Pathophysiology and Potential Therapeutic Candidates for COVID-19: A Poorly Understood Arena

Abstract

Coronavirus disease 2019 (COVID-19), an acute onset pneumonia caused by a novel Betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in the Wuhan City of China in December 2019 and evolved into a global pandemic. To date, there are no proven drugs or vaccines against this virus. Hence, the situation demands an urgent need to explore all potential therapeutic strategies that can be made available to prevent the disease progression and improve patient outcomes. In absence of clinically proven treatment guidelines, several repurposed drugs and investigational agents are currently being evaluated in clinical trials for their probable benefits in the treatment of COVID-19. These include antivirals (remdesivir, lopinavir/ ritonavir, umifenovir, and favipiravir), interferon, antimalarials (chloroquine/ hydroxychloroquine), antiparasitic drugs (ivermectin and nitazoxanide), biologics (monoclonal antibodies and interleukin receptor antagonist), cellular therapies (mesenchymal stem cells and natural killer cells), convalescent plasma, and cytokine adsorber. Though several observational studies have claimed many of these agents to be effective based on their in vitro activities and extrapolated evidence from SARS and Middle East respiratory syndrome (MERS) epidemics, the currently available data remains inconclusive because of ill-defined patient selection criteria, small sample size, lack of concurrent controls, and use of intermediary outcomes instead of patient-relevant outcomes. Moreover, there is a need to clearly define the patient populations who warrant therapy and also the timing of initiation of treatment. Understanding the disease pathology responsible for the clinical manifestations of COVID-19 is imperative to identify the potential targets for drug development. This review explains the pathophysiology of COVID-19 and summarizes the potential treatment candidates, which can provide guidance in developing effective therapeutic strategies.

Lung Ultrasound Patterns and Clinical-Laboratory Correlates during COVID-19 Pneumonia: A Retrospective Study from North East Italy

“…In addition, we reconstructed COVID-19 progression through stages using data from different patients while this should be ideally done by serial imaging of the same patients. Therapies administered during the hospitalization were highly variable, also in relation to the evolving evidence during the pandemic [ 23 ]. Therefore, it is possible that part of the LUS changes observed according to disease stage and severity were due to in-hospital therapies, even though most have so far proven ineffective (except for glucocorticoids) [ 24 , 25 , 26 , 27 ].…”

COVID-19: a historicidade das terapêuticas no primeiro ano da Pandemia

“…Na ausência de diretrizes de tratamento clinicamente comprovadas, vários medicamentos estão sendo reaproveitados clinicamente. Estes incluem antivirais (remdesivir, lopinavir/ritonavir, umifenovir e favipiravir), interferon, antimaláricos (cloroquina/ hidroxicloroquina), medicamentos antiparasitários (ivermectina e nitazoxanida), imunobiológicos (anticorpos monoclonais e antagonista do receptor de interleucinas), terapias celulares (células-tronco mesenquimais e células assassinas naturais, plasma convalescente e adsorvente de citocinas) (Samaddar et al, 2020;Zhao, 2020).…”

May mesenchymal stem cell transplantation be a solution for COVID-19 induced cytokine storm?

“…Besides, Th, T suppressor (Ts), and regulatory T (Treg) cell count were determined as more obviously decreased in severe cases[ 50 ]. While studies on the pathophysiology of the disease are continuing, the following substances were found high in patients who suffer from cytokine storm: interleukin (IL)-1β, IL-2, IL-6, IL-7, IL-8, IL-9, IL-10, and IL-17; granulocyte-macrophage colony-stimulating factor (GM-CSF); TNF-α, IFN-γ, and IFN-γ inducible protein 10 (IP10); monocyte chemoattractant protein 1 (MCP-1); macrophage inflammatory protein 1α (MIP-1α) and MIP-1β; chemokines like CC chemokine ligand 2 (CCL2), CCL3, and CCL5; and C-X-C motif chemokine ligand 8 (CXCL8), CXCL9, and CXCL10[ 4 , 51 ]. In the detailed clustering analyses of the patients, higher C-reactive-protein (CRP), D-Dimer, ferritin, IP-10 (CXCL10), IL-10, IL-6 were founded to strongly correlated with poor clinical prognosis[ 52 , 53 ].…”