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All Studies   Meta Analysis       

Mitigating the risks of post-acute sequelae of SARS-CoV-2 infection (PASC) with intranasal chlorpheniramine: perspectives from the ACCROS studies

Valerio-Pascua et al., BMC Infectious Diseases, doi:10.1186/s12879-024-10211-8, ACCROS
Nov 2024  
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PASC score 90% Improvement Relative Risk PASC, affecting daily funct.. 98% PASC, medical attention 99% PASC, fatigue 97% PASC, headaches 98% PASC, joint/muscle pain 87% PASC, difficulty concentrat.. 98% PASC, loss of taste/smell 94% Chlorpheniramine for COVID-19  ACCROS  EARLY TREATMENT Is early treatment with chlorpheniramine beneficial for COVID-19? Prospective study of 259 patients in Honduras (Dec 2021 - Mar 2022) Lower PASC with chlorpheniramine (p=0.001) c19early.org Valerio-Pascua et al., BMC Infectious .., Nov 2024 Favorschlorpheniramine Favorscontrol 0 0.5 1 1.5 2+
10th treatment shown to reduce risk in December 2020, now with p = 0.00006 from 15 studies.
Lower risk for mortality, recovery, and cases.
No treatment is 100% effective. Protocols combine treatments.
5,100+ studies for 112 treatments. c19early.org
Prospective study of 259 COVID-19 outpatients from the ACROSS-I and ACROSS-III RCTs showing significantly lower long COVID with intranasal chlorpheniramine (iCPM) compared to placebo. 72% of placebo patients experienced at least one PASC symptom compared to 0.7% with iCPM (p<0.001). Treated patients had significantly lower rates of fatigue, headaches, difficulty concentrating, and impaired daily functioning.
4 studies use direct respiratory tract administration1-4
Targeted administration to the respiratory tract provides treatment directly to the typical source of initial SARS-CoV-2 infection and replication, and allows for rapid onset of action, higher local drug concentration, and reduced systemic side effects.
Study covers antihistamine H1RAs and chlorpheniramine.
relative PASC score, 90.4% better, RR 0.10, p < 0.001, treatment 139, control 120, relative average composite PASC score.
risk of PASC, 97.7% lower, RR 0.02, p < 0.001, treatment 1 of 139 (0.7%), control 38 of 120 (31.7%), NNT 3.2, affecting daily function.
risk of PASC, 99.0% lower, RR 0.010, p < 0.001, treatment 0 of 139 (0.0%), control 48 of 120 (40.0%), NNT 2.5, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), medical attention.
risk of PASC, 97.3% lower, RR 0.03, p < 0.001, treatment 0 of 139 (0.0%), control 17 of 120 (14.2%), NNT 7.1, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), fatigue.
risk of PASC, 97.7% lower, RR 0.02, p < 0.001, treatment 1 of 139 (0.7%), control 37 of 120 (30.8%), NNT 3.3, headaches.
risk of PASC, 86.6% lower, RR 0.13, p = 0.10, treatment 0 of 139 (0.0%), control 3 of 120 (2.5%), NNT 40, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), joint/muscle pain.
risk of PASC, 97.9% lower, RR 0.02, p < 0.001, treatment 0 of 139 (0.0%), control 22 of 120 (18.3%), NNT 5.5, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), difficulty concentrating.
risk of PASC, 93.8% lower, RR 0.06, p = 0.004, treatment 0 of 139 (0.0%), control 7 of 120 (5.8%), NNT 17, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), loss of taste/smell.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Valerio-Pascua et al., 26 Nov 2024, prospective, Honduras, peer-reviewed, mean age 46.0, 14 authors, study period December 2021 - March 2022, ACCROS trial. Contact: rahaghf@ccf.org.
This PaperH1RAsAll
Mitigating the risks of post-acute sequelae of SARS-CoV-2 infection (PASC) with intranasal chlorpheniramine: perspectives from the ACCROS studies
Fernando Valerio-Pascua, Fernando Baires, Anupamjeet Kaur Sekhon, Mari L Tesch, Estela Jackeline Pineda, Syed A A Rizvi, Jarmanjeet Singh, David Abraham Cortes-Bandy, Amy C Madril, Jana Radwanski, Anita S Lewis, Miguel Sierra-Hoffman, Mark L Stevens, Franck F Rahaghi
BMC Infectious Diseases, doi:10.1186/s12879-024-10211-8
Background The World Health Organization (WHO) declared the end of the COVID-19 (SARS-CoV-2) global public health emergency on May 5, 2023, but its long-term consequences have still been haunting the global population. Post-acute sequelae of COVID-19 (PASC) and long-term COVID-19 are serious concerns and present with various symptoms. Intranasal chlorpheniramine (iCPM) has been shown to decrease the viral burden of SARS-COV-2. iCPM uses decreased COVID-19 disease progression and severity in Accelerating COVID-19 Clinical Recovery in an Outpatient Setting (ACROSS)-I & III randomized control trials (RCT). Methods This prospective survey study included 259 participants in ACROSS I and III RCTs. We compared the effect of iCPM versus placebo on the reduction of PASC symptoms. A PASC questionnaire containing 17 questions regarding the most common PASC symptoms was used in this study. T-test and Pearson chi-square statistics were performed according to continuous and categorical data using STATA 17.0 Basic Edition software. Findings The iCPM cohort had a lower proportion of patients with fatigue or tiredness vs. placebo (0 Vs 17, 21, p < 0.001). iCPM cohort had a lower proportion of patients with difficulty concentrating or mental confusion (0 vs. 22, 27, p < 0.001). iCPM cohort had also a lower number of patients with difficulty in the ability to perform daily activities or work vs. placebo (1 Vs 38, 48, p < 0.001). A smaller number of patients in the iCPM cohort sought medical attention for PACS symptoms compared to placebo (0 vs. 48, 68, p < 0.001). Interpretation The use of intranasal chlorpheniramine shows promise in preventing COVID-19 progression to the often-debilitating post-COVID-19 syndrome PASC. The association between iCPM use and a lower prevalence of PASC symptoms is strong. Further studies are needed to establish the role of ICPM in preventing PASC.
Declarations Ethics approval and consent to participate This study was approved by the Institutional Review Board (IRB) of the Ethics Committee of Investigation of Infectious and Zoonotic Disease at the Universidad Nacional Autónoma de Honduras. Written informed consent was obtained from all participants prior to their involvement in the study. In cases where verbal consent was required (e.g., remote participation), this consent was documented and witnessed by study personnel. No waivers of consent were requested or provided by the ethics committee, and no minors were included in the study. Consent for publication Competing interests The authors declare no competing interests. Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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' 'bioRxiv. 2021. https://doi.org/10.1101/2021.05.31.21255594', 'DOI': '10.1101/2021.05.31.21255594'}, { 'key': '10211_CR24', 'doi-asserted-by': 'publisher', 'DOI': '10.1101/2023.08.28.554806', 'author': 'YAMM Elshaier', 'year': '2023', 'unstructured': 'Elshaier YAMM, Mostafa A, Valerio-Pascua F, Tesch ML, Costin JM, Rahaghi ' 'FF. Chlorpheniramine maleate displays multiple modes of antiviral action ' 'against SARS-CoV-2: a mechanistic study. bioRxiv. 2023. ' 'https://doi.org/10.1101/2023.08.28.554806.', 'journal-title': 'bioRxiv'}, { 'issue': '1', 'key': '10211_CR25', 'doi-asserted-by': 'publisher', 'first-page': 'e20980', 'DOI': '10.7759/cureus.20980', 'volume': '14', 'author': 'SD Black', 'year': '2022', 'unstructured': 'Black SD. Molecular modeling and preliminary Clinical Data suggesting ' 'antiviral activity for chlorpheniramine (chlorphenamine) against ' 'COVID-19. Cureus. 2022;14(1):e20980. ' 'https://doi.org/10.7759/cureus.20980. PMID: 35154957; PMCID: PMC8820487.', 'journal-title': 'Cureus'}, { 'issue': '2', 'key': '10211_CR26', 'doi-asserted-by': 'publisher', 'first-page': '43', 'DOI': '10.1691/pharmazie.2021.2', 'volume': '76', 'author': 'SA Kumar', 'year': '2021', 'unstructured': 'Kumar SA, Cheng W. A hypothesis: bitter taste receptors as a therapeutic ' 'target for the clinical symptoms of SARS-CoV-2. Pharmazie. ' '2021;76(2):43–54. https://doi.org/10.1691/pharmazie.2021.2.', 'journal-title': 'Pharmazie'}, { 'issue': '2', 'key': '10211_CR27', 'doi-asserted-by': 'publisher', 'first-page': '131', 'DOI': '10.2500/105065898781390271', 'volume': '12', 'author': 'S-Y Fang', 'year': '1998', 'unstructured': 'Fang S-Y, Druce HM, Baraniuk JN. Anticholinergic properties of ' 'brompheniramine, chlorpheniramine, and atropine in human nasal mucosa in ' 'vitro. Am J Rhinol. 1998;12(2):131–4. ' 'https://doi.org/10.2500/105065898781390271.', 'journal-title': 'Am J Rhinol'}, { 'issue': '1', 'key': '10211_CR28', 'doi-asserted-by': 'publisher', 'first-page': '67', 'DOI': '10.1007/s00011-020-01422-1', 'volume': '70', 'author': 'M Ennis', 'year': '2021', 'unstructured': 'Ennis M, Tiligada K. Histamine receptors and COVID-19. Inflamm Res. ' '2021;70(1):67–75. https://doi.org/10.1007/s00011-020-01422-1.', 'journal-title': 'Inflamm Res'}, { 'key': '10211_CR29', 'doi-asserted-by': 'publisher', 'first-page': '275', 'DOI': '10.35248/2161-1459.21.10.275', 'volume': '10', 'author': 'J Torres', 'year': '2021', 'unstructured': 'Torres J, Go CC, Chohan F, Genesis Camacho L, Sanchez-Gonzalez MA, ' 'Ferrer G. Chlorpheniramine maleate nasal spray in COVID-19Patients: Case ' 'Series. J Clin Exp Pharmacol. 2021;10:275. ' 'https://doi.org/10.35248/2161-1459.21.10.275.', 'journal-title': 'J Clin Exp Pharmacol'}, { 'key': '10211_CR30', 'doi-asserted-by': 'publisher', 'unstructured': 'Wang Y, Zhao D, Xiao W, Shi J, Chen W, Jia Q, et al. Paxlovid reduces ' 'the risk of long COVID in patients six months after hospital discharge. ' 'J Med Virol. 2023;95(8). https://doi.org/10.1002/jmv.29014.', 'DOI': '10.1002/jmv.29014'}, { 'issue': '11', 'key': '10211_CR31', 'doi-asserted-by': 'publisher', 'first-page': '1486', 'DOI': '10.7326/M23-1394', 'volume': '176', 'author': 'GN Ioannou', 'year': '2023', 'unstructured': 'Ioannou GN, Berry K, Rajeevan N, Li Y, Mutalik P, Yan L, et al. ' 'Effectiveness of nirmatrelvir-ritonavir against the development of ' 'post-COVID-19 conditions among U.S. veterans: a target trial emulation. ' 'Ann Intern Med. 2023;176(11):1486–97. https://doi.org/10.7326/M23-1394.', 'journal-title': 'Ann Intern Med'}], 'container-title': 'BMC Infectious Diseases', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://link.springer.com/content/pdf/10.1186/s12879-024-10211-8.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/article/10.1186/s12879-024-10211-8/fulltext.html', 'content-type': 'text/html', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/content/pdf/10.1186/s12879-024-10211-8.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2024, 11, 26]], 'date-time': '2024-11-26T16:19:07Z', 'timestamp': 1732637947000}, 'score': 1, 'resource': { 'primary': { 'URL': 'https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-024-10211-8'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2024, 11, 26]]}, 'references-count': 31, 'journal-issue': {'issue': '1', 'published-online': {'date-parts': [[2024, 12]]}}, 'alternative-id': ['10211'], 'URL': 'http://dx.doi.org/10.1186/s12879-024-10211-8', 'relation': {}, 'ISSN': ['1471-2334'], 'subject': [], 'container-title-short': 'BMC Infect Dis', 'published': {'date-parts': [[2024, 11, 26]]}, 'assertion': [ { 'value': '4 January 2024', 'order': 1, 'name': 'received', 'label': 'Received', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '12 November 2024', 'order': 2, 'name': 'accepted', 'label': 'Accepted', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '26 November 2024', 'order': 3, 'name': 'first_online', 'label': 'First Online', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, {'order': 1, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Declarations'}}, { 'value': 'This study was approved by the Institutional Review Board (IRB) of the Ethics ' 'Committee of Investigation of Infectious and Zoonotic Disease at the ' 'Universidad Nacional Autónoma de Honduras. Written informed consent was ' 'obtained from all participants prior to their involvement in the study. In ' 'cases where verbal consent was required (e.g., remote participation), this ' 'consent was documented and witnessed by study personnel. No waivers of consent ' 'were requested or provided by the ethics committee, and no minors were included ' 'in the study.', 'order': 2, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Ethics approval and consent to participate'}}, { 'value': 'N/A-Not Applicable.', 'order': 3, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Consent for publication'}}, { 'value': 'The authors declare no competing interests.', 'order': 4, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Competing interests'}}], 'article-number': '1348'}
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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.
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