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Review
. 2020 Sep:129:110493.
doi: 10.1016/j.biopha.2020.110493. Epub 2020 Jul 3.

Natural history of COVID-19 and current knowledge on treatment therapeutic options

Wagner Gouvea Dos Santos  1
Affiliations
Review

Natural history of COVID-19 and current knowledge on treatment therapeutic options

Wagner Gouvea Dos Santos. Biomed Pharmacother. 2020 Sep.

Abstract

Despite intense research there is currently no effective vaccine available against the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in the later 2019 and responsible for the COVID-19 pandemic. This infectious and communicable disease has become one of the major public health challenges in the world. The clinical management of COVID-19 has been limited to infection prevention and control measures associated with supportive care such as supplemental oxygen and mechanical ventilation. Meanwhile efforts to find an effective treatment to inhibit virus replication, mitigate the symptoms, increase survival and decrease mortality rate are ongoing. Several classes of drugs, many of them already in use for other diseases, are being evaluated based on the body of clinical knowledge obtained from infected patients regarding to the natural history and evolution of the infection. Herein we will provide an updated overview of the natural history and current knowledge on drugs and therapeutic agents being tested for the prevention and treatment of COVID-19. These include different classes of drugs such as antiviral agents (chloroquine, ivermectin, nitazoxanide, hydroxychloroquine, lopinavir, remdesivir, tocilizumab), supporting agents (Vitamin C, Vitamin D, azithromycin, corticosteroids) and promising investigational vaccines. Considering the controversies and excessive number of compounds being tested and reported in the literature we hope that this review can provide useful and updated consolidated information on potential drugs used to prevent, control and treat COVID-19 patients worldwide.

Keywords: Anakinra; Convalescent plasma; Corticosteroids; Hydroxychloroquine; SARS-CoV-2; Vaccine.

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Conflict of interest statement

There is no conflict of interest

Figures

None
Graphical abstract
Fig. 1
Fig. 1
Preventive measures to avoid the spread of SARS-CoV-2. The virus spread mainly from person-to-person between people who are in close contact with one another and through respiratory droplets produced when an infected person cough, sneezes or talk. The best way to prevent is to avoid being exposed to the virus.
Fig. 2
Fig. 2
Life cycle of SARS-CoV-2 and potential drug targets. 1) SARS-CoV-2 enters target cells via two ways, either via endosomes or plasma membrane fusion. In both ways spike proteins (S1 e S2) mediate attachment to the cell membrane by binding to the ACE2 receptor, 2) In the endosomal via, spike proteins are activated by cathepsin L or alternatively by transmembrane protease serine 2 (TMPRSS2) in close proximity to ACE2 receptor, which initiates fusion of the viral membrane with the plasma membrane, 3) viral RNA is released and part is translated to produce polyproteins pp1a and ppab, which are cleaved by proteases PIpro and 3CLpro to yield 16 non-structural proteins that form the RNA replicase-transcriptase complex, 4) This complex drives the production of negative-sense RNAs through both replication and transcription. A subset of around 9 subgenomic RNAs including those encoding all structural proteins (S-spike, M-membrane, N-nucleocapsid and E-envelope) are translated, 5) Viral nucleocapsids are assembled from genomic RNA and N protein in the cytoplasm, followed by budding into the lumen of endoplasmic reticulum (ER)- Golgi complex, 6) Virions are then released through exocytosis. Potential SARS-CoV-2 targets and drugs are shown in red. The drugs and treatment strategies investigated aim to inhibit viral entry/replication into human cells, avoid cytokine storm or decrease hyperinflammation and lung injury. ACE - Angiotensin-Converting Enzyme, ARB – Angiotensin Receptor Blocker, CQ - Chloroquine, HQ - Hydroxychloroquine, TMPRSS2–Transmembrane serine protease 2, IL-interleukin, JAK- Janus kinase.
Fig. 3
Fig. 3
Schematic representation of the natural history of COVID-19 from the onset to recovery or death. There are basically three stages or phases in the natural history of COVID-19, regarding disease severity. The first phase is related to the onset of the disease and is generally characterized by the development of influenza-like symptoms from mild to moderate. Some individuals recover and some progress to the second phase. In this phase, it is possible to detect pneumonia-like symptoms evidenced as lung opacities as seen in chest radiography or as glass opacities in computed tomography (CT). Depending on the severity of phase 2 patients can improve or worsen with the necessity of intubation and ventilation. These patients are typical examples of the phase 3 which is characterized by hyperinflammation and sepsis of lungs and patient often requires intensive care unit (ICU) and most of them unfortunately can not overcome the infection and eventually die.
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