Older adults with COVID-19, the illness caused by the coronavirus, have several "atypical" symptoms, complicating efforts to ensure they get timely and appropriate treatment, according to physicians.
COVID-19 is typically signaled by three symptoms: a fever, an insistent cough and shortness of breath. But older adults — the age group most at risk of severe complications or death from this condition ― may have none of these characteristics.
Instead, seniors may seem "off" — not acting like themselves ― early on after being infected by the coronavirus. They may sleep more than usual or stop eating. They may seem unusually apathetic or confused, losing orientation to their surroundings. They may become dizzy and fall. Sometimes, seniors stop speaking or simply collapse.
"With a lot of conditions, older adults don't present in a typical way, and we're seeing that with COVID-19 as well," said Dr. Camille Vaughan, section chief of geriatrics and gerontology at Emory University.
The reason has to do with how older bodies respond to illness and infection.
At advanced ages, "someone's immune response may be blunted and their ability to regulate temperature may be altered," said Dr. Joseph Ouslander, a professor of geriatric medicine at Florida Atlantic University's Schmidt College of Medicine.
"Underlying chronic illnesses can mask or interfere with signs of infection," he said. "Some older people, whether from age-related changes or previous neurologic issues such as a stroke, may have altered cough reflexes. Others with cognitive impairment may not be able to communicate their symptoms."
Recognizing danger signs is important: If early signs of COVID-19 are missed, seniors may deteriorate before getting needed care. And people may go in and out of their homes without adequate protective measures, risking the spread of infection.
Dr. Quratulain Syed, an Atlanta geriatrician, describes a man in his 80s whom she treated in mid-March. Over a period of days, this patient, who had heart disease, diabetes and moderate cognitive impairment, stopped walking and became incontinent and profoundly lethargic. But he didn't have a fever or a cough. His only respiratory symptom: sneezing off and on.
The man's elderly spouse called 911 twice. Both times, paramedics checked his vital signs and declared he was OK. After another worried call from the overwhelmed spouse, Syed insisted the patient be taken to the hospital, where he tested positive for COVID-19.
"I was quite concerned about the paramedics and health aides who'd been in the house and who hadn't used PPE [personal protective equipment]," Syed said.
Dr. Sam Torbati, medical director of the Ruth and Harry Roman Emergency Department at Cedars-Sinai Medical Center, describes treating seniors who initially appear to be trauma patients but are found to have COVID-19.
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"They get weak and dehydrated," he said, "and when they stand to walk, they collapse and injure themselves badly."
Torbati has seen older adults who are profoundly disoriented and unable to speak and who appear at first to have suffered strokes.
"When we test them, we discover that what's producing these changes is a central nervous system effect of coronavirus," he said.
Dr. Laura Perry, an assistant professor of medicine at the University of California-San Francisco, saw a patient like this several weeks ago. The woman, in her 80s, had what seemed to be a cold before becoming very confused. In the hospital, she couldn't identify where she was or stay awake during an examination. Perry diagnosed hypoactive delirium, an altered mental state in which people become inactive and drowsy. The patient tested positive for coronavirus and is still in the ICU.
Dr. Anthony Perry, an associate professor of geriatric medicine at Rush University Medical Center in Chicago, tells of an 81-year-old woman with nausea, vomiting and diarrhea who tested positive for COVID-19 in the emergency room. After receiving IV fluids, oxygen and medication for her intestinal upset, she returned home after two days and is doing well.
Another 80-year-old Rush patient with similar symptoms — nausea and vomiting, but no cough, fever or shortness of breath ― is in intensive care after getting a positive COVID-19 test and due to be put on a ventilator. The difference? This patient is frail with "a lot of cardiovascular disease," Perry said. Other than that, it's not yet clear why some older patients do well while others do not.
So far, reports of cases like these have been anecdotal. But a few physicians are trying to gather more systematic information.
In Switzerland, Dr, Sylvain Nguyen, a geriatrician at the University of Lausanne Hospital Center, put together a list of typical and atypical symptoms in older COVID-19 patients for a paper to be published in the Revue Médicale Suisse. Included on the atypical list are changes in a patient's usual status, delirium, falls, fatigue, lethargy, low blood pressure, painful swallowing, fainting, diarrhea, nausea, vomiting, abdominal pain and the loss of smell and taste.
Data comes from hospitals and nursing homes in Switzerland, Italy and France, Nguyen said in an email.
On the front lines, physicians need to make sure they carefully assess an older patient's symptoms.
"While we have to have a high suspicion of COVID-19 because it's so dangerous in the older population, there are many other things to consider," said Dr. Kathleen Unroe, a geriatrician at Indiana University's School of Medicine.
Seniors may also do poorly because their routines have changed. In nursing homes and most assisted living centers, activities have stopped and "residents are going to get weaker and more deconditioned because they're not walking to and from the dining hall," she said.
At home, isolated seniors may not be getting as much help with medication management or other essential needs from family members who are keeping their distance, other experts suggested. Or they may have become apathetic or depressed.
"I'd want to know 'What's the potential this person has had an exposure [to the coronavirus], especially in the last two weeks?'" said Vaughan of Emory. "Do they have home health personnel coming in? Have they gotten together with other family members? Are chronic conditions being controlled? Is there another diagnosis that seems more likely?"
"Someone may be just having a bad day. But if they're not themselves for a couple of days, absolutely reach out to a primary care doctor or a local health system hotline to see if they meet the threshold for [coronavirus] testing," Vaughan advised. "Be persistent. If you get a 'no' the first time and things aren't improving, call back and ask again."
The risk of death among kidney transplant patients infected with COVID-19 is so high that at least one transplant center in New York City has stopped offering kidney transplantation until it is safer to do so.
Enver Akalin, MD, medical director, kidney and pancreas transplant program, Montefiore Medical Center in New York City, and colleagues detail the trajectory of a small group of their own COVID-19-infected kidney transplant patients in a letter published online April 24 in the New England Journal of Medicine.
Of 36 patients assessed between March 16 and April 1, 2020, 10 have died, leading them to temporarily halt their program.
"Our results show a very high early mortality among kidney-transplant recipients with COVID-19 — 28% at 3 weeks as compared with the reported 1% to 5% mortality among patients with COVID-19 in the general population, who have undergone testing in the United States," say Akalin and colleagues.
This mortality rate is also much higher than the reported 8% to 15% mortality rate among patients with COVID-19 older than age 70 years, they add.
Akalin told Medscape Medical News: "Over 80% of patients in the Montefiore hospital are COVID-19 patients, and if more than 80% of your hospital is full of COVID-positive patients, how can you find a safe place to do transplantation?"
"So we stopped our kidney transplantation program 5 weeks ago because we have dialysis, so to delay transplantation a few months until the pandemic is cleared is not going to hurt the patient," he explained.
Almost 80% Admitted to Hospital, 40% Received Mechanical Ventilation
The median age of the group of transplant patients at the Montefiore hospital was 60 years and approximately 80% were black or Hispanic. Some 75% of patients had received a deceased donor kidney. Almost all of them had hypertension and over two thirds had diabetes.
"Twenty-eight [of the 36] patients (78%) were admitted to the hospital," Akalin detailed.
The most common initial symptom was fever, present in 58% of the group, and diarrhea was observed in 22%. However, almost all patients (96%) had radiographic findings consistent with viral pneumonia.
Eleven of the 28 patients admitted to hospital (39%) were so severely ill that they required mechanical ventilation.
Eight patients (22%) were stable enough to be monitored at home, although two of these patients ultimately died.
At a median follow-up of 21 days, 10 of the 36 patients had died, including seven of the 11 patients who required intubation (64%).
"However, with 2 additional weeks of follow-up, the remaining four [intubated] patients are still alive," Akalin noted.
The two outpatients who died were both recent kidney transplant recipients “who had received antithymocyte globulin within the previous 5 weeks,” the authors note.
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Antithymocyte globulin decreases all T-cell subsets for many weeks, and with no T-lymphocytes, "patients can't mount an immune response to clear the virus," Akalin explained.
Initial Treatment: Stop Mycophenolate, Trials of Other Drugs
In terms of immunosuppressive therapy, on presentation with COVID-19, 97% of the kidney transplant patients were receiving tacrolimus, 94% prednisone, and 86% were taking mycophenolate mofetil or mycophenolic acid.
Akalin said they "decrease the mycophenolate dose by half or withdraw drug altogether" in the setting of any infection requiring hospital admission, including COVID-19, because transplant patients would never be able to clear the infection with such heavy immunosuppression.
In their 28 hospitalized patients, the dose of mycophenolate was reduced in 14% of the group and was stopped altogether in the remainder of the patients.
Moreover, when the New York team first started tracking their COVID-19-infected transplant patients, there was speculation that the antimalaria drug hydroxychloroquine might help patients recover more quickly, so almost all of their hospitalized patients were treated with that drug.
But since a French study found no difference in outcomes between patients treated with hydroxychloroquine or not, they no longer use it, nor do they use azithromycin, which initially they also felt might benefit COVID-19 recovery in these patients, Akalin explained.
Intriguingly, however, they did treat two patients with the interleukin-6 (IL-6) inhibitor tocilizumab (Actemra, Roche), while six others received the CCR5 inhibitor leronlimab (CytoDyn), both of which blunt high IL-6 levels characteristic of the cytokine storm that can occur in patients with moderate and severe COVID-19.
Before and after laboratory results indicated that leronlimab markedly reduced elevated IL-6 levels in five patients with high pretreatment levels, Akalin noted.
Moreover, while only eight patients in total received tocilizumab or leronlimab, all of these patients were all among the group who received mechanical ventilation and the mortality rate was 50% in this small group, lower than that seen among intubated patients with COVID-19 in the general population, he noted.
Don't Halt All Kidney Transplants...Nor Any Others
Akalin told Medscape Medical News that their policy to put kidney transplantation on hold until the pandemic is under control does not necessarily apply to other regions of the country where COVID-19 is not as prevalent as it is in New York City.
"With very careful selection of recipients and donors, and very careful precautions taken during hospitalization, you could do the transplantation," he suggested.
However, providers still need to be aware that the nasopharyngeal swabs used to test patients for COVID-19 are only about 70% accurate, so even if all possible deceased donor candidates are tested, "you may still miss some who are positive," he cautioned.
Furthermore, if the deceased donor does test positive for COVID-19, there is always a potential for transmission of COVID-19 to the waiting recipient, so it is too risky to use kidneys from these donors, he believes.
"This policy is just for kidney transplant patients," he emphasized.
The same policy "does not apply in heart, lung, or liver transplantation because heart, lung, and liver transplantation is life-saving and if these patients don't get [a donor organ] soon, they will die within a few months."
Akalin has reported no relevant financial relationships.
N Engl J Med. Published online April 24, 2020. Letter
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