Estudios en 184 millones de personas demuestran que las inyecciones Covid no son seguras

Las «vacunas» ARNm contra Covid no son seguras de acuerdo a estudios realizados que incluyen 184 millones de personas. Los 4 estudios que así lo demuestran son:

FAKSOVA ET AL (n=99 millones):

• ➊ Miocarditis (+510% después de la inyección de ARNm)
• ➋ Encefalomielitis diseminada aguda (+278% después de la inyección de ARNm)
• ➌ Trombosis del seno venoso cerebral (+223% después de la inyección del vector viral)
• ➍ Síndrome de Guillain-Barré (+149% tras la inyección del vector viral)

• RAHELEH ET AL (n= 85 millones):

• ➊ Ataque cardíaco (+286% después de la segunda dosis)
• ➋ Accidente cerebrovascular (+240% después de la primera dosis)
• ➌ Enfermedad de la arteria coronaria (+244% después de la segunda dosis)
• ➍ Arritmia cardíaca (+199% después de la primera dosis)

• HULSCHER ET AL (n= 325 autopsias):

Se demostró un vínculo causal entre las inyecciones contra la COVID-19 y la muerte a través de múltiples sistemas orgánicos.

• ALLESSANDRIA ET AL (n=290.727):

Los sujetos vacunados con 2 dosis perdieron el 37% de la esperanza de vida en comparación con la población no vacunada durante el seguimiento.

La retirada inmediata del mercado de las inyecciones de ARNm de COVID-19 es esencial para evitar más pérdidas de vidas entre millones personas que aún están inyectando.

La proteína pico o spike que produce la inyección contra Covid es tóxica

La siguiente sección recopila más de 300 estudios científicos revisados ​​por pares que confirman que la proteína pico o spike es altamente patógena por sí misma; la mayoría de los estudios citados aquí utilizaron proteínas de espiga recombinantes o proteínas de espiga en vectores pseudovirales y produjeron efectos patológicos independientes de la maquinaria viral del SARS-CoV2.

La segunda sección (II. Categorías) organiza la investigación en categorías generales que incluyen tejidos y sistemas orgánicos afectados, mecanismos y evidencia de patología clínica. Debido a que estas áreas se superponen, muchos artículos aparecen más de una vez en la segunda sección.

CATEGORIAS

A. General/Overview (32)
B. ACE2 (19)
C. Amyloid, prion-like properties (12)
D. Autoimmune (7)
E. Blood pressure/hypertension (2)
F. CD147 (13)
G. Cell membrane permeability, barrier dysfunction (13)
H. Cerebral, cerebrovascular, neurologic, blood-brain barrier, cognitive (24)
I. Clinical pathology (22)
J. Clotting, platelets, hemoglobin (30)
K. Cytokines, chemokines, interferon, interleukins (27)
L. Endothelial (25)
M. Gastrointestinal (8)
N. Immune dysfunction (5)
O. Macrophages , monocytes, neutrophils (28)
P. MAPK/NF-kB (10)
Q. Mast cells (3)
R. Microglia (6)
S. Microvascular (8)
T. MIS-C, pediatric (7)
U. Mitochondria / metabolism (9)
V. Myocarditis, cardiac, cardiomyopathy (22)
W. NLRP3 (15)
X. Ocular, ophthalmic, conjunctival (3)
Y. Other cell signaling (16)
Z. PASC, post COVID, long COVID (20)
AA. Pregnancy, fetal, placenta (7)
BB. Pulmonary, respiratory (28)
CC. Renin – Angiotensin-Aldosterone System (3)
DD. Senescence/aging (3)
EE. Stem cells (3)
FF. Syncytia / cell fusion (10)
GG. Therapeutics (37)
HH. Toll-like receptors (TLRs) (15)

A. General/Overview

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   Infection 2021, 49, 5: 855–876. doi: https://doi.org/10.1007/s15010-021-01677-8
3. Baldari CT et al., “Emerging Roles of SARS-CoV-2 Spike-ACE2 in Immune Evasion and Pathogenesis,”
   Trends Immunol. 2023, 44, 6. doi: https://doi.org/10.1016/j.it.2023.04.001
4. Bansal S et al., “Cutting Edge: Circulating Exosomes with COVID Spike Protein Are Induced by
   BNT162b2 (Pfizer-BioNTech) Vaccination prior to Development of Antibodies: A Novel Mechanism for
   Immune Activation by mRNA Vaccines,” J. Immunol. 2021, 207, 10: 2405–2410. doi:
   https://doi.org/10.4049/jimmunol.2100637
5. Bellucci M et al., “Post-SARS-CoV-2 infection and post-vaccine-related neurological complications
   share clinical features and the same positivity to anti-ACE2 antibodies,” Front. Immunol. 2024, 15
   (Sec. Multiple Sclerosis and Neuroimmunology). doi: https://doi.org/10.3389/fimmu.2024.1398028
6. Boros LG et al., “Long-lasting, biochemically modified mRNA, and its frameshifted recombinant
   spike proteins in human tissues and circulation after COVID-19 vaccination,” Pharmacol Res
   Perspect 2024, 12, 3: e1218. doi: https://doi.org/10.1002/prp2.1218
7. Brady M et al., “Spike protein multiorgan tropism suppressed by antibodies targeting SARS-CoV-2,”
   Comm. Biol. 2021, 4, 1318. doi: https://doi.org/10.1038/s42003-021-02856-x
8. Cosentino M and Franca Marino, “Understanding the Pharmacology of COVID- 19 mRNA Vaccines:
   Playing Dice with the Spike?” Int. J. Mol. Sci. 2022, 23, 18: 10881. doi:
   https://doi.org/10.3390/ijms231810881
9. Fertig TE et al., “Beyond the injection site: identifying the cellular targets of mRNA vaccines,” J Cell
   Ident 2024, 3, 1. doi: 10.47570/joci.2024.004
10. Fertig TE et al., “Vaccine mRNA Can Be Detected in Blood at 15 Days Post
    Vaccination,” Biomedicines 2022, 10, 7: 1538. doi: https://doi.org/10.3390/biomedicines10071538
11. Gussow AB et al., “Genomic Determinants of Pathogenicity in SARS-CoV-2 and Other Human
    Coronaviruses,” PNAS 117, 2020, 26: 15193–15199. doi: https://doi.org/10.1073/pnas.2008176117
12. Halma MTJ et al., “Strategies for the Management of Spike Protein-Related Pathology,”
    Microorganisms 2023, 11, 5: 1308, doi: https://doi.org/10.3390/microorganisms11051308
13. Kent SJ et al., “Blood Distribution of SARS-CoV-2 Lipid Nanoparticle mRNA Vaccine in Humans,” ACS
    Nano 2024, 18, 39: 27077-27089. doi: https://doi.org/10.1021/acsnano.4c11652
14. Kowarz E et al., “Vaccine-induced COVID-19 mimicry syndrome,” eLife 2022, 11: e74974.
    doi: https://doi.org/10.7554/eLife.74974
15. Lehmann KJ, “Impact of SARS-CoV-2 Spikes on Safety of Spike-Based COVID-19 Vaccinations,”
    Immunome Res. 2024, 20, 2: 1000267. doi: 10.35248/1745-7580.24.20.267
16. Lehmann KJ, “Suspected Causes of the Specific Intolerance Profile of Spike-Based Covid-19
    Vaccines,” Med. Res. Arch 2024, 12, 9. doi: 10.18103/mra.v12i9.5704
17. Lesgard JF et al., “Toxicity of SARS-CoV-2 Spike Protein from the Virus and Produced from COVID-19
    mRNA or Adenoviral DNA Vaccines,” Arch Microbiol Immun 2023, 7, 3: 121- 138. doi:
    10.26502/ami.936500110
18. Letarov AV et al., “Free SARS-CoV-2 Spike Protein S1 Particles May Play a Role in the Pathogenesis of
    COVID-19 Infection,” Biochemistry (Moscow) 2021, 86, 257–261. doi:
    https://doi.org/10.1134/S0006297921030032
19. Nuovo JG et al., “Endothelial Cell Damage Is the Central Part of COVID-19 and a Mouse Model
    Induced by Injection of the S1 Subunit of the Spike Protein,” Ann. Diagn. Pathol. 2021, 51, 151682.
    doi: https://doi.org/10.1016/j.anndiagpath.2020.151682
20. Pallas RM, “Innate and adaptative immune mechanisms of COVID-19 vaccines. Serious adverse
    events associated with SARS-CoV-2 vaccination: A systematic review,” Vacunas (English ed.) 2024,
    25, 2: 285.e1-285.e94. doi: https://doi.org/10.1016/j.vacune.2024.05.002
21. Parry PL et al., “‘Spikeopathy’: COVID-19 Spike Protein Is Pathogenic, from Both Virus and Vaccine
    mRNA,” Biomedicine 2023, 11, 8: 2287. doi: https://doi.org/10.3390/biomedicines11082287
22. Pateev I et al., “Biodistribution of RNA Vaccines and of Their Products: Evidence from Human and
    Animal Studies,” Biomedicines 2024, 12, 1: 59. doi: https://doi.org/10.3390/biomedicines12010059
23. Peluso MJ et al., “Plasma-based antigen persistence in the post-acute phase of COVID-19,” Lancet
    2024, 24, 6: E345-E347. doi: 10.1016/S1473-3099(24)00211-1
24. Rzymski P and Andrzej Fal, “To aspirate or not to aspirate? Considerations for the COVID-19
    vaccines,” Pharmacol. Rep 2022, 74: 1223–1227. doi: https://doi.org/10.1007/s43440-022-00361-4
25. Saadi F et al., “Spike glycoprotein is central to coronavirus pathogenesis-parallel between m-CoV
    and SARS-CoV-2,” Ann Neurosci. 2021, 28 (3-4): 201–218. doi:
    https://doi.org/10.1177/09727531211023755
26. Sacco K et al., “Immunopathological signatures in multisystem inflammatory syndrome in children
    and pediatric COVID-19,” Nat. Med. 2022, 28: 1050-1062. doi: https://doi.org/10.1038/s41591-022-
    01724-3
27. Scholkmann F and CA May, “COVID-19, post-acute COVID-19 syndrome (PACS, ‘long COVID’) and
    post-COVID-19 vaccination syndrome (PCVS, ‘post-COVIDvac-syndrome’): Similarities and
    diberences,” Pathol Res Pract. 2023, 246: 154497. doi: https://doi.org/10.1016/j.prp.2023.154497
28. Swank Z, et al. “Persistent Circulating Severe Acute Respiratory Syndrome Coronavirus 2 Spike Is
    Associated With Post-acute Coronavirus Disease 2019 Sequelae,” Clin. Infect. Dis 2023, 76, 3: e487–
    e490. doi: https://doi.org/10.1093/cid/ciac722
29. Theoharides TC, “Could SARS-CoV-2 Spike Protein Be Responsible for Long-COVID Syndrome?” Mol.
    Neurobiol. 2022, 59, 3: 1850–1861, doi: https://doi.org/10.1007/s12035-021-02696-0
30. Theoharides TC and P. Conti, “Be Aware of SARS-CoV-2 Spike Protein: There Is More Than Meets the
    Eye,” J Biol Reg Homeostat Agents 2021, 35, 3: 833–838 doi: 10.23812/THEO_EDIT_3_21
31. Trougakos IP et al., “Adverse Ebects of COVID-19 mRNA Vaccines: The Spike Hypothesis,” Trends Mol
    Med. 2022, 28, 7: 542–554. doi: 10.1016/j.molmed.2022.04.007
32. Tyrkalska SD et al., “Diberential proinflammatory activities of spike proteins of SARS-CoV-2 variants
    of concern,” Sci. Adv. 2022, 8, 37: eabo0732. doi: 10.1126/sciadv.abo0732

B. ACE2

1. Aboudounya MM and RJ Heads, “COVID-19 and Toll-Like Receptor 4 (TLR4): SARS-CoV-2 May Bind
   and Activate TLR4 to Increase ACE2 Expression, Facilitating Entry and Causing Hyperinflammation,”
   Mediators Inflamm. 2021, 8874339. doi: https://doi.org/10.1155/2021/8874339
2. Aksenova AY et al., “The increased amyloidogenicity of Spike RBD and pH-dependent binding to
   ACE2 may contribute to the transmissibility and pathogenic properties of SARS-CoV-2 omicron as
   suggested by in silico study,” Int J Mol Sci. 2022, 23, 21: 13502. doi:
   https://doi.org/10.3390/ijms232113502
3. Angeli F et al., “COVID-19, vaccines and deficiency of ACE2 and other angiotensinases. Closing the
   loop on the ‘Spike ebect’,” Eur J. Intern. Med. 2022, 103: 23–28. doi: 10.1016/j.ejim.2022.06.015
4. Baldari CT et al., “Emerging Roles of SARS-CoV-2 Spike-ACE2 in Immune Evasion and Pathogenesis,”
   Trends Immunol. 2023, 44, 6. doi: https://doi.org/10.1016/j.it.2023.04.001
5. Bellucci M et al., “Post-SARS-CoV-2 infection and post-vaccine-related neurological complications
   share clinical features and the same positivity to anti-ACE2 antibodies,” Front. Immunol. 2024, 15
   (Sec. Multiple Sclerosis and Neuroimmunology). doi: https://doi.org/10.3389/fimmu.2024.1398028
6. Devaux CA and L. Camoin-Jau, “Molecular mimicry of the viral spike in the SARS-CoV-2 vaccine
   possibly triggers transient dysregulation of ACE2, leading to vascular and coagulation dysfunction
   similar to SARS-CoV-2 infection,” Viruses 2023, 15, 5: 1045. doi: https://doi.org/10.3390/v15051045
7. Gao X et al., “Spike-Mediated ACE2 Down-Regulation Was Involved in the Pathogenesis of SARS-CoV-
   2 Infection,” J. Infect. 2022, 85, 4: 418–427. doi: 10.1016/j.jinf.2022.06.030
8. Kato Y et al., “TRPC3-Nox2 Protein Complex Formation Increases the Risk of SARS-CoV-2 Spike
   Protein-Induced Cardiomyocyte Dysfunction through ACE2 Upregulation,” Int. J. Mol. Sci. 2023, 24, 1:
9. doi: https://doi.org/10.3390/ijms24010102
10. Ken W et al., “Low dose radiation therapy attenuates ACE2 depression and inflammatory cytokines
    induction by COVID-19 viral spike protein in human bronchial epithelial cells,” Int J Radiat Biol. 2022,
    98, 10: 1532-1541. doi: https://doi.org/10.1080/09553002.2022.2055806
11. Lei Y et al., “SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE 2,”
    Circulation Research 2021, 128, 9: 1323–1326. doi:
    https://doi.org/10.1161/CIRCRESAHA.121.318902
12. Lu J and PD Sun, “High abinity binding of SARS-CoV-2 spike protein enhances ACE2
    carboxypeptidase activity,” J. Biol. Chem 2020, 295, 52: p18579-18588. doi:
    10.1074/jbc.RA120.015303
13. Maeda Y et al., “Diberential Ability of Spike Protein of SARS-CoV-2 Variants to Downregulate ACE2,”
    Int. J. Mol. Sci. 2024, 25, 2: 1353. doi: https://doi.org/10.3390/ijms25021353
14. Magro N et al., “Disruption of the blood-brain barrier is correlated with spike endocytosis by ACE2 +
    endothelia in the CNS microvasculature in fatal COVID-19. Scientific commentary on ‘Detection of
    blood-brain barrier disruption in brains of patients with COVID-19, but no evidence of brain
    penetration by SARS-CoV-2’,” Acta Neuropathol. 2024, 147, 1: 47. doi:
    https://doi.org/10.1007/s00401-023-02681-y
15. Satta S et al., “An engineered nano-liposome-human ACE2 decoy neutralizes SARS-CoV-2 Spike
    protein-induced inflammation in both murine and human macrophages,” Theranostics 2022, 12, 6:
    2639–2657. doi: 10.7150/thno.66831
16. Sui Y et al., “SARS-CoV-2 Spike Protein Suppresses ACE2 and Type I Interferon Expression in Primary
    Cells From Macaque Lung Bronchoalveolar Lavage,” Front. Immunol. 2021, 12. doi:
    https://doi.org/10.3389/fimmu.2021.658428
17. Tetz G and Victor Tetz, “Prion-Like Domains in Spike Protein of SARS-CoV-2 Diber across Its Variants
    and Enable Changes in Abinity to ACE2,” Microorganisms 2025, 10, 2: 280. doi:
    https://doi.org/10.3390/microorganisms10020280
18. Vargas-Castro R et al., “Calcitriol prevents SARS-CoV spike-induced inflammation in human
    trophoblasts through downregulating ACE2 and TMPRSS2 expression,” J Steroid Biochem Mol
    Biol 2025, 245: 106625. doi: https://doi.org/10.1016/j.jsbmb.2024.106625
19. Youn JY et al., “Therapeutic application of estrogen for COVID-19: Attenuation of SARS-CoV-2 spike
    protein and IL-6 stimulated, ACE2-dependent NOX2 activation, ROS production and MCP-1
    upregulation in endothelial cells,” Redox Biol. 2021, 46: 102099. doi:
    https://doi.org/10.1016/j.redox.2021.102099
20. Zhang S et al., “SARS-CoV-2 Binds Platelet ACE2 to Enhance Thrombosis in COVID-19,” J. Hematol.
    Oncol. 2020, 13, 120: 120. doi: https://doi.org/10.1186/s13045-020-00954-7
    C. Amyloid, prion-like properties

C. Amyloid, prion-like properties

1. Aksenova AY et al., “The increased amyloidogenicity of Spike RBD and pH-dependent binding to
   ACE2 may contribute to the transmissibility and pathogenic properties of SARS-CoV-2 omicron as
   suggested by in silico study,” Int. J. Mol. Sci. 2022, 23, 21: 13502. doi:
   https://doi.org/10.3390/ijms232113502
2. Cao S et al., “Spike Protein Fragments Promote Alzheimer’s Amyloidogenesis,” ACS Appl. Mater.
   Interfaces 2023, 15, 34: 40317-40329. doi: https://doi.org/10.1021/acsami.3c09815
3. Freeborn J, “Misfolded Spike Protein Could Explain Complicated COVID-19 Symptoms,” Medical
   News Today, May 26, 2022, https://www.medicalnewstoday.com/articles/misfolded-spike-proteincould- explain-complicated-covid-19-symptoms
4. Idrees D and Vijay Kumar, “SARS-CoV-2 Spike Protein Interactions with Amyloidogenic Proteins:
   Potential Clues to Neurodegeneration,” Biochemical and Biophysical Research Communications
   2021, 554 : 94–98. doi: https://doi.org/10.1016/j.bbrc.2021.03.100
5. Ma G et al., “SARS-CoV-2 Spike protein S2 subunit modulates γ-secretase and enhances amyloid-β
   production in COVID-19 neuropathy,” Cell Discov 2022, 8, 99. doi: https://doi.org/10.1038/s41421-
   022-00458-3
6. Nahalka J, “1-L Transcription of SARS-CoV-2 Spike Protein S1 Subunit,” Int. J. Mol. Sci. 2024, 25, 8: doi: https://doi.org/10.3390/ijms25084440
7. Nyström S, “Amyloidogenesis of SARS-CoV-2 Spike Protein,” J. Am. Chem. Soc. 2022, 144, 8945– doi: https://doi.org/10.1021/jacs.2c03925
8. Petrlova J et al., “SARS-CoV-2 spike protein aggregation is triggered by bacterial lipopolysaccharide,”
   FEBS Lett. 2022, 596:2566–2575. doi: https://doi.org/10.1002/1873-3468.14490
9. Petruk G et al., “SARS-CoV-2 spike protein binds to bacterial lipopolysaccharide and boosts
   proinflammatory activity,” J. Mol. Cell Biol. 2020, 12: 916-932. doi:
   https://doi.org/10.1093/jmcb/mjaa067
10. Rong Z et al., “Persistence of spike protein at the skull-meninges-brain axis may contribute to the
    neurological sequelae of COVID-19,” Cell Host Microbe 2024, 26: S1931-3128(24)00438-4. doi:
    10.1016/j.chom.2024.11.007
11. Tetz G and Victor Tetz, “Prion-Like Domains in Spike Protein of SARS-CoV-2 Diber across Its Variants
    and Enable Changes in Abinity to ACE2,” Microorganisms 2022, 10, 2: 280, doi:
    https://doi.org/10.3390/microorganisms10020280
12. Wang J et al., “SARS-CoV-2 Spike Protein S1 Domain Accelerates α-Synuclein Phosphorylation and
    Aggregation in Cellular Models of Synucleinopathy,” Mol Neurobiol. 2024, 61, 4: 2446-2458. doi:
    https://doi.org/10.1007/s12035-023-03726-9
    

D. Autoimmune

1. Heil M, “Self-DNA driven inflammation in COVID-19 and after mRNA-based vaccination: lessons for
   non-COVID-19 pathologies,” Front. Immunol., 2023, 14. doi:
   https://doi.org/10.3389/fimmu.2023.1259879
2. Kanduc D, “From Anti-SARS-CoV-2 Immune Responses to COVID-19 via Molecular Mimicry,”
   Antibodies 2020, 9, 3: 33. doi: https://doi.org/10.3390/antib9030033
3. Kanduc D and Y Shoenfeld, “Molecular mimicry between SARS-CoV-2 spike glycoprotein and
   mammalian proteomes: implications for the vaccine,” Immunol Res 2020, 68: 310-313. doi:
   https://doi.org/10.1007/s12026-020-09152-6
4. Nunez-Castilla J et al., “Potential autoimmunity resulting from molecular mimicry between SARSCoV-
   2 spike and human proteins,” Viruses 2022, 14, 7: 1415. https://doi.org/10.3390/v14071415
5. Rodriguez Y et al., “Autoinflammatory and autoimmune conditions at the crossroad of COVID-19,” J.
   Autoimmun. 2020, 114: 102506. doi: https://doi.org/10.1016/j.jaut.2020.102506
6. Vojdani A and D Kharrazian, “Potential antigenic cross-reactivity between SARS-CoV-2 and human
   tissue with a possible link to an increase in autoimmune diseases,” Clin Immunol. 2020, 217:doi: https://doi.org/10.1016/j.clim.2020.108480
7. Vojdani A et al., “Reaction of Human Monoclonal Antibodies to SARS-CoV-2 Proteins With Tissue
   Antigens: Implications for Autoimmune Diseases,” Front. Immunol. 2021, 11 (Sec. Autoimmune and
   Autoinflammatory Disorders). doi: https://doi.org/10.3389/fimmu.2020.617089

E. Blood pressure/hypertension

1. Angeli F et al., “The spike ebect of acute respiratory syndrome coronavirus 2 and coronavirus disease
   2019 vaccines on blood pressure,” Eur J Intern Med. 2023, 109: 12-21. doi:
   10.1016/j.ejim.2022.12.004
2. Sun Q et al., “SARS-coV-2 spike protein S1 exposure increases susceptibility to angiotensin IIinduced
   hypertension in rats by promoting central neuroinflammation and oxidative
   stress,” Neurochem. Res. 2023, 48, 3016–3026. doi: https://doi.org/10.1007/s11064-023-03949-1

F. CD147

1. Avolio E et al., “The SARS-CoV-2 Spike Protein Disrupts Human Cardiac Pericytes Function through
   CD147 Receptor-Mediated Signalling: A Potential Non-infective Mechanism of COVID-19
   Microvascular Disease,” Clin. Sci. 2021, 135, 24: 2667–2689. doi:
   https://doi.org/10.1042/CS20210735
2. Loh D, “The potential of melatonin in the prevention and attenuation of oxidative hemolysis and
   myocardial injury from cd147 SARS-CoV-2 spike protein receptor binding,” Melatonin Research 2020,
   3, 3: 380-416. doi: https://doi.org/10.32794/mr11250069
3. Maugeri N et al., “Unconventional CD147-Dependent Platelet Activation Elicited by SARS-CoV-2 in
   COVID-19,” J. Thromb. Haemost. 2021, 20, 2: 434–448. doi: https://doi.org/10.1111/jth.15575
   

G. Cell membrane permeability, barrier dysfunction

1. Asandei A et al., “Non-Receptor-Mediated Lipid Membrane Permeabilization by the SARS-CoV-2
   Spike Protein S1 Subunit,” ACS Appl. Mater. Interfaces 2020, 12, 50: 55649–55658. doi:
   https://doi.org/10.1021/acsami.0c17044
2. Biancatelli RMLC, et al. “The SARS-CoV-2 spike protein subunit S1 induces COVID-19-like acute lung
   injury in Kappa18-hACE2 transgenic mice and barrier dysfunction in human endothelial cells,” Am. J.
   Physiol. Lung Cell. Mol. Physiol. 2021, 321: L477–L484. doi:
   https://doi.org/10.1152/ajplung.00223.2021
3. Biering SB et al., “SARS-CoV-2 Spike Triggers Barrier Dysfunction and Vascular Leak via Integrins and
   TGF-β Signaling,” Nat. Commun. 2022, 13: 7630. doi: https://doi.org/10.1038/s41467-022-34910-5
4. Buzhdygan TP et al., “The SARS-CoV-2 Spike Protein Alters Barrier Function in 2D Static and 3D
   Microfluidic in-Vitro Models of the Human Blood-Brain Barrier,” Neurobiol. Dis. 2020, 146: 105131.
   doi: https://doi.org/10.1016/j.nbd.2020.105131
5. Chaves JCS et al., “Diberential Cytokine Responses of APOE3 and APOE4 Blood–brain Barrier Cell
   Types to SARS-CoV-2 Spike Proteins,” J. Neuroimmune Pharmacol. 2024, 19, 22. doi:
   https://doi.org/10.1007/s11481-024-10127-9
6. Correa Y et al., “SARS-CoV-2 spike protein removes lipids from model membranes and interferes with the capacity of high-density lipoprotein to exchange lipids,” J. Colloid Interface Sci. 2021, 602: 732- doi: https://doi.org/10.1016/j.jcis.2021.06.056
7. DeOre BJ et al., “SARS-CoV-2 Spike Protein Disrupts Blood-Brain Barrier Integrity via RhoA
   Activation,” J Neuroimmune Pharmacol. 2021, 16, 4:722-728. Doi: https://doi.org/10.1007/s11481-
   021-10029-0
8. Guo Y and V Kanamarlapudi, “Molecular Analysis of SARS-CoV-2 Spike Protein-Induced Endothelial
   Cell Permeability and vWF Secretion,” Int. J. Mol. Sci. 2023, 24, 6: 5664. doi:
   https://doi.org/10.3390/ijms24065664
9. Luchini A et al., “Lipid bilayer degradation induced by SARS-CoV-2 spike protein as revealed by
   neutron reflectometry,” Sci. Rep. 2021, 11: 14867. doi: https://doi.org/10.1038/s41598-021-93996-x
10. Luo Y et al., “SARS-Cov-2 spike induces intestinal barrier dysfunction through the interaction
    between CEACAM5 and Galectin-9,” Front. Immunol. 2024, 15. doi:
    https://doi.org/10.3389/fimmu.2024.1303356
11. Magro N et al., “Disruption of the blood-brain barrier is correlated with spike endocytosis by ACE2 +
    endothelia in the CNS microvasculature in fatal COVID-19. Scientific commentary on ‘Detection of
    blood-brain barrier disruption in brains of patients with COVID-19, but no evidence of brain
    penetration by SARS-CoV-2’,” Acta Neuropathol. 2024, 147, 1: 47. doi:
    https://doi.org/10.1007/s00401-023-02681-y
12. Raghavan S et al., “SARS-CoV-2 Spike Protein Induces Degradation of Junctional Proteins That
    Maintain Endothelial Barrier Integrity,” Front. Cardiovasc. Med. 2021, 8, 687783. doi:
    https://doi.org/10.3389/fcvm.2021.687783
13. Ruben ML et al., “The SARS-CoV-2 spike protein subunit S1 induces COVID-19-like acute lung injury
    in Κ18-hACE2 transgenic mice and barrier dysfunction in human endothelial cells,” Am J Physiol Lung
    Cell Mol Physiol. 2021, 321, 2: L477-L484. doi: https://doi.org/10.1152/ajplung.00223.2021

H. Cerebral, cerebrovascular, neurologic, blood-brain barrier, cognitive

1. Bellucci M et al., “Post-SARS-CoV-2 infection and post-vaccine-related neurological complications
   share clinical features and the same positivity to anti-ACE2 antibodies,” Front. Immunol. 2024, 15
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2. Burnett FN et al., “SARS-CoV-2 Spike Protein Intensifies Cerebrovascular Complications in Diabetic
   hACE2 Mice through RAAS and TLR Signaling Activation,” Int. J. Mol. Sci. 2023, 24, 22: 16394.
   doi: https://doi.org/10.3390/ijms242216394
3. Choi JY et al., “SARS-CoV-2 spike S1 subunit protein-mediated increase of beta-secretase 1 (BACE1)
   impairs human brain vessel cells,” Biochem. Biophys. Res. Commun. 2022, 625, 20: 66-71.
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4. Clough E et al., “Mitochondrial Dynamics in SARS-COV2 Spike Protein Treated Human Microglia:
   Implications for Neuro-COVID,” J. Neuroimmune Pharmacol. 2021, 4, 16: 770–784. doi:
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5. Coly M, et al., “Subacute monomelic radiculoplexus neuropathy following Comirnaty(c) (Pfizer-
   BioNTech COVID-19) vaccination: A case report,” Revue Neurologique 2023, 179, 6: 636-639. doi:
   https://doi.org/10.1016/j.neurol.2023.02.063
6. DeOre BJ et al., “SARS-CoV-2 Spike Protein Disrupts Blood-Brain Barrier Integrity via RhoA
   Activation,” J Neuroimmune Pharmacol. 2021, 16, 4: 722-728. Doi: https://doi.org/10.1007/s11481-
   021-10029-0
7. Erdogan MA, “Prenatal SARS-CoV-2 Spike Protein Exposure Induces Autism-Like Neurobehavioral
   Changes in Male Neonatal Rats,” J Neuroimmune Pharmacol. 2023, 18, 4: 573-591. doi:
   10.1007/s11481-023-10089-4
8. Erickson MA et al., “Blood-brain barrier penetration of non-replicating SARS-CoV-2 and S1 variants of
   concern induce neuroinflammation which is accentuated in a mouse model of Alzheimer’s disease,”
   Brain Behav Immun 2023, 109: 251-268. doi: https://doi.org/10.1016/j.bbi.2023.01.010
9. Fontes-Dantas FL, “SARS-CoV-2 Spike Protein Induces TLR4-Mediated Long- Term Cognitive
   Dysfunction Recapitulating Post-COVID-19 Syndrome in Mice,” Cell Reports 2023, 42, 3: 112189. doi:
   https://doi.org/10.1016/j.celrep.2023.112189
10. Frank MG et al., “Exploring the immunogenic properties of SARS-CoV-2 structural proteins:
    PAMP:TLR signaling in the mediation of the neuroinflammatory and neurologic sequelae of COVID-
    19,” Brain Behav Immun 2023, 111. doi: https://doi.org/10.1016/j.bbi.2023.04.009
11. Frank MG et al., “SARS-CoV-2 S1 subunit produces a protracted priming of the neuroinflammatory,
    physiological, and behavioral responses to a remote immune challenge: A role for corticosteroids,”
    Brain Behav. Immun. 2024, 121: 87-103. doi: https://doi.org/10.1016/j.bbi.2024.07.034
12. Heath SP et al., “SARS-CoV-2 Spike Protein Exacerbates Thromboembolic Cerebrovascular
    Complications in Humanized ACE2 Mouse Model,” Transl Stroke Res. 2024. doi:
    https://doi.org/10.1007/s12975-024-01301-5
13. Khaddaj-Mallat R et al., “SARS-CoV-2 deregulates the vascular and immune functions of brain
    pericytes via Spike protein,” Neurobiol. Dis. 2021, 161, 105561. doi:
    https://doi.org/10.1016/j.nbd.2021.105561
14. Kim ES et al., “Spike Proteins of SARS-CoV-2 Induce Pathological Changes in Molecular Delivery and
    Metabolic Function in the Brain Endothelial Cells,” Viruses 2021, 13, 10: 2021. doi:
    https://doi.org/10.3390/v13102021
15. Lykhmus O et al., “Immunization with 674–685 fragment of SARS-Cov-2 spike protein induces
    neuroinflammation and impairs episodic memory of mice,” Biochem. Biophys. Res.
    Commun. 2022, 622: 57–63. doi: https://doi.org/10.1016/j.bbrc.2022.07.016
16. Magro N et al., “Disruption of the blood-brain barrier is correlated with spike endocytosis by ACE2 +
    endothelia in the CNS microvasculature in fatal COVID-19. Scientific commentary on ‘Detection of
    blood-brain barrier disruption in brains of patients with COVID-19, but no evidence of brain
    penetration by SARS-CoV-2’,” Acta Neuropathol. 2024, 147, 1: 47. doi:
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17. Oh J et al., “SARS-CoV-2 Spike Protein Induces Cognitive Deficit and Anxiety-Like Behavior in Mouse
    via Non-cell Autonomous Hippocampal Neuronal Death,” Scientific Reports 2022, 12, 5496. doi:
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18. Oka N et al., “SARS-CoV-2 S1 protein causes brain inflammation by reducing intracerebral
    acetylcholine production,” iScience 2023, 26, 6: 106954. doi: 10.1016/j.isci.2023.106954
19. Peluso MJ et al., “SARS-CoV-2 and mitochondrial proteins in neural-derived exosomes of COVID-19,”
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20. Petrovszki D et al., “Penetration of the SARS-CoV-2 Spike Protein across the Blood-Brain Barrier, as
    Revealed by a Combination of a Human Cell Culture Model System and Optical
    Biosensing,” Biomedicines 2022, 10, 1: 188. doi: https://doi.org/10.3390/biomedicines10010188
21. Rong Z et al., “Persistence of spike protein at the skull-meninges-brain axis may contribute to the
    neurological sequelae of COVID-19,” Cell Host Microbe 2024, 26: S1931-3128(24)00438-4. doi:
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22. Suprewicz L et al., “Blood-brain barrier function in response to SARS-CoV-2 and its spike
    protein,” Neurol. Neurochir Pol. 2023, 57: 14–25. doi: 10.5603/PJNNS.a2023.0014
23. Suprewicz L et al., “Recombinant human plasma gelsolin reverses increased permeability of the
    blood-brain barrier induced by the spike protein of the SARS-CoV-2 virus,” J Neuroinflammation 2022,
    19, 1: 282, doi: https://doi.org/10.1186/s12974-022-02642-4
24. Wu ML et al., “Mast cell activation triggered by SARS-CoV-2 causes inflammation in brain
    microvascular endothelial cells and microglia,” Front. Cell. Infect. Microbiol., 2024, 14. doi:
    https://doi.org/10.3389/fcimb.2024.1358873
    

I. Clinical pathology

1. Baumeier C et al., “Intramyocardial Inflammation after COVID-19 Vaccination: An Endomyocardial
   Biopsy-Proven Case Series,” Int. J. Mol. Sci. 2022, 23: 6940. doi:
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2. Burkhardt A, “Pathology Conference: Vaccine-Induced Spike Protein Production in the Brain, Organs
   etc., now Proven,” Report24.news. 2022, https://report24.news/pathologie-konferenzimpfinduzierte-
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3. Craddock V et al., “Persistent circulation of soluble and extracellular vesicle-linked Spike protein in
   individuals with postacute sequelae of COVID-19,” J Med. Virol. 2023, 95, 2: e28568. doi:
   https://doi.org/10.1002/jmv.28568
4. De Michele M et al., “Evidence of SARS-CoV-2 Spike Protein on Retrieved Thrombi from COVID-19
   Patients,” J. Hematol. Oncol. 2022, 15, 108. doi: https://doi.org/10.1186/s13045-022-01329-w
5. De Sousa PMB et al., “Fatal Myocarditis following COVID-19 mRNA Immunization: A Case Report and
   Diberential Diagnosis Review,” Vaccines 2024, 12, 2: 194.
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6. Gamblicher T et al., “SARS-CoV-2 spike protein is present in both endothelial and eccrine cells of a
   chilblain-like skin lesion,” J Eur Acad Dermatol Venereol. 2020, 1, 10: e187-e189. doi:
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7. Gawaz A et al., “SARS-CoV-2–Induced Vasculitic Skin Lesions Are Associated with Massive Spike
   Protein Depositions in Autophagosomes,” J Invest Dermatol. 2024, 144, 2: 369-377.e4. doi:
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8. Hulscher N et al., “Autopsy findings in cases of fatal COVID-19 vaccine-induced myocarditis,” ESC
   Heart Failure 2024. doi: https://doi.org/10.1002/ehf2.14680
9. Ko CJ et al., “Discordant anti-SARS-CoV-2 spike protein and RNA staining in cutaneous perniotic
   lesions suggests endothelial deposition of cleaved spike protein,” J. Cutan Pathol 2021, 48, 1: 47–
10. doi: https://doi.org/10.1111/cup.13866
11. Magen E et al., “Clinical and Molecular Characterization of a Rare Case of BNT162b2 mRNA COVID-
    19 Vaccine-Associated Myositis,” Vaccines 2022, 10: 1135. doi:
    https://doi.org/10.3390/vaccines10071135
12. Magro N et al., “Disruption of the blood-brain barrier is correlated with spike endocytosis by ACE2 +
    endothelia in the CNS microvasculature in fatal COVID-19. Scientific commentary on ‘Detection of
    blood-brain barrier disruption in brains of patients with COVID-19, but no evidence of brain
    penetration by SARS-CoV-2’,” Acta Neuropathol. 2024, 147, 1: 47. doi:
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13. Matschke J et al., “Neuropathology of patients with COVID-19 in Germany: a post-mortem case
    series,” Lancet Neurol. 2020, 19, 11: 919-929. doi: 10.1016/S1474-4422(20)30308-2
14. Mörz M, “A Case Report: Multifocal Necrotizing Encephalitis and Myocarditis after BNT162b2 mRNA
    Vaccination against COVID-19,” Vaccines 2022, 10, 10: 1651. doi:
    https://doi.org/10.3390/vaccines10101651
15. Rong Z et al., “Persistence of spike protein at the skull-meninges-brain axis may contribute to the
    neurological sequelae of COVID-19,” Cell Host Microbe 2024, 26: S1931-3128(24)00438-4. doi:
    10.1016/j.chom.2024.11.007
16. Sano H et al., “A case of persistent, confluent maculopapular erythema following a COVID-19 mRNA
    vaccination is possibly associated with the intralesional spike protein expressed by vascular
    endothelial cells and eccrine glands in the deep dermis,” J. Dermatol. 2023, 50: 1208–1212. doi:
    https://doi.org/10.1111/1346-8138.16816
17. Sano S et al., “SARS-CoV-2 spike protein found in the acrosyringium and eccrine gland of repetitive
    miliaria-like lesions in a woman following mRNA vaccination,” J. Dermatol. 2024, 51, 9: e293-e295.
    doi: https://doi.org/10.1111/1346-8138.17204
18. Santonja C et al., “COVID-19 chilblain-like lesion: immunohistochemical demonstration of SARSCoV-
    2 spike protein in blood vessel endothelium and sweat gland epithelium in a polymerase chain
    reaction-negative patient,” Br J Dermatol. 2020, 183, 4: 778-780. doi:
    https://doi.org/10.1111/bjd.19338
19. Soares CD et al., “Oral vesiculobullous lesions as an early sign of COVID-19: immunohistochemical
    detection of SARS-CoV-2 spike protein,” Br. J. Dermatol. 2021, 184, 1: e6.
    doi: https://doi.org/10.1111/bjd.19569
20. Wu H et al., “Molecular evidence suggesting the persistence of residual SARS-CoV-2 and immune
    responses in the placentas of pregnant patients recovered from COVID-19,” Cell Prolif. 2021, 54, 9:
    e13091. doi: https://doi.org/10.1111/cpr.13091
21. Yamamoto M et al., “Persistent varicella zoster virus infection following mRNA COVID-19 vaccination
    was associated with the presence of encoded spike protein in the lesion,” J. Cutan Immunol. Allergy.
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22. Yonker LM et al., “Circulating Spike Protein Detected in Post–COVID-19 mRNA Vaccine Myocarditis,”
    Circulation 2023, 147, 11. doi: https://doi.org/10.1161/CIRCULATIONAHA.122.061025
23. Yonker LM et al., “Multisystem inflammatory syndrome in children is driven by zonulin-dependent
    loss of gut mucosal barrier,” J Clin Invest. 2021, 131, 14: e149633. doi:
    https://doi.org/10.1172/JCI149633
    

J. Clotting, platelets, hemoglobin

1. Al-Kuraishy HM et al., “Changes in the Blood Viscosity in Patients With SARS-CoV-2 Infection,” Front.
   Med. 2022, 9: 876017. doi: 10.3389/fmed.2022.876017
2. Al-Kuraishy HM et al., “Hemolytic anemia in COVID-19,” Ann. Hematol. 2022, 101: 1887–1895. doi:
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3. Appelbaum K et al., “SARS-CoV-2 spike-dependent platelet activation in COVID-19 vaccine-induced
   thrombocytopenia,” Blood Adv. 2022, 6: 2250–2253. doi: 10.1182/bloodadvances.2021005050
4. Boschi C et al., “SARS-CoV-2 Spike Protein Induces Hemagglutination: Implications for COVID-19
   Morbidities and Therapeutics and for Vaccine Adverse Ebects,” Int. J. Biol. Macromol. 2022, 23, 24:
   15480, doi: https://doi.org/10.3390/ijms232415480
5. Bye AP et al., “Aberrant glycosylation of anti-SARS-CoV-2 spike IgG is a prothrombotic stimulus for
   platelets,” Blood 2021, 138, 6: 1481–9. doi: https://doi.org/10.1182/blood.2021011871
6. Carnevale R et al., “Toll-Like Receptor 4-Dependent Platelet-Related Thrombosis in SARS-CoV-2
   Infection,” Circ. Res. 2023, 132, 3: 290– 305, doi: https://doi.org/10.1161/CIRCRESAHA.122.321541
7. Cossenza LC et al., “Inhibitory ebects of SARS-CoV-2 spike protein and BNT162b2 vaccine on
   erythropoietin-induced globin gene expression in erythroid precursor cells from patients with β-
   thalassemia,” Exp. Hematol. 2024, 129, 104128. doi: https://doi.org/10.1016/j.exphem.2023.11.002
8. De Michele M et al., “Vaccine-induced immune thrombotic thrombocytopenia: a possible
   pathogenic role of ChAdOx1 nCoV-19 vaccine-encoded soluble SARS-CoV-2 spike protein,”
   Haematologica 2022, 107, 7: 1687–92. https://doi.org/10.3324/haematol.2021.280180
9. Grobbelaar LM et al., “SARS-CoV-2 Spike Protein S1 Induces Fibrin(ogen) Resistant to Fibrinolysis:
   Implications for Microclot Formation in COVID-19,” Biosicence Reports 2021, 41, 8: BSR20210611.
   doi: https://doi.org/10.1042/BSR20210611
10. Heath SP et al., “SARS-CoV-2 Spike Protein Exacerbates Thromboembolic Cerebrovascular
    Complications in Humanized ACE2 Mouse Model,” Transl Stroke Res. 2024. doi:
    https://doi.org/10.1007/s12975-024-01301-5
11. Iba T and JH Levy, “The roles of platelets in COVID-19-associated coagulopathy and vaccine-induced
    immune thrombotic thrombocytopenia,” Trends Cardiovasc Med. 2022, 32, 1: 1-9. doi:
    https://doi.org/10.1016/j.tcm.2021.08.012
12. Huynh TV et al., “Spike Protein of SARS-CoV-2 Activates Cardiac Fibrogenesis through NLRP3
    Inflammasomes and NF-κB Signaling,” Cells 2024, 13, 16: 1331.
    doi: https://doi.org/10.3390/cells13161331
13. Iba T and JH Levy, “The roles of platelets in COVID-19-associated coagulopathy and vaccine-induced
    immune thrombotic thrombocytopenia,” Trends Cardiovasc Med. 2022, 32, 1: 1-9. doi:
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14. Jana S et al., “Cell-free hemoglobin does not attenuate the ebects of SARS-CoV-2 spike protein S1
    subunit in pulmonary endothelial cells,” Int. J. Mol. Sci. 2021, 22, 16: 9041. doi:
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15. Kim SY et al., “Characterization of heparin and severe acute respiratory syndrome-related
    coronavirus 2 (SARS-CoV-2) spike glycoprotein binding interactions,” Antivir Res. 2020, 181: 104873.
    doi: https://doi.org/10.1016/j.antiviral.2020.104873
16. Kircheis R, “Coagulopathies after Vaccination against SARS-CoV-2 May Be Derived from a Combined
    Ebect of SARS-CoV-2 Spike Protein and Adenovirus Vector-Triggered Signaling Pathways,” Int. J. Mol.
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17. Kuhn CC et al. “Direct Cryo-ET observation of platelet deformation induced by SARS-CoV-2 spike
    protein,” Nat. Commun. 2023, 14, 620. doi: https://doi.org/10.1038/s41467-023-36279-5
18. Li T et al., “Platelets Mediate Inflammatory Monocyte Activation by SARS-CoV-2 Spike Protein,” J.
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19. Maugeri N et al., “Unconventional CD147-Dependent Platelet Activation Elicited by SARS-CoV-2 in
    COVID-19,” J. Thromb. Haemost. 2021, 20, 2: 434–448, doi: https://doi.org/10.1111/jth.15575
20. Passariello M et al., “Interactions of Spike-RBD of SARS-CoV-2 and Platelet Factor 4: New Insights in
    the Etiopathogenesis of Thrombosis,” Int. J. Mol. Sci. 2021, 22, 16: 8562.
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21. Perico L et al., “SARS-CoV-2 Spike Protein 1 Activates Microvascular Endothelial Cells and
    Complement System Leading to Platelet Aggregation,” Front. Immunol. 2022, 13, 827146. doi:
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22. Roytenberg R et al., “Thymidine phosphorylase mediates SARS-CoV-2 spike protein enhanced
    thrombosis in K18-hACE2TG mice,” Thromb. Res. 2024, 244, 8: 109195. doi:
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23. Russo A, et al., “Implication of COVID-19 on Erythrocytes Functionality: Red Blood Cell Biochemical
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24. Ryu JK et al., “Fibrin drives thromboinflammation and neuropathology in COVID-19,” Nature 2024,
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25. Scheim, DE. “A Deadly Embrace: Hemagglutination Mediated by SARS-CoV-2 Spike Protein at its 22
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26. Scheim DE et al., “Sialylated Glycan Bindings from SARS-CoV-2 Spike Protein to Blood and
    Endothelial Cells Govern the Severe Morbidities of COVID-19,” Int. J. Mol. Sci. 2023, 24, 23: 17039.
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27. Sirsendu J et al., “Cell-Free Hemoglobin Does Not Attenuate the Ebects of SARS-CoV-2 Spike Protein
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28. Zhang S et al., “SARS-CoV-2 Binds Platelet ACE2 to Enhance Thrombosis in COVID-19,” J. Hematol.
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29. Zhang Z et al., “SARS-CoV-2 spike protein dictates syncytium-mediated lymphocyte
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K. Cytokines, chemokines, inteferon, interleukins

1. Ao Z et al., “SARS-CoV-2 Delta spike protein enhances the viral fusogenicity and inflammatory
   cytokine production,” iScience 2022, 25, 8: 104759. doi: 10.1016/j.isci.2022.104759
2. Chaves JCS et al., “Diberential Cytokine Responses of APOE3 and APOE4 Blood–brain Barrier Cell
   Types to SARS-CoV-2 Spike Proteins,” J. Neuroimmune Pharmacol. 2024, 19, 22. doi:
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3. Chittasupho C et al., “Targeting spike glycoprotein S1 mediated by NLRP3 inflammasome machinery
   and the cytokine releases in A549 lung epithelial cells by nanocurcumin,” Pharmaceuticals (Basel)
   2023, 16, 6: 862. doi: https://doi.org/10.3390/ph16060862
4. Das T et al., “N-glycosylation of the SARS-CoV-2 spike protein at Asn331 and Asn343 is involved in
   spike-ACE2 binding, virus entry, and regulation of IL-6,” Microbiol. Immunol. 2024, 68, 5: 165-178.
   doi: https://doi.org/10.1111/1348-0421.13121
5. Duarte C, “Age-dependent ebects of the recombinant spike protein/SARS-CoV-2 on the M-CSF- and
   IL-34-diberentiated macrophages in vitro,” Biochem. Biophys. Res. Commun. 2021, 546: 97–102. doi:
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6. Forsyth CB et al., “The SARS-CoV-2 S1 spike protein promotes MAPK and NF-kB activation in human
   lung cells and inflammatory cytokine production in human lung and intestinal epithelial
   cells,” Microorganisms 2022, 10, 10: 1996. doi: https://doi.org/10.3390/microorganisms10101996
7. Freitas RS et al., “SARS-CoV-2 Spike antagonizes innate antiviral immunity by targeting interferon
   regulatory factor 3,” Front Cell Infect Microbiol. 2021, 11: 789462. doi:
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8. Gasparello J et al., “Sulforaphane inhibits the expression of interleukin-6 and interleukin-8 induced in
   bronchial epithelial IB3-1 cells by exposure to the SARS-CoV-2 Spike protein,” Phytomedicine 2021,
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9. Ghazanfari D et al., “Mechanistic insights into SARS-CoV-2 spike protein induction of the chemokine
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10. Gracie NP et al., “Cellular signalling by SARS-CoV-2 spike protein,” Microbiology Australia 2024, 45, 1:
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11. Gu T et al., “Cytokine Signature Induced by SARS-CoV-2 Spike Protein in a Mouse Model,” Front.
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12. Jugler C et al, “SARS-CoV-2 Spike Protein-Induced Interleukin 6 Signaling Is Blocked by a Plant-
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13. Liang S et al., “SARS-CoV-2 spike protein induces IL-18-mediated cardiopulmonary inflammation via
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14. Liu T et al., “RS-5645 attenuates inflammatory cytokine storm induced by SARS-CoV-2 spike protein
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15. Liu X et al., “SARS-CoV-2 spike protein-induced cell fusion activates the cGAS-STING pathway and
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16. Niu C et al., “SARS-CoV-2 spike protein induces the cytokine release syndrome by stimulating T cells
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17. Norris B et al., “Evaluation of Glutathione in Spike Protein of SARS-CoV-2 Induced
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18. Olajide OA et al., “Induction of Exaggerated Cytokine Production in Human Peripheral Blood
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19. Park YJ et al., “D-dimer and CoV-2 spike-immune complexes contribute to the production of PGE2
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20. Patra T et al., “SARS-CoV-2 spike protein promotes IL-6 trans-signaling by activation of angiotensin II
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21. Samsudin S et al., “SARS-CoV-2 spike protein as a bacterial lipopolysaccharide delivery system in an
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    https://doi.org/10.1093/jmcb/mjac058
22. Schroeder JT and AP Bieneman, “The S1 Subunit of the SARS-CoV-2 Spike protein activates human
    monocytes to produce cytokines linked to COVID-19: relevance to galectin-3,” Front Immunol. 2022,
    13: 831763. doi: https://doi.org/10.3389/fimmu.2022.831763
23. Sharma VK et al., “Nanocurcumin Potently Inhibits SARS-CoV-2 Spike Protein-Induced Cytokine
    Storm by Deactivation of MAPK/NF-κB Signaling in Epithelial Cells,” ACS Appl. Bio Mater. 2022, 5, 2:
    483–491. doi: https://doi.org/10.1021/acsabm.1c00874
24. Sui Y et al., “SARS-CoV-2 Spike Protein Suppresses ACE2 and Type I Interferon Expression in Primary
    Cells From Macaque Lung Bronchoalveolar Lavage,” Front. Immunol. 2021, 12. doi:
    https://doi.org/10.3389/fimmu.2021.658428
25. Youn JY et al., “Therapeutic application of estrogen for COVID-19: Attenuation of SARS-CoV-2 spike
    protein and IL-6 stimulated, ACE2-dependent NOX2 activation, ROS production and MCP-1
    upregulation in endothelial cells,” Redox Biol. 2021, 46: 102099. doi:
    https://doi.org/10.1016/j.redox.2021.102099
26. Zhang Q et al., “Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) membrane (M) and
    spike (S) proteins antagonize host type i interferon response,” Front Cell Infect Microbiol 2021, 11: doi: https://doi.org/10.3389/fcimb.2021.766922
27. Zhang RG et al., “SARS-CoV-2 spike protein receptor binding domain promotes IL-6 and IL-8 release
    via ATP/P2Y2 and ERK1/2 signaling pathways in human bronchial epithelia,” Mol. Immunol. 2024, 167: 53-61. doi: https://doi.org/10.1016/j.molimm.2024.02.005
    

L. Endothelial

1. Bhargavan B and GD Kanmogne, “SARS-CoV-2 spike proteins and cell–cell communication inhibits
   TFPI and induces thrombogenic factors in human lung microvascular endothelial cells and
   neutrophils: implications for COVID-19 coagulopathy pathogenesis,” Int. J. Mol. Sci. 2022, 23, 18:doi: https://doi.org/10.3390/ijms231810436
2. Biancatelli RMLC, et al. “The SARS-CoV-2 spike protein subunit S1 induces COVID-19-like acute lung
   injury in Kappa18-hACE2 transgenic mice and barrier dysfunction in human endothelial cells,” Am. J.
   Physiol. Lung Cell. Mol. Physiol. 2021, 321: L477–L484. doi:
   https://doi.org/10.1152/ajplung.00223.2021
3. Gamblicher T et al., “SARS-CoV-2 spike protein is present in both endothelial and eccrine cells of a
   chilblain-like skin lesion,” J Eur Acad Dermatol Venereol. 2020, 1, 10: e187-e189. doi:
   https://doi.org/10.1111/jdv.16970
4. Guo Y and V Kanamarlapudi, “Molecular Analysis of SARS-CoV-2 Spike Protein-Induced Endothelial
   Cell Permeability and vWF Secretion,” Int. J. Mol. Sci. 2023, 24, 6: 5664.
   doi: https://doi.org/10.3390/ijms24065664
5. Jana S et al., “Cell-free hemoglobin does not attenuate the ebects of SARS-CoV-2 spike protein S1
   subunit in pulmonary endothelial cells,” Int. J. Mol. Sci. 2021, 22, 16: 9041. doi:
   https://doi.org/10.3390/ijms22169041
6. Kulkoviene G et al., “Diberential Mitochondrial, Oxidative Stress and Inflammatory Responses to
   SARS-CoV-2 Spike Protein Receptor Binding Domain in Human Lung Microvascular, Coronary Artery
   Endothelial and Bronchial Epithelial Cells,” Int. J. Mol. Sci. 2024, 25, 6: 3188.
   doi: https://doi.org/10.3390/ijms25063188
7. Marrone L et al., “Tirofiban prevents the ebects of SARS-CoV-2 spike protein on macrophage
   activation and endothelial cell death,” Heliyon, 2024, 10, 15, e35341. doi:
   10.1016/j.heliyon.2024.e35341
8. Meyer K et al., “SARS-CoV-2 Spike Protein Induces Paracrine Senescence and Leukocyte Adhesion in
   Endothelial Cells,” J. Virol. 2021, 95: e0079421. doi: https://doi.org/10.1128/jvi.00794-21
9. Nuovo JG et al., “Endothelial Cell Damage Is the Central Part of COVID-19 and a Mouse Model
   Induced by Injection of the S1 Subunit of the Spike Protein,” Ann. Diagn. Pathol. 2021, 51, 151682.
   doi: https://doi.org/10.1016/j.anndiagpath.2020.151682
10. Perico L et al., “SARS-CoV-2 and the spike protein in endotheliopathy,” Trends Microbiol. 2024, 32, 1:
    53-67. doi: 10.1016/j.tim.2023.06.004
11. Perico L et al., “SARS-CoV-2 Spike Protein 1 Activates Microvascular Endothelial Cells and
    Complement System Leading to Platelet Aggregation,” Front. Immunol. 2022, 13, 827146. doi:
    https://doi.org/10.3389/fimmu.2022.827146
12. Raghavan S et al., “SARS-CoV-2 Spike Protein Induces Degradation of Junctional Proteins That
    Maintain Endothelial Barrier Integrity,” Front. Cardiovasc. Med. 2021, 8, 687783. doi:
    https://doi.org/10.3389/fcvm.2021.687783
13. Ratajczak MZ et al., “SARS-CoV-2 Entry Receptor ACE2 Is Expressed on Very Small CD45- Precursors
    of Hematopoietic and Endothelial Cells and in Response to Virus Spike Protein Activates the Nlrp3
    Inflammasome,” Stem Cell Rev Rep. 2021, 17, 1: 266-277. doi: https://doi.org/10.1007/s12015-020-
    10010-z
14. Robles JP et al., “The Spike Protein of SARS-CoV-2 Induces Endothelial Inflammation through Integrin
    α5β1 and NF-κB Signaling,” J. Biol. Chem. 2022, 298, 3: 101695. doi:
    https://doi.org/10.1016/j.jbc.2022.101695
15. Rotoli BM et al., “Endothelial cell activation by SARS-CoV-2 spike S1 protein: A crosstalk between
    endothelium and innate immune cells,” Biomedicines 2021, 9, 9: 1220. doi:
    https://doi.org/10.3390/biomedicines9091220
16. Ruben ML et al., “The SARS-CoV-2 spike protein subunit S1 induces COVID-19-like acute lung injury
    in Κ18-hACE2 transgenic mice and barrier dysfunction in human endothelial cells,” Am J Physiol Lung
    Cell Mol Physiol. 2021, 321, 2: L477-L484. doi: https://doi.org/10.1152/ajplung.00223.2021
17. Sano H et al., “A case of persistent, confluent maculopapular erythema following a COVID-19 mRNA
    vaccination is possibly associated with the intralesional spike protein expressed by vascular
    endothelial cells and eccrine glands in the deep dermis,” J. Dermatol. 2023, 50: 1208–1212. doi:
    https://doi.org/10.1111/1346-8138.16816
18. Santonja C et al., “COVID-19 chilblain-like lesion: immunohistochemical demonstration of SARSCoV-
    2 spike protein in blood vessel endothelium and sweat gland epithelium in a polymerase chain
    reaction-negative patient,” Br J Dermatol. 2020, 183, 4: 778-780. doi:
    https://doi.org/10.1111/bjd.19338
19. Scheim DE et al., “Sialylated Glycan Bindings from SARS-CoV-2 Spike Protein to Blood and
    Endothelial Cells Govern the Severe Morbidities of COVID-19,” Int. J. Mol. Sci. 2023, 24, 23: 17039.
    doi: https://doi.org/10.3390/ijms242317039
20. Sirsendu J et al., “Cell-Free Hemoglobin Does Not Attenuate the Ebects of SARS-CoV-2 Spike Protein
    S1 Subunit in Pulmonary Endothelial Cells,” Int. J. Mol. Sci., 2021, 22, 16: 9041. doi:
    https://doi.org/10.3390/ijms22169041
21. Stern B et al., “SARS-CoV-2 spike protein induces endothelial dysfunction in 3D engineered vascular
    networks,” J. Biomed. Mater. Res. A. 2023, 112, 4: 524-533. doi: https://doi.org/10.1002/jbm.a.37543
22. Villacampa A et al., “SARS-CoV-2 S protein activates NLRP3 inflammasome and deregulates
    coagulation factors in endothelial and immune cells,” Cell Commun. Signal. 2024, 22, 38. doi:
    https://doi.org/10.1186/s12964-023-01397-6
23. Wu ML et al., “Mast cell activation triggered by SARS-CoV-2 causes inflammation in brain
    microvascular endothelial cells and microglia,” Front. Cell. Infect. Microbiol. 2024, 14. doi:
    https://doi.org/10.3389/fcimb.2024.1358873
24. Youn JY et al., “Therapeutic application of estrogen for COVID-19: Attenuation of SARS-CoV-2 spike
    protein and IL-6 stimulated, ACE2-dependent NOX2 activation, ROS production and MCP-1
    upregulation in endothelial cells,” Redox Biol. 2021, 46: 102099. doi:
    https://doi.org/10.1016/j.redox.2021.102099
25. Zekri-Nechar K et al., “Spike Protein Subunits of SARS-CoV-2 Alter Mitochondrial Metabolism in
    Human Pulmonary Microvascular Endothelial Cells: Involvement of Factor Xa,” Dis. Markers 2022, doi: https://doi.org/10.1155/2022/1118195
    

M. Gastrointestinal

1. Forsyth CB et al., “The SARS-CoV-2 S1 spike protein promotes MAPK and NF-kB activation in human
   lung cells and inflammatory cytokine production in human lung and intestinal epithelial
   cells,” Microorganisms 2022, 10, 10: 1996. doi: https://doi.org/10.3390/microorganisms10101996
2. Li Z et al., “SARS-CoV-2 pathogenesis in the gastrointestinal tract mediated by Spike-induced
   intestinal inflammation,” Precis. Clin. Med. 2024, 7, 1: pbad034. doi:
   https://doi.org/10.1093/pcmedi/pbad034
3. Luo Y et al., “SARS-Cov-2 spike induces intestinal barrier dysfunction through the interaction
   between CEACAM5 and Galectin-9,” Front. Immunol. 2024, 15. doi:
   https://doi.org/10.3389/fimmu.2024.1303356
4. Nascimento RR et al., “SARS-CoV-2 Spike protein triggers gut impairment since mucosal barrier to
   innermost layers: From basic science to clinical relevance,” Mucosal Immunol. 2024, 17, 4: 565-583.
   doi: https://doi.org/10.1016/j.mucimm.2024.03.00
5. Yilmaz A et al., “Diberential proinflammatory responses of colon epithelial cells to SARS-CoV-2 spike
   protein and Pseudomonas aeruginosa lipopolysaccharide,” Turk J Biochem. 2024. doi:
   https://doi.org/10.1515/tjb-2024-0144
6. Yonker LM et al., “Multisystem inflammatory syndrome in children is driven by zonulin-dependent
   loss of gut mucosal barrier,” J Clin Invest. 2021, 131, 14: e149633. doi:
   https://doi.org/10.1172/JCI149633
7. Zeng FM et al., “SARS-CoV-2 spike spurs intestinal inflammation via VEGF production in enterocytes,”
   EMBO Mol Med. 2022, 14: e14844. doi: https://doi.org/10.15252/emmm.202114844
8. Zollner A et al., “Postacute COVID-19 is Characterized by Gut Viral Antigen Persistence in
   Inflammatory Bowel Diseases,” Gastroenterology 2022, 163, 2: 495-506.e8. doi:
   https://doi.org/10.1053/j.gastro.2022.04.037
   

N. Immune dysfunction

1. Baldari CT et al., “Emerging Roles of SARS-CoV-2 Spike-ACE2 in Immune Evasion and Pathogenesis,”
   Trends Immunol. 2023, 44, 6. doi: https://doi.org/10.1016/j.it.2023.04.001
2. Bocquet-Garcon A, “Impact of the SARS-CoV-2 Spike Protein on the Innate Immune System: A
   Review,” Cureus 2024, 16, 3: e57008. doi: 10.7759/cureus.57008
3. Delgado JF et al., “SARS-CoV-2 spike protein vaccine-induced immune imprinting reduces
   nucleocapsid protein antibody response in SARS-CoV-2 infection,” J. Immunol. Res. 2022: 8287087.
   doi: https://doi.org/10.1155/2022/8287087
4. Freitas RS et al., “SARS-CoV-2 Spike antagonizes innate antiviral immunity by targeting interferon
   regulatory factor 3,” Front Cell Infect Microbiol. 2021, 11: 789462. doi:
   https://doi.org/10.3389/fcimb.2021.789462
5. Irrgang P et al., “Class switch toward noninflammatory, spike-specific IgG4 antibodies after repeated
   SARS-CoV-2 mRNA vaccination,” Sci. Immunol. 2022, 8, 79. doi: 10.1126/sciimmunol.ade2798
6. Kim MJ et al., “The SARS-CoV-2 spike protein induces lung cancer migration and invasion in a TLR2-
   dependent manner,” Cancer Commun (London), 2023, 44, 2: 273–277.
   doi: https://doi.org/10.1002/cac2.12485
7. Onnis A et al., “SARS-CoV-2 Spike protein suppresses CTL-mediated killing by inhibiting immune
   synapse assembly,” J Exp Med 2023, 220, 2: e20220906. doi: https://doi.org/10.1084/jem.20220906
   

O. Macrophages, monocytes, neutrophils

1. Ahn WM et al., “SARS-CoV-2 Spike Protein Stimulates Macropinocytosis in Murine and Human
   Macrophages via PKC-NADPH Oxidase Signaling,” Antioxidants 2024, 13, 2: 175.
   doi: https://doi.org/10.3390/antiox13020175
2. Ait-Belkacem I et al., “SARS-CoV-2 spike protein induces a diberential monocyte activation that may
   contribute to age bias in COVID-19 severity,” Sci. Rep. 2022, 12: 20824. doi:
   https://doi.org/10.1038/s41598-022-25259-2
3. Barhoumi T et al., “SARS-CoV-2 coronavirus Spike protein-induced apoptosis, inflammatory, and
   oxidative stress responses in THP-1-like-macrophages: potential role of angiotensin-converting
   enzyme inhibitor (perindopril),” Front. Immunol. 2021, 12: 728896. doi:
   https://doi.org/10.3389/fimmu.2021.728896
4. Bortolotti D et al., “SARS-CoV-2 Spike 1 Protein Controls Natural Killer Cell Activation via the HLAE/
   NKG2A Pathway,” Cells 2020, 9, 9: 1975. doi: https://doi.org/10.3390/cells9091975
5. Cao X et al., “Spike protein of SARS-CoV-2 activates macrophages and contributes to induction of
   acute lung inflammation in male mice,” FASEB J. 2021, 35, e21801. doi:
   https://doi.org/10.1096/fj.202002742RR
6. Chiok K et al., “Proinflammatory Responses in SARS-CoV-2 and Soluble Spike Glycoprotein S1
   Subunit Activated Human Macrophages,” Viruses 2023, 15, 3: 754.
   doi: https://doi.org/10.3390/v15030754
7. Cory TJ et al., “Metformin Suppresses Monocyte Immunometabolic Activation by SARS-CoV-2 Spike
   Protein Subunit 1,” Front. Immunol. 2021, 12 (Sec. Cytokines and Soluble Mediators in Immunity):doi: https://doi.org/10.3389/fimmu.2021.733921
8. Del Re A et al., “Ultramicronized Palmitoylethanolamide Inhibits NLRP3 Inflammasome Expression
   and Pro-Inflammatory Response Activated by SARS-CoV-2 Spike Protein in Cultured Murine Alveolar
   Macrophages,” Metabolites 2021, 11, 9: 592. doi: https://doi.org/10.3390/metabo11090592
9. Duarte C, “Age-dependent ebects of the recombinant spike protein/SARS-CoV-2 on the M-CSF- and
   IL-34-diberentiated macrophages in vitro,” Biochem. Biophys. Res. Commun. 2021, 546: 97–102. doi:
   https://doi.org/10.1016/j.bbrc.2021.01.104
10. Karwaciak I et al., “Nucleocapsid and Spike Proteins of the Coronavirus Sars-Cov-2 Induce Il6 in
    Monocytes and Macrophages—Potential Implications for Cytokine Storm Syndrome,” Vaccines 2021,
    9, 1, 54: 1–10. doi: https://doi.org/10.3390/vaccines9010054
11. Li T et al., “Platelets Mediate Inflammatory Monocyte Activation by SARS-CoV-2 Spike Protein,” J.
    Clin. Invest. 2022, 132, 4: e150101. doi: 10.1172/JCI150101
12. Loh JT et al., “Dok3 restrains neutrophil production of calprotectin during TLR4 sensing of SARS-CoV- 2 spike protein,” Front. Immunol. 2022, 13 (Sec. Molecular Innate Immunity). doi:
    https://doi.org/10.3389/fimmu.2022.996637
13. Marrone L et al., “Tirofiban prevents the ebects of SARS-CoV-2 spike protein on macrophage
    activation and endothelial cell death,” Heliyon, 2024, 10, 15: e35341. doi:
    10.1016/j.heliyon.2024.e35341
14. Miller GM et al., “SARS-CoV-2 and SARS-CoV-2 Spike protein S1 subunit Trigger Proinflammatory
    Response in Macrophages in the Absence of Productive Infection,” J. Immunol. 2023, 210
    (1_Supplement): 71.30. doi: https://doi.org/10.4049/jimmunol.210.Supp.71.30
15. Onnis A et al., “SARS-CoV-2 Spike protein suppresses CTL-mediated killing by inhibiting immune
    synapse assembly,” J Exp Med 2023, 220, 2: e20220906. doi: https://doi.org/10.1084/jem.20220906
16. Palestra F et al. “SARS-CoV-2 Spike Protein Activates Human Lung Macrophages,” Int. J. Mol.
    Sci. 2023, 24, 3: 3036. doi: https://doi.org/10.3390/ijms24033036
17. Park C et al., “Murine alveolar Macrophages Rapidly Accumulate intranasally Administered SARSCoV-
    2 Spike Protein leading to neutrophil Recruitment and Damage,” Elife 2024, 12, RP86764. doi:
    https://doi.org/10.7554/eLife.86764.3
18. Park YJ et al., “D-dimer and CoV-2 spike-immune complexes contribute to the production of PGE2
    and proinflammatory cytokines in monocytes,” PLoS Pathog. 2022, 18, 4: e1010468. doi:
    https://doi.org/10.1371/journal.ppat.1010468
19. Park YJ et al., “Pyrogenic and inflammatory mediators are produced by polarized M1 and M2
    macrophages activated with D-dimer and SARS-CoV-2 spike immune complexes,” Cytokine 2024,
    173: 156447. doi: https://doi.org/10.1016/j.cyto.2023.156447
20. Patterson BK et al., “Persistence of SARS CoV-2 S1 Protein in CD16+ Monocytes in Post-Acute
    Sequelae of COVID-19 (PASC) up to 15 Months Post-Infection,” Front. Immunol. 12 (Sec. Viral
    Immunology). doi: https://doi.org/10.3389/fimmu.2021.746021
21. Pence B, “Recombinant SARS-CoV-2 Spike Protein Mediates Glycolytic and Inflammatory Activation
    in Human Monocytes,” Innov Aging 2020, 4, sp. 1: 955. doi:
    https://doi.org/10.1093/geroni/igaa057.3493
22. Satta S et al., “An engineered nano-liposome-human ACE2 decoy neutralizes SARS-CoV-2 Spike
    protein-induced inflammation in both murine and human macrophages,” Theranostics 2022, 12, 6:
    2639–2657. doi: 10.7150/thno.66831
23. Schroeder JT and AP Bieneman, “The S1 Subunit of the SARS-CoV-2 Spike protein activates human
    monocytes to produce cytokines linked to COVID-19: relevance to galectin-3,” Front Immunol. 2022,
    13: 831763. doi: https://doi.org/10.3389/fimmu.2022.831763
24. Shirato K and Takako Kizaki, “SARS-CoV-2 Spike Protein S1 Subunit Induces Pro- inflammatory
    Responses via Toll-Like Receptor 4 Signaling in Murine and Human Macrophages,” Heliyon 2021, 7, 2:
    e06187, doi: https://doi.org/10.1016/j.heliyon.2021.e06187
25. Theobald SJ et al., “Long-lived macrophage reprogramming drives spike protein-mediated
    inflammasome activation in COVID-19,” EMBO Mol. Med. 2021, 13:e14150. doi:
    https://doi.org/10.15252/emmm.202114150
26. Vettori M et al., “Ebects of Diberent Types of Recombinant SARS-CoV-2 Spike Protein on Circulating
    Monocytes’ Structure,” Int. J. Mol. Sci. 2023, 24, 11, 9373. doi: https://doi.org/10.3390/ijms24119373
27. Youn YJ et al., “Nucleocapsid and spike proteins of SARS-CoV-2 drive neutrophil extracellular trap
    formation,” Immune Netw. 2021, 21, 2: e16. doi: https://doi.org/10.4110/in.2021.21.e16
28. Zaki H and S Khan, “SARS-CoV-2 spike protein induces inflammatory molecules through TLR2 in
    macrophages and monocytes,” J. Immunol. 2021, 206 (1_supplement): 62.07. doi:
    https://doi.org/10.4049/jimmunol.206.Supp.62.07
    

P. MAPK

1. Arjsri P et al., “Hesperetin from root extract of Clerodendrum petasites S. Moore inhibits SARS-CoV-2
   spike protein S1 subunit-induced Nlrp3 inflammasome in A549 lung cells via modulation of the
   Akt/Mapk/Ap-1 pathway,” Int. J. Mol. Sci. 2022, 23, 18: 10346. doi:
   https://doi.org/10.3390/ijms231810346
2. Bhattacharyya S and JK Tobacman, “SARS-CoV-2 spike protein-ACE2 interaction increases
   carbohydrate sulfotransferases and reduces N-acetylgalactosamine-4-sulfatase by p38 MAPK,”
   Signal Transduct Target Ther 2024, 9, 39. doi: https://doi.org/10.1038/s41392-024-01741-3
3. Forsyth CB et al., “The SARS-CoV-2 S1 spike protein promotes MAPK and NF-kB activation in human
   lung cells and inflammatory cytokine production in human lung and intestinal epithelial
   cells,” Microorganisms 2022, 10, 10: 1996. doi: https://doi.org/10.3390/microorganisms10101996
4. Johnson EL et al., “The S1 spike protein of SARS-CoV-2 upregulates the ERK/MAPK signaling pathway
   in DC-SIGN-expressing THP-1 cells,” Cell Stress Chaperones 2024, 29, 2: 227-234. doi:
   https://doi.org/10.1016/j.cstres.2024.03.002
5. Khan S et al., “SARS-CoV-2 Spike Protein Induces Inflammation via TLR2-Dependent Activation of the
   NF-κB Pathway,” eLife 2021, 10: e68563, doi: https://doi.org/10.7554/elife.68563
6. Kircheis R and O Planz, “Could a Lower Toll-like Receptor (TLR) and NF-κB Activation Due to a
   Changed Charge Distribution in the Spike Protein Be the Reason for the Lower Pathogenicity of
   Omicron?” Int. J. Mol. Sci. 2022, 23, 11: 5966. doi: https://doi.org/10.3390/ijms23115966
7. Kyriakopoulos AM et al., “Mitogen Activated Protein Kinase (MAPK) Activation, p53, and Autophagy
   Inhibition Characterize the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike
   Protein Induced Neurotoxicity,” Cureus 2022, 14, 12: e32361. doi: 10.7759/cureus.32361
8. Robles JP et al., “The Spike Protein of SARS-CoV-2 Induces Endothelial Inflammation through Integrin
   α5β1 and NF-κB Signaling,” J. Biol. Chem. 2022, 298, 3: 101695. doi:
   https://doi.org/10.1016/j.jbc.2022.101695
9. Sharma VK et al., “Nanocurcumin Potently Inhibits SARS-CoV-2 Spike Protein-Induced Cytokine
   Storm by Deactivation of MAPK/NF-κB Signaling in Epithelial Cells,” ACS Appl. Bio Mater. 2022, 5, 2:
   483–491. doi: https://doi.org/10.1021/acsabm.1c00874
10. Bhattacharyya S and JK Tobacman, “SARS-CoV-2 spike protein-ACE2 interaction increases
    carbohydrate sulfotransferases and reduces N-acetylgalactosamine-4-sulfatase by p38 MAPK,”
    Signal Transduct Target Ther 2024, 9, 39. doi: https://doi.org/10.1038/s41392-024-01741-3
12. 
    

Q. Mast cells

1. Cao JB et al., “Mast cell degranulation-triggered by SARS-CoV-2 induces tracheal-bronchial epithelial
   inflammation and injury,” Virol. Sin. 2024, 39, 2: 309-318. doi:
   https://doi.org/10.1016/j.virs.2024.03.001
2. Fajloun Z et al., “SARS-CoV-2 or Vaccinal Spike Protein can Induce Mast Cell Activation Syndrome
   (MCAS),” Infect Disord Drug Targets, 2025, 25, 1: e300424229561. doi:
   10.2174/0118715265319896240427045026
3. Wu ML et al., “Mast cell activation triggered by SARS-CoV-2 causes inflammation in brain
   microvascular endothelial cells and microglia,” Front. Cell. Infect. Microbiol., 2024, 14. doi:
   https://doi.org/10.3389/fcimb.2024.1358873
   

R. Microglia

1. Chang MH et al., “SARS-CoV-2 Spike Protein 1 Causes Aggregation of α-Synuclein via Microglia-
   Induced Inflammation and Production of Mitochondrial ROS: Potential Therapeutic Applications of
   Metformin,” Biomedicines 2024, 12, 6: 1223. doi: https://doi.org/10.3390/biomedicines12061223
2. Clough E et al., “Mitochondrial Dynamics in SARS-COV2 Spike Protein Treated Human Microglia:
   Implications for Neuro-COVID,” J. Neuroimmune Pharmacol. 2021, 16, 4: 770–784. doi:
   https://doi.org/10.1007/s11481-021-10015-6
3. Frank MG et al., “SARS-CoV-2 Spike S1 Subunit Induces Neuroinflammatory, Microglial and
   Behavioral Sickness Responses: Evidence of PAMP-Like Properties,” Brain Behav. Immun. 2022, 100:doi: https://doi.org/10.1016/j.bbi.2021.12.007
4. Mishra R and AC Banerjea, “SARS-CoV-2 Spike targets USP33-IRF9 axis via exosomal miR-148a to
   activate human microglia,” Front. Immunol. 2021, 12: 656700. doi:
   https://doi.org/10.3389/fimmu.2021.656700
5. Olajide OA et al., “SARS-CoV-2 spike glycoprotein S1 induces neuroinflammation in BV-2 microglia,”
   Mol. Neurobiol. 2022, 59: 445-458. doi: https://doi.org/10.1007/s12035-021-02593-6
6. Wu ML et al., “Mast cell activation triggered by SARS-CoV-2 causes inflammation in brain
   microvascular endothelial cells and microglia,” Front. Cell. Infect. Microbiol. 2024, 14. doi:
   https://doi.org/10.3389/fcimb.2024.1358873
   

S. Microvascular

1. Avolio E et al., “The SARS-CoV-2 Spike Protein Disrupts Human Cardiac Pericytes Function through
   CD147 Receptor-Mediated Signalling: A Potential Non-infective Mechanism of COVID-19
   Microvascular Disease,” Clin. Sci. 2021, 135, 24: 2667–2689. doi:
   https://doi.org/10.1042/CS20210735
2. Bhargavan B and GD Kanmogne, “SARS-CoV-2 spike proteins and cell–cell communication inhibits
   TFPI and induces thrombogenic factors in human lung microvascular endothelial cells and
   neutrophils: implications for COVID-19 coagulopathy pathogenesis,” Int. J. Mol. Sci. 2022, 23, 18:doi: https://doi.org/10.3390/ijms231810436
3. Kulkoviene G et al., “Diberential Mitochondrial, Oxidative Stress and Inflammatory Responses to
   SARS-CoV-2 Spike Protein Receptor Binding Domain in Human Lung Microvascular, Coronary Artery
   Endothelial and Bronchial Epithelial Cells,” Int. J. Mol. Sci. 2024, 25, 6: 3188.
   doi: https://doi.org/10.3390/ijms25063188
4. Magro N et al., “Disruption of the blood-brain barrier is correlated with spike endocytosis by ACE2 +
   endothelia in the CNS microvasculature in fatal COVID-19. Scientific commentary on ‘Detection of
   blood-brain barrier disruption in brains of patients with COVID-19, but no evidence of brain
   penetration by SARS-CoV-2’,” Acta Neuropathol. 2024, 147, 1: 47. doi:
   https://doi.org/10.1007/s00401-023-02681-y
5. Panigrahi S et al., “SARS-CoV-2 Spike Protein Destabilizes Microvascular Homeostasis,” Microbiol
   Spectr. 2021, 9, 3: e0073521. doi: https://doi.org/10.1128/Spectrum.00735-21
6. Perico L et al., “SARS-CoV-2 Spike Protein 1 Activates Microvascular Endothelial Cells and
   Complement System Leading to Platelet Aggregation,” Front. Immunol. 2022, 13, 827146. doi:
   https://doi.org/10.3389/fimmu.2022.827146
7. Wu ML et al., “Mast cell activation triggered by SARS-CoV-2 causes inflammation in brain
   microvascular endothelial cells and microglia,” Front. Cell. Infect. Microbiol. 2024, 14. doi:
   https://doi.org/10.3389/fcimb.2024.1358873
8. Zekri-Nechar K et al., “Spike Protein Subunits of SARS-CoV-2 Alter Mitochondrial Metabolism in
   Human Pulmonary Microvascular Endothelial Cells: Involvement of Factor Xa,” Dis. Markers 2022:doi: https://doi.org/10.1155/2022/1118195
   

T. MIS-C, pediatric

1. Colmenero I et al., “SARS-CoV-2 endothelial infection causes COVID-19 chilblains:
   histopathological, immunohistochemical and ultrastructural study of seven paediatric cases,” Br
   J Dermatol. 2020, 183: 729-737. doi: https://doi.org/10.1111/bjd.19327/
2. De Sousa PMB et al., “Fatal Myocarditis following COVID-19 mRNA Immunization: A Case Report
   and Diberential Diagnosis Review,” Vaccines 2024, 12, 2: 194.
   doi: https://doi.org/10.3390/vaccines12020194
3. Mayordomo-Colunga J et al., “SARS-CoV-2 spike protein in intestinal cells of a patient with
   coronavirus disease 2019 multisystem inflammatory syndrome,” J Pediatr. 2022, 243: 214-18e215.
   doi: https://doi.org/10.1016/j.jpeds.2021.11.058
4. Rivas MN et al., “COVID-19–associated multisystem inflammatory syndrome in children (MIS-C):
   A novel disease that mimics toxic shock syndrome—the superantigen hypothesis,” J Allergy Clin
   Immunol 2021, 147, 1: 57-59. doi: 10.1016/j.jaci.2020.10.008
5. Rivas MN et al., “Multisystem Inflammatory Syndrome in Children and Long COVID: The SARSCoV-
   2 Viral Superantigen Hypothesis,” Front Immunol. 2022, 13 (Sec. Molecular Innate Immunity)
   doi: https://doi.org/10.3389/fimmu.2022.941009
6. Sacco K et al., “Immunopathological signatures in multisystem inflammatory syndrome in
   children and pediatric COVID-19,” Nat. Med. 2022, 28: 1050-1062. doi:
   https://doi.org/10.1038/s41591-022-01724-3
7. Yonker LM et al., “Multisystem inflammatory syndrome in children is driven by zonulin-dependent
   loss of gut mucosal barrier,” J Clin Invest. 2021, 131, 14: e149633. doi:
   https://doi.org/10.1172/JCI149633
9. 
   

U. Mitochondria/metabolism

1. Cao X et al., “The SARS-CoV-2 spike protein induces long-term transcriptional perturbations of
   mitochondrial metabolic genes, causes cardiac fibrosis, and reduces myocardial contractile in
   obese mice,” Mol. Metab. 2023, 74, 101756. doi: https://doi.org/10.1016/j.molmet.2023.101756
2. Chang MH et al., “SARS-CoV-2 Spike Protein 1 Causes Aggregation of α-Synuclein via Microglia-
   Induced Inflammation and Production of Mitochondrial ROS: Potential Therapeutic Applications of
   Metformin,” Biomedicines 2024, 12, 6: 1223. doi: https://doi.org/10.3390/biomedicines12061223
3. Clough E et al., “Mitochondrial Dynamics in SARS-COV2 Spike Protein Treated Human Microglia:
   Implications for Neuro-COVID,” Journal of Neuroimmune Pharmacology 2021, 16, 4: 770–784. doi:
   https://doi.org/10.1007/s11481-021-10015-6
4. Huynh TV et al., “Spike Protein Impairs Mitochondrial Function in Human Cardiomyocytes:
   Mechanisms Underlying Cardiac Injury in COVID-19,” Cells 2023, 12, 877. doi:
   https://doi.org/10.3390/cells12060877
5. Kulkoviene G et al., “Diberential Mitochondrial, Oxidative Stress and Inflammatory Responses to
   SARS-CoV-2 Spike Protein Receptor Binding Domain in Human Lung Microvascular, Coronary Artery
   Endothelial and Bronchial Epithelial Cells,” Int. J. Mol. Sci. 2024, 25, 6: 3188.
   doi: https://doi.org/10.3390/ijms25063188
6. Mercado-Gómez M et al., “The spike of SARS-CoV-2 promotes metabolic rewiring in
   hepatocytes,” Commun. Biol. 2022, 5, 827. doi: https://doi.org/10.1038/s42003-022-03789-9
7. Nguyen V, “The Spike Protein of SARS-CoV-2 Impairs Lipid Metabolism and Increases Susceptibility
   to Lipotoxicity: Implication for a Role of Nrf2,” Cells 2022, 11, 12: 1916. doi:
   https://doi.org/10.3390/cells11121916
8. Yeung-Luk BH et al., “SARS-CoV-2 infection alters mitochondrial and cytoskeletal function in human
   respiratory epithelial cells mediated by expression of spike protein,” mBio 2023, 14, 4: e00820-23.
   doi: https://doi.org/10.1128/mbio.00820-23
9. Zekri-Nechar K et al., “Spike Protein Subunits of SARS-CoV-2 Alter Mitochondrial Metabolism in
   Human Pulmonary Microvascular Endothelial Cells: Involvement of Factor Xa,” Dis. Markers 2022,doi: https://doi.org/10.1155/2022/1118195
11. 
    

V. Myocarditis/cardiac/cardiomyopathy

1. Abdi A et al., “Biomed Interaction of SARS-CoV-2 with cardiomyocytes: Insight into the underlying
   molecular mechanisms of cardiac injury and pharmacotherapy,” Pharmacother. 2022, 146: 112518.
   doi: 10.1016/j.biopha.2021.112518
2. Avolio E et al., “The SARS-CoV-2 Spike Protein Disrupts Human Cardiac Pericytes Function through
   CD147 Receptor-Mediated Signalling: A Potential Non-infective Mechanism of COVID-19
   Microvascular Disease,” Clin. Sci. 2021, 135, 24: 2667–2689. doi:
   https://doi.org/10.1042/CS20210735
3. Baumeier C et al., “Intramyocardial Inflammation after COVID-19 Vaccination: An Endomyocardial
   Biopsy-Proven Case Series,” Int. J. Mol. Sci. 2022, 23: 6940. doi:
   https://doi.org/10.3390/ijms23136940
4. Bellavite P et al., “Immune response and molecular mechanisms of cardiovascular adverse ebects
   of spike proteins from SARS-coV-2 and mRNA vaccines,” Biomedicines 2023, 11, 2: 451. doi:
   https://doi.org/10.3390/biomedicines11020451
5. Boretti A. “PQQ Supplementation and SARS-CoV-2 Spike Protein-Induced Heart Inflammation,” Nat.
   Prod. Commun. 2022, 17, 1934578×221080929. doi: https://doi.org/10.1177/1934578X221080929
6. Buoninfante A et al., “Myocarditis associated with COVID-19 vaccination,” npj Vaccines 2024, 122.
   doi: https://doi.org/10.1038/s41541-024-00893-1
7. Cao X et al., “The SARS-CoV-2 spike protein induces long-term transcriptional perturbations of
   mitochondrial metabolic genes, causes cardiac fibrosis, and reduces myocardial contractile in
   obese mice,” Mol. Metab. 2023, 74, 101756. doi: https://doi.org/10.1016/j.molmet.2023.101756
8. Clemens DJ et al., “SARS-CoV-2 spike protein-mediated cardiomyocyte fusion may contribute to
   increased arrhythmic risk in COVID-19,” PLoS One 2023, 18, 3: e0282151.
   doi: https://doi.org/10.1371/journal.pone.0282151
9. De Sousa PMB et al., “Fatal Myocarditis following COVID-19 mRNA Immunization: A Case Report and
   Diberential Diagnosis Review,” Vaccines 2024, 12, 2: 194.
   doi: https://doi.org/10.3390/vaccines12020194
10. Forte E, “Circulating spike protein may contribute to myocarditis after COVID-19 vaccination,” Nat.
    Cardiovasc. Res. 2023, 2: 100. doi: https://doi.org/10.1038/s44161-023-00222-0
11. Huang X et al., “Sars-Cov-2 Spike Protein-Induced Damage of hiPSC-Derived Cardiomyocytes,” Adv.
    Biol. 2022, 6, 7: e2101327. doi: https://doi.org/10.1002/adbi.202101327
12. Hulscher N et al., “Autopsy findings in cases of fatal COVID-19 vaccine-induced myocarditis,” ESC
    Heart Failure 2024. doi: https://doi.org/10.1002/ehf2.14680
13. Huynh TV et al., “Spike Protein Impairs Mitochondrial Function in Human Cardiomyocytes:
    Mechanisms Underlying Cardiac Injury in COVID-19,” Cells 2023, 12, 877. doi:
    https://doi.org/10.3390/cells12060877
14. Huynh TV et al., “Spike Protein of SARS-CoV-2 Activates Cardiac Fibrogenesis through NLRP3
    Inflammasomes and NF-κB Signaling,” Cells 2024, 13, 16: 1331.
    doi: https://doi.org/10.3390/cells13161331
15. Imig JD, “SARS-CoV-2 spike protein causes cardiovascular disease independent of viral infection,”
    Clin Sci (Lond) 2022, 136, 6: 431–434. doi: https://doi.org/10.1042/CS20220028
16. Kato Y et al., “TRPC3-Nox2 Protein Complex Formation Increases the Risk of SARS-CoV-2 Spike
    Protein-Induced Cardiomyocyte Dysfunction through ACE2 Upregulation,” Int. J. Mol. Sci. 2023, 24, 1: doi: https://doi.org/10.3390/ijms24010102
17. Kawano H et al., “Fulminant Myocarditis 24 Days after Coronavirus Disease Messenger Ribonucleic
    Acid Vaccination,” Intern. Med. 2022, 61, 15: 2319-2325. doi:
    https://doi.org/10.2169/internalmedicine.9800-22
18. Li C. et al., “Intravenous Injection of Coronavirus Disease 2019 (COVID-19) MRNA Vaccine Can
    Induce Acute Myopericarditis in Mouse Model,” Clin. Infect. Dis. 2022, 74, 11: 1933-1950. doi:
    https://doi.org/10.1093/cid/ciab707
19. Lin Z, “More than a key—the pathological roles of SARS-CoV-2 spike protein in COVID-19 related
    cardiac injury,” Sports Med Health Sci 2023, 6, 3: 209-220.
    doi: https://doi.org/10.1016/j.smhs.2023.03.004
20. Rzymski P and Andrzej Fal, “To aspirate or not to aspirate? Considerations for the COVID-19
    vaccines,” Pharmacol. Rep 2022, 74: 1223–1227. doi: https://doi.org/10.1007/s43440-022-00361-4
21. Schreckenberg R et al., “Cardiac side ebects of RNA-based SARS-CoV-2 vaccines: Hidden
    cardiotoxic ebects of mRNA-1273 and BNT162b2 on ventricular myocyte function and structure,” Br.
    J. Pharmacol. 2024, 181, 3: 345-361. doi: https://doi.org/10.1111/bph.16262
22. Yonker LM et al., “Circulating Spike Protein Detected in Post–COVID-19 mRNA Vaccine Myocarditis,”
    Circulation 2023, 147, 11. doi: https://doi.org/10.1161/CIRCULATIONAHA.122.061025
    

W. NLRP3

1. Albornoz EA et al., “SARS-CoV-2 drives NLRP3 inflammasome activation in human microglia through
   spike protein,” Mol. Psychiatr. 2023, 28: 2878–2893. doi: https://doi.org/10.1038/s41380-022-01831-
   0
2. Arjsri P et al., “Hesperetin from root extract of Clerodendrum petasites S. Moore inhibits SARS-CoV-2
   spike protein S1 subunit-induced Nlrp3 inflammasome in A549 lung cells via modulation of the
   Akt/Mapk/Ap-1 pathway,” Int. J. Mol. Sci. 2022, 23, 18: 10346. doi:
   https://doi.org/10.3390/ijms231810346
3. Chittasupho C et al., “Inhibition of SARS-CoV-2-Induced NLRP3 Inflammasome-Mediated Lung Cell
   Inflammation by Triphala-Loaded Nanoparticle Targeting Spike Glycoprotein S1,”
   Pharmaceutics 2024, 16, 6: 751. https://doi.org/10.3390/pharmaceutics16060751
4. Chittasupho C et al., “Targeting spike glycoprotein S1 mediated by NLRP3 inflammasome machinery
   and the cytokine releases in A549 lung epithelial cells by nanocurcumin,” Pharmaceuticals (Basel)
   2023, 16, 6: 862. doi: https://doi.org/10.3390/ph16060862
5. Corpetti C et al., “Cannabidiol inhibits SARS-Cov-2 spike (S) protein-induced cytotoxicity and
   inflammation through a PPARγ-dependent TLR4/NLRP3/Caspase-1 signaling suppression in Caco-2
   cell line,” Phytother. Res. 2021, 35, 12: 6893–6903. doi: https://doi.org/10.1002/ptr.7302
6. Del Re A et al., “Ultramicronized Palmitoylethanolamide Inhibits NLRP3 Inflammasome Expression
   and Pro-Inflammatory Response Activated by SARS-CoV-2 Spike Protein in Cultured Murine Alveolar
   Macrophages.” Metabolites 2021, 11, 9: 592. dsoi: https://doi.org/10.3390/metabo11090592
7. Dissook S et al., “Luteolin-rich fraction from Perilla frutescens seed meal inhibits spike glycoprotein
   S1 of SARS-CoV-2-induced NLRP3 inflammasome lung cell inflammation via regulation of
   JAK1/STAT3 pathway: A potential anti-inflammatory compound against inflammation-induced long-
   COVID,” Front. Med. 2023, 9: 1072056. doi: https://doi.org/10.3389/fmed.2022.1072056
8. Huynh TV et al., “Spike Protein of SARS-CoV-2 Activates Cardiac Fibrogenesis through NLRP3
   Inflammasomes and NF-κB Signaling,” Cells 2024, 13, 16: 1331.
   doi: https://doi.org/10.3390/cells13161331
9. Jiang Q et al., “SARS-CoV-2 spike S1 protein induces microglial NLRP3-dependent
   neuroinflammation and cognitive impairment in mice,” Exp. Neurol. 2025, 383: 115020. doi:
   https://doi.org/10.1016/j.expneurol.2024.115020
10. Kucia M et al. “An evidence that SARS-Cov-2/COVID-19 spike protein (SP) damages hematopoietic
    stem/progenitor cells in the mechanism of pyroptosis in Nlrp3 inflammasome-dependent
    manner,” Leukemia 2021, 35: 3026-3029. doi: https://doi.org/10.1038/s41375-021-01332-z
11. Ratajczak MZ et al., “SARS-CoV-2 Entry Receptor ACE2 Is Expressed on Very Small CD45- Precursors
    of Hematopoietic and Endothelial Cells and in Response to Virus Spike Protein Activates the Nlrp3
    Inflammasome,” Stem Cell Rev Rep. 2021, 17, 1: 266-277. doi: https://doi.org/10.1007/s12015-020-
    10010-z
12. Semmarath W et al., “Cyanidin-3-O-glucoside and Peonidin-3-O-glucoside-Rich Fraction of Black
    Rice Germ and Bran Suppresses Inflammatory Responses from SARS-CoV-2 Spike Glycoprotein S1-
    Induction In Vitro in A549 Lung Cells and THP-1 Macrophages via Inhibition of the NLRP3
    Inflammasome Pathway,” Nutrients 2022, 14, 13: 2738. doi: https://doi.org/10.3390/nu14132738
13. Villacampa A et al., “SARS-CoV-2 S protein activates NLRP3 inflammasome and deregulates
    coagulation factors in endothelial and immune cells,” Cell Commun. Signal. 2024, 22, 38. doi:
    https://doi.org/10.1186/s12964-023-01397-6
    

X. Ocular, ophthalmic, conjunctival

1. Golob-Schwarzl N et al., “SARS-CoV-2 spike protein functionally interacts with primary human
   conjunctival epithelial cells to induce a pro-inflammatory response,” Eye 2022, 36: 2353–5. doi:
   https://doi.org/10.1038/s41433-022-02066-7
2. Grishma K and Das Sarma, “The Role of Coronavirus Spike Protein in Inducing Optic Neuritis in Mice:
   Parallels to the SARS-CoV-2 Virus,” J Neuroophthalmol 2024, 44, 3: 319-329. doi:
   10.1097/WNO.0000000000002234
3. Zhu G et al., “SARS-CoV-2 spike protein-induced host inflammatory response signature in human
   corneal epithelial cells,” Mol. Med. Rep. 2021, 24: 584. doi: https://doi.org/10.3892/mmr.2021.12223
   

Y. Other cell signaling

1. Caohuy H et al., “Inflammation in the COVID-19 airway is due to inhibition of CFTR signaling by the
   SARS-CoV-2 spike protein,” Sci. Rep. 2024, 14: 16895. doi: https://doi.org/10.1038/s41598-024-
   66473-4
2. Choi JY et al., “SARS-CoV-2 spike S1 subunit protein-mediated increase of beta-secretase 1 (BACE1)
   impairs human brain vessel cells,” Biochem. Biophys. Res. Commun. 2022, 625, 20: 66-71.
   doi: https://doi.org/10.1016/j.bbrc.2022.07.113
3. Corpetti C et al., “Cannabidiol inhibits SARS-Cov-2 spike (S) protein-induced cytotoxicity and
   inflammation through a PPARγ-dependent TLR4/NLRP3/Caspase-1 signaling suppression in Caco-2
   cell line,” Phytother. Res. 2021, 35, 12: 6893–6903. doi: https://doi.org/10.1002/ptr.7302
4. Gracie NP et al., “Cellular signalling by SARS-CoV-2 spike protein,” Microbiology Australia 2024, 45, 1:
   13-17. doi: https://doi.org/10.1071/MA24005
5. Li F et al., “SARS-CoV-2 Spike Promotes Inflammation and Apoptosis Through Autophagy by ROSSuppressed
   PI3K/AKT/mTOR Signaling,” Biochim Biophys Acta BBA – Mol Basis Dis 2021, 1867: doi: https://doi.org/10.1016/j.bbadis.2021.166260
6. Li K et al., “SARS-CoV-2 Spike protein promotes vWF secretion and thrombosis via endothelial
   cytoskeleton-associated protein 4 (CKAP4),” Signal Transduct Targ Ther 2022, 7, 332. doi:
   https://doi.org/10.1038/s41392-022-01183-9
7. Moutal A et al., “SARS-CoV-2 Spike protein co-opts VEGF-A/Neuropilin-1 receptor signaling to induce
   analgesia,” Pain 2020, 162, 1: 243–252. doi: 10.1097/j.pain.0000000000002097
8. Munavilli GG et al., “COVID-19/SARS-CoV-2 virus spike protein-related delayed inflammatory
   reaction to hyaluronic acid dermal fillers: a challenging clinical conundrum in diagnosis and
   treatment,” Arch. Dermatol. Res. 2022, 314: 1-15. doi: https://doi.org/10.1007/s00403-021-02190-6
9. Prieto-Villalobos J et al., “SARS-CoV-2 spike protein S1 activates Cx43 hemichannels and disturbs
   intracellular Ca2+ dynamics,” Biol Res. 2023, 56, 1: 56. doi: https://doi.org/10.1186/s40659-023-
   00468-9
10. Rotoli BM et al., “Endothelial cell activation by SARS-CoV-2 spike S1 protein: A crosstalk between
    endothelium and innate immune cells,” Biomedicines 2021, 9, 9: 1220. doi:
    https://doi.org/10.3390/biomedicines9091220
11. Singh N and Anuradha Bharara Singh, “S2 Subunit of SARS-nCoV-2 Interacts with Tumor Suppressor
    Protein p53 and BRCA: An in Silico Study,” Translational Oncology 2020, 13, 10: 100814. doi:
    https://doi.org/10.1016/j.tranon.2020.100814
12. Singh RD, “The spike protein of sars-cov-2 induces heme oxygenase-1: pathophysiologic
    implications,” Biochim Biophys Acta, Mol Basis Dis 2022, 1868, 3: 166322. doi:
    https://doi.org/10.1016/j.bbadis.2021.166322
13. Solis O et al., “The SARS-CoV-2 spike protein binds and modulates estrogen receptors,” Sci.
    Adv. 2022, 8, 48: eadd4150. doi: 10.1126/sciadv.add4150
14. Suzuki YJ et al., “SARS-CoV-2 spike protein-mediated cell signaling in lung vascular cells,” Vascul.
    Pharmacol. 2021, 137: 106823. doi: https://doi.org/10.1016/j.vph.2020.106823
15. Suzuki YJ and SG Gychka, “SARS-CoV-2 Spike Protein Elicits Cell Signaling in Human Host Cells:
    Implications for Possible Consequences of COVID-19 Vaccines,” Vaccines 2021, 9, 1: 36.
    doi: https://doi.org/10.3390/vaccines9010036
16. Tillman TS et al., “SARS-CoV-2 Spike Protein Downregulates Cell Surface alpha7nAChR through a
    Helical Motif in the Spike Neck,” ACS Chem. Neurosci. 2023, 14, 4: 689–698. doi:
    https://doi.org/10.1021/acschemneuro.2c00610
    

Z. PASC, post COVID, long COVID

1. Bellucci M et al., “Post-SARS-CoV-2 infection and post-vaccine-related neurological complications
   share clinical features and the same positivity to anti-ACE2 antibodies,” Front. Immunol. 2024, 15
   (Sec. Multiple Sclerosis and Neuroimmunology). doi: https://doi.org/10.3389/fimmu.2024.1398028
2. Craddock V et al., “Persistent circulation of soluble and extracellular vesicle-linked Spike protein in
   individuals with postacute sequelae of COVID-19,” J Med. Virol. 2023, 95, 2: e28568. doi:
   https://doi.org/10.1002/jmv.28568
3. Dissook S et al., “Luteolin-rich fraction from Perilla frutescens seed meal inhibits spike glycoprotein
   S1 of SARS-CoV-2-induced NLRP3 inflammasome lung cell inflammation via regulation of JAK1/STAT3 pathway: A potential anti-inflammatory compound against inflammation-induced long-COVID,” Front.
   Med. 2023, 9: 1072056. doi: https://doi.org/10.3389/fmed.2022.1072056
4. Frank MG et al., “Exploring the immunogenic properties of SARS-CoV-2 structural proteins: PAMP:TLR signaling in the mediation of the neuroinflammatory and neurologic sequelae of COVID-19,” Brain Behav Immun 2023, 111. doi: https://doi.org/10.1016/j.bbi.2023.04.009
5. Frank MG et al., “SARS-CoV-2 S1 subunit produces a protracted priming of the neuroinflammatory,
   physiological, and behavioral responses to a remote immune challenge: A role for corticosteroids,”
   Brain Behav. Immun. 2024, 121: 87-103. doi: https://doi.org/10.1016/j.bbi.2024.07.034
6. Fraser ME at al., “SARS-CoV-2 Spike Protein and Viral RNA Persist in the Lung of Patients With Post-
   COVID Lung Disease (abstract),” Am J Respir Crit Care Med 2024, 209: A4193. doi:
   https://doi.org/10.1164/ajrccm-conference.2024.209.1_MeetingAbstracts.A4193
7. Goh D et al., “Case report: Persistence of residual antigen and RNA of the SARS-CoV-2 virus in tissues
   of two patients with long COVID,” Front. Immunol. 2022, 13 (Sec. Viral Immunology). doi:
   https://doi.org/10.3389/fimmu.2022.939989
8. Halma MTJ et al., “Exploring autophagy in treating SARS-CoV-2 spike protein-related pathology,”
   Endocrinol Metab (EnM) 2024, 14: 100163. doi: https://doi.org/10.1016/j.endmts.2024.100163
9. Halma MTJ et al., “Strategies for the Management of Spike Protein-Related Pathology,” Microorganisms
   2023, 11, 5: 1308, doi: https://doi.org/10.3390/microorganisms11051308
10. Hano S et al., “A case of persistent, confluent maculopapular erythema following a COVID-19 mRNA
    vaccination is possibly associated with the intralesional spike protein expressed by vascular
    endothelial cells and eccrine glands in the deep dermis,” J Dermatol 2023, 50, 9: 1208-1212. doi:
    https://doi.org/10.1111/1346-8138.16816
11. Patterson BK et al., “Persistence of SARS CoV-2 S1 Protein in CD16+ Monocytes in Post-Acute
    Sequelae of COVID-19 (PASC) up to 15 Months Post-Infection,” Front. Immunol. 12 (Sec. Viral
    Immunology). doi: https://doi.org/10.3389/fimmu.2021.746021
12. Peluso MJ et al., “Plasma-based antigen persistence in the post-acute phase of COVID-19,” Lancet
    2024, 24, 6: E345-E347. doi: 10.1016/S1473-3099(24)00211-1
13. Rong Z et al., “Persistence of spike protein at the skull-meninges-brain axis may contribute to the
    neurological sequelae of COVID-19,” Cell Host Microbe 2024, 26: S1931-3128(24)00438-4. doi:
    10.1016/j.chom.2024.11.007
14. Scholkmann F and CA May, “COVID-19, post-acute COVID-19 syndrome (PACS, ‘long COVID’) and
    post-COVID-19 vaccination syndrome (PCVS, ‘post-COVIDvac-syndrome’): Similarities and
    diberences,” Pathol Res Pract. 2023, 246: 154497. doi: https://doi.org/10.1016/j.prp.2023.154497
15. Schultheiss C et al., “Liquid biomarkers of macrophage dysregulation and circulating spike protein
    illustrate the biological heterogeneity in patients with post-acute sequelae of COVID-19,” J Med Virol
    2023, 95, 1: e28364. doi: https://doi.org/10.1002/jmv.28364
16. Swank Z, et al. “Persistent Circulating Severe Acute Respiratory Syndrome Coronavirus 2 Spike Is
    Associated With Post-acute Coronavirus Disease 2019 Sequelae,” Clin. Infect. Dis. 2023, 76, 3: e487–
    e490. doi: https://doi.org/10.1093/cid/ciac722
17. Theoharides TC, “Could SARS-CoV-2 Spike Protein Be Responsible for Long-COVID Syndrome?” Mol.
    Neurobiol. 2022, 59, 3: 1850–1861. doi: https://doi.org/10.1007/s12035-021-02696-0
18. Visvabharathy L et al., “Case report: Treatment of long COVID with a SARS-CoV-2 antiviral and IL-6
    blockade in a patient with rheumatoid arthritis and SARS-CoV-2 antigen persistence,” Front. Med.
    2022, 9 (Sec. Infectious Diseases – Surveillance). doi: https://doi.org/10.3389/fmed.2022.1003103
19. Yamamoto M et al., “Persistent varicella zoster virus infection following mRNA COVID-19 vaccination
    was associated with the presence of encoded spike protein in the lesion,” J. Cutan Immunol. Allergy.
    2022:1–6. doi: https://doi.org/10.1002/cia2.12278
20. Zollner A et al., “Postacute COVID-19 is Characterized by Gut Viral Antigen Persistence in
    Inflammatory Bowel Diseases,” Gastroenterology 2022, 163, 2: 495-506.e8. doi:
    https://doi.org/10.1053/j.gastro.2022.04.037
    

AA. Pregnancy

1. Erdogan MA, “Prenatal SARS-CoV-2 Spike Protein Exposure Induces Autism-Like Neurobehavioral
   Changes in Male Neonatal Rats,” J Neuroimmune Pharmacol. 2023, 18, 4: 573-591. doi:
   10.1007/s11481-023-10089-4
2. Guo X et al., “Regulation of proinflammatory molecules and tissue factor by SARS-CoV-2 spike
   protein in human placental cells: implications for SARS-CoV-2 pathogenesis in pregnant women,”
   Front. Immunol. 2022, 13: 876555–876555. doi: https://doi.org/10.3389/fimmu.2022.876555
3. Kammala AK et al., “In vitro mRNA-S maternal vaccination induced altered immune regulation at the
   maternal-fetal interface,” Am. J. Reprod. Immunol. 2024, 91, 5: e13861. doi:
   https://doi.org/10.1111/aji.13861
4. Karrow NA et al., “Maternal COVID-19 Vaccination and Its Potential Impact on Fetal and Neonatal
   Development,” Vaccines 2021, 9: 1351. doi: https://doi.org/10.3390/vaccines9111351
5. Parcial ALN et al., “SARS-CoV-2 Is Persistent in Placenta and Causes Macroscopic,
   Histopathological, and Ultrastructural Changes,” Viruses 2022, 14, 9: 1885.
   doi: https://doi.org/10.3390/v14091885
6. Wu H et al., “Molecular evidence suggesting the persistence of residual SARS-CoV-2 and immune
   responses in the placentas of pregnant patients recovered from COVID-19,” Cell Prolif. 2021, 54, 9:
   e13091. doi: https://doi.org/10.1111/cpr.13091
7. Zurlow M et al., “The anti-SARS-CoV-2 BNT162b2 vaccine suppresses mithramycin-induced erythroid
   diberentiation and expression of embryo-fetal globin genes in human erythroleukemia K562 cells.”
   Exp Cell Res 2023, 433, 2: 113853. doi: https://doi.org/10.1016/j.yexcr.2023.113853
9. 
   

BB. Pulmonary, respiratory

1. Bhargavan B and GD Kanmogne, “SARS-CoV-2 spike proteins and cell–cell communication inhibits
   TFPI and induces thrombogenic factors in human lung microvascular endothelial cells and
   neutrophils: implications for COVID-19 coagulopathy pathogenesis,” Int. J. Mol. Sci. 2022, 23, 18:doi: https://doi.org/10.3390/ijms231810436
2. Biancatelli RMLC et al., “The SARS-CoV-2 spike protein subunit S1 induces COVID-19-like acute lung
   injury in Kappa18-hACE2 transgenic mice and barrier dysfunction in human endothelial cells,” Am. J.
   Physiol. Lung Cell. Mol. Physiol. 2021, 321: L477–L484. doi:
   https://doi.org/10.1152/ajplung.00223.2021
3. Cao JB et al., “Mast cell degranulation-triggered by SARS-CoV-2 induces tracheal-bronchial epithelial
   inflammation and injury,” Virol. Sin. 2024, 39, 2: 309-318. doi:
   https://doi.org/10.1016/j.virs.2024.03.001
4. Cao X et al., “Spike protein of SARS-CoV-2 activates macrophages and contributes to induction of
   acute lung inflammation in male mice,” FASEB J. 2021, 35, e21801. doi:
   https://doi.org/10.1096/fj.202002742RR
5. Caohuy H et al., “Inflammation in the COVID-19 airway is due to inhibition of CFTR signaling by the
   SARS-CoV-2 spike protein,” Sci. Rep. 2024, 14: 16895. doi: https://doi.org/10.1038/s41598-024-
   66473-4
6. Chittasupho C et al., “Inhibition of SARS-CoV-2-Induced NLRP3 Inflammasome-Mediated Lung Cell
   Inflammation by Triphala-Loaded Nanoparticle Targeting Spike Glycoprotein S1,”
   Pharmaceutics 2024, 16, 6: 751. https://doi.org/10.3390/pharmaceutics16060751
7. Chittasupho C et al., “Targeting spike glycoprotein S1 mediated by NLRP3 inflammasome machinery
   and the cytokine releases in A549 lung epithelial cells by nanocurcumin,” Pharmaceuticals (Basel)
   2023, 16, 6: 862. doi: https://doi.org/10.3390/ph16060862
8. Del Re A et al., “Intranasal delivery of PEA-producing Lactobacillus paracasei F19 alleviates SARSCoV-
   2 spike protein-induced lung injury in mice,” Transl. Med. Commun. 2024, 9, 9. doi:
   https://doi.org/10.1186/s41231-024-00167-x
9. Forsyth CB et al., “The SARS-CoV-2 S1 spike protein promotes MAPK and NF-kB activation in human
   lung cells and inflammatory cytokine production in human lung and intestinal epithelial
   cells,” Microorganisms 2022, 10, 10: 1996. doi: https://doi.org/10.3390/microorganisms10101996
10. Fraser ME at al., “SARS-CoV-2 Spike Protein and Viral RNA Persist in the Lung of Patients With Post-
    COVID Lung Disease (abstract),” Am J Respir Crit Care Med 2024, 209: A4193. doi:
    https://doi.org/10.1164/ajrccm-conference.2024.209.1_MeetingAbstracts.A4193
11. Greenberger JS et al., “SARS-CoV-2 Spike Protein Induces Oxidative Stress and Senescence in Mouse
    and Human Lung,” In Vivo 2024, 38, 4: 1546-1556; doi: https://doi.org/10.21873/invivo.13605
12. Jana S et al., “Cell-free hemoglobin does not attenuate the ebects of SARS-CoV-2 spike protein S1
    subunit in pulmonary endothelial cells,” Int. J. Mol. Sci. 2021, 22, 16: 9041. doi:
    https://doi.org/10.3390/ijms22169041
13. Kulkoviene G et al., “Diberential Mitochondrial, Oxidative Stress and Inflammatory Responses to
    SARS-CoV-2 Spike Protein Receptor Binding Domain in Human Lung Microvascular, Coronary Artery
    Endothelial and Bronchial Epithelial Cells,” Int. J. Mol. Sci. 2024, 25, 6: 3188.
    doi: https://doi.org/10.3390/ijms25063188
14. Liang S et al., “SARS-CoV-2 spike protein induces IL-18-mediated cardiopulmonary inflammation via
    reduced mitophagy,” Signal Transduct Target Ther 2023, 8, 103. doi: https://doi.org/10.1038/s41392-
    023-01368-w
15. Liu T et al., “RS-5645 attenuates inflammatory cytokine storm induced by SARS-CoV-2 spike protein
    and LPS by modulating pulmonary microbiota,” Int J Biol Sci. 2021, 17, 13: 3305–3319.
    doi: 10.7150/ijbs.63329
16. Palestra F et al. “SARS-CoV-2 Spike Protein Activates Human Lung Macrophages,” Int. J. Mol.
    Sci. 2023, 24, 3: 3036. doi: https://doi.org/10.3390/ijms24033036
17. Park C et al., “Murine alveolar Macrophages Rapidly Accumulate intranasally Administered SARSCoV-
    2 Spike Protein leading to neutrophil Recruitment and Damage,” Elife 2024, 12: RP86764. doi:
    https://doi.org/10.7554/eLife.86764.3
18. Puthia MTL et al., “Experimental model of pulmonary inflammation induced by SARS-CoV-2 spike
    protein and endotoxin,” ACS Pharmacol Transl Sci. 2022, 5, 3: 141–8. doi:
    https://doi.org/10.1021/acsptsci.1c00219
19. Rahman M et al., “Diberential Ebect of SARS-CoV-2 Spike Glycoprotein 1 on Human Bronchial and
    Alveolar Lung Mucosa Models: Implications for Pathogenicity,” Viruses 2021, 13, 12: 2537. doi:
    https://doi.org/10.3390/v13122537
20. Ruben ML et al., “The SARS-CoV-2 spike protein subunit S1 induces COVID-19-like acute lung injury
    in Κ18-hACE2 transgenic mice and barrier dysfunction in human endothelial cells,” Am J Physiol Lung
    Cell Mol Physiol. 2021, 321, 2: L477-L484. doi: https://doi.org/10.1152/ajplung.00223.2021
21. Segura-Villalobos D et al., “Jacareubin inhibits TLR4-induced lung inflammatory response caused by
    the RBD domain of SARS-CoV-2 Spike protein,” Pharmacol. Rep. 2022, 74: 1315–1325. doi:
    https://doi.org/10.1007/s43440-022-00398-5
22. Semmarath W et al., “Cyanidin-3-O-glucoside and Peonidin-3-O-glucoside-Rich Fraction of Black
    Rice Germ and Bran Suppresses Inflammatory Responses from SARS-CoV-2 Spike Glycoprotein S1-
    Induction In Vitro in A549 Lung Cells and THP-1 Macrophages via Inhibition of the NLRP3
    Inflammasome Pathway,” Nutrients 2022, 14, 13: 2738. doi: https://doi.org/10.3390/nu14132738
23. Sirsendu J et al., “Cell-Free Hemoglobin Does Not Attenuate the Ebects of SARS-CoV-2 Spike Protein
    S1 Subunit in Pulmonary Endothelial Cells,” Int. J. Mol. Sci. 2021, 22, 16: 9041. doi:
    https://doi.org/10.3390/ijms22169041
24. Sui Y et al., “SARS-CoV-2 Spike Protein Suppresses ACE2 and Type I Interferon Expression in Primary
    Cells From Macaque Lung Bronchoalveolar Lavage,” Front. Immunol. 2021, 12. doi:
    https://doi.org/10.3389/fimmu.2021.658428
25. Sung PS et al., “CLEC5A and TLR2 Are Critical in SARS-CoV-2-Induced NET Formation and Lung
    Inflammation,” J. Biomed. Sci. 2022, 29, 52. doi: https://doi.org/10.1186/s12929-022-00832-z
26. Suzuki YJ et al., “SARS-CoV-2 spike protein-mediated cell signaling in lung vascular cells,” Vascul.
    Pharmacol. 2021, 137: 106823. doi: https://doi.org/10.1016/j.vph.2020.106823
27. Yeung-Luk BH et al., “SARS-CoV-2 infection alters mitochondrial and cytoskeletal function in human
    respiratory epithelial cells mediated by expression of spike protein,” mBio 2023, 14, 4: e00820-23.
    doi: https://doi.org/10.1128/mbio.00820-23
28. Zekri-Nechar K et al., “Spike Protein Subunits of SARS-CoV-2 Alter Mitochondrial Metabolism in
    Human Pulmonary Microvascular Endothelial Cells: Involvement of Factor Xa,” Dis. Markers 2022,doi: https://doi.org/10.1155/2022/1118195
    

CC. Renin-Angiotensin-Aldosterone System

1. Burnett FN et al., “SARS-CoV-2 Spike Protein Intensifies Cerebrovascular Complications in Diabetic
   hACE2 Mice through RAAS and TLR Signaling Activation,” Int. J. Mol. Sci. 2023, 24, 22: 16394.
   doi: https://doi.org/10.3390/ijms242216394
2. Lehmann KJ, “SARS-CoV-2-Spike Interactions with the Renin-Angiotensin-Aldosterone System –
   Consequences of Adverse Reactions of Vaccination,” J Biol Today’s World 2023, 12/4: 001-013. doi:
   https://doi.org/10.31219/osf.io/27g5h
3. Matsuzawa Y et al., “Impact of Renin–Angiotensin–Aldosterone System Inhibitors on COVID-19,”
   Hypertens. Res. 2022, 45, 7: 1147–1153, doi: https://doi.org/10.1038/s41440-022-00922-3
5. 
   

DD. Senescence/aging

1. Duarte C, “Age-dependent ebects of the recombinant spike protein/SARS-CoV-2 on the M-CSF- and
   IL-34-diberentiated macrophages in vitro,” Biochem. Biophys. Res. Commun. 2021, 546: 97–102. doi:
   https://doi.org/10.1016/j.bbrc.2021.01.104
2. Greenberger JS et al., “SARS-CoV-2 Spike Protein Induces Oxidative Stress and Senescence in Mouse
   and Human Lung,” In Vivo 2024, 38, 4: 1546-1556. doi: https://doi.org/10.21873/invivo.13605
3. Meyer K et al., “SARS-CoV-2 Spike Protein Induces Paracrine Senescence and Leukocyte Adhesion in
   Endothelial Cells,” J. Virol. 2021, 95, e0079421. doi: https://doi.org/10.1128/jvi.00794-21
   

EE. Stem cells

1. Balzanelli MG et al., “The Role of SARS-CoV-2 Spike Protein in Long-term Damage of Tissues and
   Organs, the Underestimated Role of Retrotransposons and Stem Cells, a Working Hypothesis,”
   Endocr Metab Immune Disord Drug Targets 2025, 25, 2: 85-98. doi:
   10.2174/0118715303283480240227113401
2. Kucia M et al. “An evidence that SARS-Cov-2/COVID-19 spike protein (SP) damages hematopoietic
   stem/progenitor cells in the mechanism of pyroptosis in Nlrp3 inflammasome-dependent
   manner,” Leukemia 2021, 35: 3026-3029. doi: https://doi.org/10.1038/s41375-021-01332-z
3. Ropa J et al., “Human Hematopoietic Stem, Progenitor, and Immune Cells Respond Ex Vivo to SARSCoV-2 Spike Protein,” Stem Cell Rev Rep. 2021, 17, 1: 253-265. doi: https://doi.org/10.1007/s12015-020-10056-z
   

FF. Syncytia/cell fusion

1. Braga L et al., “Drugs that inhibit TMEM16 proteins block SARS-CoV-2 spike-induced syncytia,”
   Nature 2021, 594: 88–93. doi: https://doi.org/10.1038/s41586-021-03491-6
2. Cattin-Ortolá J et al., “Sequences in the cytoplasmic tail of SARS-CoV-2 Spike facilitate expression at
   the cell surface and syncytia formation,” Nat Commun 2021, 12, 1: 5333. doi:
   https://doi.org/10.1038/s41467-021-25589-1
3. Clemens DJ et al., “SARS-CoV-2 spike protein-mediated cardiomyocyte fusion may contribute to
   increased arrhythmic risk in COVID-19,” PLoS One 2023, 18, 3: e0282151.
   doi: https://doi.org/10.1371/journal.pone.0282151
4. Lazebnik Y, “Cell fusion as a link between the SARS-CoV-2 spike protein, COVID-19 complications,
   and vaccine side ebects,” Oncotarget 2021, 12, 25: 2476-2488. doi:
   https://doi.org/10.18632/oncotarget.28088
5. Liu X et al., “SARS-CoV-2 spike protein-induced cell fusion activates the cGAS-STING pathway and
   the interferon response,” Sci Signal. 2022, 15, 729: eabg8744. doi: 10.1126/scisignal.abg8744
6. Martinez-Marmol R et al., “SARS-CoV-2 infection and viral fusogens cause neuronal and glial fusion
   that compromises neuronal activity,” Sci. Adv. 2023, 9, 23. doi: 10.1126/sciadv.adg2248
7. Rajah MM et al., “SARS-CoV-2 Alpha, Beta, and Delta variants display enhanced spike-mediated
   syncytia formation,” EMBO J. 2021, 40: e108944. doi: https://doi.org/10.15252/embj.2021108944
8. Shirato K and Takako Kizaki, “SARS-CoV-2 Spike Protein S1 Subunit Induces Pro- inflammatory
   Responses via Toll-Like Receptor 4 Signaling in Murine and Human Macrophages,” Heliyon 2021, 7, 2:
   e06187. doi: https://doi.org/10.1016/j.heliyon.2021.e06187
9. Theuerkauf SA et al., “Quantitative assays reveal cell fusion at minimal levels of SARS-CoV-2 spike
   protein and fusion from without,” iScience 2021, 24, 3: 102170.
   doi: https://doi.org/10.1016/j.isci.2021.102170
10. Zhang Z et al., “SARS-CoV-2 spike protein dictates syncytium-mediated lymphocyte
    elimination,” Cell Death Di^er. 2021, 28: 2765–2777. doi: https://doi.org/10.1038/s41418-021-00782-
    3
    

GG. Therapeutics

1. Almehdi AM et al., “SARS-CoV-2 Spike Protein: Pathogenesis, Vaccines, and Potential Therapies,”
   Infection 2021, 49, 5: 855–876. doi: https://doi.org/10.1007/s15010-021-01677-8
2. Boretti A, “PQQ Supplementation and SARS-CoV-2 Spike Protein-Induced Heart Inflammation,” Nat.
   Prod. Commun. 2022, 17, 1934578×221080929. doi: https://doi.org/10.1177/1934578X221080929
3. Boschi C et al., “SARS-CoV-2 Spike Protein Induces Hemagglutination: Implications for COVID-19
   Morbidities and Therapeutics and for Vaccine Adverse Ebects,” Int. J. Biol. Macromol. 2022, 23, 24:doi: https://doi.org/10.3390/ijms232415480
4. Braga L et al., “Drugs that inhibit TMEM16 proteins block SARS-CoV-2 spike-induced syncytia,”
   Nature 2021, 594: 88–93. doi: https://doi.org/10.1038/s41586-021-03491-6
5. Chang MH et al., “SARS-CoV-2 Spike Protein 1 Causes Aggregation of α-Synuclein via Microglia-
   Induced Inflammation and Production of Mitochondrial ROS: Potential Therapeutic Applications of
   Metformin,” Biomedicines 2024, 12, 6: 1223. doi: https://doi.org/10.3390/biomedicines12061223
6. Chittasupho C et al., “Inhibition of SARS-CoV-2-Induced NLRP3 Inflammasome-Mediated Lung Cell
   Inflammation by Triphala-Loaded Nanoparticle Targeting Spike Glycoprotein S1,”
   Pharmaceutics 2024, 16, 6: 751. doi: https://doi.org/10.3390/pharmaceutics16060751
7. Chittasupho C et al., “Targeting spike glycoprotein S1 mediated by NLRP3 inflammasome machinery
   and the cytokine releases in A549 lung epithelial cells by nanocurcumin,” Pharmaceuticals (Basel)
   2023, 16, 6: 862. doi: https://doi.org/10.3390/ph16060862
8. Corpetti C et al., “Cannabidiol inhibits SARS-Cov-2 spike (S) protein-induced cytotoxicity and
   inflammation through a PPARγ-dependent TLR4/NLRP3/Caspase-1 signaling suppression in Caco-2
   cell line,” Phytother. Res. 2021, 35, 12: 6893–6903. doi: https://doi.org/10.1002/ptr.7302
9. Cory TJ et al., “Metformin Suppresses Monocyte Immunometabolic Activation by SARS-CoV-2 Spike
   Protein Subunit 1,” Front. Immunol. 2021, 12 (Sec. Cytokines and Soluble Mediators in Immunity):doi: https://doi.org/10.3389/fimmu.2021.733921
10. Del Re A et al., “Intranasal delivery of PEA-producing Lactobacillus paracasei F19 alleviates SARSCoV-
    2 spike protein-induced lung injury in mice,” Transl. Med. Commun. 2024, 9, 9. doi:
    https://doi.org/10.1186/s41231-024-00167-x
11. Del Re A et al., “Ultramicronized Palmitoylethanolamide Inhibits NLRP3 Inflammasome Expression
    and Pro-Inflammatory Response Activated by SARS-CoV-2 Spike Protein in Cultured Murine Alveolar
    Macrophages,” Metabolites 2021, 11, 9: 592. doi: https://doi.org/10.3390/metabo11090592
12. Ferrer MD et al., “Nitrite Attenuates the In Vitro Inflammatory Response of Immune Cells to the
    SARS-CoV-2 S Protein without Interfering in the Antioxidant Enzyme Activation,” Int. J. Mol.
    Sci. 2024, 25, 5: 3001. https://doi.org/10.3390/ijms25053001
13. Frank MG et al., “SARS-CoV-2 S1 subunit produces a protracted priming of the neuroinflammatory,
    physiological, and behavioral responses to a remote immune challenge: A role for corticosteroids,”
    Brain Behav. Immun. 2024, 121: 87-103. doi: https://doi.org/10.1016/j.bbi.2024.07.034
14. Frühbeck G et al., “FNDC4 and FNDC5 reduce SARS-CoV-2 entry points and spike glycoprotein S1-
    induced pyroptosis, apoptosis, and necroptosis in human adipocytes,” Cell Mol Immunol. 2021, 18,
    10: 2457–9. doi: https://doi.org/10.1038/s41423-021-00762-0
15. Gasparello J et al., “Sulforaphane inhibits the expression of interleukin-6 and interleukin-8 induced in
    bronchial epithelial IB3-1 cells by exposure to the SARS-CoV-2 Spike protein,” Phytomedicine 2021,
    87: 153583. doi: https://doi.org/10.1016/j.phymed.2021.153583
16. Halma MTJ et al., “Exploring autophagy in treating SARS-CoV-2 spike protein-related pathology,”
    Endocrinol Metab (EnM) 2024, 14: 100163. doi: https://doi.org/10.1016/j.endmts.2024.100163
17. Halma MTJ et al., “Strategies for the Management of Spike Protein-Related Pathology,”
    Microorganisms 2023, 11, 5: 1308. doi: https://doi.org/10.3390/microorganisms11051308
18. Jana S et al., “Cell-free hemoglobin does not attenuate the ebects of SARS-CoV-2 spike protein S1
    subunit in pulmonary endothelial cells,” Int. J. Mol. Sci. 2021, 22, 16: 9041. doi:
    https://doi.org/10.3390/ijms22169041
19. Jugler C et al., “SARS-CoV-2 Spike Protein-Induced Interleukin 6 Signaling Is Blocked by a Plant-
    Produced Anti-Interleukin 6 Receptor Monoclonal Antibody,” Vaccines 2021, 9, 11: 1365.
    doi: https://doi.org/10.3390/vaccines9111365
20. Ken W et al., “Low dose radiation therapy attenuates ACE2 depression and inflammatory cytokines
    induction by COVID-19 viral spike protein in human bronchial epithelial cells,” Int J Radiat Biol. 2022,
    98, 10:1532-1541. doi: https://doi.org/10.1080/09553002.2022.2055806
21. Kumar N et al., “SARS-CoV-2 spike protein S1-mediated endothelial injury and pro-inflammatory
    state Is amplified by dihydrotestosterone and prevented by mineralocorticoid
    antagonism,” Viruses 2021, 13, 11: 2209. doi: https://doi.org/10.3390/v13112209
22. Liu T et al., “RS-5645 attenuates inflammatory cytokine storm induced by SARS-CoV-2 spike protein
    and LPS by modulating pulmonary microbiota,” Int J Biol Sci. 2021, 17, 13: 3305–3319.
    doi: 10.7150/ijbs.63329
23. Loh D, “The potential of melatonin in the prevention and attenuation of oxidative hemolysis and
    myocardial injury from cd147 SARS-CoV-2 spike protein receptor binding,” Melatonin Research 2020,
    3, 3: 380-416. doi: https://doi.org/10.32794/mr11250069
24. Loh JT et al., “Dok3 restrains neutrophil production of calprotectin during TLR4 sensing of SARS-CoV-2 spike protein,” Front. Immunol. 2022, 13 (Sec. Molecular Innate Immunity). doi:
    https://doi.org/10.3389/fimmu.2022.996637
25. Marrone L et al., “Tirofiban prevents the ebects of SARS-CoV-2 spike protein on macrophage
    activation and endothelial cell death,” Heliyon 2024, 10, 15: e35341. doi:
    10.1016/j.heliyon.2024.e35341
26. Norris B et al., “Evaluation of Glutathione in Spike Protein of SARS-CoV-2 Induced
    Immunothrombosis and Cytokine Dysregulation,” Antioxidants 2024, 13, 3: 271.
    doi: https://doi.org/10.3390/antiox13030271
27. Oka N et al., “SARS-CoV-2 S1 protein causes brain inflammation by reducing intracerebral
    acetylcholine production,” iScience 2023, 26, 6: 106954. doi: 10.1016/j.isci.2023.106954
28. Olajide OA et al., “Induction of Exaggerated Cytokine Production in Human Peripheral Blood
    Mononuclear Cells by a Recombinant SARS-CoV-2 Spike Glycoprotein S1 and Its Inhibition by
    Dexamethasone,” Inflammation 2021, 44: 1865–1877. doi: https://doi.org/10.1007/s10753-021-
    01464-5
29. Petrosino S and N Matende, “Elimination/Neutralization of COVID-19 Vaccine-Produced Spike
    Protein: Scoping Review,” Mathews Journal of Nutrition & Dietetics 2024, 7, 2. doi:
    https://doi.org/10.30654/MJND.10034
30. Satta S et al., “An engineered nano-liposome-human ACE2 decoy neutralizes SARS-CoV-2 Spike
    protein-induced inflammation in both murine and human macrophages,” Theranostics 2022, 12, 6:
    2639–2657. doi: 10.7150/thno.66831
31. Segura-Villalobos D et al., “Jacareubin inhibits TLR4-induced lung inflammatory response caused by
    the RBD domain of SARS-CoV-2 Spike protein,” Pharmacol. Rep. 2022, 74: 1315–1325. doi:
    https://doi.org/10.1007/s43440-022-00398-5
32. Semmarath W et al., “Cyanidin-3-O-glucoside and Peonidin-3-O-glucoside-Rich Fraction of Black
    Rice Germ and Bran Suppresses Inflammatory Responses from SARS-CoV-2 Spike Glycoprotein S1-
    Induction In Vitro in A549 Lung Cells and THP-1 Macrophages via Inhibition of the NLRP3
    Inflammasome Pathway,” Nutrients 2022, 14, 13: 2738. doi: https://doi.org/10.3390/nu14132738
33. Suprewicz L et al., “Recombinant human plasma gelsolin reverses increased permeability of the
    blood-brain barrier induced by the spike protein of the SARS-CoV-2 virus,” J Neuroinflammation 2022, 19, 1: 282. doi: https://doi.org/10.1186/s12974-022-02642-4
34. Vargas-Castro R et al., “Calcitriol prevents SARS-CoV spike-induced inflammation in human
    trophoblasts through downregulating ACE2 and TMPRSS2 expression,” J Steroid Biochem Mol
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35. Visvabharathy L et al., “Case report: Treatment of long COVID with a SARS-CoV-2 antiviral and IL-6
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36. Yonker LM et al., “Multisystem inflammatory syndrome in children is driven by zonulin-dependent
    loss of gut mucosal barrier,” J Clin Invest. 2021, 131, 14: e149633. doi:
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37. Youn JY et al., “Therapeutic application of estrogen for COVID-19: Attenuation of SARS-CoV-2 spike
    protein and IL-6 stimulated, ACE2-dependent NOX2 activation, ROS production and MCP-1
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38. Yu J et al., “Direct activation of the alternative complement pathway by SARS-CoV-2 spike proteins is
    blocked by factor D inhibition,” Blood 2020, 136, 18: 2080–2089. doi:
    https://doi.org/10.1182/blood.2020008248
    

HH. Toll-like receptors (TLRs)

1. Aboudounya MM and RJ Heads, “COVID-19 and Toll-Like Receptor 4 (TLR4): SARS-CoV-2 May Bind
   and Activate TLR4 to Increase ACE2 Expression, Facilitating Entry and Causing Hyperinflammation,”
   Mediators Inflamm. 2021: 8874339. doi: https://doi.org/10.1155/2021/8874339
2. Burnett FN et al., “SARS-CoV-2 Spike Protein Intensifies Cerebrovascular Complications in Diabetic
   hACE2 Mice through RAAS and TLR Signaling Activation,” Int. J. Mol. Sci. 2023, 24, 22: 16394.
   doi: https://doi.org/10.3390/ijms242216394
3. Carnevale R et al., “Toll-Like Receptor 4-Dependent Platelet-Related Thrombosis in SARS-CoV-2
   Infection,” Circ. Res. 2023, 132, 3: 290– 305. doi: https://doi.org/10.1161/CIRCRESAHA.122.321541
4. Corpetti C et al., “Cannabidiol inhibits SARS-Cov-2 spike (S) protein-induced cytotoxicity and
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