Why METH users are at high risk of fatality due to COVID-19 infection?

KEYWORDS:

• METH addiction
• coronavirus
• COVID-19
• vaccine
• lung infection
• methamphetamine
• SARS-CoV-2
• drug addiction
• substance abuse

Coronavirus disease (COVID-19) is caused by a new strain of coronavirus called SARS-CoV-2 which has created a world-wide stop and catastrophic consequences to the economy, job losses, mental health, and physical health. Since its declaration as a pandemic on 11 March 2020, there have been over 972,000 deaths and 31.7 million infections worldwide (worldometers.info/coronavirus). COVID-19 has impacted all segments of the communities around the world. Recent studies have reported that people with weak immunity, cardiac disease, diabetes, chronic respiratory disease, and other underlying secondary disease conditions are more prone to developing COVID-19 mild-severe symptoms and there is subsequently a higher death rate from these particular risk groups [1]. Methamphetamine (METH) users, along with other drug abusers, are amongst the most vulnerable groups in our community, with multiple risk factors such as, less access to health care, suffer from weaker immunity and poorer health, respiratory issues, metabolic problems, or cardiac diseases are more susceptible to various infections [2]. With the emergence of the COVID-19 pandemic, the topic reemerged as the experts consider that regular users of substances of abuse such as, opioids or METH are at increased risk due to the likelihood that they already suffer from existing diseases, weakened immunity, poor decision making, and impaired judgment. All of these may increase their vulnerability to COVID-19 infection [3–5]. Regular administration of METH is associated with various neurological symptoms such as anxiety, depression, psychosis, psychiatric impairment [6], cardiac [7], respiratory complications [8], and overall decreased immune health. METH users group is much stigmatized and marginalized, and tend to remain well hidden in large population groups. It is very difficult to identify this risk group from the larger population and this may lead them to the brink of death in some cases. The homelessness, less access to medical system, poor immune system, underlying secondary diseases, and inability to take correct decisions may contribute to increased death rate for all drug users including METH. The mortality rate of drug users including METH is 3% to 5% higher compared to non-drugs users [9]. In addition, the chance of death among homeless young female drug users is 5% to 30% higher than for young women living in homes [10].

Acute and chronic use of METH has critical immunological implications in humans as it affects both the innate and adaptive immune system so that the individual becomes increasingly vulnerable to opportunistic microorganisms [11]. The innate immune system, which is the first line of defense, removes pathogens by phagocytosis, while the adaptive immune system presents the foreign pathogens to immune cells to generate antibody and T cell responses [11]; however, METH use, greatly impacts the development of appropriate immunity against pathogens [12]. METH can reduce the production of antibodies by altering the efficiency of B cells [11]. METH can also alter the communication between the innate and adaptive immune cells mediated by cytokines, and this may eventually delay response to pathogens [13,14]. To be more specific, METH is able to reduce the number of important immune cells such as dendritic cells, monocytes, natural killer cells, and macrophages that are necessary in providing immunity against pathogenic attack [11,15]. These eventually result in weaker immunity and as such, METH users are more vulnerable to infection, including SARS-CoV-2 infection leading to COVID-19 (Figure 1). In addition to the effect of METH on the immune system, its effect on the respiratory system is also critical here, as COVID-19 mainly affects the respiratory system. Many studies report that METH causes lung injury due to the over production of free radicals in animal models [16,17]. Pulmonary hypertension, pulmonary edema, and eosinophilic pneumonia are the most common types of lung injury reported from METH exposure [18]. Pneumonia can be caused by adulterated drug use, significant negative changes in the resident bacterial population, or aspiration [18].

Figure 1. Graphical illustration showing the relationship and immunological implications of methamphetamine drug use and SARS-CoV-2 infection (Figure generated using biorender.com)

METH addiction is a serious psychological problem and often difficult to treat. There is no successful treatment for METH addiction and psychotherapy remains as the sole management option. Due to lack of efficacy of pharmacological and psychotherapy therapy, there is a need of a therapeutic agent to treat METH addiction as an alternative option. The anti-METH immunotherapeutic approaches such as vaccines and monoclonal antibody treatment concepts have drawn the attention of the scientific community due to its immunoprophylactic and treatment attributes. As such, in recent years a significant amount of information has been generated predominantly in preclinical stages with just one monoclonal antibody candidate being translated to Phase I human clinical trial. A vaccine against METH addiction and COVID-19 infection could be the best solution at this pandemic time. Anti-METH vaccine could help METH users to stay away from METH addiction and associated complications, and, the much needed vaccine against SARS-CoV-2 virus could help global populations along with this specific vulnerable group.

We believe that this particular vulnerable group, METH users, should be considered at the development time of any treatment-related task force, intervention system, vaccine, or treatment model to ensure that they are inclusive to reduce the chance of contracting COVID-19 infection and related fatalities. Individual’s immunity is the key protection and programs should be developed for these vulnerable people in the community, to identify them from the large population group, educate them regarding the nature of SARS-CoV-2 infection, and provide methods to improve their immune system to reduce their risk of being infected or if they do get infected, to be minor and not severe. METH users are a vulnerable group in the community and should be treated with due importance. Like COVID-19 vaccine, the development of anti-METH vaccine should be coordinated globally to expedite the vaccine development process to protect this vulnerable group in our community.

Although the development of anti-METH vaccine candidates have demonstrated some promising results in preclinical studies, no anti-METH vaccine candidate has been evaluated in human clinical trials. This platform is in its infancy and has its own limitations. Upon administration, METH reaches the central nervous system immediately to activate the dopamine pathway. Hence, a strong antibody response is required to stop the METH going to the central nervous system. This high levels of antibody can be achieved by several booster immunizations and this could be a potential compliance issue for the METH abusers who have limited access to healthcare system. Currently, anti-drug vaccine for cocaine and nicotine failed in clinical trials due to lack of adequate antibody responses [19].

Expert opinion

The lack of developing high titer antibody levels post vaccinations are the major challenges in the development of vaccines against substance abuse drugs. The same true holds for a vaccine against SARS-CoV-2 where strong neutralizing antibodies are required to provide protection against SARS-CoV-2 infection. Therefore, successful vaccines for both METH and SARS-CoV-2 will be depend on their ability to generate strong and stable antibody responses.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

All authors contributed to the conceptualization, design, writing, and editing of the article. All authors have read, reviewed, and approved the final paper.

Acknowledgments

The authors would like to thank Graeme and Angelina Wise, The Thelma and Paul Constantinou Foundation, and The Pappas Family, whose generous philanthropic support made possible the preparation of this paper. The authors would also like to thank the Immunology and Translational Research Group for their significant contribution. M.H is supported by Graeme and Angelina Wise, and Md. K.H was supported by the Victoria University Postgraduate Scholarship and the Vice-Chancellors top-up Scholarship Award. This article was supported by the funds of the Place Based Planetary Health Grant PH098 to VA from VU Research, Victoria University. Figure 1 was generated using biorender.com.

Additional information

Funding

This article was supported by the funds of the Place Based Planetary Health Grant PH098 to VA from VU Research, Victoria University.