Beijing and Wuhan - Chinese researchers have imaged the 2019-nCoV with an electron microscope. According to its report in the New England Journal of Medicine (2020; DOI), the gene sequence has the greatest similarity to SARS-like viruses previously detected in bats.
In the Lancet, doctors from the Jin Yin-tan Hospital in Wuhan presented the clinical picture of NCIP (“novel coronavirus-infected pneumonia”) based on the course in the first 41 patients. Doctors from the University of Hong Kong describe how several members of family fell ill with NCIP (Lancet 2020; DOI).
The 3 patients in whom the virus was first detected were admitted to the Jin Yin-tan Hospital on December 27th. All 3 had severe pneumonia at this point, from which 2, 49-year-old woman and 32-year-old man, have since recovered. They were released from the clinic on January 16. The third patient, 61-year-old man, died as result of the infection.
The patients with this unusual disease were not the only ones. The accumulation of cases prompted the clinic to alert the Chinese Center for Disease Control () in Beijing in December. From there, “Rapid Response Team” arrived in Wuhan on December 31st.
The researchers examined bronchial lavage samples using the RespiFinder Smart kit for known pathogens. After all of the results were negative, the RNA was extracted from the bronchial lavage and sequenced. A previously unknown beta coronavirus was discovered on January 7th.
Similarities with SARS allow conclusions to be drawn about animal reservoirs
According to Na Zhu and employees of the China CDC, its gene sequence is 86, 9% identical to 2 SARS-like coronaviruses ("bat-SL-CoVZC45, MG772933.1") that were previously found in bats. These 3 viruses form new subclade. Together with 2 other SARS-like coronaviruses ("ZC45" and "ZXC21"), this belongs to clade from the B line of coronaviruses. The next higher class is the subgenus of the Sarbecoviruses, to which the SARS-CoV also belongs, which also occurred in China in 2002.
The high degree of correspondence between the gene sequences suggests that the 2019-nCoV and the SARS CoV has its reservoir in bats. It could then have been transferred to the Chinese weekly markets via an intermediary host. However, the detection of 2019-nCoV or its immediate precursor in bats is still pending.
The researchers reproduced the viruses in cell lines of human respiratory epithelia. The first cytopathic effects were found there after 96 hours. They consisted of the loss of ciliary movements, which was visible under the light microscope.
After 6 days, spherical viruses with size of 60 to 140 nanometers were seen under transmission electron microscope. They had spikes 9 to 12 nanometers in size on the surface, which, according to Zhu, surrounded the virus like solar corona. The viruses were seen outside and inside cells. In the cells they were in inclusion bodies. The morphology corresponds to that of other known coronaviruses.
The rapid identification of the virus has enabled the development of detection tests that can be used to search for the new virus. The next step will be the development of an antibody test with which the spread of the pathogen in the population can be examined.
Whether the virus can gain foothold in the population depends on whether it is asymptomatic or There are mild infections for which people do not see doctor. The replication of the viruses in cell cultures will facilitate the search for potential drugs, the effectiveness of which could first be tested on the cell cultures.
The Beijing health authorities arranged for all patients to be treated at the Jin Yin-tan Hospital at the end of December . A total of 51 patients were cared for there up to January 2, of which the suspicion was later confirmed in 41 patients.
Diagnostic differences to seasonal flu
According to Chaolin Huang and colleagues, the disease begins the clinic with fever, dry cough, myalgia and fatigue. Within 1 week there is significant worsening with shortness of breath, which makes admission to clinic necessary.
In contrast to common coronavirus infections, the upper respiratory tract seems to be affected less often. This could be an important differential diagnostic clue for differentiating it from seasonal flu. There is also hope that the disease will not be easily transmitted. The diarrhea often observed with SARS seems to be rather unusual.
All 41 patients were diagnosed with pneumonia on admission to the clinic. 2/3 of the patients had lymphopenia in their blood count. Frosted glass infiltrates were observed on computed tomography. The patients who were treated in the intensive care unit later developed multiple lobular consolidation.
The disease then progressed rapidly. A total of 12 patients developed acute lung failure (ARDS) within 2 days, 4 patients had to be ventilated mechanically. Extracorporeal membrane oxygenation (ECMO) was carried out in 2 of the 4 patients.
In 5 patients there was acute cardiac damage, in 4 patients secondary infections. By January 22nd, 28 patients had been discharged and 6 patients died from the NCIP. The case fatality rate in the clinic was 14.6%.
Since only the severe cases were treated in the clinic, the proportion of cases that lead to death is likely to be lower overall. There were 25 deaths among the first 835 cases in Wuhan. This results in case fatality rate (CFR) of 2.9%. That would be less than with MERS-CoV (37%) and SARS (10%).
Among the deceased was patient who probably infected his 53-year-old wife. Huang therefore assumes that the disease can be transmitted from person to person. This is also supported by the fact that 1/3 of the patients had no contact with the seafood market, which is considered the starting point of the epidemic.
A cluster of diseases in family from Shenzhen in the neighborhood continues to favor direct transferability Hong Kong. 6 members of the family had visited Wuhan between December 29 and January 4, but there was no connection to the seafood market.
Possibly shorter incubation period than the SARS pathogen
After their return 5 of the 6 people developed NCIP. Another family member who had not visited Wuhan also fell ill, as reported by Jasper Fuk-Woo Chan and colleagues from Hong Kong University, where the patients were hospitalized 6 to 10 days after returning from Wuhan. Some of the patients' first symptoms had already set in during their seven-day stay in Wuhan. Chan estimates the incubation period to be 3 to 6 days.
The director of the National Health Commission, Ma Xiaowei, reported in Beijing yesterday that the incubation period is usually around ten days. The shortest recorded time span was only one day - the longest 14 days. The infected are already contagious during this time, even if no symptoms are noticeable.
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This distinguishes the new variant of the coronavirus from the closely related SARS pathogen that triggered the 2002/2003 pandemic. SARS could only be transmitted after symptoms appeared, that is, the incubation period was shorter than the latency period, said Bernd Salzberger, Head of Infectious Diseases at the Regensburg University Hospital and President of the German Society for Infectious Diseases, an important difference.
Another person in the Lancet study, an asymptomatic child, was also found to be infected. The child had frosted glass infiltrates on the computed tomogram despite the lack of symptoms. The illness of 15 doctors and nurses at clinic in Wuhan, reported in the media, also shows that "superspreading" events can occur. These were an important hallmark of SARS.
There, the proportion of nosocomial infections was 58%. With MERS-CoV it is even 70%. While no people have been infected with the SARS-CoV since 2003, MERS-CoV is still active in the Middle East, as cluster announced in ProMED these days shows.