Simple and Economical Multifunctional Therapeutic Swab Device System for Treating Upper Respiratory Infections, Including COVID-19, on a Mass-Scale

Thursday, March 24, 2022

Subhash Dhawan, Retired Senior FDA Research & Regulatory Scientist, Gaithersburg, MD

The work described in this article is U.S. and PCT Patent Pending 

New tools are urgently needed to control the current out-of-control COVID-19 pandemic which can be further complicated by annually emerging influenza infections, especially in the winter months. This article offers a simple and economical Therapeutic Swab Device System comprising multifunctional drugs for their direct application to nasal cavity, oral cavity, nasopharynx and posterior pharynx that are the primary sites of upper respiratory infection, including SARS- CoV-2. This system can be used on a mass-scale to retard disease progression, minimize the spread of infection to others, and help control the COVID-19 pandemic. 

infections caused by upper respiratory pathogens, including influenza, respiratory syncytial virus, and, especially, the most concerning novel class of COVID-19-causing novel coronavirus SARS-CoV-2 and its mutant variant strains are responsible for a large number of hospitalizations and deaths every year and present a significant threat to human health.1-3 These pathogens are readily transmissible in close proximity and trigger serious respiratory illnesses resulting in major health complications. As of February 15, 2022, according to the World Health Organization, COVID-19 has infected nearly 412 million individuals worldwide claiming more than 5.8 million lives with 77 million infections and in excess of 912,000 deaths in the United States (World Health Organization Dashboard: February 15, 2022). These numbers are increasing daily at an alarming rate. Traveling across the country and around the world is of immense global public health concern for the spread of this deadly disease. 

Rapid mutational changes in SARS-CoV-2 resulting in new highly contagious and more deadly variants have worsened the pandemic, posing difficult challenges to effective treatment.4-6 Although vaccines are reportedly effective in reducing the severity of COVID-19 illnesses, hospitalizations, and deaths, none is yet known to prevent new infections or reinfections of the fully vaccinated or boosted individuals against rapidly emerging highly contagious and more deadly mutant viral variants. In addition, children, the older population, and individuals with underlying health conditions, all are at a significantly higher risk of acquiring the infection, developing hyperinflammatory syndrome, and other severe health consequences.7-10 

Among enormously growing general concerns are: (a) rapid increase of SARS-CoV-2 variants with reduced capacity of neutralization by the antibodies, in addition to their increased transmissibility and pathogenicity4,5,11,12 and (b) global surge of COVID-19-positive cases, hospitalizations, and deaths. These serious issues constitute the highest priority for the safety of global public health, and are being taken into account for the development of effective vaccines and therapeutic drugs. However, options for treating COVID-19 patients are limited and require hospitalizations. Therefore, the dire COVID-19 pandemic situation calls for an urgent need for safe and effective therapeutics along with convenient, preferably self-administering approaches, to treat the infected individuals at early asymptomatic and symptomatic stage of infection. It is critical for our own safety and also for minimizing the spread of the disease to others. 

Systemic administration of drugs either orally, by injections, or via other routes is not without the risk of causing adverse effects, sometimes serious in nature. For example, intravenous administration of remdesivir and recently authorized oral drugs Paxlovid (nirmatrelvir and ritonavir tablets co-packaged for oral use) and Molnupiravir (a prodrug of the synthetic nucleoside derivative N4-hydroxycytidine)  are shown to significantly reduce the severity of COVID-19 and COVID- 19-related deaths. However, some of the side effects of these drugs due to systemic absorption may limit their prescription particularly to children, older high-risk, and immunocompromised population. Therefore, it is time for us now to find alternative safe, effective,  creative and economic therapeutic ways to retard the spread of SARS- CoV-2 infections, and yet with low or no toxicity. 

Respiratory pathogens are known to primarily target the lung.13 These pathogens enter through the nasal or oral cavity. Therefore, it is desirable to target the nasal cavity, oral cavity, nasopharynx, and posterior pharynx where the primary infections occur to provide rapid and robust protection. Since one single drug may generally not exhibit multiple antiviral and host defense functions effective enough against upper respiratory viral infections, this article presents a multifunctional Therapeutic Swab Device System approach comprising plurality of drugs possessing various crucial cellular protective functions (e.g., antiviral, cytoprotective, anti-inflammatory, and anticoagulant) intended to specifically target the primary sites of upper respiratory infections. Accordingly, this article proposes selection of plurality of drugs possessing: (a) antiviral activity to inhibit viral replication; (b) anti-inflammatory activity to reduce inflammation associated with viral infections; (c) cytoprotective function to prevent virus-induced cell death; and (d) anticoagulant activity to reduce blood clot formation – all for the infection-site-directed delivery – using a Therapeutic Swab Device System. 

The Therapeutic Swab Device System for delivering plurality of drugs exhibiting distinct antiviral and cytoprotective functions directly to the nasal cavity, nasopharynx, posterior pharynx, and throat, provides a unique opportunity for treating primary sites of upper respiratory infection, as these sites can be easily reachable through the nostrils. Figure 1 depicts the configuration of the Therapeutic Swab Device System with various drug-loaded swabs B are mounted on a stem A. The dimensional specifications (e.g., size, appearance, material density, and physical or chemical composition) for the stem and swabs used in the Therapeutic Swabs Device System may be adjusted for drug delivery in humans (children and adults) and in animals according to the anatomy of their nasal and oral cavities.  

“Figure

Drug adsorbed or drug conjugated swabs are mounted on both ends of the stem [A]. If desired, swab on only end of the stem of the Therapeutic Swabs can be mounted. Drug-loaded swabs are defined as swabs either pre-loaded with drugs or loading the swabs by dipping into drug formulations in either aqueous-based, oil-based, cream-based, lotion-based, or any other desired media. This simple, economical and easy to use Therapeutic Swab Device System broadens the scope of current treatment options for mitigating SARS-CoV-2 infections with constantly emerging new viral variants by administering various drugs that can be easily, locally, and directly applied to the primary sites of infections at a dose much lower than those either administered via other routes such as intravenously or orally. 

Figure 2 depicts basic anatomy of the nasal cavity. The locations of various components are shown as: 1. anterior nares; 2. mid-turbinate; 3. nasopharynx; and 4. oropharynx. For drug delivery, the Therapeutic Swab Device System either pre-loaded or post-loaded with various drugs is inserted through the nostrils until it reaches to the far back of the nose (i.e., to the nasopharynx), as shown in Figure 3, or through mouth to the oropharynx, for about 15 seconds on each side with gentle rotation and then taken out with gentle rotation. The posterior pharyngeal wall is located on the base of the tongue and it is beneath the soft palate and uvula where drugs can be delivered using a fresh Therapeutic Swab Device System. As described above, the unique configuration design consisting of plurality of drugs possessing distinct functions, such as antiviral activity to inhibit virus replication, induce strong innate cytoprotective response to prevent virus-induced cell death, anti-inflammatory activity to reduce inflammation associated with upper respiratory infections – intended to simultaneously and specifically deliver to the nasal and oral cavities, nasopharynx, and posterior pharynx, the primary sites of upper respiratory infections. This is highly desirable to maximize protection against deadly respiratory infections, including SARS-CoV-2, yet alleviating the undesired adverse side effects associated with systemic absorption of drugs administered via other routes. 

”Figure

Importantly, since the Therapeutic Swab Device System for drug delivery complements to specimen collectors intended for a completely different purpose (i.e., diagnosis of COVID-19 infection). Therefore, the Therapeutic Swab Device System poses little or no risk to the recipients. Furthermore, drug application can be completed on the spot within 30 seconds both in asymptomatic individuals and also those tested positive for COVID-19, thereby immediately retarding the progression of the disease and minimizing the spread of infections to others. 

”Figure

Using the Therapeutic Swab Device System, one or more crucial drugs are delivered simultaneously and directly to the infected sites of upper respiratory infections for maximizing their effectiveness, signifying a broader public health implication. Thus, this system presents a significant advantage over conventional administration of antiviral and antimicrobial drugs for treating upper respiratory infections via other routes (e.g., pills, capsules, via injections, etc.) in terms of minimizing high systemic absorption of the drugs, or perhaps likely their degradation in circulation. In addition, this approach presents an enormous advantage over the conventional antiviral and antimicrobial drug administration by nasal drops or nasal sprays in terms of minimizing the dripping or spilling of the drugs and/or contaminated nasal secretions. 

The seriousness of the travel-related spread of SARS-CoV-2 variants is widely recognized; yet, realistically, it is beyond strict enforcement of regulatory control to prohibit individuals from traveling. This is neither practically possible nor is a permanent solution to the problem. By virtue of the unique configuration of the Therapeutic Swab Device System comprising multiple drugs with distinctive functions, this system is highly desirable to maximize protection of travelers, school children, and high-risk immunocompromised individuals. Because the upper respiratory disease-causing pathogens spread primarily through breathing, droplets of saliva, discharge from nasal secretions, or via other direct contacts, this system offers a useful broadly  applicable therapeutic approach to effectively control the current out-of-control COVID-19 pandemic and also future viral outbreaks.  

Importantly, numerous recent publications have recognized the clinical utility of cytoprotective enzyme heme oxygenase-1 (HO-1), originally reported for HIV-1 in 2006,14 as a viable therapeutic option for treating COVID-19.15-17 Accordingly, the present report proposes a unique combination of antiviral and anti-inflammatory drugs along with a powerful innate cytoprotective enzyme HO-1-inducing drug hemin. While numerous agents efficiently induce HO-1, hemin is particularly important because it is the active component of a previously FDA-approved drug for the treatment of acute porphyria with thus far no known serious adverse effects.18 In addition, hemin serves as a natural substrate for HO-1 (it is a strong inducer of endogenous enzyme HO-1) that provides a strong “generic innate cellular protection” against a wide variety of infections, regardless of types, mutants, or strains of the pathogens, such as HIV-1, Ebola virus, Vaccinia virus, Zika virus, Dengue virus, even a mycoplasma and, more recently, SARS-CoV-2.19-28 Therefore, the utility of innate HO-1 inducers in the configuration of this article presents a significant therapeutic advancement in providing the much-needed combination of antiviral, anti-inflammatory, anticoagulant and a general robust innate host protection against deadly respiratory viral infections. 

An effective protection during the early stage of pathogen exposure is pivotal for our first defense against upper respiratory infections. The Therapeutic Swab Device System presents tremendous utility for global public health safety on a mass-scale to control the current COVID-19 pandemic crisis as well as in preparing us for the unforeseen future viral outbreaks. The therapeutic system reported here addresses the critical and unmet public health need related to upper respiratory infections – one of which is caused by the most prevalent, highly contagious, and deadly novel coronavirus SARS-CoV-2. It is of enormous global public health concern. Accordingly, the present report relates to first one-of-its-kind therapeutic approach consisting of multifunctional drugs intended for their direct delivery to the nasal cavity, nasopharynx, and posterior pharynx, the primary sites of upper respiratory infection, by means of drug-loaded simple, easy and economical Therapeutic Swabs Device System that can be used on a mass-scale. 

By virtue of the upper respiratory disease-causing pathogens spread primarily through breathing, droplets of saliva, discharge from nasal secretions, or via other direct contacts, as emphasized above, the system presented here offers a useful broadly applicable therapeutic approach to effectively control the current out-of-control COVID-19 pandemic and future viral outbreaks, and can be utilized by healthcare professionals, other individuals, friends and family members, or even by self-administration on a mass-scale. It can also reduce the risk of severe adverse side effects associated with high systemic absorption of drugs that are administered in the form of oral medicines or injections. Collectively, this report presents a novel design, first to my knowledge, of an ideal therapeutic modality for targeting the primary infected sites of upper respiratory infections enabling a useful remedy for treating upper respiratory infections in humans and in animals.

Conflict of Interest

The author declares no conflict of interest.

Acknowledgment 

This article is dedicated to sweet memories of my lovely kitty son Frisky Dhawan. I thank Dr. Hemant Joshi for valuable suggestions and critical review of the manuscript.  

References 

  1. Satia I, Cusack R, Greene JM, O’Byrne PM, Killian KJ, Johnston N. Prevalence and contribution of respiratory viruses in the community to rates of emergency department visits and hospitalizations with respiratory tract infections, chronic obstructive pulmonary disease and asthma. (2020) PLoS One. 15:e0228544. Published 2020 Feb 6. 
  2. Lai C-C, Shih T-P, Ko W-C, Tang H-J, and Hsueh P-R (2020) Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and corona virus disease-2019 (COVID-19): The epidemic and the challenges. Int J Antimicrob Agents. 2020;55(3):10592. doi.org/10.1016/j. ijantimicag.2020.105924 
  3. Nakamichi K, Shen JZ, Lee CS, Lee A, Roberts EA, Simonson PW et al. Hospitalization and mortality associated with SARS-CoV-2 viral clades in COVID-19. Sci Rep. 2021;11:4802. doi. org/10.1038/s41598-021-82850-9 
  4. Volz E, Hill V, McCrone JT, Price A, Jorgensen D, O’Toole AO, Southgate J, et al. Cell 2021;184(1):64-75. doi:10.1016/j.cell.2020.11.020 
  5. Korber B, Fischer WM, Gnanakaran S, Yoon H, Theiler J, Abfalterer W, Hengartner N, et al. Tracking changes in SARS-CoV-2 spike: Evidence that D614G increases infectivity of the COVID-19 virus. Cell 2020;182(4):812-827.e19. doi.org/10.1016/j.cell.2020.06.043 
  6. Davies NG, Abbott S, Barnard RC, Jarvis CI, Kucharski AJ, Munday JD, et al. Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England. Science 2021; 372(6538):eabg3055. doi:10.1126/science.abg3055 
  7. Toniati P, Piva S, Cattalini M, et al. Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: A single center study of 100 patients in Brescia, Italy. Autoimmun Rev. 2020;19:102568. doi:10.1016/j.autrev.2020.102568. doi:10.1016/j.autrev.2020.102568 
  8. Gustine JN, Jones D (2021) Immunopathology of hyperinflammation in COVID-19. Am J Pathol. 2021;191(1):4-17. doi:10.1016/j.ajpath.2020.08.009 
  9. Nikolich-Zugich J, Knox KS, Rios CT, Natt B, Bhattacharya D, Fain MJ. SARS-CoV-2 and COVID-19 in older adults: what we may expect regarding pathogenesis, immune responses, and outcomes. Geroscience. 2020;342:505-514. doi:10.1007/s11357-020-00186-0 
  10. CDC, August 2021. 
  11. Wang P, Nair MS, Liu L, et al. Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7. 2021. bioRxiv. 2021;2021.01.25.428137. Published 2021 Feb 12. doi. org/10.1101/2021.01.25.428137 
  12. Yurkovetskiy L, Wang X, Pascal KE, et al. Structural and functional analysis of the D614G SARS-CoV-2 spike protein variant. Cell 2020;183(3):739-751.e8. doi:10.1016/j. cell.2020.09.032 
  13. Subbarao K, Mahanty S. Respiratory Virus Infections: Understanding COVID-19. Immunity 2020;52(6):905-909. doi:10.1016/j.immuni.2020.05.004 
  14. Devadas K, Dhawan S. Hemin activation ameliorates HIV-1 infection via heme oxygenase-1 induction. J Immunol 2006; 176(7):4252-4257. doi.org/10.4049/jimmunol.176.7.4252 
  15. Singh D, Wasan H, Reeta KH. Heme oxygenase-1 modulation: A potential therapeutic target for COVID-19 and associated complications. Free Radic Biol Med. 2020;161:263-271. doi:10.1016/j.freeradbiomed.2020.10.016 
  16. Maiti B. Heme/haemoxygenase-1 system is a potential therapeutic intervention for COVID-19 patients with severe complications. ACS Pharmacol Transl Sci 2020;3,5:1032- 1034. doi.org/10.1021/acsptsci.0c00136  
  17. Hooper PL. COVID-19 and heme oxygenase: novel insight into the disease and potential therapies [published correction appears in Cell Stress Chaperones. Cell Stress Chaperones. 2020;25(5):707-710. doi:10.1007/s12192-020-01126-9 
  18. Siegert SWK, Holt RJ Physicochemical properties, pharmacokinetics, and pharmacodynamics of intravenous hematin: a literature review. Adv Therapy. 2008;5:842– 857. doi.org/10.1007/s12325-008-0094-y 
  19. Meseda CA, Srinivasan K, Wise J, Catalano J, Yamada KM, Dhawan S. Non-coding RNAs and heme oxygenase-1 in vaccinia virus infection. Biochem Biophys Res Commun 2014;454(1):84-88. doi:10.1016/j.bbrc.2014.10.035 
  20. Hill-Batorski L, Halfmann P, Neumann G, Kawaoka Y. The cytoprotective enzyme heme oxygenase-1 suppresses Ebola virus replication. J Virol 2013;87(24):13795-13802. doi:10.1128/JVI.02422-13 
  21. Huang H, Falgout B, Takeda K, Yamada KM, Dhawan S (2017) Nrf2-dependent induction of innate host defense via heme oxygenase-1 inhibits Zika virus infection. Virology. 2017; 503:1-5. doi:10.1016/j.virol.2016.12.019 
  22. Wagener FADTG, Pickkers P, Peterson SJ, Immenschuh S, Abraham NG. Targeting the heme-heme oxygenase system to prevent severe complications following COVID-19 infections. Antioxidants (Basel) 2020;9(6):540. Published 2020 Jun 19. doi.org/10.3390/ antiox9060540  
  23. Rossi M, Piagnerelli M, Van Meerhaeghe A, Zouaoui Boudjeltia K. Heme oxygenase-1 (HO- 1) cytoprotective pathway: A potential treatment strategy against coronavirus disease  (COVID-19)-induced cytokine storm syndrome. Med Hypotheses. 2020;144:110242. doi:10.1016/j.mehy.2020.110242 
  24. Huang H, Dabrazhynetskaya A, Pluznik J, Zheng J, Wu Y, Chizhikov V, Buehler PW, Yamada KM and Dhawan S (2021) Hemin activation abrogates Mycoplasma hyorhinis replication in chronically infected prostate cancer cells via heme oxygenase-1 induction. FEBS Open Bio. 2021;11(10):2727-2739. doi.org/10.1002/2211-5463.13271 
  25. Toro A, Ruiz MS, Lage-Vickers S, Sanchis P, Sabater A, Pascual G, Seniuk R, Cascardo F, Ledesma-Bazan S, Vilicich F, Vazquez E, Gueron G. A Journey into the Clinical Relevance of Heme Oxygenase 1 for Human Inflammatory Disease and Viral Clearance: Why Does It Matter on the COVID-19 Scene? Antioxidants 2022;11:276.doi.org/10.3390/ antiox11020276 
  26. Dhawan S. Innate cellular immunity for suppressing viral infections. Curr Trends Immunol. 2021;22:19-21. http://researchtrends.net/tia/article_pdf.asp?in=0&vn=22&tid=36&aid =6762  
  27. Dhawan S. Necessity for the evaluation of stimulated cellular immunity against SARS- CoV-2 infection. Curr Trends Immunol 2021;22:43-47.  
  28. Dhawan S. Significance of innate immunity in mitigating SARS-CoV-2 infection. Am Pharm Rev. 2021;24(4):48-49.  

Author Biographies 

Dr. Subhash Dhawan is a viral immunologist. He retired after serving for nearly 25 years as Chief of Viral Immunology Section in the Laboratory of Molecular Virology, Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration. Dr. Dhawan is now an independent writer and provides guidance on research and regulatory projects related to in vitro diagnostics, vaccines, and therapeutics. 

Dr. Subhash Dhawan 9890 Washingtonian Blvd., #703 Gaithersburg, MD 20878, USA E-mail: [email protected] Tel: (202) 731-9886

Subscribe to our e-Newsletters
Stay up to date with the latest news, articles, and events. Plus, get special offers
from American Pharmaceutical Review – all delivered right to your inbox! Sign up now!

  • <<
  • >>

Join the Discussion