September 1st, 2020, by Labtoo's team
Since the alert sent by China in December 2019, the COVID-19 has not stopped to challenge the international scientific community and its research capacities. From its pathogenesis to its eradication, there are still many grey areas surrounding this new coronavirus. More than eight months after the alert, what are the key points to consider on the pandemic?
The first case of COVID-19 has been identified in Wuhan on 08 December 2019. An epidemic of pneumonia from unknown origin expands across the Hubei province and throughout China, then progressively to other countries. The virus is named SARS-CoV-2 by the International Committee on Taxonomy of Viruses on 11 February 2020 and belongs to the Coronavirus family. This family includes several viral strains, some of them being pathogenic towards humans: the SARS-CoV strain is responsible for the Severe Acute Respiratory Syndrome (SARS) that also appeared in China in 2003, while MERS-CoV is responsible for an epidemic evolving in Middle East since 2012.
The COVID-19 is usually spread by droplets and bioaerosols through the respiratory route or by direct contact. First stagnating in the upper respiratory tract and intensely multiplying in the nasopharynx, it then goes down to the lungs and alveolar cells. The virus is then able to spread in the blood and target organs expressing the angiotensin-converting enzyme 2 (ACE2) receptor such as the heart, the kidneys or the intestines.
A recent study has confirmed the susceptibility of SARS-CoV-2 to replicate itself in nasal cells, suggesting a gradient of SARS-CoV-2 infection in proximal (high) versus distal (low) respiratory tracts. Nasal cavities might be especially favorable to the virus replication and its spread through the produced droplets and secretions.
In order to achieve these results, researchers have utilized a reverse genetics system to generate a GFP reporter virus to explore SARS-CoV-2 pathogenesis and a luciferase reporter virus to demonstrate sera collected from SARS-CoV-2 patients exhibited limited cross-CoV neutralization. High-sensitivity RNA in situ mapping revealed the highest angiotensin-converting enzyme 2 (ACE2) expression in the nose with decreasing expression throughout the lower respiratory tract; the most infected cells were ciliated cells and type II pneumocytes.
These results allow to realize how important it is to wear a mask to limit exposition to bioaerosols, droplets and other nasal secretions in order to limit SARS-CoV-2 contamination.
Finally, these significant advances could also be useful to identify neutralizing antibodies from nasal cells, blood and lower respiratory secretions in order to accelerate research projects on therapeutic monoclonal antibodies aimed at the SARS-CoV-2.
Control of the virus transmission differs across countries and their respective public health policies, but globally takes into account the following measures: respect of the barrier measures, lockdown for all or parts of a population, massive screening of the population, development of a new medicine and vaccination.
As for the therapeutic strategies against the coronavirus, they mainly consist in inhibiting the viral replication in the body. Treating severe cases of SARS-CoV-2 involves inhibiting inflammation by modulating the immune response. Two types of targets are tested to inhibit the viral replication: viral targets (structural viral proteins for example) and cellular targets (involved in the virus replication). Using neutralizing antibodies to inhibit the interaction or fusion of the virus with human cells is at the core of many research projects. As for the cellular targets, they include proteins involved in the virus entry in cells and interferons. The second therapeutic strategy which consist in inhibiting the inflammation involves immunosuppressants and immunomodulators, that are currently studied in clinical trials.
The implementation of reliable diagnostic tests for sanitary services also constitutes a major issue to control the epidemic. The tests rely on PCR and RT-PCR techniques. These methods consist in amplifying viral RNA sequences by using primers to initiate the polymerization. Primers and target sequences optimization essays are still ongoing to this day in order to improve tests' reliability.
The pandemic continues to spread, and many countries fear a second wave that would occur in the upcoming months. Researchers have still a lot of points to elucidate about COVID-19, which will hopefully allow the development of treatments and vaccines against the virus.
In France, the first three cases of COVID-19 have appeared on 24 January 2020. Researchers from the Pasteur Institute had therefore access to biological samples containing the virus strain and have sequenced its entire genome in three days. The sequencing has been realized by the team of the P2M platform thanks to the Illumina technology. This technique of high throughput Next Generation Sequencing relies on the amplification and polymerization of the previously fragmented genome.
The access of the genome sequence is a critical aspect in the fight against the pandemic, and especially for the development of diagnostic tests relying on the genome analysis. The biological samples collected on COVID-19 positive patients have also allowed researchers from the Pasteur Institute to isolate and cultivate the virus. Thanks to the previous studies conducted by the Institute on SARS-CoV and MERS-CoV strains, the virus was successfully cultivated on Vero E6 cells. The in vitro cultivation step is also crucial to make the virus available for research, especially to develop new treatments options.