Immunomodulatory and Preventive Effects of Olive Leaf Tea Against COVID-19
Condition: Immunomodulation
Study type: Observational

Summary: 
      During the Coronavirus Disease-2019 (COVID-19) pandemic, in addition to the current measures,
      boosting the immune system seems to be one of preventive measures that can be taken against
      COVID-19 infection. Various natural agents have been recommended to boost the immune system.
      The aim of this study was to investigate the possible immunomodulatory and preventive effects
      of Olive Leaf Tea (OLT) drinking with regards to COVID-19 infection. The study was conducted
      among 249 workers in a tractor factory where OLT was served. Of the 249 workers, 168 of them
      were OLT drinkers and 81 were not OLT drinkers. Drinking at least one cup of OLT per day for
      a minimum of one month was the inclusion criteria used in the study. The workers with a
      history of infection or vaccination of COVID-19 were excluded. Lymphocyte subsets, IL2,
      INF-gamma, specific IgM, and IgG levels were analyzed in all the study subjects. The results
      showed higher values of CD3-/CD16/56 (NK) cells, CD3+/CD16/56 (NKT) cells, total NK (NK+NKT)
      cells, and serum IFN-gamma and IL-2 levels in OLT drinkers as compared to the nondrinkers.
      These immune changes are indicative of immune defense mechanisms. Although all the OLT
      drinkers and non-drinkers reported no history of COVID-19, specific COVID-19 IgG levels were
      found positive in 60% of OLT drinkers and 38% OLT non-drinkers. There were significant
      negative correlations between age and NK cells, number of cigarettes smoked and NK cells,
      number of cigarettes smoked and TNK; and there were positive correlations between OLT
      drinking frequency and TNF-alpha, IL-2 and IFN-gamma. Also, serum creatinine levels in OLT
      non-drinkers were found significantly higher than in the OLT drinkers. In conclusion,
      drinking OLT may contribute fighting against COVID-19 by boosting the innate immune system.
    

Detailed description: 
      Coronavirus Disease-2019 (COVID-19) is caused by severe acute respiratory syndrome
      coronavirus 2 (SARS-CoV-2). It emerged out of China in late 2019 and rapidly led to a
      pandemic in early 2020. As the mutations of the virus continue to increase, the pandemic has
      become difficult to control and no specific treatment has been proven to be effective.

      According to the European Centre for Disease Prevention and Control (ECDC), until a safe and
      effective vaccine is available, non-pharmaceutical tools are accepted as the most effective
      public health interventions against COVID-19. World Health Organization (WHO) states that in
      addition to public health and social measures, it is also beneficial for individuals to
      maintain a balanced diet, stay well hydrated, exercise regularly and sleep well.

      It is now clear that there is a close interaction between the COVID-19 and the immune system
      of an individual resulting in diverse clinical manifestations of the disease. While some
      patients present severe complications, some individuals remain asymptomatic. Weakened
      immunity is responsible for most COVID-19 deaths, therefore, elderly people with chronic
      diseases are considered at high risk from COVID-19.

      As soon as SARS-CoV-2 binds to angiotensin converting enzyme 2 (ACE2) receptors and releases
      viral RNA for replication, both the innate and adaptive immune responses are triggered.
      Natural killer (NK) cells are innate effector lymphocytes that play a critical role in the
      first line of defense against tumor cells and viral infections. They are essential in the
      early immune response against viral infections, mainly through the clearance of
      virus-infected cells. Human NK cells, CD3-CD56+ NK, represent an average of 15% of peripheral
      blood and they can be subdivided based on the relative expression of the surface markers CD16
      and CD56. Additionally, in chronic viral infections, CD56-CD16+ NK cells are expanded and
      seems to represent an exhausted/anergic subset of NK cells. Through several mechanisms, NK
      cells provide exocytosis of perforin and granzyme causing lysis of the infected cell, Fas
      ligand-mediated induction of apoptosis, and antibody-dependent cellular cytotoxicity (ADCC),
      while having an essential role as immunomodulatory cells that bridge the innate and adaptive
      immune responses. Natural killer T cells (NKT) are cells that express a semi-invariant T cell
      receptor (TCR). Crucial cytokines for the cytotoxic activity of NK and NKT cells are IL-2 and
      INF-gamma, and these cytokines enhance the killing properties and proliferation of these
      cells. Both IL-2 and IFN-gamma secretions are induced in a healthy young individual while
      this effect decreases in the elderly.

      Immune system boosting nutrition may play a role to lower the risk of infections by
      inhibiting virus replication, promoting virus clearance, inducing tissue repair, and
      triggering a prolonged adaptive immune response against viruses. Besides, certain medicinal
      plants are known for their antiviral bioactivities and immune boosting capacity. Some herbs
      have immunomodulatory potential and can be applied as a preventive medicine to combat
      COVID-19. Olive-leaf tea (OLT) is widely used in the traditional medicine in the
      Mediterranean region. Due to the high concentration of phenolic compounds, of which most
      abundant is oleuropein, interest in olive leaf has increased recently. The components of the
      olive leaves are known for their immune-modulatory, anti-inflammatory, antioxidant,
      hypoglycemic, antihypertensive, antimicrobial, and anti-atherosclerotic effects. Although its
      antiviral mechanism of action is not fully known, many studies have been conducted on the
      antiviral effects of olive leaf extract . However, studies on the protective or immune system
      strengthening effect of olive leaf extract against viral diseases are limited. There is only
      one available in vitro study that shows olive leaf extract alters the immune response by
      increasing the number of CD8 + and NK cells and IFN-gamma. The aim of this study is to
      investigate the possible immunomodulatory and preventive effects of OLT against COVID-19.
    

Intervention name(s): Olive Leaf Tea
Intervention type(s): Dietary Supplement
Intervention description(s): Olive-leaf tea (OLT) is widely used in the traditional medicine in the Mediterranean region. Due to the high concentration of phenolic compounds, of which most abundant is oleuropein, interest in olive leaf has increased recently [22, 23]. The components of the olive leaves are known for their immune-modulatory, anti-inflammatory, antioxidant, hypoglycemic, antihypertensive, antimicrobial, and anti-atherosclerotic effects [24, 25]. Although its antiviral mechanism of action is not fully known, many studies have been conducted on the antiviral effects of olive leaf extract .
Observational model: Cohort
Time perspective: Cross-Sectional
Sampling method: Probability Sample
Study population: 
        workers at the Tumosan Konya tractor factory