# Honey as an Adjuvant in the Treatment of COVID-19 Infection: A Review
## 4 Honey as a Co-Adjuvant of SARS-CoV-2 Infection Treatment  
Honey and its related products are used as natural therapies for several health problems, including pulmonary and cardiovascular disorders, diabetes, hypertension, gastrointestinal tract disorders, edema, cancer, autophagy dysfunction, bacterial, viral, and fungal infections [99, 100]. These biological properties are principally due to honey's potential antioxidant and anti-inflammatory activities, which may not only attenuate the oxidative damage induced by pathogens but also improve the immune system. In the specific case of viral infections, honey is employed due to its abilities to decrease acute inflammation by promoting an immune response [101, 102]. In fact, honey can modulate the molecular targets involved in cellular signaling pathways, such as apoptosis and inflammation, as well as signaling cascades needed for virus replication and attachment to the host cells [103, 104]. Varicella zoster [105], rubella [106], influenza [107], herpes simplex [108], respiratory syncytial virus [109], immunodeficiency virus [110], viral hepatitis A [110], are among the pathogens effectively inhibited by honey. Honey is mainly composed of sugars and water, while minor compounds such as organic acids, amino acids, enzymes, phenolic compounds, vitamins, minerals, and antioxidants, are related with its biological properties [111, 112, 113, 114, 115]. As previously mentioned, the foraging activity of honeybees during honey production can lead to variations in honey composition, and are highly dependent of the plant species visited. Additionally, seasonal, environmental, and processing factors, as well as genus and bee species, may also influence honey composition and its biological effects [39, 116]. Some research has suggested that many of the therapeutic properties of plants can be transmitted to honey, honey being a transport vector for the plant's medicinal properties [117]. Some honey varieties with similar botanical origins, and derived within close geographic proximity, have different biological properties because of the type and quantities of their bioactive components (Tables 1-3). Due to its composition and biological properties, honey and its related products are applied directly, or as components, in the treatment of several diseases. These products have proven their virucidal effect on several enveloped viruses such as HIV, influenza virus, herpes simplex, and varicella-zoster virus [105, 118, 119, 107]. Among the different biological properties of honey, the most reported is its antioxidant activity. It is well known that antioxidants can prevent cell death by draining lymphocytes, which leads to antiviral action [114, 120, 121]. [PERSON] and [PERSON] [122] observed that a polyphenol-rich environment stimulates the activation of the immune system and the mechanisms involved in tissue repair. Manuka honey, a monofolar honey derived from the nectar of the manuka tree (_Leptospermum scorarium_), an indigenous plant of New Zealand, has greatly attracted the attention of researchers due to its biological properties; especially its antimicrobial and antioxidant capacities [99, 121]. The chemical composition of Manuka honey includes an abundant suite of polyphenols and other bioactive compounds such as glyoxal and methylglyoxal (MGO), methyl syringae, and leptosis [99, 121]. Particularly, the \(\alpha\)-ketoaldehyde compound, MGO, can inhibit growth of the enveloped virus [107] and, together with the antiseptic effect of hydrogen peroxide, this aldehyde increases the antibacterial effect reported for this honey [113]. [PERSON] et al. [121] analyzed 16 different honey samples to select the best one for therapeutic purposes. The antioxidant activity, the main bioactive compounds and the phenolic profiles were determined.