SARS-CoV-2: Pathogenesis, and Advancements in Diagnostics and Treatment

Abstract

The emergence and rapid spread of SARS-CoV-2 in December 2019 has brought the world to a standstill. While less pathogenic than the 2002–2003 SARS-CoV, this novel betacoronavirus presents a global threat due to its high transmission rate, ability to invade multiple tissues, and ability to trigger immunological hyperactivation. The identification of the animal reservoir and intermediate host were important steps toward slowing the spread of disease, and its genetic similarity to SARS-CoV has helped to determine pathogenesis and direct treatment strategies. The exponential increase in cases has necessitated fast and reliable testing procedures. Although RT-PCR remains the gold standard, it is a time-consuming procedure, paving the way for newer techniques such as serologic tests and enzyme immunoassays. Various clinical trials using broad antiviral agents in addition to novel medications have produced controversial results; however, the advancement of immunotherapy, particularly monoclonal antibodies and immune modulators is showing great promise in clinical trials. Non-orthodox medications such as anti-malarials have been tested in multiple institutions but definitive conclusions are yet to be made. Adjuvant therapies have also proven to be effective in decreasing mortality in the disease course. While no formal guidelines have been established, the multitude of ongoing clinical trials as a result of unprecedented access to research data brings us closer to halting the SARS-CoV-2 pandemic.

SARS-CoV-2 RNA-dependent RNA polymerase as a therapeutic target for COVID-19

“…Patients with severe COVID-19 may develop acute respiratory distress syndrome (ARDS) and hypoxia with oxygen saturation levels under 90%, multiorgan dysfunction syndrome, and other extrapulmonary manifestations [ 2 ]. As exhaustively described in recent reviews [ 5 , 6 ], severe COVID-19 symptoms are mostly the consequence of immune dysregulation and uncontrolled inflammatory response. Indeed, the rapid activation of the cell-mediated response leads to an increased pro-inflammatory status with a massive release of cytokines, particularly IL-6, IL-2, IL-10, and TNF-α, causing acute lung injury and contributing to the COVID-19 pathology.…”

The Abstruse Side of Type I Interferon Immunotherapy for COVID-19 Cases with Comorbidities

“…Since ISGs regulate a vast range of cellular functions, ranging from transcription to translation of proinflammatory and metabolic molecules in phagocytic cells, any impairment in IFN-I signaling can be harmful to the host. Thus, optimal and timely activation of IFN-I signaling is crucial for a well-coordinated antiviral effect of phagocytes with minimal damage to the host [1][2][3][4].…”

“…In the absence of any proven vaccine and/or targeted therapeutic agent available, COVID-19 cases are currently treated empirically, based on the disease symptoms. Several clinical trials are ongoing for COVID-19 therapy, including antiviral agents, antibodies against inflammatory cytokines, and repurposing of drugs used for other ailments [2]. There are currently at least 60 clinical trials at various stages of implementation to determine the beneficial effects of type I interferon (IFN-I) (α, β, or both), either alone or in-combination with antiviral or anti-inflammatory drugs, in reducing COVID-19 mortality [3].…”

Long-term antibody-response monitoring following primary exposure to SARS-COV-2 and afterward mRNA COVID-19 vaccination: A case report

“…The most important pre-conditions for COVID-19 "expansion" are: 1) high potential of virus transmission from "human-to-human" and 2) existence of an "immunologically-naive" background, i.e. population [1][2][3][4] .…”