The Covid disease caused by the Sars-CoV-2 coronavirus leads to pneumonia and shortness of breath in severe cases – that much is known. But now researchers have uncovered for the first time what reactions the virus causes in the lungs at an early stage of infection. This was only possible by accident: two Chinese patients had parts of their lungs removed because of a tumor before the first symptoms of Covid appeared. When the pathologists examined these lung samples, they could already see clear changes in them.
The Sars-CoV-2 coronavirus continues to spread, more than 85,000 people worldwide have been diagnosed so far. Several new cases have also occurred in Germany in the past few days. Attempts are still being made to curb further spread – among other things by quarantining suspected cases and finding possible contacts. But epidemiologists expect the virus to spread further to us. According to current knowledge, an infection with Sars-CoV-2 is mild in around 80 percent of cases and produces only mild flu-like symptoms. However, around 14 percent of Covid patients need treatment for shortness of breath and pneumonia, and a further six percent need intensive medical help such as ventilation. Covid-19 can be fatal, particularly in patients with pre-existing conditions.
How does the infection manifest in the lungs?
An aggravating factor in containing the epidemic is the relatively easy transferability of the coronavirus by droplet infection and the fact that infected people are contagious even during the incubation period – before they develop symptoms themselves. However, why this is the case with Sars-CoV-2 and what happens in the body of the infected before the onset of the first symptoms has so far been unclear. “There have been several studies describing clinical features and radiological findings, but so far there have been no pathological studies based on autopsies or biopsies,” said Sufang Tian from Zhongnan Hospital in Wuhan and his colleagues. The reasons for this are above all the rapid progress of the epidemic and the sheer overload of the hospitals in the outbreak areas. And even if such examinations are carried out, they can usually only detect the late stage of the disease – the phase in which the patient shows severe symptoms or even died of Covid.
But by luck, Tian and his team obtained lung samples that reveal the early stages of Covid disease for the first time. The lung parts come from two patients who had had parts of their lungs removed because of a tumor. At the time of these operations, both patients still appeared healthy and free of infection, the researchers report. They showed neither fever nor respiratory symptoms. It was not until several days after the lung operation that both patients developed the first signs of infection and were tested for the coronavirus – with a positive result. The scientists then subjected the previously removed parts of the lungs to a thorough examination. “To our knowledge, this is the first pathology data for Sars-CoV-2 pneumonia,” they report. “Thanks to this rare coincidence, we now have the only description of the early phase of Covid-19.”
Clear damage before the end of the incubation period
The tests revealed that the coronavirus had already caused visible changes in the lung tissue at the time of the lung operation. Tian and his team found numerous edema and accumulations of protein-rich mucus in the lung tissue in both samples. In addition, there were clear signs of inflammation, including in the form of lumps from fused lung cells and fibrin fibers released by the cells, as the scientists report. The delicate mucous membranes of the alveoli were also affected by these changes. “It is remarkable that these pathological changes preceded the development of clinical symptoms,” say the researchers. “This suggests that it takes a long time for Covid-19’s early lung lesions to become severe enough to cause symptoms.”
According to Tian and his colleagues, these findings are not only important to understand the process of Covid-19. It also suggests that detection methods such as throat swabs may not be sufficient to make a diagnosis in some cases. “During an epidemic, it could therefore be advisable to search for lung infiltration using radiological methods and to use serological tests,” the researchers emphasize.
Searching for antidotes is ongoing
In parallel to research into Covid disease, scientists around the world are also looking intensively for antidotes to the coronavirus. The antiviral remdesivir of the US pharmaceutical company Gilead is traded as one of the most promising candidates to date. This drug was originally developed against the Ebola virus, but proved to be ineffective in clinical studies in 2014. However, in animal experiments, Remdesivir showed good activity against other RNA viruses, including the coronaviruses Sars and Mers-CoV. Remdesivir is a so-called nucleotide analog. In parts of its structure, the active substance is similar to the RNA building blocks that RNA viruses need to replicate their genetic material. If this active ingredient is incorporated into the growing RNA by the virus enzymes, it stops further replication – the virus can no longer multiply. The first clinical studies with Remdesivir on Covid patients are already underway in China. Further studies are beginning in Asia, but also in the USA.
Source: Sufang Tian (Zhongnan Hospital, Wuhan) et al., Journal of Thoracic Oncology, doi: 10.1016 / j.jtho.2020.02.010