COVID-19 Infection Has More Than 50 Long-Term Effects

MADRID, Spain — Clinical experiences in approaching COVID-19 from different perspectives, results obtained by various therapeutic options and, above all, the challenges posed by a new healthcare reality — long COVID — were all the focus of a recent discussion at the 7th International Congress of the Spanish Society of Precision Health.

In this forum, titled Precision Health: A COVID-19 Professional Debate, Mayca González, MD, a specialist in microbiology and an expert in age management medicine at the University of Granada, reviewed the most recent data regarding long COVID. "According to the latest evidence, 9 out of 10 COVID-19 patients (87%) discharged from hospital experience at least one symptom 60 days after illness onset, with 32% reporting one or two symptoms and 55% presenting three or more. Additionally, more than 50% of symptomatic cases have at least one symptom of the disease 1 year after infection."

Another study found that 12.8% of the infected study participants continued to have dyspnea after 6 months, even in the absence of a pneumonia diagnosis, González added.

Research on this topic has also shed light on the main risk factors for developing long COVID. "First of all, gender, age, and even the number of symptoms" are risk factors, said González. "Therefore, women and people between 40 and 54 years of age are more likely to suffer from long COVID. It is also known that the more severe the acute illness, the greater the number of symptoms that appear after post-infection.

"Having a body mass index equal to or greater than 25, reporting three to seven symptoms of COVID-19 in the acute phase, and patients with more than five symptoms during the first week of the disease are factors associated with being prone to suffer from long COVID. All this sets up a health problem that will undoubtedly be a major challenge from now on."

González stressed that studies have shown that there are more than 50 long-term effects of COVID-19, the most prevalent being fatigue (58%), headache (44%), attention disorders (27%), and hair loss (25%).

Among all the research projects carried out on this topic, González highlighted a study published in January that, in her opinion, is one of the most relevant to date "because it delves into the pathophysiologic circumstances behind symptoms at all levels, something that we did not fully know until now.

"For example, it has been shown that dyspnea, hypoxia, fatigue, 'ground-glass' opacities, and pulmonary fibrosis are due to damage to the lung parenchyma [primarily] mediated by the virus and secondarily due to immunological microvascular damage. On the other hand, at a cardiovascular level, up to 20 cardiovascular conditions can occur 1 year after overcoming COVID-19. This allows us to foresee that these patients will be a significant demand on health systems in the coming years."

Microbiome and Vagus Nerve

Regarding the digestive and intestinal system, González highlighted a hitherto unknown mechanism: the involvement of the vagus nerve and the intestinal microbiota.

"There are studies that suggest a pattern of persistent or recurrent viremia in some patients, causing a clinical evolution of nonspecific symptoms associated with personal limitations," she said. "This could lead us to think about the possibility that the virus would have a reservoir at this level. Along the same lines, research currently in progress points to a possible involvement of the vagus nerve as the cause of the manifestations of long COVID. We must not forget that this nerve connects the brain and the gastrointestinal tract, in addition to controlling heart rate, sweat production, and the gag reflex."

In her analysis of this pilot study carried out by a group of Spanish researchers, González commented that two thirds (228) of the 348 participants involved had at least one symptom suggestive of vagus nerve dysfunction. Upon further evaluation of these 228 patients, in the first 22 subjects with vagus nerve dysfunction, 20 were women with a median age of 44 years.

"The study also reflects that the most frequent vagus nerve dysfunction related symptoms were diarrhea (73%), tachycardia (59%), dizziness (45%), dysphagia (45%), and dysphonia (45%); 86% of the patients had three different vagus nerve dysfunction related symptoms. Six of the 22 patients displayed alteration of the vagus nerve in the neck shown by ultrasound, including both thickening of the nerve and mild inflammatory reactive changes," she noted.

Another important fact of this research was that 10 of the patients showed abnormal breathing patterns and reduced maximum inspiratory pressures, which, according to González, indicated the weakness of the respiratory muscles connected to the vagus nerve. "Seventy-two percent also had oropharyngeal dysphagia or difficulty swallowing, and eight patients showed reduced or impaired ability to move food from the esophagus to the stomach and acid reflux."

Prescription: Exercise

At the same conference, Wilson Martínez, MD, a specialist in sports and exercise medicine, addressed the role of physical exercise in the recovery of people who have suffered from COVID-19. "It should be kept in mind that many patients with mild or severe COVID-19 do not fully recover and have a wide variety of chronic symptoms for months or weeks after infection that are often neurological, cognitive, or psychiatric in nature. This is what is known as post-COVID-19 syndrome, reported by between 10% and 20% of patients."

In his presentation, The Value of Exercise in the Post-COVID Patient, Martínez reviewed the most recent studies that show the link between exercise and the benefits for health in general and against SARS-CoV-2 and its consequences in particular. "In these investigations," he told the audience, "exerkines are discussed, understanding as such the substances that are produced or generated with the practice of physical activity (including hormones and metabolites) with healthy benefits at different levels. There is a varied repertoire of exerkines in the systemic circulation, and it is known that the higher the intensity and momentum with which exercise is performed, provided it is done properly, that these exerkines manifest in a more positive way."

In the context of COVID-19, Martínez explained this positive impact "taking into account that SARS-CoV-2 affects the angiotensin-converting enzyme-2 receptor, and this in turn involves the appearance of fibrosis, inflammation, vasoconstriction, reduced neurogenesis, and cardiovascular damage. This activation of a series of vascular signaling chains that occurs with exercise makes it possible to counteract a good number of the symptoms of the post-COVID-19 syndrome, acting in a certain sense like a polypill."

Specifying the potential benefits of exercise in post-COVID-19 syndrome, Martínez highlighted that there is an improvement in the psychological component, since it reduces stress, which translates into an improvement in mood and a feeling of well-being.

"At the neurological level, it stimulates brain plasticity, improves cognitive abilities, decreases allostatic load and optimizes sleep quality," he explained. "As for the cardiovascular system, angiogenesis occurs, improving the vascular system and cardiovascular function, lowering blood pressure, normalizing dysautonomia, and notably increasing mitochondrial biogenesis.

"In the respiratory system, it decreases dyspnea and improves oxygen consumption and lung function. In muscles, it improves exercise tolerance, increases muscle strength and muscle mass, with better intramuscular coordination. In relation to the immune system, it decreases inflammatory cytokines and increases anti-inflammatory cytokines, generally improving immune function," Martínez continued.

Strength Training Essential

Martínez stressed that there is no known drug that produces all these benefits. "Unfortunately, we are not taught or used to prescribing exercise. Based on all this evidence, it is obvious that it should be incorporated into the prevention of and approach toward not only COVID-19 and post-COVID-19, but in general, for the care of cardiovascular and metabolic health, both to prevent diseases and as an adjuvant in many pathologies."

Regarding what type of activity is most recommended in these patients, Martínez pointed out that "there is sufficient evidence to suggest that adapted and supervised training with aerobic and strength endurance exercises can be an effective multisystemic therapy for post-COVID-19 syndrome."

In this sense, Martínez stressed the need to value the importance of strength training. "Although a good part of the population practices aerobic activity, the percentage drops when it comes to strength routines, especially among women, since they associate it with the risk of excessive bodybuilding. In the case of post-COVID-19, this training is essential, since one of the most worrying signs of this syndrome is the loss of muscle mass.

"A little more research is required in this field, but without a doubt, it is a perfect tool to counteract and manage the multiple signs and symptoms that persist after having suffered from COVID-19," Martínez concluded.

González and Martínez have disclosed no relevant financial relationships.

Follow Carla Nieto of Medscape Spanish edition on Twitter @carlanmartinez.

This article was translated from the Medscape Spanish edition.

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