Long Haul Covid-19

This post has been updated 04 May 2021. Quoted from the blogpage of NIH director Francis Collins, “If you’d like to find a way to pitch in and help, getting involved in the COVID Symptom Study is as easy as downloading the app .”

How do the symptoms of the active Coivd-19 infection compare with “Long Haul” Covid symptoms that linger after the infection has cleared?

Active Covid-19 versus long haul

Covid-19 active infection [1]	Long haul Covid-19 symptoms [2]	comments
fatigue	fatigue
Shortness of breath or difficulty breathing	Shortness of breath
cough	Cough
Muscle or body aches	Muscle pain
	Chest pain	noticeable in active infection?
	Joint pain	Rheumatoid arthritis?
Head ache	Head ache
	Heart palpitations
	Depression
	Brain fog
Fever or chills	Intermittent fever
New loss of taste or smell	Smell/taste loss	less common in long haul
Sore throat
Congestion or runny nose
Nausea or vomiting, diarrhea

The gastrointestinal symptoms seem to be restricted to the active infection. Neurological symptoms seem to be features of long haul Covid-19.

According to the CDC less common symptoms may also include cardiac inflammation, renal injury, rashes, and hair loss. Skin rashes and hair loss may also be part of the less common long term symptoms of Covid-19. [2]

Covid-19 and rheumatoid arthritis cytokines

A report from June of 2020 points out that many of the cytokines observed in active Coivd-19 infections are also observed in Rheumatoid arthritis, an autoimmune disorder affecting the joints.[3] According to these authors back in June of 2020, a small percentage of Covid-19 patients experience arthalgia. [3]

Exhausted T cells and neurological symptoms of Covid-19

A report from January of 2021 correlated neurological symptoms of Covid-19 with dediffferentiated monocytes and “exhausted” T cells in the cerebral spinal fluid (CSF). [4]. Neurological Covid-19 symptoms may include anosmia, ageusia, headache, dizziness. Some of the causes may include damage from oxygen deprivation, hyperpyrexia, direct viral damage, or indirect damage from immune sytem activation [4]. Exhausted T cells were defined by cell surface receptors. [4] T cell exhaustion can also be described as a metabolic phenomenon that occurs when T cells migrate into a nutrient poor environment. [5] The mitochondrial transcription factor Peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-1α) is given able discussion in this review of the role of mitochondria in the life cycle of T cells. [5] It may be worth noting that body temperature and heart rate are under brain stem control.

The role of the gastrointestinal tract

Note that gastrointestinal symptoms are largely ignored in long haul Coivd-19 Zhang and co authors used resources at proteinatlas.org to make a argument that the gastrointestinal symptoms seen in Covid-19 could be explained by the presence of angiotensin converting enzyme 2 (ACE2) receptor for Covid-19 being expressed on the these cells [6]. The need for copper supplements to preserve eye health in a Cu for gastric bypass patients post. Part of the stomach and duodenum are removed in this operation. Much of our dietary copper is absorbed in this same region.

Note that both the duodenum and rest of the small intestine express medium levels of Ctr1 with smaller levels of expression in the stomach and colon. Note that the duodenum and small intestine express more ACE2 than the bronchus and nasopharynx. We can certainly make the argument that in ab active Covid-19 infection with diarrhea, the stomach absorption of Cu⁺ may be the only option.

An international survey of 3762 “Long Covid” patients

revealed several trends [7]:

• “Brain fog” or some form of cognitive impairment occurred in 85.1% (3203). For instance, over 80% were mildly or seriously unable to make serious decisions or work. [7]
• Memory impairments were reported in 72.8% of the respondents. Only 20% were mildly or seriously unable to return home without getting lost. Remembering medication was experienced by 60% of the respondents.[7]
• Difficulties with speech and language was experienced by about half of the respondents. These difficulties included word retrieval, communicating verbally, and processing written text. [7]
• Sensorimotor symptoms were experienced by about 80% of the respondents. These symptoms included pins and needles, electric zaps, coldness in a body part, facial numbness, and more. [7]
• Sleep disturbances were experienced by about 80%. These disturbances ranged from insomnia and restless legs to changes in dreams. About a fifth of those that experienced these symptoms had similar issues prior to Covid-19.
• Headaches were reported in 77% of the respondents. [7]
• Emotion and mood disturbances were reported by about 8% of the respondents. These disturbances ranged from apathy, difficulty controlling emotions, irritability, anxiety, and depression. Over half that reported post Covid anxiety and depression did not have these symptoms prior to Covid.[7]
• Lost of taste and/or smell was experienced by about 60% of the respondents. About a third experienced lost of taste and another third experienced a lost of smell leading the reader to conclude that the phenomenon tended to be “either or.” Respondents also reported phantom smells that tended to be smoke and cigarettes. [7]
• Hallucinations were primarily olfactory (25%) with 10% or less experiencing visual, auditory, or tactile hallucinations. [7]
• Fatigue or post exertion al malaise were experienced by close to 80%.
• Low and high grade fevers were also common. [7]

Is Long Covid many syndromes?

One study [8] suggests long Covid is actually four syndromes:

1. permanent damage to lung and heart A recent in the journal Nature suggests that Long Covid may be an autoimmune disease. [9] Auto-antibodies against the annexin A2 are important as because annexin A2 helps maintain membrane in small blood vessels of the lung.[9] Streptococcus pyrogens M protein mimics proteins in the heart explaining how strept throat can lead to rheumatic fever. [9]
2. post-intensive care syndrome has been hypothesized to be due to a breakdown of the hypothalamic-pituitary-adrenal (HPA) axis and related to chronic fatigue syndrome. [10] The author proposed that the cytokine IL-1β, that is a hallmark of Covid-19 infections, is known to modulate CRH release by the hypothalamus. It was proposed that related series of events lead to adrenal atrophy.
3. post-viral fatigue syndrome, also myalgic encephalomyelitis/chronic fatigue syndrome It has been argued that CFS has at its roots mitochondrial coenzyme Q10 deficiency and that CoQ10 supplementation may help Long Covid sufferers. [11] Oxidative stress associated with mitochondrial dysfunction was also reviewed.
4. long term covid symptoms It is not clear what the authors meant by this 4th explanation of Long Covid.

A study out of the UK published in April 2021 in Nature Medicine reported symptoms of patients suffering symptoms < 28 days, >28 day, >28 days, and >28 > 56 days. [12] Those that were hospitalized with short Covid or who had multiple short Covid symptoms were more likely to develop Long Covid. [12] Co-occurance of multiple symptoms is frequent in Lng Covid. Co-occurrence network of symptom pairs in which nodes represent symptoms, the frequency of symptoms corresponds to the size of the node, and the likelihood of symptom pair co-occurrence is represented by the weight of the edges linking them. Edges representing a co-occurrence of less than 10% were removed.

• Delirium seems to be associated with all other Covid sysymptoms in Long Covid.
• Diarrhea (DI) and abdominal pain (AP) seem to require better definition as to the etiology if the primary infection has cleared. Is there permanent intestinal damage? If so, does this effect nutrient absorption?

Conclusions

It would appear that the scientific community has more hypotheses as to the cause of Long Covid than this post can even scratch the surface of. A few we have covered:

1. Active Covid-19 infections and Long Covid have similar symptoms.
2. Covid and autoimmune disease rheumatoid arthritis share common cytokines.
3. Exhausted T cells may play a roll in neurological issues of Long Covid. We don’t know if Cu(I)NA₂ will be a cure for mitochondrial issues in T cells.
4. The Covid receptor ACE2 is widely expressed in the G.I. tract. It is conceivable that a short term consequence of an active Covid infection would be impaired absorption of copper.
5. Long Covid has an extremely large range of symptoms, many of which resemble the symptoms of current Mitosynergy customers.
6. Long Covid might be just four disorders, that have considerable overlap in terms of root cause.

It would be over speculative to suggest that Cu(I)NA₂ supplies copper to one critical enzyme in any of these processes to cytochrome C oxidase in exhausted T cells to Cu/Zn superoxide dismutase trying to detoxify excess superoxide in the wake of autoimmune reactions. We can only point to similarities between Long Covid and the current Mitosynergy customer base.

References

1. https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html
2. https://www.cdc.gov/coronavirus/2019-ncov/long-term-effects.html
3. Schett G, Manger B, Simon D, Caporali R. (2020) COVID-19 revisiting inflammatory pathways of arthritis. Nat Rev Rheumatol. 2020 Aug;16(8):465-470 PMC free article
4. Heming M, Li X, Räuber S, Mausberg AK, Börsch AL, Hartlehnert M, Singhal A, Lu IN, Fleischer M, Szepanowski F, Witzke O, Brenner T, Dittmer U, Yosef N, Kleinschnitz C, Wiendl H, Stettner M, Meyer Zu Hörste G.(2021) Neurological Manifestations of COVID-19 Feature T Cell Exhaustion and Dedifferentiated Monocytes in Cerebrospinal Fluid. Immunity. 2021 Jan 12;54(1):164-175.e6. PMC free article
5. Desdín-Micó G, Soto-Heredero G, Mittelbrunn M.(2018) Mitochondrial activity in T cells. Mitochondrion. 2018 Jul;41:51-57. PMC free article
6. Zhang H, Li HB, Lyu JR, Lei XM, Li W, Wu G, Lyu J, Dai ZM. (2020) Specific ACE2 expression in small intestinal enterocytes may cause gastrointestinal symptoms and injury after 2019-nCoV infection. Int J Infect Dis. 2020 Jul;96:19-24. PMC free article
7. Davis HE, Assaf GS, McCorkell L, Wei H, Low RJ, Reeme Y, Redfield S, Austin JP, Akrami A.Characterizing Long COVID in an International Cohort: 7 Months of Symptoms and Their Impact Cross Ref
8. Mahase E (October 2020). “Long covid could be four different syndromes, review suggests”. BMJ. 371: m3981. Cross Ref
9. Khamsi R. (2021) Rogue antibodies could be driving severe COVID-19. Nature. 2021 Feb;59 (7844):29-31. PMC free article
10. Stanculescu D, Larsson L, Bergquist J. (2021) Hypothesis: Mechanisms That Prevent Recovery in Prolonged ICU Patients Also Underlie Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Front Med (Lausanne). 2021 Jan 28;8:628029. PMC free article
11. Wood E, Hall KH, Tate W. (2020) Role of mitochondria, oxidative stress and the response to antioxidants in myalgic encephalomyelitis/chronic fatigue syndrome: a possible approach to SARS-CoV-2 ‘long-haulers’? Chronic Dis Transl Med. 2020 Nov 21. doi: 10.1016/j.cdtm.2020.11.002. PMC free article
12. Sudre CH et al (2021) Attributes and predictors of long COVID. Nat Med. 2021 Apr;27(4):626-631. PMC free article