Mayo Clinic study into body’s immune response to virus supports need for widespread vaccination
As of early September 2021, the COVID-19 pandemic caused by the SARS-CoV-2 virus has affected more than 200 million people and caused 4.4 million deaths worldwide. India alone has reported 3,30,00,000 COVID-19 cases and 4,42,000 COVID-19 related deaths so far. While most infections are mild with no respiratory symptoms, a severe form of the disease is seen in older adults and people with chronic heart, kidney and lung diseases, diabetes or other conditions that weaken the immune system. COVID-19 damages many organs, including the lungs, heart and kidneys.
Commonly observed complication
Kidney injury as a complication of COVID-19 is commonly seen in hospitalized patients. While the prevalence of kidney injury was 7% in a large study of 2,650 hospitalized patients in southern India, a recent large study in the United States reported kidney injury in 46% of 3,993 hospitalized patients. Of which 19% required dialysis. With the increase in health care costs in patients with COVID-19 kidney injury, the length of hospitalization has also increased. Unfortunately, many more deaths occur in people with severe kidney injury.
Understanding the subtle changes that occur in the kidney after infection with the SARS-CoV-2 virus is important and has been the focus of extensive research. Researchers around the world, especially pathologists, are unified in their observation of COVID-19 kidney injury – that is, acute tubular injury (injury to the transport channels in the kidney) is a hallmark of kidney pathology. Thrombi or blood clots, as seen in the lungs and heart, can also be seen in the kidney. Inflammation (influx of white blood cells) in the kidney has also been described by researchers. Kidney injury is most commonly seen in kidneys that already have chronic injury, such as seen in diabetes or severe blood vessel diseases.
The precise mechanism by which the SARS-CoV-2 virus induces kidney injury has been studied in varying detail by different centers. The first question that is asked is whether the virus directly damages the kidney? Many centers around the world use a very special microscope called an electron microscope to look for evidence of the virus in the kidney. Early studies that emerged from China and the United States identified structures within kidney cells that looked like viral particles. This seemed logical, given that the kidney has high concentrations of ACE2, the major protein structure on a cell to which the SARS-CoV-2 virus attaches. This step is important for the virus to enter the cell. However, as more research was done, it became clear that what was once thought to be a viral particle in cells was, in fact, an increase in the number of vesicles (structures in the cell that are used to send vital signals) and There were only viral mimics. Specific staining techniques for detecting very small amounts of viral proteins also failed to show virus in the kidney. All of these suggested that direct viral injury was not the main mode of kidney injury. If not, how was the SARS-CoV-2 virus damaging the kidneys?
change after infection
The main focus of our own research was to understand how SARS-CoV-2 causes kidney injury and how proteins and genes change in the kidney after COVID-19 infection. this study Mayo Clinic, recently published In Mayo Clinic Proceedings , indicates a strong immune response (the immune response is the way the body fights off substances it sees as foreign or harmful) in the kidneys. The immune response was observed in all parts of the kidney tissue, including the small blood vessels and the glomerulus (the filtering unit of the kidney). This was mostly seen in people with severe cases of COVID-19. We were able to show the kidney two pathways of immune response; Innate immunity, which is a non-specific response you are born with to fight off harmful organisms. In the COVID-19 kidney, we found a rich infiltration of white blood cells (called macrophages) in the kidney. The adaptive immune response, which is the body’s acquired immune response to the SARS-CoV-2 virus, was evidenced by an increase in specific types of immunity (T cells) in kidney tissue. This was demonstrated using state-of-the-art techniques including transcriptomics, proteomics and mass-cytometry.
sepsis injury
Several experts in the field were suggesting that kidney injury in severe COVID-19 behaves similarly to kidney injury from sepsis, which is the body’s overreaction to infection. In our study, we were able to compare the findings of COVID-19 kidney injury with the kidneys of individuals with known sepsis, and in fact, the immune response was very similar in both. This finding perhaps emphasizes the need to manage COVID-19 patients in the same way as patients with sepsis. Our tissue protein analysis and ultrastructural analysis observations also point to the mitochondria, (which is the powerhouse of the cell) carrying the ultimate insult of SARS-CoV-2. Although this finding is unique to COVID-19 kidney injury, it provides important insights into potential treatment strategies that can be used in the management of COVID-19.
key takeaways
In conclusion, this Mayo Clinic study is significant in that it emphasizes some important facts. First, there is a great need for researchers to capitalize on patient samples collected during the pandemic and collect and store data for current and future use. The archived data will potentially provide valuable information in the event of another pandemic for future studies. Second, it will allow the study of tissue injury associated with COVID-19 in different populations. Third, using state-of-the-art technology tools, we were able to analyze the body’s immune response to the virus, and how this response can damage the kidneys. Taken together, the severe kidney injury seen in COVID-19 supports the need for widespread vaccination to protect everyone from this viral infection.
Dr. Maryam Priya Alexander is Associate Professor of Pathology, Mayo Clinic, Rochester, Minnesota, US
Dr. Timusin Tanner is Associate Professor, Transplant Surgeon and Immunologist, Mayo Clinic, Rochester, Minnesota, US
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