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Tuberculosis (TB) and COVID-19 are currently two of the main infectious diseases leading to death. An increasing number of studies are trying to elucidate the interactions between Mycobacterium tuberculosis and SARS-CoV-2. Some of the first case reports point to a worsening of respiratory symptoms in co-infected TB/COVID-19 individuals. However, data from cohort studies has shown some conflicting results. This study conducts a systematic review on the current literature on TB/COVID-19 co-infection cohorts, evaluating clinical and epidemiological data, focusing on its implications to the immune system. From an immunological perspective, the TB/COVID-19 co-infection has the potential to converge in a perfect storm. The paper emphasizes that the disorders induced by each pathogen to the immunomodulation tend to induce an unbalanced inflammatory response, which can promote the progression and worsening of both diseases. Understanding the nature of the interactions between M. tuberculosis and SARS-CoV-2 are crucial for the development of therapeutic strategies against co-infection. This is a useful review for implementers. Click here to read the review.