Covid-19 vaccines share many side effects with the actual infection. Wikipedia has a page on Coivd-19 vaccines at various stages of clinical trials. Fever, fatigue, and muscle pain are many recorded side effects from clinical trials with results. The mRNA-1273 vaccine, sponsored by Moderna, NIAID, BARDA has a different set of side effects. One of the issues with the current Covid-19 vaccines is that they are based on non replicating viruses that cause the common cold. They come with side effects of fever and fatigue. One the other hand, the cytokines that cause the fever also call in the T cells to mount an immune response. As long as the inflammasomes are turned off after the T cells have been called in, perhaps these adenovirus based vaccines are not so bad. Prehaps BARDA may be interested in Cu(I)NA₂ in a way of modulating any inflammatory response.

What is BARDA?

The Biomedical advanced Research Authority, BARDA, is particularly high on the list of potential CLAB Pharma partners.

• Part of the U.S. Department of Health and Human Services (HHS)
• Responsible for the procurement and development of medical countermeasures
• bioterrorism
• chemical, radiological, and nuclear (CBRN) threats
• pandemic influenza and emerging diseases
• manages Project BioShield

Adenovirus vaccines

Ad5 and Ad26 are “replication incompetent” members of Adenoviridae. The goal is to make protein without a full blown infection. Just the presence of the virus sets off the immune system such that “adjuncts” are not needed to stimulate the immune system. Adenoviruses have be used for years as vaccine vectors. These vectors have been engineered such they only replicate in cell culture. [1] This review covers biphasic synthesis of pro-inflammatory proteins such as IL-6, TNFα, IFNγ, IL-1β, and IL-12 as well as a number of chemokines. Assembly of inflammasomes is also mentioned. [1] This review does not cover the complexity of cells that adenoviruses may infect, and how many of these cells are antigen presenting cells. At any rate, these virus vectors elicit a strong T cell response. [1] Throughout this review fever and fatigue were mentioned as side effects of adenoviral based vaccines and therapies. [1]

A Russian Study

A study used recombinant adenovirus type 26 (rAd26) and recombinant adenovirus type 5 (rAd5), both of which carry the gene for SARS-CoV-2 full-length spike glycoprotein S (rAd26-S and rAd5-S). [2]. These vaccines were given as intramuscular injections. The frozen vaccine elicited low grade fevers of 37·0–38·4°C in 95% of the rAd26-S plus rAd5-S (n=20) group. The other patient experienced a fever of 38·5–38·9°C; grade 2)[2]. The lyophilized vaccine was less pyrogenic [2]

A Chinese Study

Fevers were also noted in another Covid-19 vaccine trial using the Covid-19 spike protein in an Ad5 vector. This Chinese study had 36 participants in each of three dosage groups [3]: The high does group received one shot containing 1·5 × 10¹¹ viral particles per 1·5 mL in one arm and double that dose in the other arm for a total of three shots. The middle dose group received just one of these shots in either arm. The low dose group received 5 × 10¹⁰ viral particles per 0·5 mL in an injection in one arm. [3]

• Fever: low dose, 15 (42%); middle dose, 15 (42%); high dose 20 (56%); total 50 (46%)
• Grade 3 fever >38.5^oC: low dose, 2 (6%); middle dose, 2 (6%); high dose, 5 (14%); total, 9 (8%)
• Fatigue: low dose, 17 (47%); middle dose, 14 (39%); high dose, 16 (44%); total, 47 (44%)
• Grade 3 fatigue: Only two patients of 36 in the high dose group experienced severe fatigue.

Severe fevers were reported within 24 hours of vaccination but lasting less than 48 hours post vaccination. [3]

A British Study

This is the Oxford study that was in the news in the summer of 2020. This group had previous experienced with a chimpanzee adenovirus-vectored vaccine that encodes the spike protein of Middle East respiratory syndrome coronavirus. Participants were randomly assigned (1:1) to receive either the ChAdOx1 nCoV-19 vaccine or the MenACWY vaccine. MenACWY was used as a comparator vaccine to maintain blinding of participants who experienced local or systemic reactions, since these reactions are a known association with viral vector vaccinations. Use of saline as a placebo would risk unblinding participants as those who had notable reactions would know they were in the ChAdOx1 nCoV-19 vaccine group. [4] This study found that paracetamol (Tylenol) could mitigate the vaccine related fevers. Fatigue was reported in about 70% of the patients with little effect of paracetamol. [4]

A U.S. mRNA study

This study used a lipid nanoparticle dispersion containing mRNA coding for the Covid-19 spike glycoprotein stabilized in its prefusion conformation. [5] Like other vaccines, this mRNA/ lipid nanoparticle dispersion was injected into the deltoid muscle. None of the patients experienced a fever with the first vaccination. No patient in the 25-μg group experienced fevers with the second vaccination. Fevers were seen in the 100-μg and 250-μg groups. Fatigue was a much more pronounced symptom in this mode of antigen deliver. Mild to moderate fatigue was experienced in over20% of all patients with the first dose. [5] Pain and headaches were experienced by even larger percentages.

After the second vaccination,
no participants in the , 6 (40%) in the
group, and 8 (57%) in
reported fever; one of the events (maximum temperature,
39.6°C) in the 250-μg group was graded
severe. (Additional details regarding adverse events
for that participant are provided in the Supplementary
Appendix.)

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Vaccine symptoms post FDA approval

According to FDA the Pfizer-BioNtech vaccine may be associated with the following side effects.

•injection site pain

• tiredness
• headache
• muscle pain
• chills
• joint pain
• fever
• injection site swelling
• injection site redness
• nausea
• feeling unwell
• swollen lymph nodes (lymphadenopathy)

Signs of allergic reaction: Difficulty breathing, Swelling of face and throat, A fast heartbeat, A bad rash all over body, Dizziness and weakness. If you feel any of these symptoms seek medical attention immediately.

According to FDA the Moderna mRNA has the same side effects after the first shot:

Injection site reactions: pain, tenderness and swelling of the lymph nodes in the same arm of the injection, swelling (hardness), and redness

• fatigue
• headache
• muscle pain
• joint pain
• chills
• nausea
• vomiting
• fever

There is a remote chance that the Moderna COVID-19 Vaccine could cause a severe allergic reaction. A severe allergic reaction would usually occur within a few minutes to one hour after getting a dose of the Moderna COVID-19 Vaccine. For this reason, your vaccination provider may ask you to stay at the place where you received your vaccine for monitoring after vaccination. Signs of a severe allergic reaction can include: •Difficulty breathing •Swelling of your face and throat •A fast heartbeat •A bad rash all over your body •Dizziness and weakness

According to the National Health Service of the UK, long term Covid may have some of the following symptoms:

• extreme tiredness (fatigue)
• shortness of breath chest pain or tightness
• problems with memory and concentration (“brain fog”)
• difficulty sleeping (insomnia)

heart palpitations dizziness pins and needles joint pain depression and anxiety tinnitus, earaches feeling sick, diarrhoea, stomach aches, loss of appetite a high temperature, cough, headaches, sore throat, changes to sense of smell or taste
rashes

If feel up to some inspiration, this link discusses how some medical doctors recorded body temperatures associated with typhoid fever back in the 1800s.

Post script in progress

The general inflammation by be mediated by the Cu/Zn superoxide dismutase. Noradrenaline is produced from dopamine by the Cu enzyme dopamine β hydrolase. Copper is a cofactor for cytochrome C oxidase of the mitochondria. This post had started out as an attempt to feel the water for use of Cu(I)NA₂ as a Covid-19 vaccine booster. Perhaps we now need to focus on mitigating the inflammatory aspects of the vaccines.

As appalling as it might sound, the mRNA vaccines can damage the cells that absorb the viral spike protein mRNA. The sequence of events is still not totally clear. Are there not enough self antigens on the myocytes expressing the spike protein that would tell the immune system to lay off?

So we have damage muscle with both doses. This means more cytochrome C oxidase since muscle have a lot of mitochondria. Muscles rely on strong collagen, whose cross-linking is catalyzed by lysyl oxidase. Strips of aorta in culture cannot make the elastin and collagen added copper [6]. While we do not have data showing how much muscle destruction is caused by the mRNA vaccines. Anecdotally it varies from one person to the next.

References

1. Wold WS, Toth K. (2013) Adenovirus vectors for gene therapy, vaccination and cancer gene therapy. Curr Gene Ther. 2013 Dec;13(6):421-33. [PubMed free article]
2. Logunov DY, Dolzhikova IV, Zubkova OV, Tukhvatullin AI, Shcheblyakov DV, Dzharullaeva AS, Grousova DM, Erokhova AS, Kovyrshina AV, Botikov AG, Izhaeva FM, Popova O, Ozharovskaya TA, Esmagambetov IB, Favorskaya IA, Zrelkin DI, Voronina DV, Shcherbinin DN, Semikhin AS, Simakova YV, Tokarskaya EA, Lubenets NL, Egorova DA, Shmarov MM, Nikitenko NA, Morozova LF, Smolyarchuk EA, Kryukov EV, Babira VF, Borisevich SV, Naroditsky BS, Gintsburg AL.(2020) Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia. Lancet. 2020 Sep 26;396(10255):887-897. [PMC free article]
3. Zhu FC, Li YH, Guan XH, Hou LH, Wang WJ, Li JX, Wu SP, Wang BS, Wang Z, Wang L, Jia SY, Jiang HD, Wang L, Jiang T, Hu Y, Gou JB, Xu SB, Xu JJ, Wang XW, Wang W, Chen W.(2020) Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial. Lancet. 2020 Jun 13;395(10240):1845-1854. [PMC free article]
4. Folegatti PM, Ewer KJ, Aley PK, Angus B, Becker S, Belij-Rammerstorfer S, Bellamy D, Bibi S, Bittaye M, Clutterbuck EA, Dold C, Faust SN, Finn A, Flaxman AL, Hallis B, Heath P, Jenkin D, Lazarus R, Makinson R, Minassian AM, Pollock KM, Ramasamy M, Robinson H, Snape M, Tarrant R, Voysey M, Green C, Douglas AD, Hill AVS, Lambe T, Gilbert SC, Pollard AJ; Oxford COVID Vaccine Trial Group.(2020) Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet. 2020 Aug 15;396(10249):467-478.[PMC free article]
5. Jackson LA, Anderson EJ, Rouphael NG, Roberts PC, Makhene M, Coler RN, et al. (mRNA-1273 Study Group) (July 2020). “An mRNA Vaccine against SARS-CoV-2 – Preliminary Report”. New England Journal of Medicine. [PMC free article]
6. Harris ED, Rayton JK, Balthrop JE, DiSilvestro RA, Garcia-de-Quevedo M. Copper and the synthesis of elastin and collagen. Ciba Found Symp. 1980;79:163-82 PubMed