Conv. Plasma
Nigella Sativa

All curcumin studies
Meta analysis
study COVID-19 treatment researchCurcuminCurcumin (more..)
Melatonin Meta
Metformin Meta
Azvudine Meta
Bromhexine Meta Molnupiravir Meta
Budesonide Meta
Colchicine Meta
Conv. Plasma Meta Nigella Sativa Meta
Curcumin Meta Nitazoxanide Meta
Famotidine Meta Paxlovid Meta
Favipiravir Meta Quercetin Meta
Fluvoxamine Meta Remdesivir Meta
Hydroxychlor.. Meta Thermotherapy Meta
Ivermectin Meta

All Studies   Meta Analysis    Recent:   

Clinical Approach to Post-acute Sequelae After COVID-19 Infection and Vaccination

Hulscher et al., Cureus, doi:10.7759/cureus.49204
Nov 2023  
  Source   PDF   All Studies   Meta AnalysisMeta
Curcumin for COVID-19
15th treatment shown to reduce risk in February 2021
*, now known with p = 0.000000046 from 26 studies.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
3,800+ studies for 60+ treatments.
Review of evidence that the SARS-CoV-2 spike protein can damage cardiovascular, hematological, neurological, respiratory, gastrointestinal, and immunological systems, and may be a primary cause of long COVID symptoms. Authors introduce a base spike detoxification protocol including oral nattokinase, bromelain, and curcumin to degrade spike protein, inhibit inflammation, dissolve microthrombi, and provide anticoagulation. Authors discuss other treatments that may also be beneficial including HCQ, colchicine, ivermectin, quercetin, glutathione, apigenin, nicotine, emodin, fisetin, rutin, silymarin, and NAC. Authors note that the safety and efficacy of this protocol warrants formal study in large clinical trials.
Reviews covering curcumin for COVID-19 include Arab, Daskou, Halma, Hegde, Hulscher, Kritis, Law, Rattis.
Hulscher et al., 21 Nov 2023, peer-reviewed, 4 authors. Contact:
This PaperCurcuminAll
Clinical Approach to Post-acute Sequelae After COVID-19 Infection and Vaccination
Nicolas Hulscher, Brian C Procter, Cade Wynn, Peter A Mccullough
Cureus, doi:10.7759/cureus.49204
The spike protein of SARS-CoV-2 has been found to exhibit pathogenic characteristics and be a possible cause of post-acute sequelae after SARS-CoV-2 infection or COVID-19 vaccination. COVID-19 vaccines utilize a modified, stabilized prefusion spike protein that may share similar toxic effects with its viral counterpart. The aim of this study is to investigate possible mechanisms of harm to biological systems from SARS-CoV-2 spike protein and vaccine-encoded spike protein and to propose possible mitigation strategies. We searched PubMed, Google Scholar, and 'grey literature' to find studies that (1) investigated the effects of the spike protein on biological systems, (2) helped differentiate between viral and vaccine-generated spike proteins, and (3) identified possible spike protein detoxification protocols and compounds that had signals of benefit and acceptable safety profiles. We found abundant evidence that SARS-CoV-2 spike protein may cause damage in the cardiovascular, hematological, neurological, respiratory, gastrointestinal, and immunological systems. Viral and vaccine-encoded spike proteins have been shown to play a direct role in cardiovascular and thrombotic injuries from both SARS-CoV-2 and vaccination. Detection of spike protein for at least 6-15 months after vaccination and infection in those with post-acute sequelae indicates spike protein as a possible primary contributing factor to long COVID. We rationalized that these findings give support to the potential benefit of spike protein detoxification protocols in those with long-term postinfection and/or vaccine-induced complications. We propose a base spike detoxification protocol, composed of oral nattokinase, bromelain, and curcumin. This approach holds immense promise as a base of clinical care, upon which additional therapeutic agents are applied with the goal of aiding in the resolution of postacute sequelae after SARS-CoV-2 infection and COVID-19 vaccination. Large-scale, prospective, randomized, double-blind, placebo-controlled trials are warranted in order to determine the relative risks and benefits of the base spike detoxification protocol.
Additional Information Author Contributions All authors have reviewed the final version to be published and agreed to be accountable for all aspects of the work. Concept and design:
Ait-Belkacem, García, Millet-Wallisky, SARS-CoV-2 spike protein induces a differential monocyte activation that may contribute to age bias in COVID-19 severity, Sci Rep, doi:10.1038/s41598-022-25259-2
Ajala, Azhar, Kalaji, A rare case of pleurodynia after the COVID-19 vaccine, Chest, doi:10.1016/j.chest.2022.08.2056
Akhter, Quéromès, Pillai, The combination of bromelain and acetylcysteine (Bromac) synergistically inactivates SARS-CoV-2, Viruses, doi:10.3390/v13030425
Almehdi, Khoder, Alchakee, Alsayyid, Sarg et al., SARS-CoV-2 spike protein: pathogenesis, vaccines, and potential therapies, Infection, doi:10.1007/s15010-021-01677-8
Avila, Long, Holladay, Gottlieb, Thrombotic complications of COVID-19, Am J Emerg Med, doi:10.1016/j.ajem.2020.09.065
Avolio, Carrabba, Milligan, 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 (Lond), doi:10.1042/CS20210735
Barati, Motavallihaghi, Nikfar, Chaichian, Momtazi-Borojeni, Potential therapeutic effects of ivermectin in COVID-19, Exp Biol Med, doi:10.1177/15353702221099579
Baumeier, Aleshcheva, Harms, Intramyocardial Inflammation after COVID-19 vaccination: an endomyocardial biopsy-proven case series, Int J Mol Sci, doi:10.3390/ijms23136940
Brogna, Cristoni, Marino, Detection of recombinant Spike protein in the blood of individuals vaccinated against SARS-CoV-2: possible molecular mechanisms, Proteomics Clin Appl, doi:10.1002/prca.202300048
Chakraborty, Mitra, Tallei, Bromelain a potential bioactive compound: a comprehensive overview from a pharmacological perspective, Life, doi:10.3390/life11040317
Cheng, Hsu, Lin, Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions, Anticancer Res
Clemens, Ye, Zhou, SARS-CoV-2 spike protein-mediated cardiomyocyte fusion may contribute to increased arrhythmic risk in COVID-19, PLoS One, doi:10.1371/journal.pone.0282151
Corbett, Edwards, Leist, SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness, Nature, doi:10.1038/s41586-020-2622-0
Craddock, Mahajan, Spikes, Persistent circulation of soluble and extracellular vesicle-linked Spike protein in individuals with postacute sequelae of COVID-19, J Med Virol, doi:10.1002/jmv.28568
Dabbagh, Negahdaripour, Berenjian, Nattokinase: production and application, Appl Microbiol Biotechnol, doi:10.1007/s00253-014-6135-3
Davis, Mccorkell, Vogel, Topol, Long COVID: major findings, mechanisms and recommendations, Nat Rev Microbiol, doi:10.1038/s41579-022-00846-2
De Michele, Amati, Leopizzi, Evidence of SARS-CoV-2 spike protein on retrieved thrombi from COVID-19 patients, J Hematol Oncol, doi:10.1186/s13045-022-01329-w
Debnath, Dewaker, Prabhakar, Bhattacharyya, Mandal, Conformational perturbation of SARS-CoV-2 spike protein using N-acetyl cysteine, a molecular scissor: a probable strategy to combat COVID-19, PREPRINT, doi:10.26434/chemrxiv.12687923.v1
Deore, Tran, Andrews, Ramirez, Galie, SARS-CoV-2 spike protein disrupts blood-brain barrier integrity via RhoA activation, J Neuroimmune Pharmacol, doi:10.1007/s11481-021-10029-0
Dormoy, Perotin, Gosset, Maskos, Polette et al., Nicotinic receptors as SARS-CoV-2 spike co-receptors?, Med Hypotheses, doi:10.1016/j.mehy.2021.110741
Engin, Engin, Engin, Two important controversial risk factors in SARS-CoV-2 infection: obesity and smoking, Environ Toxicol Pharmacol, doi:10.1016/j.etap.2020.103411
Espinoza, Emmady, Histology, monocytes
Finterer, Scorza, A retrospective analysis of clinically confirmed long post-COVID vaccination syndrome, J Clin Transl Res
Fiolet, Opstal, Mosterd, Efficacy and safety of low-dose colchicine in patients with coronary disease: a systematic review and meta-analysis of randomized trials, Eur Heart J, doi:10.1093/eurheartj/ehab115
Fontes-Dantas, Fernandes, Gutman, SARS-CoV-2 Spike protein induces TLR4-mediated long-term cognitive dysfunction recapitulating post-COVID-19 syndrome in mice, Cell Rep, doi:10.1016/j.celrep.2023.112189
Forsyth, Zhang, Bhushan, 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, doi:10.3390/microorganisms10101996
Grobbelaar, Venter, Vlok, SARS-CoV-2 spike protein S1 induces fibrin(ogen) resistant to fibrinolysis: implications for microclot formation in COVID-19, Biosci Rep, doi:10.1042/BSR20210611
Groff, Sun, Ssentongo, Short-term and long-term rates of postacute sequelae of SARS-CoV-2 infection: a systematic review, JAMA Netw Open, doi:10.1001/jamanetworkopen.2021.28568
Hassaniazad, Eftekhar, Inchehsablagh, A triple-blind, placebo-controlled, randomized clinical trial to evaluate the effect of curcumin-containing nanomicelles on cellular immune responses subtypes and clinical outcome in COVID-19 patients, Phytother Res, doi:10.1002/ptr.7294
Hegde, Girisa, Bharathwajchetty, Vishwa, Kunnumakkara, Curcumin formulations for better bioavailability: what we learned from clinical trials thus far?, ACS Omega, doi:10.1021/acsomega.2c07326
Hillary, Ceasar, An update on COVID-19: SARS-CoV-2 variants, antiviral drugs, and vaccines, Heliyon, doi:10.1016/j.heliyon.2023.e13952
Ho, Wu, Chen, Li, Hsiang, Emodin blocks the SARS coronavirus spike protein and angiotensin-converting enzyme 2 interaction, Antiviral Res, doi:10.1016/j.antiviral.2006.04.014
Hulscher, Alexander, Amerling, A systematic review of autopsy findings in deaths after COVID-19 vaccination, PREPRINT, doi:10.5281/zenodo.8120771
Huynh, Rethi, Lee, Higa, Kao et al., Spike protein impairs mitochondrial function in human cardiomyocytes: mechanisms underlying cardiac injury in COVID-19, Cells, doi:10.3390/cells12060877
Karatza, Ismailos, Karalis, Colchicine for the treatment of COVID-19 patients: efficacy, safety, and model informed dosage regimens, Xenobiotica, doi:10.1080/00498254.2021.1909782
Kim, Jeon, Kim, Lee, Kim et al., Spike proteins of SARS-CoV-2 induce pathological changes in molecular delivery and metabolic function in the brain endothelial cells, Viruses, doi:10.3390/v13102021
Kritis, Karampela, Kokoris, Dalamaga, The combination of bromelain and curcumin as an immuneboosting nutraceutical in the prevention of severe COVID-19, Metabol Open, doi:10.1016/j.metop.2020.100066
Kucia, Ratajczak, Bujko, 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, doi:10.1038/s41375-021-01332-z
Kurosawa, Nirengi, Homma, Esaki, Ohta et al., A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles, Sci Rep, doi:10.1038/srep11601
Lotz-Winter, On the pharmacology of bromelain: an update with special regard to animal studies on dosedependent effects, Planta Med, doi:10.1055/s-2006-960949
Maurer, Bromelain: biochemistry, pharmacology and medical use, Cell Mol Life Sci, doi:10.1007/PL00000936
Mayordomo-Colunga, Vivanco-Allende, López-Alonso, López-Martínez, Vega et al., SARS-CoV-2 spike protein in intestinal cells of a patient with coronavirus disease 2019 multisystem inflammatory syndrome, J Pediatr, doi:10.1016/j.jpeds.2021.11.058
Mccullough, Wynn, Procter, Clinical rationale for SARS-CoV-2 base spike protein detoxification in post COVID-19 and vaccine injury syndromes, J Am Physicians Surg
Murae, Shimizu, Yamamoto, The function of SARS-CoV-2 spike protein is impaired by disulfide-bond disruption with mutation at cysteine-488 and by thiol-reactive N-acetyl-cysteine and glutathione, Biochem Biophys Res Commun, doi:10.1016/j.bbrc.2022.01.106
Nag, Banerjee, Paul, Kundu, Curcumin inhibits spike protein of new SARS-CoV-2 variant of concern (VOC) Omicron, an in silico study, Comput Biol Med, doi:10.1016/j.compbiomed.2022.105552
Oba, Rongduo, Saito, Natto extract, a Japanese fermented soybean food, directly inhibits viral infections including SARS-CoV-2 in vitro, Biochem Biophys Res Commun, doi:10.1016/j.bbrc.2021.07.034
Oh, Cho, Barcelon, Kim, Hong et al., SARS-CoV-2 spike protein induces cognitive deficit and anxiety-like behavior in mouse via non-cell autonomous hippocampal neuronal death, Sci Rep, doi:10.1038/s41598-022-09410-7
Omoboyowa, Balogun, Chukwudozie, SARS-CoV-2 spike glycoprotein as inhibitory target for Insilico screening of natural compounds, Biointerface Res Appl Chem, doi:10.33263/BRIAC116.1497414985
Palestra, Poto, Ciardi, SARS-CoV-2 spike protein activates human lung macrophages, Int J Mol Sci, doi:10.3390/ijms24033036
Pandey, Rane, Chatterjee, Kumar, Khan et al., Targeting SARS-CoV-2 spike protein of COVID-19 with naturally occurring phytochemicals: an in silico study for drug development, J Biomol Struct Dyn, doi:10.1080/07391102.2020.1796811
Parry, Lefringhausen, Turni, Neil, Cosford et al., Spikeopathy': COVID-19 spike protein is pathogenic, from both virus and vaccine mRNA, Biomedicines, doi:10.3390/biomedicines11082287
Patel, Kaki, Potluri, Kahar, Khanna, A comprehensive review of SARS-CoV-2 vaccines: Pfizer, Moderna & Johnson & Johnson, Hum Vaccin Immunother, doi:10.1080/21645515.2021.2002083
Patterson, Francisco, Yogendra, 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, doi:10.3389/fimmu.2021.746021
Perico, Morigi, Pezzotta, SARS-CoV-2 spike protein induces lung endothelial cell dysfunction and thrombo-inflammation depending on the C3a/C3a receptor signalling, Sci Rep, doi:10.1038/s41598-023-38382-5
Praditya, Kirchhoff, Brüning, Rachmawati, Steinmann et al., Anti-infective properties of the golden spice curcumin, Front Microbiol, doi:10.3389/fmicb.2019.00912
Rabbani, Parikh, Rafique, Colchicine for the treatment of myocardial injury in patients with coronavirus disease 2019 (COVID-19)-an old drug with new life?, JAMA Netw Open, doi:10.1001/jamanetworkopen.2020.13556
Robles, Zamora, Castro, Siqueiros-Marquez, De La Escalera et al., The spike protein of SARS-CoV-2 induces endothelial inflammation through integrin α5β1 and NF-κB signaling, J Biol Chem, doi:10.1016/j.jbc.2022.101695
Rowan, Buttle, Barrett, The cysteine proteinases of the pineapple plant, Biochem J
Sadeghizadeh, Asadollahi, Jahangiri, Promising clinical outcomes of nano-curcumin treatment as an adjunct therapy in hospitalized COVID-19 patients: a randomized, double-blinded, placebo-controlled trial, Phytother Res, doi:10.1002/ptr.7844
Said, Al-Otaibi, Aljaloud, Al-Anazi, Alsolami et al., The frequency and patterns of post-COVID-19 vaccination syndrome reveal initially mild and potentially Immunocytopenic signs in primarily young Saudi women, Vaccines, doi:10.3390/vaccines10071015
Schroeder, 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, doi:10.3389/fimmu.2022.831763
Sheng, Yang, Wang, Sun, Yan, Microbial nattokinase: from synthesis to potential application, Food Funct, doi:10.1039/d2fo03389e
Shrestha, Venkataraman, The prevalence of post-COVID-19 vaccination syndrome and quality of life among COVID-19-vaccinated individuals, IN PRESS, doi:10.1016/j.vacun.2023.10.002
Sogut, Can, Guven, Safety and efficacy of hydroxychloroquine in 152 outpatients with confirmed COVID-19: a pilot observational study, Am J Emerg Med, doi:10.1016/j.ajem.2020.12.014
Soni, Mehta, Ratre, Curcumin, a traditional spice component, can hold the promise against COVID-19?, Eur J Pharmacol, doi:10.1016/j.ejphar.2020.173551
Speciale, Muscarà, Molonia, Cimino, Saija et al., Silibinin as potential tool against SARS-CoV-2: in silico spike receptor-binding domain and main protease molecular docking analysis, and in vitro endothelial protective effects, Phytother Res, doi:10.1002/ptr.7107
Tanikawa, Kiba, Yu, Degradative effect of nattokinase on spike protein of SARS-CoV-2, Molecules, doi:10.3390/molecules27175405
Tardif, Bouabdallaoui, Allier, Colchicine for community-treated patients with COVID-19 (COLCORONA): a phase 3, randomised, double-blinded, adaptive, placebo-controlled, multicentre trial, Lancet Respir Med, doi:10.1016/S2213-2600(21)00222-8
Tenório, Graciliano, Moura, Oliveira, Goulart, N-acetylcysteine (NAC): impacts on human health, Antioxidants, doi:10.3390/antiox10060967
Theoharides, Could SARS-CoV-2 spike protein be responsible for long-COVID syndrome?, Mol Neurobiol, doi:10.1007/s12035-021-02696-0
Tuli, Sood, Pundir, Molecular docking studies of apigenin, kaempferol, and quercetin as potential target against spike receptor protein of SARS CoV, J Exp Biol Agric Sci, doi:10.18006/2022.10(1).144.149
Turner, Khan, Putrino, Woodcock, Kell et al., Long COVID: pathophysiological factors and abnormalities of coagulation, Trends Endocrinol Metab, doi:10.1016/j.tem.2023.03.002
Vettori, Dima, Henry, Effects of different types of recombinant SARS-CoV-2 spike protein on circulating monocytes' structure, Int J Mol Sci, doi:10.3390/ijms24119373
Wrapp, Wang, Corbett, Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation, Science, doi:10.1126/science.abb2507
Yasmin, Najeeb, Moeed, Safety and efficacy of colchicine in COVID-19 patients: a systematic review and meta-analysis of randomized control trials, PLoS One, doi:10.1371/journal.pone.0266245
Yonker, Swank, Bartsch, Circulating spike protein detected in post-COVID-19 mRNA vaccine myocarditis, Circulation, doi:10.1161/CIRCULATIONAHA.122.061025
Yuan, Pavel, Wang, Hydroxychloroquine blocks SARS-CoV-2 entry into the endocytic pathway in mammalian cell culture, Commun Biol, doi:10.1038/s42003-022-03841-8
Zeng, Li, Deng, SARS-CoV-2 spike spurs intestinal inflammation via VEGF production in enterocytes, EMBO Mol Med, doi:10.15252/emmm.202114844
Zheng, Zhao, Li, SARS-CoV-2 spike protein causes blood coagulation and thrombosis by competitive binding to heparan sulfate, Int J Biol Macromol, doi:10.1016/j.ijbiomac.2021.10.112
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Vaccines and treatments are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
  or use drag and drop