We are still accustomed to consider Covid-19 as a disease of the respiratory system. But what we observe in some of convalescent patients leads us to the conclusion that we should now speak of a syndrome rather than a disease. The word syndrome in medicine is used to define complex clinical situations involving more than one organ and system. This is the case of Long Covid: a very varied set of symptoms and pathological conditions that follow the acute infection and indicate a multi-organ involvement.Today’s article is the first of a series dedicated to the Long Covid to investigate its diagnostic and therapeutic aspects and the perspectives of research. SoLongevity’s commitment into this field comes from the observation that its symptoms and conditions are, in some way, reconnectable to the same molecular mechanisms that lead to the physiological ageing, therefore the healthy aging technologies could be able to help Long Covid patients.

The Long Covid symptoms and conditions appear to be related to the same molecular mechanisms underling the ageing process 

Long Covid Symptoms

A recent  scientific paper published in the journal Scientific Reports looked at 15 scientific articles on a total of 48,000 patients and listed more than 55 symptoms that can last well beyond 120 days after the last negative swab and clinical recovery. The study found that symptoms persisted in 80% of patients. The most common are: fatigue (58%), headaches (44%), difficulty concentrating (27%), hair loss (25%) and shortness of breath (24%). Other symptoms and conditions include: cough, chest pain, sleep apnea, pulmonary fibrosis and decreased alveolar diffusion capacity, arrhythmias and myocarditis, depression, anxiety, attention disorders, cognitive fog, and obsessive-compulsive disorder.Of the three most frequent categories of disorders/symptoms, the study found the following:

• Fatigue: present even 100 days after the acute phase. The authors note that in other respiratory distress syndromes, fatigue can last for more than a year. In post-Covid patients, symptoms very similar to those of Chronic Fatigue Syndrome (CFS) are also noted, including pain, neurocognitive impairment, sleep disturbance, and worsening of symptoms after physical or mental exertion. Of note, CFS typically follows viral infections as diverse as cytomegalovirus, Ebstein Barr virus, and herpes viruses.

 

• Neuropsychiatric disorders: headaches, attention disorders, anosmia, cognitive fog and neurogenic pain, insomnia.

 

• Respiratory disorders: 35% of patients have CT (chest thoracic) abnormalities even 100 days after infection. 35% report dyspnea and 25% cough. 10% of patients have reduced alveolar diffusion. In other studies pulmonary abnormalities have been detected in variable percentages (53% / 28% of patients) depending on the diagnostic investigations used. We can therefore speak of Long Covid Syndrome.

Long Covid origins

The overall clinical picture is still difficult to pin down from the point of view of causes and mechanisms. It is very likely that at the basis of the multitude of symptoms there is a state of systemic inflammation triggered in the acute phase of the disease and then getting chronic. In fact, the study found numerous alterations in the inflammation markers.It has been hypothesized an autoimmune genesis of Long Covid but for now there are no supporting data. It is true that in subjects with autoimmune diseases the infection can trigger a relapse of the disease, but this is common to many viral infections and in any case does not imply a specific autoimmune mechanism triggered by the SARS-CoV-2 virus.In a significant percentage of patients, the virus may remain nested in tissues other than the mucous membranes of the respiratory tract, primarily the intestine. However, we do not yet know to what extent the intestine presence of the virus contributes to the Long Covid syndrome.

What is most striking is the Long Covid difference in symptoms among patients who have done a mild form of Covid without pulmonary involvement versus those who have suffered a more severe one with pulmonary involvement. In the former, Long Covid tends to be characterized by neurologic symptoms, in the latter by respiratory symptoms. This strange dichotomy could be explained by individual phisiological differences about those cellular tissues’ features, exploited by the virus for contaminating and replicating itself. Differences that could direct the virus in one direction or another, triggering different symptoms. But for now we are only in the field of hypothesis.The biggest problem in any case is the management of neurological symptoms (headaches, asthenia / fatigue, depression, cognitive fog, etc. ..) because we do not know the cause and we do not have specific therapies available.

at the core of the multiple Long Covid’s symptoms there is a state of systemic inflammation triggered in the acute phase of the disease and then getting chronic

80% of patients report that they still have symptoms months after Covid-19 “acute stage.” Of these, neurological disorders are still the most difficult to manage since the cause is still unknown

What to do?

First of all, when a new unknown pathologic condition emerges, the priority is to frame it with the right diagnostic protocol and standardize it as much as possible. In this regard, the symptomatic expression of the Long-Covid syndrome can be measured in both the physical and neurological components.The possibility of scoring fatigue, energy level and cognitive ability (involved in 1/3 of patients) helps to frame the clinical picture and to establish the diagnostic approach and areas of intervention.The physiological parameters assessment for cardiac and respiratory activity is also key to clarify what has been the virus impact on the most exposed physiological systems. Based on the patient’s history, a decision can be made, for example, whether to perform

• continuous monitoring of heart rate variability (a parameter of autonomic nervous system alterations) an exercise ECG
• a pulmonary and diaphragmatic ultrasound scan
• a spirometry
• a high resolution pulmonary CT scan
• a cardiopulmonary exercise test (CPET), a tool that allows an integrated assessment of the cardio-respiratory component.

The laboratory markers can obviously be of great help. As already mentioned, alterations in inflammatory parameters are often observed, supporting a substantially inflammatory genesis of Long Covid. But in order to go to the roots of the problem it will be very important to measure other parameters, not yet available in analytical laboratories but already used in research laboratories. Long Covid syndrome should be framed through analysis and testing to measure the physical and neurological dimension, to assess the impact of infection

SoLongevity’s research on the Long Covid front

SoLongevity research is following that research direction by focusing on three main dimensions.The first concerns the study of immune parameters that could help us in future therapeutic approaches. For this purpose, we leverage on lab analysis assessing  several type of immune cells expression, to evaluate them both quantitatively and qualitatively (study of lymphoid and myeloid subpopulations).The second arises from molecular considerations derived from the scientific literature on Covid. For example, we know that the virus entering the cells uses cell’s energy reserves to replicate. This mechanism  puts under pressure the cell’s energy engine, the mitochondria, and when the mitochondria go wild the whole cell suffers. SoLongevity has developed a test for the “mitochondria vitality” based on measuring the copies of DNA they contain. The test offers a very sensitive read-out of overall health status, and specifically the impact the infection has had on the cells of the immune system.The third stems from the observation that the Long Covid multi-organ impact creates the conditions to lump with an accelerated aging state. Leveraging the results of our research in the years preceding the epidemic, we are now able to accurately measure the impact of the infection on the biological ageDifferent from chronological age. It is a measure of the body's ageing, based on the effectiveness of the mechanisms that keep cells young and on markers of the functionality of organs and apparatus. of the person, an index that can in turn be disaggregated providing useful indications on the impact of the disease on the different organs.

In order investigate Long Covid causes, it will be very important to measure other parameters, not yet available in analytical laboratories but already used in research laboratories

Research is working to identify new therapeutic frontiers for Long Covid, including bioavailable supervitamins with a high safety profile