Analgesics
Antiandrogens
Antihistamines
Azvudine
Bromhexine
Budesonide
Colchicine
Conv. Plasma
Curcumin
Famotidine
Favipiravir
Fluvoxamine
Hydroxychlor..
Ivermectin
Lifestyle
Melatonin
Metformin
Minerals
Molnupiravir
Monoclonals
Naso/orophar..
Nigella Sativa
Nitazoxanide
Paxlovid
Quercetin
Remdesivir
Thermotherapy
Vitamins
More

Other
Feedback
Home
Top
Abstract
All vitamin D studies
Meta analysis
 
Feedback
Home
next
study
previous
study
c19early.org COVID-19 treatment researchVitamin DVitamin D (more..)
Melatonin Meta
Metformin Meta
Antihistamines Meta
Azvudine Meta Molnupiravir Meta
Bromhexine Meta
Budesonide Meta
Colchicine Meta Nigella Sativa Meta
Conv. Plasma Meta Nitazoxanide Meta
Curcumin Meta Paxlovid Meta
Famotidine Meta Quercetin Meta
Favipiravir Meta Remdesivir Meta
Fluvoxamine Meta Thermotherapy Meta
Hydroxychlor.. Meta
Ivermectin Meta

All Studies   Meta Analysis    Recent:   

Calcitriol Downregulates ACE1/ACE2, Renin and TMPRSS2 Gene Expression in the Human Placenta

Vargas-Castro et al., MDPI AG, doi:10.20944/preprints202311.0402.v1
Nov 2023  
  Post
  Facebook
Share
  Source   PDF   All Studies   Meta AnalysisMeta
Vitamin D for COVID-19
8th treatment shown to reduce risk in October 2020
 
*, now with p < 0.00000000001 from 122 studies, recognized in 9 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,400+ studies for 79 treatments. c19early.org
In Vitro study showing calcitriol downregulated ACE2 and TMPRSS2 (involved in SARS-CoV-2 entry), renin (involved in blood pressure regulation), and ACE1/ACE2 ratio in cultured human placental cells. Authors suggest calcitriol could potentially reduce susceptibility to SARS-CoV-2 infection, mitigate COVID-19 severity through blood pressure modulation, and decrease the ACE1/ACE2 ratio associated with poor COVID-19 outcomes.
21 preclinical studies support the efficacy of vitamin D for COVID-19:
Vitamin D has been identified by the European Food Safety Authority (EFSA) as having sufficient evidence for a causal relationship between intake and optimal immune system function20-23. Vitamin D inhibits SARS-CoV-2 replication in vitro10,17, mitigates lung inflammation, damage, and lethality in mice with an MHV-3 model for β-CoV respiratory infections10,17, reduces SARS-CoV-2 replication in nasal epithelial cells via increased type I interferon expression13, downregulates proinflammatory cytokines IL-1β and TNF-α in SARS-CoV-2 spike protein-stimulated cells9, attenuates nucleocapsid protein-induced hyperinflammation by inactivating the NLRP3 inflammasome through the VDR-BRCC3 signaling pathway14, may be neuroprotective by protecting the blood-brain barrier, reducing neuroinflammation, and via immunomodulatory effects24, minimizes platelet aggregation mediated by SARS-CoV-2 spike protein via inhibiting integrin αIIbβ3 outside-in signaling8, and improves regulatory immune cell levels and control of proinflammatory cytokines in severe COVID-1925. Symptomatic COVID-19 is associated with a lower frequency of natural killer (NK) cells and vitamin D has been shown to improve NK cell activity26,27.
Vargas-Castro et al., 7 Nov 2023, preprint, 6 authors. Contact: lorenza.diazn@incmnsz.mx (corresponding author), lorenza.diazn@incmnsz.mx (corresponding author), rrvvcc14@gmail.com, janice.garciaq@incmnsz.mx, euclides.avilac@incmnsz.mx, fernando.larreag@incmnsz.mx, nut.aolmos@gmail.com.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperVitamin DAll
Calcitriol Downregulates ACE1/ACE2, Renin and TMPRSS2 Gene Expression in the Human Placenta
Rafael Vargas-Castro, Andrea Olmos-Ortiz, Janice García-Quiroz, Euclides Avila, Fernando Larrea, Lorenza Díaz
doi:10.20944/preprints202311.0402.v1
Angiotensin-converting enzyme (ACE)1, ACE2, and renin are components of the renin-angiotensin system (RAS), which regulates blood pressure. ACE2 also serves as a receptor for SARS-CoV-2 and together with the transmembrane serine protease 2 (TMPRSS-2), mediates viral cell-endocytosis. As the placenta expresses all these factors, it acts as a target for SARS-CoV-2 and also as a source of blood pressure modulators. An ACE1/ACE2 ratio imbalance can lead to RAS dysregulation and a bad prognosis in COVID-19 patients. Calcitriol, the vitamin D active metabolite, negatively regulates RAS, reduces inflammation, and enhances antiviral immunity, thereby playing a protective role against COVID-19 severity. Placental calcitriol has been inversely correlated with maternal blood pressure; however, its regulatory role in RAS components and SARS-CoV-2 receptors within the fetomaternal unit has been barely explored. Therefore, we investigated the effects of calcitriol on placental RAS components. Calcitriol downregulated ACE1, ACE2, TMPRSS-2, and renin gene expression in cultured syncytiotrophoblasts and the extravillous trophoblast cell line HTR-8/SVneo. The ACE1/ACE2 ratio was also downregulated by calcitriol. Similar results were obtained in syncytiotrophoblasts treated with calcidiol, the precursor of calcitriol. Altogether, these results support that vitamin D is essential in restricting SARS-CoV-2 placental infection while helping to regulate maternal blood pressure during pregnancy.
Funding: This study was supported by the Annual Acquisition Program from the Departamento de Biología de la Reproducción Dr. Carlos Gual Castro, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, REF 2221 to L.D. The funders had no role in the study design, analysis and interpretation of the data, writing of the manuscript or the decision to submit the article for publication. Institutional Review Board Statement: Not applicable. Informed Consent Statement: Not applicable Conflicts of Interest: The authors declare no conflict of interest.
References
Abate, Kassie, Kassaw, Aragie, Masresha, Sex difference in coronavirus disease (COVID-19): a systematic review and meta-analysis, BMJ Open, doi:10.1136/bmjopen-2020-040129
Alexander, Cockrell, Massey, Bennett, Granger, Tumor necrosis factor-alphainduced hypertension in pregnant rats results in decreased renal neuronal nitric oxide synthase expression, Am J Hypertens, doi:10.1016/s0895-7061(01)02255-5
Aranow, Vitamin D and the immune system, J Investig Med, doi:10.2310/JIM.0b013e31821b8755
Arboleda, Urcuqui-Inchima, Vitamin D Supplementation: A Potential Approach for Coronavirus/COVID-19 Therapeutics?, Front Immunol, doi:10.3389/fimmu.2020.01523
Ashique, Gupta, Gupta, Mishra, Singh et al., Vitamin D-A prominent immunomodulator to prevent COVID-19 infection, Int J Rheum Dis, doi:10.1111/1756-185X.14477
Barrera, Avila, Hernandez, Halhali, Biruete et al., Estradiol and progesterone synthesis in human placenta is stimulated by calcitriol, J Steroid Biochem Mol Biol, doi:10.1016/j.jsbmb.2006.12.097
Barrera, Avila, Hernandez, Mendez, Gonzalez et al., Calcitriol affects hCG gene transcription in cultured human syncytiotrophoblasts, Reprod Biol Endocrinol, doi:10.1186/1477-7827-6-3
Bloise, Zhang, Nakpu, Hamada, Dunk et al., Expression of severe acute respiratory syndrome coronavirus 2 cell entry genes, angiotensinconverting enzyme 2 and transmembrane protease serine 2, in the placenta across gestation and at the maternal-fetal interface in pregnancies complicated by preterm birth or preeclampsia, Am J Obstet Gynecol, doi:10.1016/j.ajog.2020.08.055
Botto, Lonati, Russo, Cazzaniga, Bulbarelli et al., Effects of PM2.5 Exposure on the ACE/ACE2 Pathway: Possible Implication in COVID-19 Pandemic, Int J Environ Res Public Health, doi:10.3390/ijerph20054393
Chen, Neil, Tan, Rudraraju, Mohenska et al., A placental model of SARS-CoV-2 infection reveals ACE2-dependent susceptibility and differentiation impairment in syncytiotrophoblasts, Nat Cell Biol, doi:10.1038/s41556-023-01182-0
Chen, Zheng, Wang, Li, Zhang et al., Regulatory Effect of Vitamin D on Renin Expression at Maternal-Fetal Interface, Sichuan Da Xue Xue Bao Yi Xue Ban, doi:10.12182/20220860107
Colotta, Jansson, Bonelli, Modulation of inflammatory and immune responses by vitamin D, J Autoimmun, doi:10.1016/j.jaut.2017.07.007
Diaz, Noyola-Martinez, Barrera, Hernandez, Avila et al., Calcitriol inhibits TNF-alpha-induced inflammatory cytokines in human trophoblasts, J Reprod Immunol, doi:10.1016/j.jri.2009.02.005
Diaz, Sanchez, Avila, Halhali, Vilchis et al., Identification of a 25-hydroxyvitamin D3 1alpha-hydroxylase gene transcription product in cultures of human syncytiotrophoblast cells, J Clin Endocrinol Metab, doi:10.1210/jcem.85.7.6693
Forman, Scott, Ng, Drake, Suarez et al., Effect of vitamin D supplementation on blood pressure in blacks, Hypertension, doi:10.1161/HYPERTENSIONAHA.111.00659
Gilani, Bin-Jumah, Nadeem, Kazmi, Vitamin D attenuates COVID-19 complications via modulation of proinflammatory cytokines, antiviral proteins, and autophagy, Expert Rev Anti Infect Ther, doi:10.1080/14787210.2021.1941871
Glinsky, Tripartite Combination of Candidate Pandemic Mitigation Agents: Vitamin D, Quercetin, and Estradiol Manifest Properties of Medicinal Agents for Targeted Mitigation of the COVID-19 Pandemic Defined by Genomics-Guided Tracing of SARS-CoV-2 Targets in Human Cells, Biomedicines, doi:10.3390/biomedicines8050129
Gomez, Albaiceta, Garcia-Clemente, Lopez-Larrea, Amado-Rodriguez et al., Angiotensin-converting enzymes (ACE, ACE2) gene variants and COVID-19 outcome, Gene, doi:10.1016/j.gene.2020.145102
Granger, Alexander, Bennett, Khalil, Pathophysiology of pregnancy-induced hypertension, Am J Hypertens, doi:10.1016/s0895-7061(01)02086-6
Grover, Brandt, Reddy, Ananth, Chronic hypertension, perinatal mortality and the impact of preterm delivery: a population-based study, BJOG, doi:10.1111/1471-0528.16932
Hoffmann, Kleine-Weber, Schroeder, Kruger, Herrler et al., SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor, Cell, doi:10.1016/j.cell.2020.02.052
Hosier, Farhadian, Morotti, Deshmukh, Lu-Culligan et al., SARS-CoV-2 infection of the placenta, J Clin Invest, doi:10.1172/JCI139569
Iwata-Yoshikawa, Okamura, Shimizu, Hasegawa, Takeda et al., TMPRSS2 Contributes to Virus Spread and Immunopathology in the Airways of Murine Models after Coronavirus Infection, J Virol, doi:10.1128/JVI.01815-18
Jackson, Farzan, Chen, Choe, Mechanisms of SARS-CoV-2 entry into cells, Nat Rev Mol Cell Biol, doi:10.1038/s41580-021-00418-x
Kliman, Nestler, Sermasi, Sanger, Strauss, 3rd. Purification, characterization, and in vitro differentiation of cytotrophoblasts from human term placentae, Endocrinology
Kristal-Boneh, Froom, Harari, Ribak, Association of calcitriol and blood pressure in normotensive men, Hypertension, doi:10.1161/01.hyp.30.5.1289
Lai, Chang, Yang, Lin, Lai et al., The role of micronutrient and immunomodulation effect in the vaccine era of COVID-19, J Chin Med Assoc, doi:10.1097/JCMA.0000000000000587
Li, Kong, Wei, Chen, Liu et al., 1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system, J Clin Invest, doi:10.1172/JCI15219
Li, Qiao, Uskokovic, Xiang, Zheng et al., Vitamin D: a negative endocrine regulator of the renin-angiotensin system and blood pressure, J Steroid Biochem Mol Biol, doi:10.1016/j.jsbmb.2004.03.004
Li, Vitamin D regulation of the renin-angiotensin system, J Cell Biochem, doi:10.1002/jcb.10343
Lin, Ferguson, White, Wang, Vessella et al., Prostate-localized and androgen-regulated expression of the membrane-bound serine protease TMPRSS2, Cancer Res
Lind, Hanni, Lithell, Hvarfner, Sorensen et al., Vitamin D is related to blood pressure and other cardiovascular risk factors in middle-aged men, Am J Hypertens, doi:10.1016/0895-7061(95)00154-H
Lind, Lithell, Skarfors, Wide, Ljunghall, Reduction of blood pressure by treatment with alphacalcidol. A double-blind, placebo-controlled study in subjects with impaired glucose tolerance, Acta Med Scand
Lind, Wengle, Wide, Ljunghall, Reduction of blood pressure during long-term treatment with active vitamin D (alphacalcidol) is dependent on plasma renin activity and calcium status. A double-blind, placebo-controlled study, Am J Hypertens, doi:10.1093/ajh/2.1.20
Liu, Kaplan, Lagishetty, Ouyang, Ouyang et al., Vitamin D and the regulation of placental inflammation, J Immunol, doi:10.4049/jimmunol.1003332
Liu, Kaplan, Low, Nguyen, Liu et al., Vitamin D induces innate antibacterial responses in human trophoblasts via an intracrine pathway, Biol Reprod, doi:10.1095/biolreprod.108.073577
Lye, Dunk, Zhang, Wei, Nakpu et al., ACE2 Is Expressed in Immune Cells That Infiltrate the Placenta in Infection-Associated Preterm Birth, Cells, doi:10.3390/cells10071724
Ma, Gu, Zhao, Sun, Groome et al., Expressions of vitamin D metabolic components VDBP, CYP2R1, CYP27B1, CYP24A1, and VDR in placentas from normal and preeclamptic pregnancies, Am J Physiol Endocrinol Metab, doi:10.1152/ajpendo.00279.2012
Marques, Pringle, Conquest, Hirst, Markus et al., Molecular characterization of renin-angiotensin system components in human intrauterine tissues and fetal membranes from vaginal delivery and cesarean section, Placenta, doi:10.1016/j.placenta.2010.12.006
Molina, Tsai, Dai, Soto, Rosenthal et al., Comparison of Pregnancy and Birth Outcomes Before vs During the COVID-19 Pandemic, JAMA Netw Open, doi:10.1001/jamanetworkopen.2022.26531
Moukayed, A Narrative Review on the Potential Role of Vitamin D(3) in the Prevention, Protection, and Disease Mitigation of Acute and Long COVID-19, Curr Nutr Rep, doi:10.1007/s13668-023-00471-2
Olmos-Ortiz, Garcia-Quiroz, Avila, Caldino-Soto, Halhali et al., Lipopolysaccharide and cAMP modify placental calcitriol biosynthesis reducing antimicrobial peptides gene expression, Am J Reprod Immunol, doi:10.1111/aji.12841
Olmos-Ortiz, Olivares-Huerta, Garcia-Quiroz, Avila, Halhali et al., Cord Serum Calcitriol Inversely Correlates with Maternal Blood Pressure in Urinary Tract Infection-Affected Pregnancies: Sex-Dependent Immune Implications, Nutrients, doi:10.3390/nu13093114
Pagliaro, Penna, ACE/ACE2 Ratio: A Key Also in 2019 Coronavirus Disease (Covid-19)?, Front Med, doi:10.3389/fmed.2020.00335
Patane, Morotti, Giunta, Sigismondi, Piccoli et al., Vertical transmission of coronavirus disease 2019: severe acute respiratory syndrome coronavirus 2 RNA on the fetal side of the placenta in pregnancies with coronavirus disease 2019-positive mothers and neonates at birth, Am J Obstet Gynecol MFM, doi:10.1016/j.ajogmf.2020.100145
Pfeifer, Begerow, Minne, Nachtigall, Hansen, Effects of a short-term vitamin D(3) and calcium supplementation on blood pressure and parathyroid hormone levels in elderly women, J Clin Endocrinol Metab, doi:10.1210/jcem.86.4.7393
Pringle, Tadros, Callister, Lumbers, The expression and localization of the human placental prorenin/renin-angiotensin system throughout pregnancy: roles in trophoblast invasion and angiogenesis?, Placenta, doi:10.1016/j.placenta.2011.09.020
Qayyum, Mohammad, Slominski, Hassan, Tuckey et al., Vitamin D and lumisterol novel metabolites can inhibit SARS-CoV-2 replication machinery enzymes, Am J Physiol Endocrinol Metab, doi:10.1152/ajpendo.00174.2021
Qayyum, Slominski, Raman, Slominski, Novel CYP11A1-Derived Vitamin D and Lumisterol Biometabolites for the Management of COVID-19, Nutrients, doi:10.3390/nu14224779
Ruan, Ye, Yuan, Li, Zhang et al., Human early syncytiotrophoblasts are highly susceptible to SARS-CoV-2 infection, Cell Rep Med, doi:10.1016/j.xcrm.2022.100849
Rysz, Al-Saadi, Sjostrom, Farm, Campoccia Jalde et al., COVID-19 pathophysiology may be driven by an imbalance in the reninangiotensin-aldosterone system, Nat Commun, doi:10.1038/s41467-021-22713-z
Schwartz, Baldewijns, Benachi, Bugatti, Collins et al., Chronic Histiocytic Intervillositis With Trophoblast Necrosis Is a Risk Factor Associated With Placental Infection From Coronavirus Disease 2019 (COVID-19) and Intrauterine Maternal-Fetal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Transmission in Live-Born and Stillborn Infants, Arch Pathol Lab Med, doi:10.5858/arpa.2020-0771-SA
Shen, Mao, Wu, Tanaka, Zhang, TMPRSS2: A potential target for treatment of influenza virus and coronavirus infections, Biochimie, doi:10.1016/j.biochi.2017.07.016
Shoemark, Colenso, Toelzer, Gupta, Sessions et al., Molecular Simulations suggest Vitamins, Retinoids and Steroids as Ligands of the Free Fatty Acid Pocket of the SARS-CoV-2 Spike Protein*, Angew Chem Int Ed Engl, doi:10.1002/anie.202015639
Shook, Bordt, Meinsohn, Pepin, De Guzman et al., Placental Expression of ACE2 and TMPRSS2 in Maternal Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Are Placental Defenses Mediated by Fetal Sex?, J Infect Dis
Siblini, Kulkarni, Aslam, Coronavirus Disease 2019 (COVID-19) and Hypertensive Disorders of Pregnancy: Is the Placenta the Problem?, doi:10.17632/8tbym9x6md.1
Song, Qayyum, Greer, Slominski, Raman et al., Vitamin D3 and its hydroxyderivatives as promising drugs against COVID-19: a computational study, J Biomol Struct Dyn, doi:10.1080/07391102.2021.1964601
Sriram, Insel, A hypothesis for pathobiology and treatment of COVID-19: The centrality of ACE1/ACE2 imbalance, Br J Pharmacol, doi:10.1111/bph.15082
Stephanou, Ross, Handwerger, Regulation of human placental lactogen expression by 1,25-dihydroxyvitamin D3, Endocrinology, doi:10.1210/endo.135.6.7988455
Taglauer, Benarroch, Rop, Barnett, Sabharwal et al., Consistent localization of SARS-CoV-2 spike glycoprotein and ACE2 over TMPRSS2 predominance in placental villi of 15 COVID-19 positive maternal-fetal dyads, Placenta, doi:10.1016/j.placenta.2020.08.015
Takimoto, Ishida, Sugiyama, Horiguchi, Murakami et al., Hypertension induced in pregnant mice by placental renin and maternal angiotensinogen, Science, doi:10.1126/science.274.5289.995
Tamanna, Lumbers, Morosin, Delforce, Pringle, ACE2: a key modulator of the reninangiotensin system and pregnancy, Am J Physiol Regul Integr Comp Physiol, doi:10.1152/ajpregu.00211.2021
Valdespino-Vazquez, Helguera-Repetto, Leon-Juarez, Villavicencio-Carrisoza, Flores-Pliego et al., Fetal and placental infection with SARS-CoV-2 in early pregnancy, J Med Virol, doi:10.1002/jmv.26965
Vanegas-Cedillo, Bello-Chavolla, Ramirez-Pedraza, Rodriguez Encinas, Perez Carrion et al., Serum Vitamin D Levels Are Associated With Increased COVID-19 Severity and Mortality Independent of Whole-Body and Visceral Adiposity, Front Nutr, doi:10.3389/fnut.2022.813485
Zhang, Dong, Liu, Gao, Risk and Protective Factors for COVID-19 Morbidity, Severity, and Mortality, Clin Rev Allergy Immunol, doi:10.1007/s12016-022-08921-5
{ 'indexed': {'date-parts': [[2023, 11, 8]], 'date-time': '2023-11-08T05:19:43Z', 'timestamp': 1699420783379}, 'posted': {'date-parts': [[2023, 11, 7]]}, 'group-title': 'Biology and Life Sciences', 'reference-count': 0, 'publisher': 'MDPI AG', 'license': [ { 'start': { 'date-parts': [[2023, 11, 7]], 'date-time': '2023-11-07T00:00:00Z', 'timestamp': 1699315200000}, 'content-version': 'unspecified', 'delay-in-days': 0, 'URL': 'http://creativecommons.org/licenses/by/4.0'}], 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'accepted': {'date-parts': [[2023, 11, 6]]}, 'abstract': '<jats:p>Angiotensin-converting enzyme (ACE)1, ACE2, and renin are components of the ' 'renin-angiotensin system (RAS), which regulates blood pressure. ACE2 also serves as a ' 'receptor for SARS-CoV-2 and together with the transmembrane serine protease 2 (TMPRSS-2), ' 'mediates viral cell-endocytosis. As the placenta expresses all these factors, it acts as a ' 'target for SARS-CoV-2 and also as a source of blood pressure modulators. An ACE1/ACE2 ratio ' 'imbalance can lead to RAS dysregulation and a bad prognosis in COVID-19 patients. Calcitriol, ' 'the vitamin D active metabolite, negatively regulates RAS, reduces inflammation, and enhances ' 'antiviral immunity, thereby playing a protective role against COVID-19 severity. Placental ' 'calcitriol has been inversely correlated with maternal blood pressure; however, its ' 'regulatory role in RAS components and SARS-CoV-2 receptors within the fetomaternal unit has ' 'been barely explored. Therefore, we investigated the effects of calcitriol on placental RAS ' 'components. Calcitriol downregulated ACE1, ACE2, TMPRSS-2, and renin gene expression in ' 'cultured syncytiotrophoblasts and the extravillous trophoblast cell line HTR-8/SVneo. The ' 'ACE1/ACE2 ratio was also downregulated by calcitriol. Similar results were obtained in ' 'syncytiotrophoblasts treated with calcidiol, the precursor of calcitriol. Altogether, these ' 'results support that vitamin D is essential in restricting SARS-CoV-2 placental infection ' 'while helping to regulate maternal blood pressure during pregnancy.</jats:p>', 'DOI': '10.20944/preprints202311.0402.v1', 'type': 'posted-content', 'created': {'date-parts': [[2023, 11, 8]], 'date-time': '2023-11-08T02:29:41Z', 'timestamp': 1699410581000}, 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Calcitriol Downregulates ACE1/ACE2, Renin and TMPRSS2 Gene Expression in the Human Placenta', 'prefix': '10.20944', 'author': [ { 'ORCID': 'http://orcid.org/0000-0002-3209-1184', 'authenticated-orcid': False, 'given': 'Rafael', 'family': 'Vargas-Castro', 'sequence': 'first', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-5456-9695', 'authenticated-orcid': False, 'given': 'Andrea', 'family': 'Olmos-Ortiz', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-3311-2258', 'authenticated-orcid': False, 'given': 'Janice', 'family': 'García-Quiroz', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0003-3063-5093', 'authenticated-orcid': False, 'given': 'Euclides', 'family': 'Avila', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0003-4431-969X', 'authenticated-orcid': False, 'given': 'Fernando', 'family': 'Larrea', 'sequence': 'additional', 'affiliation': []}, {'given': 'Lorenza', 'family': 'Díaz', 'sequence': 'additional', 'affiliation': []}], 'member': '1968', 'container-title': [], 'original-title': [], 'deposited': { 'date-parts': [[2023, 11, 8]], 'date-time': '2023-11-08T02:33:11Z', 'timestamp': 1699410791000}, 'score': 1, 'resource': {'primary': {'URL': 'https://www.preprints.org/manuscript/202311.0402/v1'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2023, 11, 7]]}, 'references-count': 0, 'URL': 'http://dx.doi.org/10.20944/preprints202311.0402.v1', 'relation': {}, 'published': {'date-parts': [[2023, 11, 7]]}, 'subtype': 'preprint'}
Loading..
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. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment 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   
Submit