It is now evident that COVID-19 is not simply an illness of the pulmonary system, but a disease that can have a long-lasting impact on organ systems.

A review article published in Nature Medicine provides an initial glimpse at the long-term multiorgan effects associated with a COVID-19 infection. The authors, who were led by Elaine Y Wan, MD, a cardiologist with Columbia University Irving Medical Center,  suggests a framework for the care of COVID-19 long-haulers through the creation of COVID-19 clinics with multidisciplinary medical teams who would address any long-term medical condition of patients who have had COVID-19. The article was published online March 22.

“It is crucial for healthcare systems and hospitals to recognize the need to establish dedicated COVID-19 clinics, where specialists from multiple disciplines are able to provide integrated care,” she and her colleagues wrote.

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Wan et al,  provide a comprehensive review of the current literature on post-acute COVID-19, its pathophysiology and its organ-specific sequelae. Fatigue, shortness of breath, brain fog, loss of sense of smell or taste, anxiety, depression, and post-traumatic stress disorder (PTSD) are among the most common symptoms of long-haulers. Published data suggest at least one-third of patients who required hospitalization for COVID-19 have experienced 1 of these long-term side effects.

“This scale of the pandemic with regards to the number of people infected with SARS-CoV-2 and substantial percentage of those with long-haul symptoms in preliminary reports has not been seen before in our lifetime. Long lasting consequences are expected for all fields of medicine, including pulmonology, cardiology, neurology, endocrinology, nephrology, psychiatry and others,” said Kartik Sehgal, MD, an oncologist at Dana-Farber Cancer Institute in Boston. Dr Sehgal served as co-corresponding author of the article with Dr Wan.

Long-haulers may have heterogeneous presentations. Common presentations include fast heart rates, dizziness, difficulties with concentration and/or memory, and difficulties with sleeping and mood. “It is crucial for internists as well as subspecialists to keep current of past infection with SARS-CoV-2 as one of the differential diagnoses. It has become an integral part of history taking now,” Dr Sehgal said.

“The roadmap for optimal management of post-acute COVID-19 is through inter-disciplinary care in COVID-19 recovery clinics.” It is crucial to multiply efforts to help identify those at highest risk for long COVID to ensure structured care in these clinics with efficient access to subspecialists as needed,” he said.


Endocrine manifestations in long-haulers appear to be due to direct viral injury, immunological and inflammatory damage, as well as iatrogenic complications. Endocrine sequelae may include new or worsening control of existing diabetes mellitus, the authors suggest.

Other concerns are subacute thyroiditis and bone demineralization. They recommend that patients with newly diagnosed diabetes—in the absence of traditional risk factors for type 2 diabetes—undergo additional diagnostic testing. Patients with suspected hypothalamic–pituitary–adrenal axis (HPA axis) suppression, or hyperthyroidism, should also undergo undergo appropriate testing.

“Abnormalities of glucose metabolism such as euglycemic ketosis and diabetic ketoacidosis, as well as new diagnoses of diabetes mellitus during or after acute COVID-19, will need follow up with an endocrinologist, preferably within the framework of multidisciplinary COVID-19 recovery clinic,” Dr Sehgal said.

“Those without traditional risk factors for type II diabetes mellitus must be screened for type I diabetes-associated autoantibodies. Hormonal abnormalities, for example involving thyroid and adrenal gland, must be considered in case of unusual symptoms and without obvious explanation after standard evaluation,” he said.

Early in the pandemic, the initial focus was to maximize prevention and control modifiable risk factors for diabetes and cardiovascular disease, said David Drucker, MD, an endocrinologist with Mount Sinai Hospital, Toronto. But now, post COVID-19 infection, patients are increasingly presenting with new symptoms.

“The extent to which COVID-19 will present new distinct challenges for individuals and the endocrine community remains uncertain and will require careful follow-up and study,” he said.

There is a lack of evidence about SARS-CoV-2 within pancreatic islet cells in those who develop COVID-19. Alvin C Powers, MD, chief of the division of diabetes, endocrinology and metabolism at Vanderbilt University Medical Center in Nashville, said COVID-19 may exacerbate or bring out undiagnosed diabetes. 

“Does COVID cause diabetes? It is controversial,” Dr Powers said. “There is going to be a lot more scrutiny of people who have had COVID. The bottom line is that we have to monitor these people.”


Pulmonary sequelae include decreased exercise capacity and hypoxia. Long-haulers have been found to have reduced diffusion capacity, restrictive pulmonary physiology, and ground-glass opacities and fibrotic changes on imaging, according to the researchers.  Palpitations, dyspnea and chest pain, increased cardiometabolic demand, myocardial fibrosis, scarring arrhythmias, tachycardia, and autonomic dysfunction are associated with cardiovascular sequelae.

Data suggest that patients with cardiovascular complications during acute infection and those experiencing persistent cardiac symptoms may need to be monitored, Wan et al. They write that mechanisms perpetuating cardiovascular sequelae in post-acute COVID-19 include direct viral invasion, downregulation of ACE2, inflammation and the immunologic response affecting the structural integrity of the myocardium, pericardium and conduction system.

A reduced eGFR has been reported at 6 months follow-up and there is concern about persistent impaired renal function. “Follow-up of renal function should be incorporated in care provided in COVID-19 recovery clinics, with engagement of nephrologists for those with impaired renal function. Approximately one-third of patients with COVID-19 had reduction in estimated glomerular filtration rate at 6 months follow-up in a study from China, including some with normal renal function during acute infection with SARS-CoV-2,” Dr Sehgal said.


The World Health Organization estimates that 10% of COVID-19 survivors will develop long-term healthcare issues. To date, here in the United States, 31.4 million people have contracted COVID-19, with estimates suggesting that 3 million people in the US could potentially develop long-term health conditions associated with COVID-19.

“These people need integrated multidisciplinary holistic care. Health systems should quickly adapt to this reality. It is not an exaggeration that long COVID is America’s next big health crisis. We should prepare for it now,” said Ziyad Al-Aly, MD, an internal medicine specialist with the Institute for Public Health in Washington, DC.

Due to the fact that COVID-19 in both the acute phase (first 4 weeks) and post-acute phase affects the lungs, heart and kidneys, some specialties have had to rise to the challenge and adapt quickly to treat COVID-19 patients, he said.

“I think that many specialties, including nephrology and cardiology, still underestimate the tide of patients with post-COVID sequelae that will likely need medical care in the next one to five years,” Dr Al-Aly said. He is working on a study to systematically characterize the post-acute manifestations of long-haulers.

It is clear that most long-haulers do not realize they have heart damage, kidney damage or liver damage because they are not experiencing symptoms. “At some point, these patients will need medical care. Health systems and specialties must be prepared for this,” he said. “If there ever was an exemplar in clinical medicine that best captures the importance of integrated multidisciplinary care, it is long-haul COVID-19. It is staring at us in the eyes,” Dr Al-Aly said.

Dr. Sehgal and his colleagues contend that clinical trials of patients with COVID-19 presenting with new long-term medical complications are urgently needed. “Active and future clinical studies, including prospective cohorts and clinical trials, along with frequent review of emerging evidence by working groups and task forces, are paramount to developing a robust knowledge database and informing clinical practice in this area,” the authors wrote. 


  1. Cortinovis M, Perico N, Remuzzi G. Long-term follow-up of recovered patients with COVID-19Lancet. 2021;397:173-175. doi:10.1016/S0140-6736(21)00039-8
  2. Nalbandian A, Sehgal K, Gupta A, et al. Post-acute COVID-19 syndromeNature Med. 2021;27:601-615. doi:10.1038/s41591-021-01283-z

This article originally appeared on Endocrinology Advisor