Duke doctors share insights on the illness during a media briefing


Thousands of COVID-19 survivors continue to grapple with symptoms many months after they were first infected. Brain fog, fatigue, even sexual dysfunction are among the symptoms people endure weeks and months after their acute COVID symptoms fade.

On some occasions, the virus reveals a pre-existing disease or causes another to inflict the patient.

But there is still much unknown about so-called long COVID, which ongoing research at Duke University and elsewhere aims to clarify.

Two Duke pulmonologists spoke Wednesday with the media about symptoms, treatments and what remains unknown about long COVID.


Dr. Coral Giovacchini, a pulmonologist and critical care specialist with Duke Health and an assistant professor of medicine

“Groups have created different definitions and so what we initially mean now, when we talk about long COVID is symptoms that last beyond the four weeks of what we would consider the acute illness.”

“… And the NIH is defining this still currently as anything after four weeks, and this is an evolving definition for us.”

“Long COVID itself can include a host of different symptoms after the acute infection, it’s usually an extension of what you have sometimes from your acute infection, but can also include other new things. The most common things that we see are persistent fatigue and persistent shortness of breath symptoms, it can also include a bunch of different things like palpitations, things that we’ve heard referred to as brain fog, memory issues, ongoing insomnia problems, neuropathic problems and a host of different things.”

Dr. Loretta Que, a pulmonologist with Duke Health and a professor of medicine

“When you look at the literature and when you look at what we see here at Duke, the literature quotes anywhere from 10 to 50% of patients can have long COVID or developed long-COVID symptoms. I think, on average, it’s about 30% that’s quoted.”

“Over here Duke we’re seeing numbers that are similar to that, if you look at that also is somewhat dependent on the symptom that you’re describing post-COVID because if you look at brain fog, even up to 80% of patients are quoting brain fog after COVID, so it is, it is a burden on patients and it’s a problem that they’re trying to deal with and that we’re trying to help them with.”


Dr. Loretta Que

“What I’m seeing with COVID is something similar to what I see with other chronic illnesses, so if you look at diseases like Lyme disease, for example, a lot of these patients can develop prolonged fatigue, fibromyalgia — that’s muscle aches and pains — difficulty concentrating, difficulty breathing. So all of those symptoms that I see with chronic diseases I’m also seeing with COVID and long COVID.”

“How do you tell the difference? It’s hard to know. We assess the patient when they come in. Our clinic at Duke primarily focuses on the lung effects of COVID. And so, if someone comes in and they’re complaining about shortness of breath or chest discomfort … post-COVID then we see them. And we often find that if they had some form of lung disease prior to COVID, then whatever symptoms they had before COVID have been amplified after COVID.”

“I think what we’re seeing is a combination of the acute effects of COVID and then the amplification of disease after they’ve had COVID.”

“COVID can unmask disease, (it) can be something predating or can be something that’s been unmasked or something new.”

Dr. Coral Giovacchini

“Another part of the definition that’s evolving right is that we want to make sure that there’s not something else going on, and so it’s really important for patients to present if you have these symptoms rather than just saying, ‘Oh, I have ongoing long COVID or post-viral syndrome.’”

“Because, and you know, even though it feels like it through this pandemic time, not everything is COVID and you really want to make sure that what we’re treating and what we’re seeing is not something else that’s maybe being masked by what you might think is COVID.”


Dr. Coral Giovacchini

“That’s another interesting question, another part of the literature that is sort of evolving as we follow this along. I think what people think of as historical risk factors for severe disease, so things like age, underlying comorbidity, … high blood pressure and diabetes are not actually the things that pan out in terms of risk factors for COVID … or for long COVID for some people.”

“That’s been quite a surprise, when they develop symptoms later or have ongoing persistent symptoms and the most consistent thing that’s been panned out so far in some of the cohort studies, in the literature, is the number of symptoms that someone presents with.”

“So if somebody has more than five different types of symptoms that they’re presenting with, with their acute COVID infection, that may predispose (them) to ongoing long COVID and symptoms. They don’t necessarily need to be the same symptoms, but that probably is something that predisposes, regardless of the initial severity of your disease.”

“So even patients who are managed as outpatient or have mild disease but have a host of symptoms when they present, may be more likely to get long COVID symptoms in the future.”

“It’s certainly not something that means that you will develop long COVID if you have that many symptoms, it’s just that that’s something that we’re seeing as a potential risk factor.”

“I think the other surprising thing for some patients and people following this is that again, it does not relate to the severity of your disease, so these patients can have had mild disease, or maybe a short hospitalization and still end up with long COVID symptoms. They’re also tending to be younger patients than we think of as those who might get severe disease.”

“Patients who are showing up with long COVID symptoms tend to be on the younger end of that spectrum. So maybe in the 40 to 55 range and even younger patients we’ve seen this pan out.”


Dr. Loretta Que

“Well, we still are seeing long covid post-vaccination. The numbers are way lower so (there’s a) marked reduction in these numbers of patients that are presenting and … seem to be different than what we see with those who have not been vaccinated. So the severity of their post COVID seems to be reduced.”

“… When I look at their lung findings on a CT scan or chest X-ray or lung-function studies, they are not as affected as those who have not been vaccinated.”


Dr. Coral Giovacchini

“I think that’s the hope for a lot of folks, but it is certainly too soon to know if it’s going to have a difference in terms of long COVID symptoms. I think … the goal of antivirals is to reduce the severity of disease and reduce the symptom burden, but again, long COVID can happen in patients who may or may not have had severe disease, and so it’s an area that will be interesting to see how that unfolds in the future as more patients get treated with antivirals that are coming out.”


Dr. Coral Giovacchini

“I think, for a lot of patients, because for some patients fatigue that goes on for months can be extremely debilitating and maybe more ‘severe’ for them in terms of their daily functioning, than perhaps their initial respiratory symptoms were up front.”

“And so I think it just it depends on the type of symptom that the patient is dealing with. … For a lot of patients, that can be very severe in terms of their ongoing daily life ability to function, particularly some of the brain fog and mental effects.”


Dr. Loretta Que

“Long COVID in children is an issue and we still don’t know the long-term impact of that.”

Dr. Coral Giovacchini

“There are data that are now coming out of countries who had higher (cases of COVID) before we did, and so we have a little bit longer-term data.”

“Countries like Italy and Israel and the UK … have shown that long COVID in kids is evolving and is becoming an issue for them, with rates of about 40% of kids still having ongoing symptom effects at an average of 162 days. So in that five and a half, six months follow-up range most of their symptoms can be things like fatigue, like adults have, but are also turning into some of the cognitive effects like memory attention disorders in kids and some anxiety.”

“Now, there has been a lot of question of this in the literature as whether or not these mental effects are coven related or pandemic related, which is going to be a whole other thing to figure out, especially in the children population.”

“But it is certainly something to follow in kids because what we’ve historically been talking about again is that this is mild disease in kids so even the children who are … outpatients can have ongoing effects and it’s something that parents and pediatricians need to be watching out for in the future, as we follow these kids along.”


Dr. Loretta Que

“A lot of what we do in medicine is trying to unravel these puzzles. I think that’s a great question, because we have a lot of ongoing research that’s been done to help us … better identify these patients and the NIH is devoting research dollars to the development of new research platforms to help us in this endeavor. Right now, it’s a broad constellation of symptoms. I suspect it’s going to continue being a broad constellation of symptoms, just like when anybody presents with viral-like illness and we have to do an evaluation, but it might be that in the future, we might have a more targeted approach to doing so. That’s our hope.”


Dr. Loretta Que

“I’ve seen patients with sexual dysfunction with long COVID. It’s not a strange abnormality, but it’s odd for me because I’m a lung doctor and they presented with sexual dysfunction and pain.”

Dr. Coral Giovacchini

“Yeah, … I have seen the same, and I think that can be shocking for some patients. I would go back to the ongoing taste abnormalities for patients. I think a lot of patients feel like that is a very strange manifestation, even if they didn’t have loss of smell or taste. Some of their favorite foods can just be almost intolerable to them going forward and it’s a challenging thing we don’t have a treatment for. And so it can also cause a lot of weight-loss problems in patients or weight gain, depending on their taste alterations.”


Dr. Loretta Que

“There are multiple studies that (are) looking at long COVID and not just within the pulmonary division and so, if you go to the Duke Hospital website, you can look at some of the different trials that are ongoing and see which one you might qualify for.”

(COVID studies open at Duke:; COVID repository:

Faculty Participants

Coral Giovacchini, M.D.
Dr. Coral Giovacchini is a pulmonologist and critical care specialist with Duke Health and an assistant professor of medicine at the Duke University School of Medicine.

Loretta Que, M.D.
Dr. Loretta Que is a pulmonologist with Duke Health and a professor of medicine at the Duke University School of Medicine.

Ophthalmic Manifestations Of Coronavirus (COVID-19)

Authors: Katherine Hu; Jay Patel; Cole Swiston; Bhupendra C. Patel.Author Information Last Update: May 19, 2021.

Several reports of suspected ocular manifestations of coronavirus disease 2019 (COVID-19) have prompted investigations into ocular signs, symptoms, and transmission. This activity reviews the evaluation and management of ocular manifestations of COVID-19 and highlights the interprofessional team’s role in managing patients with this condition.


  • Summarize the epidemiology of ocular manifestations of COVID-19.
  • Describe the typical presentation of a patient with ocular manifestations of COVID-19.
  • Outline management considerations for patients with ocular manifestations of COVID-19, including key patient counseling on disease transmission prevention.
  • Explain the importance of collaboration and communication among the interprofessional team to improve outcomes for patients affected by COVID-19.


Since December 2019, coronavirus disease 2019 (COVID-19) has become a global pandemic caused by the highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).[1] Initially, there were several reports of eye redness and irritation in COVID-19 patients, both anecdotal and published, suggesting that conjunctivitis is an ocular manifestation of SARS-CoV-2 infection. Reports continue to emerge on further associations of COVID-19 with uveitic, retinovascular, and neuro-ophthalmic disease.

During the 2003 severe acute respiratory syndrome (SARS) outbreak, a study detected SARS-CoV in tear samples in SARS patients in Singapore.[2] Lack of eye protection was a primary risk factor of SARS-CoV transmission from SARS patients to healthcare workers in Toronto, prompting a concern that respiratory illness could be transmitted through ocular secretions.[3][4] Similar concerns have been raised with SARS-CoV-2, especially among eye care providers and those on the front lines triaging what could be initial symptoms of COVID-19.

As conjunctivitis is a common eye condition, ophthalmologists may be the first medical professionals to evaluate a patient with COVID-19. Indeed, one of the first providers to voice concerns regarding the spread of coronavirus in Chinese patients was Dr. Li Wenliang, MD, an ophthalmologist. He later died from COVID-19 and was believed to have contracted the virus from an asymptomatic glaucoma patient in his clinic.

The authors of this article have attempted to collect the most up-to-date information on ophthalmic manifestations of COVID-19 as a resource for identifying symptoms, providing diagnostic pearls, and mitigating transmission.


SARS-CoV-2 is a novel enveloped, positive single-stranded RNA beta coronavirus that causes COVID-19, originally linked to an outbreak in Wuhan of China’s Hubei province.[1] Direct contact with mucous membranes, including the eye, is a suspected route of transmission.

Coronaviruses can cause severe ocular disease in animals, including anterior uveitis, retinitis, vasculitis, and optic neuritis in feline and murine species. However, ocular manifestations in humans are typically mild and rare, [5] although there are increasing numbers of associated ocular findings in patients positive for the COVID-19. There are no described ocular manifestations of Middle East respiratory syndrome (MERS) or SARS, though, as previously stated, SARS-CoV was isolated in ocular secretions.[2] Other coronaviruses have been found to cause viral conjunctivitis in humans.[6]


At the time of writing the initial article on April 4, 2020, there were 1,272,953 confirmed cases and 69,428 deaths due to COVID-19 worldwide, according to the World Health Organization (WHO), with 79,332 new cases confirmed in the previous 24 hours. At the time, the Center for Disease Control and Prevention (CDC) had reported 337,278 cases and 9,637 deaths in the United States to that date. On April 16, 2021, just over a year since our initial review, the number of deaths worldwide has crossed the 3 million mark. The severity of the pandemic is emphasized by noting the rate of deaths: it took 8.5 months after the first fatality in China to mark the loss of the first 1 million lives, 3.5 months to reach 2 million, and 3 months for the loss to cross 3 million lives. 

As of May 17, 2021, there have been over 164 million confirmed cases globally (the real number is, of course, far in excess of this as the number does not include infected individuals who were not tested or asymptomatic cases) and 3,403,722 deaths. India, Iran, and Brazil are currently experiencing the highest number of infections in a 24 hour period ever with new viral strains being discovered in different parts of the world. The United States has had the most infections (33,745,500) and deaths (600,514), followed by India, Brazil, France, Turkey, Russia and the United Kingdom. Increasing infections are currently being seen in Canada, France, Germany, and other countries, necessitating further shutdowns. In the United States, there is an overall uptick in infections as restrictions are relaxed. 

Viral mutations leading to variants of SARS-CoV-2 have been found around the world: the B.1.525 in the United Kingdom and Nigeria in December 2020, the B.1.526in the United States in November 2020, the B.1.1.7 in the United Kingdom in early 202, the B.1.351 in South Africa in late 2020, and the Indian variant in April 2021. 

Early studies postulated that ocular manifestations of COVID-19 were rare overall. Only 9 (0.8%) out of 1,099 patients from 552 hospitals across 30 provinces in China were reported to have “conjunctival congestion” from December 2019 through January 2020.[7] More recent data, however, have supported a much higher incidence of ocular signs and symptoms. A 2021 meta-analysis by Nasiri et al. reported a pooled prevalence of all ocular manifestations among 7,300 COVID-19 patients as 11.03%, with the most frequent ocular disease being conjunctivitis (88.8%).[8] In the same meta-analysis, dry eye or foreign body sensation (16%), eye redness (13.3%), tearing (12.8%), and itching (12.6%) were among the most frequent symptoms reported. 

A case series reported ocular symptoms in 12 (31.6%) of 38 hospitalized patients with COVID-19 in Hubei province, China.[9] These 12 of 38 patients had conjunctival hyperemia (3 patients), chemosis (7 patients), epiphora (7 patients), or increased secretions (7 patients). Of note is that one patient who had epiphora presented with epiphora as the first symptom of COVID-19. Of those with ocular manifestations, 2 (16.7%) patients had positive results of SARS-CoV-2 on reverse-transcriptase polymerase chain reaction (RT-PCR) by a conjunctival swab, as well as by nasopharyngeal swabs. Only one patient in this study presented with conjunctivitis as the first symptom.[9] The authors noted that patients with ocular symptoms had higher white blood cell and neutrophil counts, C-reactive protein, and higher levels of procalcitonin and lactate dehydrogenase compared to patients without ocular abnormalities. 

Out of 30 hospitalized patients with COVID-19 tested by Xia et al., one patient had conjunctivitis and was also the sole patient in the study to test positive for SARS-CoV-2 in ocular secretions by a conjunctival swab. This patient did not have a severe fever or respiratory symptoms at the time of testing.[10]

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COVID-19: A Mitochondrial Perspective

Authors: Pankaj Prasun 1

Coronavirus disease 2019 (COVID-19) is the worst public health crisis of the century. Although we have made tremendous progress in understanding the pathogenesis of this disease, a lot more remains to be learned. Mitochondria appear to be important in COVID-19 pathogenesis because of its role in innate antiviral immunity, as well as inflammation. This article examines pathogenesis of COVID-19 from a mitochondrial perspective and tries to answer some perplexing questions such as why the prognosis is so poor in those with obesity, metabolic syndrome, or type 2 diabetes. Although effective vaccines and antiviral drugs will be the ultimate solution to this crisis, a better understanding of disease mechanisms will open novel avenues for treatment and prevention.

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COVID-19 Vasculopathy: Mounting Evidence for an Indirect Mechanism of Endothelial Injury

Authors: Roberto F. Nicosia,∗∗ Giovanni Ligresti, Nunzia Caporarello, Shreeram Akilesh, and Domenico Ribatti§

Patients with coronavirus disease 2019 (COVID-19) who are critically ill develop vascular complications characterized by thrombosis of small, medium, and large vessels. Dysfunction of the vascular endothelium due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been implicated in the pathogenesis of the COVID-19 vasculopathy. Although initial reports suggested that endothelial injury was caused directly by the virus, recent studies indicate that endothelial cells do not express angiotensin-converting enzyme 2, the receptor that SARS-CoV-2 uses to gain entry into cells, or express it at low levels and are resistant to the infection. These new findings, together with the observation that COVID-19 triggers a cytokine storm capable of injuring the endothelium and disrupting its antithrombogenic properties, favor an indirect mechanism of endothelial injury mediated locally by an augmented inflammatory reaction to infected nonendothelial cells, such as the bronchial and alveolar epithelium, and systemically by the excessive immune response to infection. Herein we review the vascular pathology of COVID-19 and critically discuss the potential mechanisms of endothelial injury in this disease.

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Endothelial dysfunction in COVID-19: Current findings and therapeutic implications

Authors: Matthias P Nägele 1Bernhard Haubner 1Felix C Tanner 1Frank Ruschitzka 1Andreas J Flammer 2

Coronavirus disease 2019 (COVID-19) increases the risk of several non-pulmonary complications such as acute myocardial injury, renal failure or thromboembolic events. A possible unifying explanation for these phenomena may be the presence of profound endothelial dysfunction and injury. This review provides an overview on the association of endothelial dysfunction with COVID-19 and its therapeutic implications. Endothelial dysfunction is a common feature of the key comorbidities that increase risk for severe COVID-19 such as hypertension, obesity, diabetes mellitus, coronary artery disease or heart failure. Preliminary studies indicate that vascular endothelial cells can be infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and evidence of widespread endothelial injury and inflammation is found in advanced cases of COVID-19. Prior evidence has established the crucial role of endothelial cells in maintaining and regulating vascular homeostasis and blood coagulation. Aggravation of endothelial dysfunction in COVID-19 may therefore impair organ perfusion and cause a procoagulatory state resulting in both macro- and microvascular thrombotic events. Angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and statins are known to improve endothelial dysfunction. Data from smaller observational studies and other viral infections suggests a possible beneficial effect in COVID-19. Other treatments that are currently under investigation for COVID-19 may also act by improving endothelial dysfunction in patients. Focusing therapies on preventing and improving endothelial dysfunction could improve outcomes in COVID-19. Several clinical trials are currently underway to explore this concept.

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Mutational Similarities Between SARS-CoV-2 and Its Predecessors

Authors: | Original story from University of Nebraska–Lincoln, Credit: Pete Linforth/ Pixabay

New research from the University of Nebraska-Lincoln has shown that the mutations arising in the COVID-19-causing SARS-CoV-2 virus seem to run in the family — or at least the genus of coronaviruses most dangerous to humans.

After comparing the early evolution of SARS-CoV-2 against that of its closest relatives, the betacoronaviruses, the Nebraska team found that SARS-CoV-2 mutations are occurring in essentially the same locations, both genetically and structurally.

The mutational similarities between SARS-CoV-2 and its predecessors, including the human-infecting SARS-CoV-1 and MERS-CoV, could help inform predictions of how the COVID-causing virus will continue to evolve, the researchers said.

“The problem of looking at only one virus at a time is that you lose the forest for the trees,” said Katherine LaTourrette, a doctoral student in the Complex Biosystems program at Nebraska. “By looking at this big picture, we were able to predict the mutational nature of SARS-CoV-2.

“That gets into these questions of: Are vaccines going to be effective long term? Which variants are going to sneak by? Do we need that booster shot? Are vaccinated people going to be infected a second time?”

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Primed” for Infection: Cells Damaged by Chronic Lung Disease Can Result in Severe COVID


Results from a TGen-led international study suggest that SARS-CoV-2 takes advantage of genetic changes among patients with pre-existing lung diseases.

The results of a study by an international scientific team co-led by the Translational Genomics Research Institute (TGen), an affiliate of City of Hope, suggest that — like pouring water atop a wellhead before pumping — the airway cells of patients with chronic lung diseases are “primed” for infection by the COVID-19 virus, resulting in more severe symptoms, poorer outcomes and a greater likelihood of death.

The study — published today in Nature Communications — details the genetic changes caused by chronic lung disease in the molecular makeup of a variety of cells, including the epithelial cells that line the lung and airways. The study details how those changes can help enable SARS-CoV-2, the virus that causes COVID-19, to enter the body, replicate and trigger an out-of-control immune response that fills the lungs with fluids and often results in patients needing respirators and lengthy hospitalizations.

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SARS-CoV-2 viral genomics

Authors: This analysis was performed primarily by Matt Olm ( in Justin Sonnenburg’s lab at Stanford University and Alex Crits-Christoph ( in Jill Banfield’s lab at University of California, Berkeley

As viruses replicate within their hosts during infection, they mutate and accrue genetic diversity in their populations. These populations are usually shared as a single genome representing the consensus genome from a particular patient, and analysis of inter-patient variation (differences between the consensus genomes from different patients) is useful for understanding how the outbreak spreads, and how the virus evolves globally.

We refer to the variation within a single individual as intra-patient variation, intraspecfic variation, or microdiversity. This genetic variation is less commonly studied, but analysis of this data has the following potential applications:

  • Identification of the genomic loci least likely to mutate during infection, which could be useful for designing universal primers / probes.
  • Comparison of viral evolution within individuals versus global evolution. This can be useful for understanding how the viral evolutionary pressures and functions.
  • Estimation of the number of viral particles acquired at the onset of infection and quantifying genetic diversity transferred during transmission.

Inter-patient SARS-CoV-2 genome variation

To analyze inter-patient variation, we downloaded publicly available SARS-CoV-2 genomes, processed and filtered them, and generated a multiple sequence alignment. Details can be found in the Methods second, and the genomes and alignment can be downloaded from the Data availability section.

After genome alignment, we can visualize genetic diversity across the genome:

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Covid-19: links between genes and disease severity

Authors: Bolzano research centre

In March 2020, thousands of scientists around the world joined forces to investigate the questions at the forefront of the medical debate on the pandemic: what genetic factors influence the severity of Covid-19 infections and why do some people develop a serious illness that requires hospitalisation while others have mild or no symptoms?

The results of the research, published in Nature only a few days ago, revealed extraordinary findings 13 loci – points in the human genome – were identified as being strongly associated with severe Covid-19 infection. This discovery comes from one of the world’s largest genetics studies: the group examined the genomes of almost 50,000 patients with Covid-19 and another two million uninfected people. The data findings included participants in the studies conducted by Eurac Research in South Tyrol over the past year.

The Covid-19 Host Genomics Initiative was launched in March 2020 by the Finnish Institute of Molecular Medicine at the University of Helsinki. The initiative has now grown to become one of the most extensive collaborations on human genetics, currently including more than 60 studies from 25 different countries. Thanks to the huge amount of data available, the researchers have been able to produce statistically robust analyses in a relatively short time, achieving results that no research institution could have achieved independently. Of the 13 loci identified, two were found most frequently in East and South Asian populations. The analyses also showed that some of these loci are located in close proximity to genes involved in serious lung diseases such as cancer or pulmonary fibrosis. In these cases, inhibiting the gene could be a therapeutic strategy to be explored further. Researchers have also identified other factors that influence the severity of the disease, such as smoking and a high body mass index.

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Authors: Cleveland Clinic

What is dysautonomia?

Dysautonomia is a general term for a group of disorders that share a common problem – that is, an autonomic nervous system (ANS) that doesn’t function as it should. The ANS is the part of the nervous system that controls involuntary body functions (functions you don’t consciously control) like your heart rate, blood pressure, breathing, digestion, body and skin temperature, hormonal function, bladder function, sexual function and many other functions.

When the ANS doesn’t work the way it should, it can cause heart and blood pressure problems, breathing trouble, loss of bladder control and many other problems.

Who might get dysautonomia?

Dysautonomia, also called autonomic dysfunction or autonomic neuropathy, is relatively common. Worldwide, it affects more than 70 million people. It can be present at birth or appear gradually or suddenly at any age. Dysautonomia can be mild to serious in severity and even fatal (rarely). It affects women and men equally.

Dysautonomia can occur as its own disorder, without the presence of other diseases. This is called primary dysautonomia. It can also occur as a condition of another disease. This is called secondary dysautonomia.

Examples of diseases in which secondary dysautonomia can occur include:

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