18-years-old who have tested positive for SARS-CoV-2 in their nose during the coronavirus pandemic. The researchers will be looking at the relationship between viral load in the upper and lower respiratory tracts by analyzing samples taken during already scheduled airway procedures.

“This would tell us more about what we think is going on in children and this virus,” Dr. Odom John said. “For instance, we don’t understand right now, why children don’t have very severe disease, by and large, with COVID-19. Understanding where the virus is, and how much virus there is in children who do get infected, might help us understand a little more.”

For example, one scientific hypothesis is that children have lower amounts of the angiotensin-converting enzyme 2, or ACE2 receptor — the spiky protein on the surface of many cell types and tissues such as lungs, heart, blood vessels, kidneys, liver, and gastrointestinal tract — than adults do. This enzyme provides the entry point for the coronavirus to bind to and infect the cells.

“It’s been one of the reasons thought to be why children aren’t so susceptible to severe COVID-19,” Dr. Odom John said. “They just have less of this receptor, and maybe that’s why the virus isn’t getting in and doesn’t replicate as much. But, that’s not perfectly clear. Our understanding of COVID-19 infection has deepened, but more remains to be understood about its pathogenesis.”