Scientific research progress of COVID‐19/SARS‐CoV‐2 in the first five months

Original Article: Li H, Liu Z, Ge J. Scientific research progress of COVID-19/SARS-CoV-2 in the first five months. J Cell Mol Med. 2020;24(12):6558-6570.

Author of summary: Valeria Gradinati; Reviewer: Marianna Coppola

Original Article Published on April 22nd, 2020

A complete overview on the COVID-19 pandemic five months after the initial outbreak in Wuhan, China, started December 2019. Information on epidemiology, pathogenesis, pathology, clinical features, detection methods and treatment.

EPIDEMIOLOGY :

  • SARS-CoV-2 has a very high transmission ability and low genetic heterogeneity. To date, there is no evidence that any particularly significant viral recombination has occurred. However, its continuous spread might favour the emergence of variants
  • Detected mutations are race-specific (European and American VS East Asia)
  • Asymptomatic patients amounting to 1% of the total number of cases show equal viral load of symptomatic patients. The virus diffuses mainly by droplets and penetrates through the nose or the eyes. Fecal-oral spread may also be possible. Avoid transmission by reducing close contact (isolation, masks)
  • Pregnant women can transmit SARS-CoV-2 to their child
  • Incubation period ranges from 1-14 days and peaks mostly at 3-7 days. 24 days incubations have also been reported
  • On average, death is expected about 18 days after symptoms onset, while hospital discharge takes place after 25 days

PATHOGENESIS :

  • SARS-CoV-2 accounts for 4 major structural protein-coding genes. Its spike protein (S) is crucial for determining host tropism and transmission capacity. Hence, it represents a good antigen for vaccine development
  • SARS-CoV-2 invades cells through the ACE2 receptor (Angiotensin Converting Enzyme II), involved in the RAAS (Renin-Angiotensin-Aldosterone System), thanks to the activating interaction receptor-S protein
  • ACE2 is expressed highly in lungs, esophagus upper and stratified epithelial cells, intestine, absorptive enterocytes from ileum and colon, cholangiocytes, myocardial cells, adipocytes, kidney proximal tubule cells and testicles
  • Like other coronavirus, SARS-CoV-2 might access the central nervous system (CNS) through the olfactory bulb. The cytokine storm occurring in severe cases of COVID-19 might increase the blood-brain barrier (BBB) permeability, thus causing a brain infection with a predilection for basal ganglia, temporal lobes and brainstem. Some deaths could be connected to the brainstem respiratory centers direct invasions
  • Adequate animal models for human SARS-CoV-2 infection are cats and ferrets

PATHOLOGY

●       A unique pathological feature of SARS-CoV-2 infection is the bilateral diffuse alveolar damage with cellular fibromyxoid exudates

●       Pneumocytes are enlarged (large nuclei, prominent nucleoli and amphophilic granular cytoplasm) and lymphocytes dominate interstitial mononuclear inflammatory infiltrates in lungs

CLINICAL FEATURES

●       The main symptoms of SARS-CoV-2 are fever, cough, difficulty breathing, nausea or vomiting, diarrhoea and dizziness (listed by frequency). Chills (occasionally accompanied by repeated shaking), muscle pain, headaches, sore throats, or new loss of taste or smell are additional symptoms officially recognized by CDC

  • Olfactory and taste disorders can last for weeks or months depending on the mechanism of damage
  • Several studies describe secondary neurological events, in particular strokes (ischemic or hemorrhagic), seizures, meningo-encephalitis, and Guillain-Barré syndrome
  • Risk factors include age (elderly), gender (males), blood type (A is weaker compared to 0), and comorbidities (hypertension, diabetes, cardiovascular diseases, obesity, and malignancies)
  • EARLY STAGE BLOOD PROFILE: peripheral blood leukocytes are normal or decreased, lymphocytes are decreased. In some patients, liver enzymes, lactate dehydrogenase (LDH), CRP, muscle enzymes, aspartate transaminase and myoglobin are increased. Severe COVID-19 shows increased percentages of naïve T cells VS reduced helper, suppressor and regulatory T cells.
  • BEFORE DEATH, a CYTOKINE STORM activates the coagulation system, induces continuous inflammatory response, and may provoke kidney injury.  Neutrophil count, D-dimer, blood urea, and creatinine levels increase, and the lymphocyte count decreases
  • COMPLICATIONS :
    • hypertension and cardiovascular disease, as well as obesity and type-2 diabetes, are predictive for both severe disease and ICU admission. Virus-related cardiac injury induces high levels of hypersensitive troponin I (hs-cTnI test). Major vigilance is needed for this category of patients
    • Kidneys: elevated serum creatinine and urea nitrogen, AKI, proteinuria, and hematuria are the independent risk factors for in-hospital death
    • CNS: possible neuropathy and myopathy after long stay in ICU, neurodegenerative diseases
    • No conclusive association with cancer
  • DETECTION METHODS: to overcome the standard NUCLEIC ACID DETECTION (RT-PCR) limits, results should be combined with ANTIBODY DETECTION. The acute phase of infections matches higher IgM levels, while late/previous infection displays higher IgG levels. Noticeably, Abbott ID NOW molecular diagnostics developed an assay that delivers results within 13 minutes (VS current 2-3 hours)

TREATMENT

●       WHO initiated a series of clinical trials for antiviral drugs such as Remdesivir, Lopinavir/Ritonavir, interferon β and Chloroquine/Hydroxychloroquine

FUNCTIONING IN VITRO CLINICALLY TESTED
EARLY STAGE COVID-19 SEVERE COVID-19
Disulfiram, Favipiravir, Arbidol and Nitazoxanide Lopinavir/Ritonavir Chloroquine/hydroxychloroquine* Remdesivir** Remdesivir (FAILED)**

*primary results indicate that this drug might be harmful for COVID-19 patients. Administer with caution

**This drug failed in Phase III clinical trials. However, preliminary data from NIH show that Remdesivir accelerated recovery from 15 to 11 days in 31% patients when compared to placebo

●       OTHERS: low doses of corticosteroids for SEVERE COVID-19 patients with ARDS (Acute Respiratory Distress Syndrome), sepsis or septic shock. Baricitinib in combination with Lopinavir/Ritonavir/Remdesivir (to be tested)

●       CONVALESCENT PLASMA THERAPY:  treatment with plasma from rehabilitate COVID-19 patients improves COVID-19 patients’ condition

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