Can I Drink Coffee If I Have Covid

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1. Introduction

In December 2019, a series of unexplained cases of atypical pneumonia were reported in Wuhan, China, with high transmission. This disease, which was subsequently named coronavirus disease 2019 (COVID-19), has spread rapidly worldwide, affecting a large part of the human population [1,2]. The World Health Organization (WHO) officially named the virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [3]. SARS-CoV-2 belongs to the coronavirus family, a group of enveloped, single-stranded, positive-sense, RNA genome viruses. The virion contains four main structural proteins: the nucleocapsid (N) located in the nucleocapsid and in the viral envelope we can find the spike (S), membrane (M), and envelope (E) proteins. The S protein has been determined to facilitate viral entry into the host cell; this occurs through the complex formed by a receptor-binding domain (RBD; a subunit of the S protein) and the angiotensin-converting enzyme 2 (ACE2) found in the membrane of the host cell, mainly pneumocyte type II cells [1,4,5,6]. The number of patients is increasing day by day around the world, but some infected patients are asymptomatic or experience a mild disease course (fever, cough, chest tightness, dyspnea, etc.). However, patients with severe symptoms may present severe respiratory tract infections, severe pneumonia, acute respiratory distress syndrome (ARDS), multiple organ failure, and death [7,8,9,10,11]. This is because the virus induces aberrant host immune responses, and modulation of the host immune response is the key to fight SARS-CoV-2 [12]. Among the theories, it is hypothesized that SARS-CoV-2 damages tissues due to the deterioration of inflammation mechanisms and cytokine storms given the pathophysiology of SARS-CoV-2 [13,14]. The WHO reported that as of 28 February 2021 there had been approximately 113,864,015 cases of COVID-19 and that the number of deaths had been approximately 2,526,793 worldwide. In Mexico, to this date there had been a total of 2,084,128 positive cases with a total of 185,257 deaths, and, unfortunately at the time of writing, the number of COVID-19 positive cases is increasing daily [15].

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Many researchers, through their respective research areas, are facing and directing contributions to overcome the COVID-19 pandemic. Although the development and use of vaccines (with high efficiency) has been the first option, at the time of writing, only 0.67% of the world’s population, according to the WHO, has been vaccinated. Therefore, current treatments are largely directed toward symptom management and vital support in severe cases [16]. Given the necessity for efficient therapeutic options in the intervention of SARS-CoV-2, two main routes in the drug discovery process for a viral infection are being undertaken: the discovery or synthesis of a new effective drug and the repurposing of an already existing drug. Drug discovery is a laborious process, usually taking several years and at large expense; therefore, taking into consideration the urgency arising from the pandemic currently plaguing our world, the option to repurpose already existing drugs or pharmacological compounds seems the more feasible option [17].

Until now, the therapeutic options to contain the COVID-19 pandemic have been based on prevention of transmission, detection of travelers, and public healthcare measures [17]. There is no effective treatment for SARS-CoV-2 infection and the drugs mainly used include antiviral protease inhibitors that impede the viral replication of SARS-CoV-2 by inactivating proteases essential for the replication [18]. The identification of specific drug targets that inhibit the life cycle of SARS-CoV-2 still require further investigation.

Another strategy is to use inflammation inhibitors, because experimental and clinical tests have shown that the damage caused by the virus is related to an altered inflammatory response and, in some patients, to an abnormal release of pro-inflammatory cytokines [18]. Low molecular heparins, plasma, and hyperimmune immunoglobulins are also utilized on a case-by-case basis, generally in severe COVID-19 patients, and are used to mitigate the complications and sequelae that can arise from the infection [18,19,20]. Although a variety of therapies may be a short-term strategy to deal with COVID-19, there is still an obvious lack of specific treatment for the disease [7]. Even if these anti-inflammatory agents are a promising line of treatment, they still require further study through randomized clinical trials.

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Caffeine (1,3,7-trimethylxanthine) is a methylxanthine alkaloid found in the seed, fruit, and leaves of a variety of plants native to Africa, Southeast Asia, and South America. In addition to coffee and tea, it can also be found in cocoa beans, yerba mate leaves (used to make herbal teas), and guarana berries (used in various beverages and supplements). It is a common stimulant that is consumed daily around the world [21]; it can be synthesized and added to beverages and foods, including soft drinks, beverages, and tablets in a wide variety of over-the-counter formulations, such as combined diet aids and pain relievers. If consumed within the recommended dose (400 mg/day for adults), its most widely sought-after effect is as a mild stimulant of the central nervous system (CNS), due to its capacity to cross with ease the blood-brain barrier, which can cause a reduction in fatigue and increase wakefulness and awareness [22,23]. Caffeine is used successfully in the treatment of apnea of prematurity [24], exerting its antagonism on the adenosine receptors in the respiratory centers of the brainstem [25]. In chronic lung disease of prematurity, it inhibits non-selective phosphodiesterase and increases cyclic adenosine monophosphate levels (cAMP), directly relaxing the pulmonary vascular muscle of the baby and improving its oxygenation [26]. In asthma, caffeine has been utilized in adults with mild asthma, showing a moderate improvement in lung function when low doses of 5 mg/kg of body weight are administered [27]. There are reports where people with exercise-induced bronchoconstriction (EIB) could alleviate it by ingesting caffeine before exercise (7 mg/kg) [28]. The mechanisms proposed for the bronchodilator effect are mostly through its activity as an inhibitor of phosphodiesterase and antagonism of the adenosine receptor [29]. It should be mentioned that consumed caffeine is easily distributed throughout the body and permeates through the cellular membrane due to its amphiphilic properties [30]. In the liver, it is metabolized by cytochrome P-450 (CYP) enzymes and biotransformed by CYP1A2 in three active metabolites, mainly paraxanthine (81.5%), theobromine (10.8%), and theophylline (5.4%), which are excreted in the urine [31]. A moderate consumption of caffeine is usually considered safe and acute toxicity is rare, but some of the symptomology that can be present are nausea, headaches, insomnia, nervousness, tachycardia, arrhythmias, gastrointestinal disturbances, and seizures. The consumption of caffeine in combination with alcohol could even result in death [23,32]. These could be the possible side effects if caffeine were to be used for treating COVID-19 patients.

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We and other research groups have studied the pharmacological activities of caffeine in the smooth muscle of the respiratory tract, including mainly adenosine receptor antagonism, phosphodiesterase inhibition, and intracellular calcium release from the sarcoplasmic reticulum (SR), and as a taste receptor type 2 ligand (TAS2R) [33,34,35,36]. It is important to emphasize that these mechanisms are found in almost all tissues and cells of the body. Recently, caffeine has taken on an essential role in the fight against SARS-CoV-2 since it can play a role in the defense against this virus [6,7,36]. In this review, we analyze our experience in the handling of caffeine and the analysis of new experimental data that may have health benefits against SARS-CoV-2 in multiple organ systems, via inactivation of the virus, blocking the viral binding with ACE2, along with its immunomodulatory and anti-inflammatory roles, as well as benefits in patients with COVID-19, especially as caffeine is consumed daily.