The Coronavirus Disease 2019 (COVID-19) pandemic has affected over 169 million people and caused the death of 3.51 million worldwide (up to May 28, 2021)(https://coronavirus. jhu. edu/map. html), becoming a serious problem of global public health and the worst epidemic in the last century, after the pandemic 1918 influenza. Researchers worldwide are trying to find valuable drugs against the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). Some of them focused as antivirals, others targeted in other ways (eg immunomodulation) to relieve the symptoms of the infected patients and help lower the death toll throughout the world. Unfortunately, there is a lack of effective drugs to manage COVID-19. The hopeful and long-awaited development of vaccines and the approval of their use in humans is a fact. The time consuming that it will take to achieve herd immunity due to waiting for the availability and distribution of the vaccines is a reality in full swing and shows significant health inequalities. Vaccines with up to 95% of efficacy and effectiveness have been developed and approved by the Food and Drug Administration (FDA), USA. Worldwide, 1.81 billion vaccine doses have been administered (up to May 28, 2021)(https://coronavirus. jhu. edu/map. html). However, it is unknown if the development of postinfection immunity detected confers medium-long term protection and the importance of mucosal immunity to protect against infection is still a matter of concern [1]. The effectiveness of a vaccine depends in part on its ability to induce a defensive immune response. Nevertheless, severe reactions have been observed in vaccine development for other respiratory viruses, including SARS-CoV [2], probably produced by vaccine-induced antibodies that facilitate viral replication [3]; or by a predominant cellular Th2 response that accelerates the tissue damage produced by the disease [4]. This reaction is of vital importance in the case of SARS-CoV-2 since the immune response in the form of a cytokine storm has been associated with severity [5]. A potential threat to patients with COVID-19 in helminths endemic areas (most of the tropical and subtropical areas of developing countries) is the systemic immunomodulatory effects of these parasites [6, 7], through protein secretion [8] and by alteration of the intestinal microbiome [9], that may influence the severity of other infections. However, some authors consider this could be protective [10]. The possible implications of the immune-regulatory role of helminth intestinal infections in humans co-infected by SARS-CoV-2 and its effect on the viral disease outcome and COVID-19 vaccines efficacy must be considered carefully using them in endemic helminth areas, in terms of more studies to understand this relationship. The individuals infected with helminths before being affected by SARS-CoV-2 are responding to the parasite infections by a specific Th2 type innate and adaptive immune responses. The Th2 pattern cytokines predominate in long-term helminth infected individuals [11]. The co-infected host needs to control the viral infection by a robust Th1 type lung microenvironment in the initial stages of SARS-CoV-2 [12]. Helminths modified intestinal microbiome can modulate host immune response. It is not well-defined if the interaction between helminth-microbiota will promote susceptibility or protection in the lungs. However, the generation of a tolerogenic and anti-inflammatory environment could stimulate less immune response and more susceptibility to co-infections [13]. In helminth-infected individuals, the immunomodulation of the innate and adaptive immune response characterized by a …