COVID-19 and its Long-term Health Implications

The growing evidence suggests that coronavirus, which was originally thought to impact only the respiratory tract, can cause damages to other vital organs like the heart, kidneys, liver, and the brain.

Though the studies on long-term effects of COVID-19 are still scant, and the medical fraternity doesn’t know whether one can fully recover from the trauma and impact of COVID-19 and how long the symptoms will last, the preliminary studies and existing research suggest that apart from the lungs, it can manifest in different body organs.

Doctors think this could explain why people experience a range of symptoms weeks and months after recovering from the infection. That means COVID-19 might not be a disease that will go away when the infection is cleared, but may linger for a long time, particularly in those who have survived the worst.

The US Centers for Disease Control and Prevention and the World Health Organization have also acknowledged long-term COVID-19 symptoms, and currently, terms like long-term COVID-19, long-hauler, or long-COVID have been used to describe the long-term sufferers of COVID-19 symptoms.

Impact on Lungs

A study published in Lancet eBioMedicine that analyzed samples of tissue from the lungs, heart, liver, and kidneys of 41 patients who died of COVID-19 in Italy’s University Hospital of Trieste between February and April 2020 reported persistent and extensive lung damage in most cases.

“The findings indicate that COVID-19 is not simply a disease caused by the death of virus-infected cells, but is likely the consequence of these abnormal cells persisting for long periods inside the lungs,” said Mauro Giacca, a professor at King’s College London who co-led the work.

Giacca said that, while his research team found no overt signs of viral infection or prolonged inflammation in other organs, they discovered “really vast destruction of the architecture of the lungs”, with healthy tissue “almost completely substituted by scar tissue.” “It could very well be envisaged that one of the reasons why there are cases of long COVID is because there is vast destruction of lung (tissue),” he said. “Even if someone recovers from COVID, the damage that is done could be massive.”

According to him, almost 90% of the 41 patients had several characteristics unique to COVID-19, compared to other forms of pneumonia. One was that, patients had extensive blood clotting of the lung arteries and veins. Another was that some lung cells were abnormally large and had many nuclei—a result of the fusion of different cells into single large cells in a process known as syncytia. “The presence of these infected cells can cause the major structural changes observed in lungs, which can persist for several weeks or months and could eventually explain ‘long COVID’,” Giacca said.
In a study of the lungs of 33 COVID-19 patients using computed tomography (CT) scanning for more than a month, clinical radiologist Ali Gholamrezanezhad and his team at the University of Southern California in Los Angeles, in their as-yet-unpublished data, suggested that more than one-third of them had tissue death leading to visible scars.
Gholamrezanezhad says, “Unfortunately, sometimes the scar never goes away.” He adds that, though the overall rate of such intermediate-term lung damage is likely to be very low (less than 10%), given that millions of people have been infected by the novel coronavirus, hundreds of thousands of people will be experiencing lasting health consequences.

Impact on Heart

According to reports, SARS-CoV-2 can impact the cardiovascular system over the long term irrespective of how severe the illness is, and the risk is higher in people who already have a heart disease.

 

A paper presented by Sean P. Pinney, MD, FACC, et al., in a three- part focus seminar on COVID-19 in the Journal of the American College of Cardiology (JACC) in October, said that both direct viral infection and indirect injury resulting from infl ammation, endothelial activation, and microvascular thrombosis occur in the context of COVID-19.

Myocardial injury occurred in about one-quarter of hospitalized COVID-19 patients and is associated with a greater need for mechanical ventilator support and higher hospital mortality (Gennaro Giustino, MD, et al). Myocardial injury results in detectable increases in serum troponin, varying degrees of ventricular dysfunction, and relatively frequent cardiac arrhythmias, according to the researchers, who add “Whether these effects are simply associated with poor patient outcomes, including death, or directly contribute to patient mortality, is as yet uncertain.”

Dr. Pinney said that most people infected with COVID-19 experience mild symptoms and recover, but the elderly and people with co- morbidities are more susceptible to infection and serious illness and complications, with development of acute respiratory distress syndrome and microthrombi in the lungs, heart, and kidneys appearing to be the drivers of fatal disease. Th e long-term risk of serious illness for survivors of severe cases of COVID-19 remain uncertain, but early observations are concerning, he added.

In one study in July, researchers at the Frankfurt University Hospital examined 100 patients two months aft er an acute COVID-19 infection and produced MRI images of their hearts. In their fi ndings, they saw 78% of the participants with drastic changes in their heart muscle, irrespective of whether their illness had been severe or they had only shown mild symptoms that they recovered from at home. Th e study cautioned that patients who have recovered from the infection need to be careful, as they may not return to full health immediately.

Dr. Frank Misselwitz, a leading German expert on cardiovascular clinical development, said that a typical change revealed by magnetic resonance imaging is scarring of the heart tissue. Th e coronavirus can trigger infl ammation of the blood vessels in all organs, including the heart. “When these inflammations heal, it can result in fi brotic changes, in other words, scarring. Th is, in turn, impairs the function of the organ, which in the case of the heart means that it pumps less blood. Th is makes it less resilient and can lead to heart failure and the full picture of a viral heart muscle infl ammation.” According to him, one crucial approach is to reduce the viral load. By simply wearing a mask one can help reduce the viral load and prevent a severe progression of the illness. Patients who have only received a low viral load and otherwise have a healthy immune system could cope with the illness quite well. But, patients receive the full viral load through close physical proximity, or the lack of a mask and a healthy immune system may not be able to cope with that, he added.

Impact on Kidneys

Studies show that acute kidney injury (AKI) is a common complication among hospitalized patients with severe corona virus disease, which can lead to serious illness, dialysis, and even death. The outcomes of patients hospitalized with COVID-19 and acute kidney injury (AKI) are, however, not well understood.

When the pandemic first started in China, the rates of kidney injuries were almost negligible, says Dr. Samira S. Farouk, MD, MS. But, as the pandemic spread to the United States, there were increasing reports of AKI. In July, the center at Mount Sinai, where the doctor works, published a preprint reporting almost 50% incidence of AKI, of which 20% required dialysis or kidney replacement therapies. She says, “At the peak, there were many more patients requiring dialysis in the ICU than we had ever seen before.”

Dr. Rajendra Baliga, Medical Director, Kidney/Pancreas Transplant Program, Tampa General Hospital, New York, said that although older adults are at risk, dialysis has also been required for patients as young as in their twenties. “Th e biggest correlation to severe cases of kidney infection has more to do with how severely infected a patient is, not necessarily their age,” he said.

Jia H. Ng, MD, MSCE and her colleagues, who investigated the survival and kidney outcomes of hospitalized COVID-19 patients in 13 hospitals in New York, stated that AKI in hospitalized patients with COVID-19 is associated with significant risk for death.

In their retrospective observational cohort study of 9657 COVID-19 patients admitted from March 1, to April 27, 2020, and followed up to June 4, 2020, there were 3854 adults that met the eligibility criteria for AKI. Of them, 3216 (83.4%) developed AKI non- KRT during their admission, and of these, 1663/ 3216 (51.7%) survived and 1233/1663 (74.1%) recovered kidney function.

For patients with AKI-KRT, 108/638 (16.9%) patients survived, and 24 (3.7%) remained hospitalized. Among those who survived, 72/108 (66.7%) had kidney recovery, i.e. not needing dialysis at discharge and a minimum of 33% decline in discharge serum creatinine from peak serum creatinine. Among patients who still needed dialysis at discharge, the majority (19/33 [57.6%]) had underlying CKD on admission (10, 7, and 2 with CKD stages 5, 4, and 3, respectively).

The study also reported that, in the AKI non-KRT group, 1313/3216 (40.8%) patients required mechanical ventilation and 1354/3216 (42.1%) required vasopressors whereas in the AKI-KRT group, 581/638 (91.0%) of patients required mechanical ventilation and 584/638 (91.5%) required vasopressors.

Among patients who required mechanical ventilation and had AKI, most 1415/1894 (74.7%) developed AKI aft er initiation of mechanical ventilation. Similarly, among those with AKI and required vasopressors, 1357/1938 (70%) developed AKI after vasopressor initiation. The study reported that the incidence rate of in-hospital death was highest among patients with AKI receiving KRT, followed by AKI without KRT and those without AKI (37.5 vs. 31.1 vs. 10.8 deaths/1000 patient-days, respectively).

On whether SARS-CoV-2 can directly damage the kidney through infection, Dr. Farouk says, “We don’t know, but there is compelling evidence on both sides. Th ere is a pathophysiologic hypothesis that angiotensin-converting enzyme 2 could be one potential mechanism of kidney injury by providing viral entry into the cell—as has been shown in the alveolar cells within the lung—and can potentiate nephrotoxic effects.”

From a pathologic standpoint, she says, “If the virus is found in the kidney, then perhaps that is an indication that there are forms of injury.” According to her, there have been conflicting reports of “viral-like” particles seen on electron microscopy. “Some groups have been able to show that there is actually RNA material, which would be more confirmatory evidence that the virus is actually there. But then we have to ask ourselves, does the presence of virus necessarily mean that there is injury? A little bit of correlation vs. causation: The virus is there, but what is it actually doing? We don’t know so far.

Impact on Nervous System

A wide array of neurological manifestations, including loss of smell and taste, stroke, seizures, swelling of the brain (encephalitis), confusion, delirium, and dizziness have been recognized in COVID-19 patients since the onset of the pandemic, yet the SARS-CoV-2-related neurological complications have not been fully understood.

A hospital network in Chicago, Illinois, reported that in their study of 509 COVID-19 patients, more than 40 % showed neurologic manifestations at the onset and the most frequent were myalgias (44.8%) followed by headaches (37.7%), encephalopathy (31.8%), dizziness (29.7%), dysgeusia (15.9%), and anosmia (11.4%). Strokes, movement disorders, motor and sensory deficits, ataxia, and seizures were uncommon (0.2 to 1.4% of patients each), the study reported.

In a study “Neuropathology of patients with COVID-19 in Germany: a post-mortem case series” published in The Lancet Neurology on November 1, 2020, researchers led by Jakob Matschket investigated the brain tissue of 43 patients (aged 51 to 94 years) who died from COVID-19 between March 13 and April 24, 2020, in Hamburg, Germany, for glial responses, inflammatory changes, and the presence of SARS-CoV-2 in the CNS.

The study found fresh territorial ischaemic lesions in six patients, 37 had astrogliosis in all assessed regions, there was activation of microglia and infiltration by cytotoxic T lymphocytes in the brainstem and cerebellum, and 34 had meningeal cytotoxic T lymphocyte infiltration.

SARS-CoV-2 was detected in the brains of 21 (53%) of 40 examined patients, with SARS-CoV-2 viral proteins found in cranial nerves originating from the lower brainstem and in isolated cells of the brainstem. The presence of SARS-CoV-2 in the CNS was, however, not associated with the severity of neuropathological changes in the study subjects. The neuropathological changes in patients with COVID-19 seem to be mild, with pronounced neuroinflammatory changes in the brainstem being the most common finding. There was no evidence for CNS damage directly caused by SARS-CoV-2, the authors wrote in the paper. They said though many symptoms of COVID-19 include the central nervous system (CNS), it is still not clear why SARS-CoV-2 causes neuropathological changes and whether and how the virus gains access to the CNS.

Two neurologists, Arun Raj Antony and Zulfi Haneef, who systematically reviewed 84 reports of EEG findings in 617 patients with COVID-19, said that EEG abnormalities were common in COVID-19 related encephalopathy, and correlates with disease severity, preexisting neurological conditions, including epilepsy, and prolonged EEG monitoring. They said frontal findings are frequent and have been proposed as a biomarker for COVID-19 encephalopathy.

According to their study, published in the European Journal of Epilepsy on October 18, 2020, the most common EEG finding was diffuse slowing, indicating that a diffuse non-specific encephalopathy was the most common brain abnormality in this condition and frontal lobe findings were common, including focal slowing, periodic discharges, and rhythmic delta activity. Half of all status epilepticus and focal slowing originated in the frontal lobes, the paper said.

“We encourage clinical alertness to identify such findings. It has been speculated that frontal EEG findings result from direct brain involvement in COVID-19, while more diffuse changes may result from either systemic involvement or more diffuse viral involvement of the brain.”

“These findings tell us that we need to try EEG on a wider range of patients, as well as other types of brain imaging, such as MRI or CT scans, that will give us a closer look at the frontal lobe,” said neurologist and co-author Zulfi Haneef of Baylor College of Medicine in Houston (Sciencealert). According to him, an EEC can help diagnose the virus or hint at possible complications that can help doctors to monitor the long-term complications of COVID-19 and detect any long-lasting effects on a patient’s brain function.

“A lot of people think they will get the illness, get well, and everything will go back to normal,” Haneef said, “but these findings tell us that there might be long-term issues, which is something we have suspected, and now we are finding more evidence to back that up (Sciencealert).

 

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