“Long after the illness is gone, the damage from coronavirus may remain - San Francisco Chronicle” plus 1 more

Long after the illness is gone, the damage from coronavirus may remain - San Francisco Chronicle

Posted: 31 May 2020 11:12 AM PDT

The roulette wheel of infection that determines which COVID-19 patients live and die has gripped the world in fear, but researchers are looking into another insidious danger — that the disease could be inflicting lasting, even permanent, damage on its victims.

Infectious disease specialists have learned that the health problems caused by the coronavirus sometimes linger for months, raising fears that the virus may have long-term consequences for people's health.

"There's no doubt there has been anecdotal evidence of symptoms lingering for a while, but we don't know if it's 1%, 5%, 20% or 50%" of the cases, said Jeffrey Martin, a clinical epidemiologist and professor of epidemiology and biostatistics at UCSF. "We need to find out how common that is. It's important that we separate the rare anecdotes from the true frequency."

Cases of chronic fatigue, heart problems, lung damage, blood clotting and neurological symptoms like dizziness and confusion have been documented in numerous patients long after the initial symptoms of COVID-19 have gone away.

The discovery of chronic symptoms could have a significant impact on human behavior as divisions erupt around the country over the speed with which businesses, parks, movie theaters and other gathering spots reopen. Boozy beach parties and concerts may not have the same lure for the young and healthy if the bacchanalia includes the prospect of prolonged disease and long-term disability.

It is what happened to Cliff Morrison, 68, of Oakland, who is still suffering from mood swings, headaches, blurry vision, aching joints and other strange symptoms nobody warned him about nearly two months after he first fell ill with COVID-19.

"I still have shortness of breath and some of the cough and no energy or strength," said Morrison, a nurse and health care administrator, who contracted the disease through his work. "My vision has improved but it's still a little blurry. No one told me that it would go on as long as it has."

Morrison, who worked as an AIDS coordinator in the 1980s, is one of 50 patients infected by COVID-19 who are enrolled in a study that Dr. Martin and a team of researchers at UCSF and San Francisco General Hospital are conducting. The investigation, called the Long-term Impact of Infection with Novel Coronavirus, or Liinc, is to determine what symptoms linger and how long the health problems last.

The study subjects, all of whom have been fever-free and tested negative for at least three weeks, were chosen because they had a wide spectrum of symptoms, from mild to severe.

Morrison, who lives alone, said he was very sick, unable to get out of bed except to go to the bathroom for three weeks. Besides being short of breath and feverish, his symptoms included vision problems, confusion and memory problems — he said there is a 10-day stretch when he can barely remember anything.

Tamareh Abualhsan, clinical research coordinator with UCSF's Long-term Impact of Infection with Novel Coronavirus study, takes a blood sample from Qin.

He suffered from unusually intense mood swings, ranging from deep depression to extreme anger. At one point he developed a rash over the lower half of his body that turned into sores, like the chicken pox, lasting two weeks.

More Information

Breathing issues, fatigue, lung damage, heart problems, blood clots, dizziness, confusion, memory loss, coughing, fever, headaches, loss of sense of smell, mood swings, blurry vision and aching joints.

In a small percentage of children who had a coronavirus infection, a condition called pediatric multisystem inflammatory syndrome surfaces weeks after exposure to the virus, causing rashes, fevers and heart inflammation — and, in a few cases, death.

Martin said the plan is to interview, take blood and saliva samples, and chart lingering health problems in study subjects for up to two years. It is important, he said, because the disease has not been around long enough to determine whether the lingering symptoms represent an abnormally long recovery process or a long-term problem.

It appears from the early evidence that Morrison's case is not unusual. Many recovering coronavirus patients have reported residual problems months after the initial infection, far longer than the experts thought was possible. The World Health Organization says patients with mild cases of COVID-19 should expect a two-week recovery process while severe infections could last up to six weeks before they clear up.

The evidence of more chronic problems is preliminary, but it is mounting.

Studies in China have found that most COVID-19 patients — well over 70% — showed lesions or patches of irritation in the lungs known as "ground glass opacities" that could develop into permanent scars, or pulmonary fibrosis.

The SARS-CoV-2 virus that causes the illness is known to target ACE2 receptors, a protein on the surface of human cells that the spiky virus attaches to. Many of the receptors are in the heart muscle. Various studies indicate cardiovascular damage is common, with one study finding it in 12% of patients studied and another showing heart damage in 19% of the patients.

High rates of blood clots have been reported in China and France. Studies in the two countries found that between 5% and 30% of the hospitalized patients suffered strokes, blockages of arteries or pulmonary embolisms, which are obstructions in the lungs.

Tony-nominated Canadian actor Nick Cordero had his right leg amputated after numerous COVID-related blood clots. The Broadway actor has now been in the hospital for about two months, much of that time on a ventilator.

Others have suffered strokes and heart attacks after being declared disease free and discharged from hospitals. The clots, which are likely caused by immune system responses to the infection, can also cause long-term problems, including heart palpitations and severe shortness of breath.

The virus also appears to attack the central nervous system, causing delirium and hallucinations in about a third of the patients in intensive care units. Morrison never had to go to the hospital, but he nevertheless suffered cognitive issues, which have mostly cleared up.

But many of the long-term problems may be a direct result of the severity of the infection. For instance, most critical patients end up suffering from acute respiratory distress syndrome, or ARDS, which is characterized by fluid in the lungs. Previous studies have shown that as many as 20% of ARDS survivors experience long-term cognitive impairment, including concentration and memory lapses, epidemiologists say.

Timothy Henrich, an associate professor of medicine and Martin's colleague at UCSF, said lingering problems can be expected in severe cases involving organ dysfunction, clotting and ARDS, but some people with mild cases of COVID-19 have also reported post-infection problems.

"It's not clear whether this is only in the severe cases," said Henrich, an infectious disease clinician, virologist and immunologist. "This may be happening in a more sub-acute fashion as well, but it needs to be studied."

Recovering COVID-19 victims, including some of Martin and Henrich's colleagues, have reported feeling foggy and having trouble focusing on work. Others say their coughs, fevers and breathing issues have cycled on and off for a month after the initial symptoms.

People have reported coughing up blood, losing their sense of smell, migraine-like headaches and short-term memory loss long after being cleared by doctors to go back to their normal routines.

Matt Willis, Marin County's public health officer, said he is still tired, weak, short of breath and has lingering circulation problems two months after his initial diagnosis.

"I feel like my lungs have been traumatized by this," said Willis, who is not part of the UCSF study. "I'm still close enough to the illness that I'm attributing some of these symptoms to post-viral inflammation."

But Henrich said some of these problems continue even after PCR, or polymerase chain reaction, tests no longer detect the virus, indicating an overzealous reaction by the human immune system.

"We are seeing immune activation even after the PCR tests are negative, suggesting that the body has cleared the initial virus, but the immune response is ongoing for quite some time," he said. "What we are interested in learning is: How long does this inflammation last, is there an ongoing immune activation?"

Infectious disease specialists believe that many of the more severe symptoms, including ARDS, are being caused by overly robust immune responses to the infection.

The human immune response may also be responsible for an inflammatory reaction similar to Kawasaki disease that has recently been affecting children exposed to the coronavirus, according to a Centers for Disease Control and Prevention warning. Experts say the ailment, known as pediatric multisystem inflammatory syndrome, can cause rashes, fevers and heart inflammation more than a month after exposure to the virus.

Doctors at UCSF's Benioff Children's Hospital have recently seen dozens of children with reddish-purple lesions on the feet and hands known as acral perniosis. The rashes all appeared weeks or months after exposure to adult relatives with flu-like symptoms, leading researchers to believe it is an after-the-fact inflammatory reaction to COVID-19.

Martin said the study at San Francisco General Hospital will test patients for antibodies and try to figure out what is going on with their immune responses. Researchers will also try to determine whether the 30 patients in the study have developed immunity and how long that immunity prevents them from being reinfected.

Morrison said the lingering fatigue, shortness of breath and blurred vision are concerns, but he is happy the phenomenon is being studied.

"We're only four months into this pandemic," he said, "and there is still so much that we don't know."

Peter Fimrite is a San Francisco Chronicle staff writer. Email: pfimrite@sfchronicle.com Twitter: @pfimrite

Anosmia and changes in brain MRI in COVID-19 - News-Medical.Net

Posted: 31 May 2020 07:59 PM PDT

Even as the COVID-19 pandemic was sweeping across the world, new symptoms and clinical presentations appeared, often confusing the picture. A case report from Italy, published in the journal JAMA Neurology in May 2020, shows that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be a neurotropic virus, and may cause infection to present primarily with anosmia.

Study: Magnetic Resonance Imaging Alteration of the Brain in a Patient With Coronavirus Disease 2019 (COVID-19) and Anosmia. Image Credit: Teeradej / Shutterstock

Human Coronavirus Infection

Human coronaviruses have already been shown to infect the nervous system in small animals. Autopsies of humans who suffered from SARS (severe acute respiratory syndrome) in 2002 to 2003 showed the presence of the SARS-CoV virus in the brain. Similarly, the SARS-CoV-2 may invade nervous tissue, and this may, partly at least, result in respiratory failure.

Coronaviruses (CoVs) are members of the largest group of viruses that are responsible for respiratory and gastrointestinal infections. Members of this group have caused three pandemics in the last two decades: first, the SARS outbreak in 2002, and the Middle East respiratory syndrome (MERS) pandemic in 2012. The current COVID-19 pandemic is thus the third outbreak caused by a coronavirus.

COVID-19 Symptoms

The symptoms of COVID-19 infection include fever, a dry cough, tiredness, anosmia, loss of taste, a sore throat, gut symptoms like diarrhea, headache, and leg pain. However, the majority of patients with COVID-19 do not know it, being completely asymptomatic, or develop only a mild bout of symptoms like sneezing or coughing.

In about 20% of cases, the infection progresses to cause severe pneumonia, acute respiratory distress syndrome (ARDS), multi-organ failure, and sometimes death, in a significant minority of cases. Despite the severe impact on the lungs, more evidence is coming in that the virus can also affect other organs and body systems, which could imply that the pandemic could leave behind acute and chronic sequelae.

The Brain and COVID-19

This could include neurological conditions. Patients with a history of stroke are among those at higher risk for COVID-19-induced ARDS, as has been shown by numerous case series. Conversely, over a third of COVID-19 patients in a Chinese study, had neurological signs such as acute stroke or loss of consciousness.

This is supported by the presence of agitation, confusion, signs of motor neuron involvement, and brain disorder in the majority of patients with this infection in a French study. In fact, the MERS-CoV outbreak was also associated with severe manifestations related to the nervous system.

The Case Report

The case study describes a female radiographer aged 25 years, with no underlying medical illness, who was working in a COVID-19 ward. She had a mild dry cough, which vanished after a day, to subsequently develop persistent and almost complete loss of smell and a weakened sense of taste. There was no fever, then or ever.

She had no history of any trauma, seizure, or hypoglycemic episode at any time. On the third day of anosmia, she underwent a fibroscopic evaluation of the nasal cavity, which failed to show any positive findings. A chest CT and CT of the maxillofacial cavities also did not show any particular findings. An MRI of the brain was also carried out, which included both 3D and 2D fluid-attenuated inversion recovery images.

The Imaging Findings

These images showed a hyperintense area in the cortex of the right gyrus rectus, as well as a less obvious hyperintense region in the olfactory bulbs. The occurrence of anosmia in many patients with COVID-19, in Italy, and because the altered cortical image suggested a viral infection of the area, the patient had a swab taken for reverse transcription-polymerase chain (RT-PCR) testing, to detect SARS-CoV-2.

The test was positive. A follow-up MRI which was taken after 28 days showed complete resolution of the hyperintensity in the right gyrus rectus cortex, while the olfactory bulbs had become less hyperintense and appeared slimmer.

The patient's anosmia eventually resolved. Interestingly, two other COVID-19 patients who also had anosmia did not show any signal alterations in MRIs of the brain at 12 and 25 days from the earliest symptom.

The Importance of This Case Report

The investigators say this is the first time that the human brain has been shown to be involved in a living patient with COVID-19, in the form of an alteration in the brain cortical signal that suggests viral invasion of the brain in a part that is linked to olfaction. The differential diagnoses in this patient could have been conditions like status epilepticus, changes like those seen in posterior reversible encephalopathy syndrome, other viral infections, and anti NMDA encephalitis, but none of these were probable in the clinical circumstances.

The subtle changes in the olfactory bulb, in addition to the other MRI findings, led the scientists to wonder if the virus could be invading the olfactory bulb and through this pathway, the brain, causing sensorineural dysfunction of the olfactory sense. However, this can be proved only if the evidence is compiled by the study of cerebrospinal fluid (CSF) and pathologic studies of the brain tissue.

A possible issue raised here is the absence of brain changes on MRI in two other COVID-19 patients who also had anosmia, as well as the disappearance of the MRI changes at the 28-day follow-up examination of this patient. This could indicate the extreme transience of these findings, which might occur only at the earliest stage of infection, or that they do not occur in all patients.

Another important finding from this case study is that some COVID-19 patients present only with anosmia, and it is necessary to evaluate this finding in the current situation to avoid missing the diagnosis in these otherwise asymptomatic patients and thus facilitating continued disease transmission from such individuals.

Journal reference:

Politi, L. S. et al. (2020). Magnetic Resonance Imaging Alteration of the Brain in a Patient with Coronavirus Disease 2019 (COVID-19) and Anosmia. JAMA Neurology doi:10.1001/jamaneurol.2020.2125.

Severe Acute Respiratory Syndrome