Anabolic Steroids and COVID-19 Infection: Comparison
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Anabolic androgenic steroids (AASs) are synthetic analogs of testosterone that can affect the immune system. Bodybuilders and sportsmen are at risk of abusing AASs. The findings suggest that the use of AASs could be an underlying risk factor for COVID-19 severity. 

  • anabolic steroids
  • androgenic
  • COVID-19
  • coronavirus
  • athletes

1. Introduction

Anabolic androgenic steroid (AAS) drugs are composed of synthetic testosterone (male sex hormone) derivatives that have both anabolic effects combined with androgenic effects by binding to the active site on androgen receptors. AAS drugs are usually prescribed by physicians for a list of indications, including cases of certain types of anemia, androgen insensitivity syndromes, some forms of breast cancer, angioedema and weight gain after serious illness [1,2][1][2]. There are no recorded cases of abuse or dependence in patients using therapeutic doses of AASs for legitimate indications. However, AASs are widely abused by bodybuilders and athletes and are not prescribed to healthy people [3]. AASs are abused by athletes who aim to improve their physical appearance and performance; however, it misuse is accompanied by several physical and psychiatric side effects, including gynecomastia and baldness in male users [4], higher risk of liver neoplasms and heart disease [5], depression, mania, psychosis and aggression [6,7,8,9,10][6][7][8][9][10]. Moreover, AAS use has been shown to affect the immune system resulting, in either immunostimulatory or immunoinhibitory effects, depending on the steroid nucleus; AASs with alterations to the steroid nucleus stimulate the proliferation of T cells as well as other immune cells [11,12][11][12]. In contrast, AASs with a preserved steroid nucleus have immunosuppressive effects as they reduce the number of immune cells and their functions [12]. These effects are more obvious following exposure to higher doses of these drugs [11,12][11][12].
Of note, by the end of 2019, an outbreak of acute respiratory syndrome of unknown origin was detected in Wuhan, Hubei Province, China [13]. Globally, the prevalence of COVID-19, its rapid transmission and increasing death rates due to the disease led the World Health Organization to announce a pandemic on 12 March 2020 [13]. In the flowing months after identification of the initial cases, COVID-19 spread to 171 countries and there were around 215,546 confirmed cases by 19 March 2020 [14]. Many COVID-19 patients were asymptomatic; however, the most common symptoms experienced by 50% of COVID-19 patients were fever, sore throat, cough, fatigue, headache and myalgia or arthralgia [15].
COVID-19 infection can affect the immune system causing lymphopenia, which is defined as a decrease in the number of blood lymphocytes, implying that cellular immune responses have been suppressed. Human immune responses to SARS-CoV and MERS-CoV have been carefully researched; however, studies on SARS-CoV-2 have yet to be thoroughly explored. The virus induces a plethora of cytokines in the most severe cases of COVID-19, which are identified by activated T-helper-1 (Th1) cell responses with elevated levels of interleukins-1b, 2, 6, 7, 8 and 10 (IL-1b, IL-2, IL-6, IL-7, IL-8 and IL-10), as well as tumor necrosis factor-a (TNF-a), granulocyte-colony stimulating factor (GSF), interferon-g, induced protein (IP-10), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory-protein 1-a (MIP-1a). Increased amounts of proinflammatory cytokines can cause pulmonary inflammation and tissue damage in the heart, liver and kidneys, which can lead to multiorgan failure. In patients with SARS-CoV, MERS-CoV, or SARS-CoV-2 infection, an excess of cytokines has been linked to the onset and progression of ARDS. A considerable increase in death rate is also linked to a dysregulated cytokine response in severe COVID-19 cases with ARDS, especially in older patients [16].
In Saudi Arabia, the prevalence of AAS use has been investigated by cross-sectional studies in the capital city of Riyadh in 2015 and Jazan city in 2017; these studies included 600 athletes in Riyadh and 465 bodybuilders in Jazan City. The studies showed that 30.5% of the study participants in Riyadh [17] and 38.7% of those in Jazan [18] were AAS abusers. Since there is a high prevalence of AAS use in the Kingdom of Saudi Arabia (KSA), recent studies have shown an association of AAS use with coronavirus disease (COVID-19) [17,18,19][17][18][19]. The hypothesis is that the illegal use of AASs by bodybuilding may worsen COVID-19 symptoms; this may be an important issue affecting young adults and athletes worldwide since the prevalence of illegal AAS use is increasing.

2. Current Insights

This study aimed to observe COVID-19 progression in AAS users infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Saudi Arabia. Based on the findings of this study, the data can be interpreted as follows: consumption of AASs may affect COVID-19 risk, symptom severity and the nature of the disease. Male participants had a higher risk of COVID-19 and higher severity of symptoms compared to female participants. This matches trends in the general population, where males are at a greater risk of contracting COVID-19. The most commonly reported COVID-19 symptom among AAS users was muscle or joint pain. The most common symptom reported by nonusers and previous users was loss of taste and smell. The severity of symptoms in participants with COVID-19, who were current users of AASs, was almost two times worse than that in previous users or non-users. These results may be a consequence of the effects of AASs on the immune system [11[11][12],12], which is directly responsible for the presentation and severity of symptoms of COVID-19 [22][20]. In addition, the genetic differences between the immune systems in men and women may lead to more susceptibility of men to severe acute infection compared to women and these differences can be seen in boys and girls even before puberty [23][21]. The first and only case report that linked COVID-19 symptom severity and AAS use was reported by Cadegiani et al., in which a healthy 28-year-old man presented at a hospital with severe COVID-19 symptoms [24][22]. Upon investigation, researchers found that the patient had been taking oxandrolone 40 mg/day to enhance his body building for the past 30 days [24][22]. Since AAS can affect the immune system, some studies have investigated the association between AAS use and COVID-19 [19]. In Yale New Haven Hospital and UK Biobank, an association between androgen imbalance and complications of COVID-19 have been identified [19]. Inhibitors of 5 alpha reductases that inhibit androgen signaling can reduce ACE2 levels and thus decrease viral spike- receptor-binding domain internalization [19]. In another study, it was suggested that COVID-19 risks could be reduced in the elderly by hormone replacement therapy (estrogen and testosterone) due to the anti-inflammatory actions of sex hormones and the anabolic actions of testosterone [22][20]. Another study showed that the COVID-19 pandemic had clearly affected the use of AAS by reducing AAS doses and training frequency as compared to pre-pandemic [25][23].

References

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