Natural history of COVID-19 and therapeutic options

Abstract

Introduction: COVID-19 presents benign forms in young patients who frequently present with anosmia. Infants are rarely infected, while severe forms occur in patients over 65 years of age with comorbidities, including hypertension and diabetes. Lymphopenia, eosinopenia, thrombopenia, increased lactate dehydrogenase, troponin, C-reactive protein, D-dimers and low zinc levels are associated with severity.Areas covered: The authors review the literature and provide an overview of the current state of knowledge regarding the natural history of and therapeutic options for COVID-19. Expert opinion: Diagnosis should rely on PCR and not on clinical presumption. Because of discrepancies between clinical symptoms, oxygen saturation or radiological signs on CT scans, pulse oximetry, and radiological investigation should be systematic. The disease evolves in successive phases: an acute virological phase, and, in some patients, a cytokine storm phase; an uncontrolled coagulopathy; and an acute respiratory distress syndrome. Therapeutic options include antivirals, oxygen therapy, immunomodulators, anticoagulants and prolonged mechanical treatment. Early diagnosis, care, and implementation of an antiviral treatment; the use of immunomodulators at a later stage; and the quality of intensive care are critical regarding mortality rates. The higher mortality observed in Western countries remains unexplained. Pulmonary fibrosis may occur in some patients. Its future is unpredictable.

Post-COVID Syndrome: An Insight on Its Pathogenesis

“…COVID-19 is a multi-system infection [ 53 ]. The cell surface angiotensin-converting enzyme 2 (ACE2) receptor, which is abundant in cells of most organs, is the main target for SARS-CoV-2 binding and infection [ 54 , 55 ].…”

“…The cell surface angiotensin-converting enzyme 2 (ACE2) receptor, which is abundant in cells of most organs, is the main target for SARS-CoV-2 binding and infection [ 54 , 55 ]. A monocyte-macrophage, CD4 and CD8 cellular response, and a controlled inflammatory response occur, which results in an uncomplicated recovery of most patients [ 53 ]. A SARS-CoV-2 immune dysregulation, associated with elevated levels of cytokines interleukin-1β (IL-1β), IL-6, IL-2, and IL-10 (“cytokine storm”) and profound inflammation, is found in patients with severe life-threatening illnesses [ 53 ].…”

“…Vascular impairment, in association with vascular endothelial growth factor, IL-6 and TNFα, is also prominent in the inflammatory phase of acute respiratory distress syndrome (ARDS) and may account for post-COVID-19 pulmonary fibrosis, which is characterized by uncontrolled fibroproliferation in the context of dysregulated release of matrix metalloproteinases, leading to injury of endothelium and epithelium [ 63 ]. Likewise, infected monocytes and macrophages, which are part of the first cellular immune response to acute SARS-CoV-2 infection, may contribute to cytokine storm and massively migrate from lungs to tissues, and appear to contribute to post-COVID complications, including fibrosis, while their manipulation may open novel therapeutic perspectives [ 53 , 55 , 64 ]. High-resolution chest computed tomography has shown architectural distortion, interlobal septal thickening and traction bronchiectasis, compatible with fibrotic lung disease, in patients who continue to have hypoxia, even after three weeks of treatment, despite the improvement of their symptoms [ 63 ].…”

“…In addition, in a previously healthy 56-year-old man with persistent neurological disorders, including short-duration epileptic seizures, and deep depression almost six months after COVID-19, CNS MRI revealed numerous hyperintense focal areas in the periventricular and subcortical white matter and in semioval centers, compatible with gliotic outcomes in association with microvascular injuries [ 71 ]. Endothelial injury, either due to virus invasion or in the context of profound inflammation increased levels of coagulation factors, hypoxia, due to respiratory impairment or anti-platelel factor 4 (PF4)-immune complexes, has been implicated in acute COVID-19 pathogenesis, predisposing to coagulopathy and thromboembolic complications in large blood vessels and microcirculation [ 53 , 72 , 73 ]. Thromboembolism may also complicate the post-COVID period in the context of a hypercoagulate state [ 74 ].…”

The role of IL-6 and IL-6 blockade in COVID-19

“…Coronavirus disease 2019 (COVID- 19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presents with a mild form of upper respiratory infection or no symptoms at all in the majority of individuals [1]. A subgroup of patients, however, may progress to severe and critical disease experiencing acute hypoxic respiratory failure, acute respiratory distress syndrome (ARDS), multi-organ failure and not infrequently death [2]. SARS-CoV-2 induces a dysregulated hyperinflammatory response in later stages as the virus was found to infect monocytes, macrophages, and dendritic cells (DCs) that increase the secretion of pro-inflammatory cytokines including interleukin-6 (IL-6) [2].…”