Abstract
More than one and a half years have elapsed since the commencement of the coronavirus disease 2019 (COVID-19) pandemic, and the world is struggling to contain it. Being caused by a previously unknown virus, in the initial period, there had been an extreme paucity of knowledge about the disease mechanisms, which hampered preventive and therapeutic measures against COVID-19. In an endeavor to understand the pathogenic mechanisms, extensive experimental studies have been conducted across the globe involving cell culture-based experiments, human tissue organoids, and animal models, targeted to various aspects of the disease, viz., viral properties, tissue tropism and organ-specific pathogenesis, involvement of physiological systems, and the human immune response against the infection. The vastly accumulated scientific knowledge on all aspects of COVID-19 has currently changed the scenario from great despair to hope. Even though spectacular progress has been made in all of these aspects, multiple knowledge gaps are remaining that need to be addressed in future studies. Moreover, multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have emerged across the globe since the onset of the first COVID-19 wave, with seemingly greater transmissibility/virulence and immune escape capabilities than the wild-type strain. In this review, we narrate the progress made since the commencement of the pandemic regarding the knowledge on COVID-19 mechanisms in the human body, including virus–host interactions, pulmonary and other systemic manifestations, immunological dysregulations, complications, host-specific vulnerability, and long-term health consequences in the survivors. Additionally, we provide a brief review of the current evidence explaining molecular mechanisms imparting greater transmissibility and virulence and immune escape capabilities to the emerging SARS-CoV-2 variants.
Highlights
The ongoing pandemic of coronavirus disease 2019 (COVID-19) has taken a heavy toll on human lives globally (~4.8 million until October 8, 2021, per WHO data)
Extensive research has been performed globally, unraveling the various mechanisms involved in the pathogenesis and host immune responses for COVID-19
A human-specific adaptation of the viral–host interaction mechanisms has been derived from the laboratory data from the patients with COVID-19 and the experimental studies involving human tissue organoids
Summary
The ongoing pandemic of coronavirus disease 2019 (COVID-19) has taken a heavy toll on human lives globally (~4.8 million until October 8, 2021, per WHO data). The emergence of multiple SARS-CoV-2 variants with greater transmissibility/virulence and immune escape capabilities is an unfortunate turn in the current course (2020–2021) of the pandemic. We precisely discuss the current evidence for the pathogenic mechanisms of COVID-19 in humans, including virus–host interactions, pulmonary and other systemic manifestations, immunological dysregulations, complications, host-specific vulnerability, and long-term health issues in survivors. We discuss in brief the current evidence explaining molecular mechanisms imparting greater transmissibility and virulence and immune escape capabilities to the emerging SARS-CoV-2 variants. COVID-19 is primarily described as a disease-causing severe acute respiratory syndrome (SARS); the systemic manifestations involving other organs, including the central nervous system (CNS), are very usual [5] (Table 1). To enter into the host cell, the priming of the viral spike protein (S) is considered essential for its fusion to host cell membrane, which involves cleavage of the “S” protein by serine proteases called
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