Is It COVID or Long COVID? Your Organs May Know

There’s little doubt long COVID is real. The federal government recognizes long COVID as a condition and said in two reports issued in August that one in five adult COVID-19 survivors have a health condition related to their illness.

COVID-19 can damage multiple organs in the body. Sometimes this damage leads to long COVID; sometimes other are reasons at play. Doctors are beginning to sort it out.

There’s a difference between long COVID and an acute infection with lasting effects, doctors say.

“COVID itself can actually cause prolonged illness, and we don’t really call that long COVID,” says Nisha Viswanathan, MD, a doctor at UCLA Health in Los Angeles. But if symptoms extend beyond 12 weeks, that puts patients in the realm of long COVID, she says.

Symptoms can range from mild to severe and can keep people from resuming their normal lives and jobs. Sometimes they last for months, according to the U.S. Department of Health and Human Services.

Multi-Organ Damage

Lung scarring and other lung problems are common after COVID, says Leora Horwitz, MD, an internal medicine specialist at the New York University Grossman School of Medicine. Even after a mild case, people can have breathing issues for months, a team at Johns Hopkins Medicine says in an online briefing. One study published in the journal Radiology found damage in people a full year after a COVID-19 diagnosis.

Some people have persistent heart, kidney, liver, and nervous system problems after COVID-19. A study published in 2020 in the journal JAMA Cardiology found 60% of people who had COVID-19 had ongoing signs of heart inflammation. Nearly a third of people hospitalized for COVID-19 get kidney damage that can become chronic, and some end up needing dialysis or a transplant, says C. John Sperati, MD, a kidney specialist at Johns Hopkins Medicine in Baltimore

This might be, in part, because SARS-CoV-2, the virus that causes COVID-19, directly infects the cells in many organs.

Nicole Bhave, MD, a cardiologist at University of Michigan Health, is concerned that COVID-19 appears to increase the risk of heart problems in some people.

“Some of the uptick may just be recognition bias, in that people with symptoms are seeking care,” she says. “But there’s definitely a biological basis by which COVID could tip people over into a new diagnosis of heart failure.”

Inflammation

Inflammation is probably a key part of the long-term effects of COVID-19.

Some people have a serious immune reaction to COVID-19 called a cytokine storm, says Nitra Aggarwal Gilotra, MD, a cardiologist at Johns Hopkins Medicine. This release of inflammation-causing molecules called cytokines is meant to attack the invading virus. But it can be so severe that it wreaks havoc on healthy tissues and organs and causes lasting damage – if patients even survive it.

In some people, inflammation can affect the heart, causing myocarditis. Myocarditis symptoms include chest pain, breathlessness, and heart palpitations. Though rare, it can be serious and can raise the risk of other heart problems, including heart failure, down the line.

Long COVID may also trigger an autoimmune condition, says Eline Luning Prak, MD, PhD, a pathologist at the Hospital of the University of Pennsylvania. Long COVID can share many hallmark symptoms with autoimmune diseases, including fatigue, widespread pain, memory problems, and mood disorders, Prak says.

Blood Clots

Studies have shown the overcharged inflammatory response to COVID-19 can cause blood clots. This sometimes overwhelming clotting was an early hallmark of COVID-19 infection, and when clots restrict blood flow in the brain, lungs, kidneys, or limbs, they can cause long-term damage. Some can be deadly. Researchers in Sweden found patients were at risk of deep vein thrombosis – a blood clot usually in the leg – up to 3 months after infection and at higher risk of a blood clot in the lung, called pulmonary embolism, for as long as 3 months.

Viral Reservoirs

The virus itself may also linger in a patient’s body, causing continued symptoms and, potentially, new flare-ups. Harvard Medical School’s Zoe Swank, PhD, and colleagues reported in a pre-print study that they found pieces of the SARS-CoV-2 virus in the blood of most patients with long COVID symptoms they tested – some as long as a year after infection. The study has not yet been peer-reviewed.

Another team found evidence of the virus in stool up to 7 months later, which suggests the virus hides out in the gut. Other early studies have found bits of viral RNA in the appendix, breast tissue, heart, eyes, and brain.

Diabetes

Diabetes is a risk factor for getting severe COVID-19, and multiple studies have shown people can get diabetes both while battling infection and afterward. One study of veterans found COVID-19 survivors were about 40% more likely to get diabetes over the next year.

Some studies have suggested a few ways this might happen. Insulin-producing cells in the pancreas have SARS-CoV-2 receptors – a type of molecular doorway the coronavirus can attach to. Damage to these cells could make the body less able to produce insulin, which in turn can lead to diabetes. The virus could also disrupt the balance in the body or cause inflammation that leads to insulin resistance, which can develop into diabetes, Ziad Al-Aly, MD, of the Veterans Affairs St. Louis Health Care System, and colleagues wrote in The Lancet Diabetes and Endocrinology.

Nervous System Issues

People who get COVID-19 are also more vulnerable to postural orthostatic tachycardia syndrome (POTS). This affects what’s known as the autonomic nervous system, which regulates blood circulation, and includes those things that happen in your body without your having to think about them, like breathing, heartbeat, and digestion. POTS can cause common long COVID neurologic symptoms, including headaches, fatigue, brain fog, insomnia, and problems thinking and concentrating. “This was a known condition prior to COVID, but it was incredibly rare,” says Viswanathan, the UCLA Health doctor. “After COVID, I’ve seen it with increasing frequency.”

Long-Term Outlook

Lasting issues after COVID-19 are much more likely after a moderate or severe infection. Still, plenty of people are battling them even after a mild illness. “As for why, that’s the billion-dollar question,” says Horwitz, the internal medicine specialist. “It’s well-known that viral infections can cause long-term dysregulation. Why that is, we really just don’t know.”

Whether it’s virus hiding out in the body, long-term organ damage, or an autoimmune reaction likely differs from person to person. “I’m believing, increasingly, that it’s a combination of all of these, just based on how different patients are responding to different medications,” says Viswanathan. “One patient will respond to something beautifully, and another patient won’t at all.”

But it’s clear a significant number of people are facing long-term health struggles because of COVID-19, which has infected at least 580 million people globally and 92 million – likely many more – in the U.S., according to Johns Hopkins University.

Even a small increased risk of conditions like heart disease or diabetes translates to a huge number of people, Horwitz says. “If even 1% of people getting COVID have long-term symptoms, that’s a major public health crisis, because that’s 1% of pretty much everybody in the country,” she says.

SOURCES:

American College of Cardiology: “ACC Issues Clinical Guidance on Cardiovascular Consequences of COVID-19.”

British Medical Journal: “Risks of Deep Vein Thrombosis, Pulmonary Embolism, and Bleeding After Covid-19: Nationwide Self-Controlled Cases Series and Matched Cohort Study,” “Study Finds Risk of Serious Blood Clots up to Six Months After COVID-19.”

British Society for Immunology: “Long-Term Immunological Health Consequences of COVID-19.”

Cardiovascular Diabetology: “Persistent Clotting Protein Pathology in Long Covid/Post-Acute Sequelae of COVID-19 (PASC) is Accompanied by Increased Levels of Antiplasmin.”

Cell: “Gastrointestinal Symptoms and Fecal Shedding of SARS-CoV-2 RNA Suggest Prolonged Gastrointestinal Infection.”

Frontiers in Endocrinology: “COVID-19 and Diabetes: Understanding the Interrelationship and Risks for a Severe Course.”

Global Autoimmune Institute: “Is Long COVID a New Autoimmune Disease?”

U.S. Department of Health and Human Services: “Services and Supports for Longer-Term Impacts of COVID-19.”

Johns Hopkins Medicine: “Coronavirus: Kidney Damage Caused by COVID-19,” “Heart Problems after COVID-19,” “Long COVID: Long-Term Effects of COVID-19,” “What Does COVID Do to Your Blood?”

Journal of the American Society of Nephrology: “Kidney Outcomes in Long COVID.”

JAMA Cardiology: “Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19).”

The Lancet Diabetes & Endocrinology: “Risks and Burdens of Incident Diabetes in Long Covid: A Cohort Study.”

Leora Horwitz, health systems specialist, co-leader, Clinical Science Core, NIH RECOVER Initiative, NYU Langone Health.

MedRxiv: “Persistent Circulating SARS-CoV-2 Spike is Associated with Post-Acute COVID-19 Sequelae.”

Nature Medicine: “Symptoms and Risk Factors for Long COVID in Non-Hospitalized Adults.”

Nature News: “Coronavirus ‘Ghosts’ Found Lingering in the Gut,” “Diabetes Risk Rises After Covid, Massive Study Finds.”

Nature Reviews Nephrology: “Long COVID and Kidney Disease.”

News release, European Society of Clinical Microbiology and Infectious Diseases.

Radiology: “Lung Abnormalities Depicted with Hyperpolarized Xenon MRI in Patients with Long COVID.”

Nicole Bhave, cardiologist, University of Michigan Health.

Nisha Viswanathan, MD, co-director, Long COVID program, UCLA Health.

PLOS Pathogens: “SARS-CoV-2-Specific T cells Associate with Inflammation and Reduced Lung Function in Pulmonary Post-Acute Sequalae of SARS-CoV-2.”

Science Translational Medicine: “Prothrombotic autoantibodies in serum from patients hospitalized with COVID-19.”

University of Michigan Health: “New Cause of COVID-19 Blood Clots Identified.”

Viruses: “Viruses and Autoimmunity: A Review on the Potential Interaction and Molecular Mechanisms.”

Yale News: “For COVID-19, Endemic Stage Could be Two Years Away.”

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