A randomized controlled trial of adjuvant inhalable sodium bicarbonate role in treatment of COVID-19
Mohammad El-Badrawy, Rehab Elmorsey, Mohammed Shehta, Tamer El-Hadidy, Ibrahim Abdelwahab, Adel El-Badrawy, Ahmed Shokeir
doi:10.21203/rs.3.rs-2214180/v1
Entry of coronavirus (SARS-CoV-2) into a host cell is pH dependent. Intracellular alkalinization by sodium bicarbonate (SB) could elevate endosomal pH and block viral entry into the host cells. So, we assessed the role of inhalable SB as an adjuvant treatment for COVID-19 in the study groups of this randomized, controlled trial. Here we show a signi cantly shorter duration to clinical improvement and hospital stay in the study group, while the number of deaths is signi cantly less only in severe grade of the study group. But the time to death is not signi cantly different in both groups. CRP and d-dimer levels are signi cantly lower in the severe cases of the study group. The overall median CT score is signi cantly better in the study group at one & 2 months. Our data thus suggest that inhaled SB (8.4%) could be a possible adjuvant therapy for patients with moderate and severe COVID-19 pneumonia. concluded that SB 8.4% inhalation with its nasal instillation could be a possible adjuvant therapy for patients with non-severe COVID-19 pneumonia [11] . Nevertheless, that study had several shortcomings, being nonrandomized, with limited number of patients and short duration of follow-up. Moreover, that study excluded mild and severe cases of COVID-19 and included moderate cases only identi ed according to CT ndings The current study was designed to avoid the disadvantages of the previous nonrandomized small study and to provide consolidated information regarding the role of inhalable SB as an adjuvant treatment of COVID-19.
Results Between -September 1st, 2021, and April 30, 2022, we recruited 956 patients presented with symptoms suggestive of COVID-19, a total of 546 ful lled the inclusion criteria, completed the study, followed and analyzed as shown in the CONSORT ow chart (Fig. 1 ). The patients were randomly assigned into study group (n = 272) and control group (n = 274). Both groups were comparable in term of demographics, vaccination, co-morbidities, clinical presentation, COVID disease grades, severity of clinical presentation, laboratory parameters, and CT score. The place of treatment was also comparable among patients of both groups (Table1). All cases of both groups completed one week of follow-up. A total of 238 patients of the study and 229 of the control groups completed one month of followup. At 2 months, 234 of the study and 220 of the control groups were available for analysis. Figure 1 shows the causes of dropouts.
Primary Outcomes Primary outcomes are shown in table (2). The overall duration to clinical improvement was signi cantly shorter in the study group. This observation is maintained in all grades of the disease. For patients requiring hospital admission, the overall duration of hospital stay was signi cantly shorter in the study group. This signi cant difference was evident in moderate and severe grades but not in critical cases. The overall frequency of death was not signi cantly different between both groups. No..
Author contributions Mohammad Khairy El-Badrawy, Mohammed Shehta, Tamer Ali El-Hadidy, and Rehab Ahmad Elmorsey Contributed to the treatment of the cases. Mohammad Khairy El-Badrawy, Ahmed A. Shokeir, Tamer Ali El-Hadidy, and Rehab Ahmad Elmorsey prepared the scienti c rational of the study. Adel El-Badrawy, performed and interpreted the CT. Ahmed A. Shokeir, Mohammad Khairy El-Badrawy, Rehab Ahmad Elmorsey, Mohammed Shehta, and Ibrahim El-Said Abdelwahab wrote the rst draft of the manuscript. Ahmed A. Shokeir, and Rehab Ahmad Elmorsey performed the statistical analysis of the study. All authors read and approved the manuscript.
Competing interests The authors declare that they have no con icts of interest with the contents of this article.
Supplementary Files This is a list of supplementary les associated with this preprint. Click to download.
rawdatalfornature.xlsx
References
Abdullah, Myers, Basu, Tintinger, Ueckermann et al., Decreased severity of disease during the rst global omicron variant covid-19 outbreak in a large hospital in tshwane, South Africa, Int J Infect Dis
Aldè, Barozzi, Berardino, Zuccotti, Consonni et al., Prevalence of symptoms in 1512 COVID-19 patients: have dizziness and vertigo been underestimated thus far?, Intern Emerg Med
Badrawy, Elela, Yousef, El-Khier, Abdelgawad et al., Effect of sodium bicarbonate 8.4% on respiratory tract pathogens, Chest and Lung Research
Becher, Goldman, Schacham, Gringauz, Justo, D-dimer and C-reactive Protein Blood Levels Over Time Used to Predict Pulmonary Embolism in Two COVID-19 Patients, Eur J Case Rep Intern Med
Bernheim, Mei, Huang, Yang, Fayad et al., Chest CT Findings in Coronavirus Disease-19 (COVID-19): Relationship to Duration of Infection, Radiology
Bonar, Casey, Plasma membrane Cl-/HCO3-exchangers: structure, mechanism, and physiology, Channels
Dessie, Zewotir, Mortality-related risk factors of COVID-19: a systematic review and meta-analysis of 42 studies and 423,117 patients, BMC Infect Dis
El-Badrawy, Arram, Abdalla, Al-Sagheer, Zahran et al., Effect of adding inhalation of sodium bicarbonate 8.4% to the usual treatment on smear-positive pulmonary tuberculosis: a prospective controlled study, Egypt J Bronchol
El-Badrawy, Saleh, El-Badrawy, El-Hadidy, Abd Ellatif et al., Role of sodium bicarbonate as adjuvant treatment of non-severe computed tomography-identi ed COVID-19 pneumonia: A preliminary report, Indian Journal of Respiratory Care
Favas, Dev, Rn, Neurological manifestations of COVID-19: a systematic review and meta-analysis of proportions, Neurol Sci
Francone, Iafrate, Masci, Coco, Cilia et al., Chest CT score in COVID-19 patients: correlation with disease severity and short-term prognosis, Eur Radiol
Gri N, Brennan-Rieder, Ngo, Kory, Confalonieri et al., The Importance of Understanding the Stages of COVID-19 in Treatment and Trials, AIDS Rev
Han, Fan, Alwalid, Li, Jia et al., Six-month follow-up chest CT ndings after severe COVID-19 pneumonia, Radiology
Hasan, Capstick, Ahmed, Kow, Mazhar et al., Mortality in COVID-19 patients with acute respiratory distress syndrome and corticosteroids use: a systematic review and meta-analysis, Expert Rev Respir med
Hsu, Stone, Worsdell, Busst, Chung, Coughing frequency in patients with persistent cough: assessment using a 24-hour ambulatory recorder, Eur Respir J
Jimenez, Codo, Sampaio, Oliveira, Ferreira et al., Acid pH Increases SARS-CoV-2 Infection and the Risk of Death by COVID-19, Front Med
Lechowicz, Drożdżal, Machaj, Rosik, Szostak et al., COVID-19: the potential treatment of pulmonary brosis associated with SARS-CoV-2 infection, Journal of clinical medicine
Liu, Li, Xu, Prognostic value of interleukin-6, C-reactive protein, and procalcitonin in patients with COVID-19, Journal of Clinical Virology
Liu, Zhang, Pan, The pulmonary sequalae in discharged patients with COVID-19: a short-term observational study, Respir Res
Lubman, Crandall, Regulation of intracellular pH in alveolar epithelial cells, American Journal of Physiology-Lung Cellular and Molecular Physiology
Lubman, Danto, Chao, Fricks, Crandall, Cl (-)-HCO3-exchanger isoform AE2 is restricted to the basolateral surface of alveolar epithelial cell monolayers, American journal of respiratory cell and molecular biology
Menni, Valdes, Polidori, Symptom prevalence, duration, and risk of hospital admission in individuals infected with SARS-CoV-2 during periods of omicron and delta variant dominance: a prospective observational study from the ZOE COVID Study, Lancet
Menéndez, Approaches to the Potential Therapy of COVID-19: A General Overview from the Medicinal Chemistry Perspective, Molecules
Menéndez, Approaches to the Potential Therapy of COVID-19: A General Overview from the Medicinal Chemistry Perspective, Molecules
Mills, Salisbury, The challenges of distributing COVID-19 vaccinations, E Clinical Medicine
Monto, Bayati, Kumar, Francis, Mcpherson, SARS-CoV-2 infects cells after viral entry via clathrin-mediated endocytosis, New England Journal of Medicine
Moratto, Chiarini, Giustini, Serana, Magro et al., Flow cytometry identi es risk factors and dynamic changes in patients with COVID-19, J Clin Immunol
Mwachari, Nduba, Nguti, Park, Sanguli et al., Validation of a new clinical scoring system for acute bronchitis, Int J Tuberc Lung Dis
Nabahati, Ebrahimpour, Khaleghnejad Tabari, Post-COVID-19 pulmonary brosis and its predictive factors: a prospective study, Egypt J Radiol Nucl Med,
doi:10.1186/s43055-021-00632-9
Parasher, COVID-19: Current understanding of its pathophysiology, clinical presentation, and treatment, Postgraduate medical journal
Rezaei, Marjani, Mahmoudi, Mortaz, Mansouri, Dynamic changes of lymphocyte subsets in the course of covid-19, International Archives of Allergy and Immunology
Rohilla, Designing therapeutic strategies to combat severe acute respiratory syndrome coronavirus-2 disease: COVID-19, Drug development research
Sahu, Kampa, Padhi, Panda, C-reactive protein: a promising biomarker for poor prognosis in COVID-19 infection, Clinica Chimica Acta
Samprathi, Jayashree, Biomarkers in COVID-19: an up-to-date review, Frontiers in pediatrics
Sdeghi-Haddad-Zavareh, Bayani, Shokri, Ebrahimpour, Babazadeh et al., C-reactive protein as a prognostic indicator in COVID-19 patients, Interdisciplinary Perspectives on Infectious Diseases
Sharifpour, Rangaraju, Liu, Alabyad, Nahab et al., On behalf of the Emory. COVID-19 Quality & Clinical Research Collaborative. C-Reactive protein as a prognostic indicator in hospitalized patients with COVID-19, PLoS ONE
Sundh, Janson, Lisspers, Stallberg, Montgomery, The Dyspnoea, Obstruction, Smoking, Exacerbation (DOSE) index is predictive of mortality in COPD, Prim Care Respir J
Tang, Bidon, Jaimes, Whittaker, Daniel, Coronavirus membrane fusion mechanism offers a potential target for antiviral development, Antiviral research
Thoracic, ATS/ACCP statement on cardiopulmonary exercise testing, American journal of respiratory and critical care medicine
Wang, Nie, Wang, Zhao, Xiong et al., Characteristics of peripheral lymphocyte subset alteration in COVID-19 pneumonia, J Infect Dis
Wu, Mcgoogan, Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention, Jama
Xu, Dong, An, Lv, Yin et al., Clinical and Computed Tomographic Imaging Features of Novel Coronavirus Pneumonia Caused by SARS-CoV-2, J. Infect
Xu, Shi, Wang, Pathological ndings of COVID-19 associated with acute respiratory distress syndrome, Lancet Respir Med
Xu, Worrell, Li, Barone, Petrovic et al., Chloride/bicarbonate exchanger SLC26A7 is localized in endosomes in medullary collecting duct cells and is targeted to the basolateral membrane in hypertonicity and potassium depletion, Journal of the American Society of Nephrology