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CU Cancer Center Research May Explain Why Some COVID-19 Patients Take Months to Recover

Research

CU Cancer Center Research May Explain Why Some COVID-19 Patients Take Months to Recover

Author Cancer Center | Publish Date July 13, 2020

Many patients diagnosed with COVID-19 have symptoms such as a persistent dry cough, shortness of breath, and in some cases, incredibly low oxygen levels in their blood. Additionally, many patients report having long-lasting side effects, for example decreased lung capacity, even after they recover from the virus. A study, posted earlier this month on medRxiv ahead of a peer review, done by the University of Colorado Cancer Center Mass Spectrometry Shared Resource (CU MSSR) may have a better understanding of why some patients take months to recover from the disease. 

CU Cancer Center member Angelo D’Alessandro, PhD, of the CU MSSR, has first-hand experience with the illness: he and his fiancé were diagnosed with the virus earlier this year.

“My fiancé and I both contracted the virus in March, immediately after the shutdown. It has been much more severe for me – with symptoms lasting for over three weeks, followed by a month-long secondary bacterial infection to my lungs,” he explains. “While I am finally getting better and recovering my lung capacity, we have had to postpone our wedding plans in May and trip to Italy to celebrate.”

D’Alessandro is one of many patients who seem to have a long road to recovery. Now, results from his study may explain why.

“We hypothesized that the virus could damage red blood cells and that damage could contribute to the severity of hypoxia in patients with COVID-19,” he explains. “Red blood cells carry oxygen from the lungs to all parts of the body with the help of a protein called hemoglobin. If the cells are damaged by the virus it could explain the low oxygen levels in some patients.”

To test his hypothesis, D’Alessandro – in collaboration with Kirk C. Hansen, PhD – Co-Director of the CU MSSR – and colleagues at Columbia University in New York combined state-of-the-art mass spectrometry-based approaches to investigate the impact of SARS-CoV-2 infection on red cell molecules. As a result, they found that red blood cells from COVID-19 patients suffer from increased oxidant stress to several components of the cell membrane.

“The main protein we found to be attacked and fragmented by oxidant stress during the infection is called band 3, the most abundant protein in red blood cell membranes,” explains D’Alessandro. “This protein is critical to stabilize red cell membrane structures, regulate red cell metabolism and stabilize deoxygenated hemoglobin – thus favoring gas exchange.”

Very basically, the virus appears to disrupt red cell structure and function by targeting the most abundant proteins in the red blood cell, band 3 in the membrane and hemoglobin in the cytosol. These two proteins play an essential role in oxygen transport and delivery to the tissues in the face of hypoxia – either when climbing a fourteener in Colorado or when recovering from blood loss following an invasive surgery or a car accident. By messing with these mechanisms, the virus may compromise the capacity of the body to sense and react to hypoxia by releasing more oxygen from red blood cells.

“Red blood cells typically circulate around the body for about120 days. Since mature red blood cells cannot synthesize new proteins to replace the ones damaged by the virus, this could help explaining why it takes so long for some people to recover from COVID-19,” says D’Alessandro. “On top of recovering from any direct damage to the lung, the body may need time to make enough new, healthy red blood cells before optimal oxygenation in the blood is achieved.”

The observation paves the way for therapeutic approaches based on counteracting oxidant stress to red blood cells following SARS-CoV-2 infection or directly replacing damaged erythrocytes with transfusion therapies. “Colleagues from Europe and the United States have already reached out to test several interventional strategies based on these observations – from supplementation of taurine to red cell exchange therapies.” 

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