Viruses: More Friends Than Foes (Revised Edition). Karin Moelling
whole of China. The virus’s gene sequence indicates a close relationship with a coronavirus from a bat. The sequence allowed the development of a test kit based on the polymerase chain reaction (PCR), a standard assay for many diseases, pathogenic viruses and other microbes or genetic disorders. The sequence then immediately allowed the development of tests and a genetic vaccine. On January 18th there still was a big festival in Wuhan, and on the 20th it was reported that the virus can be transmitted from human to human. This is what makes a virus dangerous!
China started with the lockdown on January 23rd in Wuhan, and this was extended to the neighboring cities, to Hubei and to the provinces, just before the Chinese traditional New Year’s Day. This event leads to the year’s highest number of visitors going home for family reunions. Around 50 million people were isolated in their homes. Airports were closed and traffic was shut down. Already then, three visitors coming back from China were placed in quarantine in France, and tracing for contact persons was initiated. First patients were identified in Australia and other Asian countries. On March 6th it was announced that closing borders would be 90% effective in containing the virus. A Chinese visitor informed a company in Munich about an infection, and this initiated the German activities, tracing contacts and imposing two-weeks quarantine. Germany had a head start compared with other European countries, with an index case number of zero, while In contrast other countries still allowed events with high potential for viral spread to proceed — such as football matches, church services, street parades and winter sport at resorts. On March 18th measures were proclaimed in Germany for social distancing, hygiene, closing of schools, restriction of travelling, and tracing of contacts by telephone — and fax machines! — in Germany the shutdown and restriction of people was less severe than in other European capitals, which were deserted, also subsequently in the USA. Was that necessary or based on China as a model, where the population densities can be locally due to skyscrapers much higher?
Starting an epidemic with many cases, such as when infected people attend a football match, results in steep exponential growth curve, as it did in Lombardy. There, other factors may have contributed, such as air pollution, family structures, the presence of many guest workers in a highly industrialized area, and a high population density. Often, Italy was projected as a horror scenario that would soon play out in Germany, even though the parameters differed considerably. The death toll was high in Italy, partly owing to comorbidities of older people, aged between 70 and 80. Other countries have other risk factors such as diabetes, coronary heart disease, asthma and obesity — the latter affects about 40% of Americans. It enhances the severity of the disease. On April 6, 2020 the isolation measures in Wuhan were lifted and replaced by strategies for exit from the pandemic, and 11 million people tried to leave immediately. One still sees face mask protection and empty streets there. Individual infections occur sporadically, mainly imported by travelers. They are traced back by help of mobile phones to prevent spreading. This is also part of the successful containment of the virus in Korea. In Germany, hotlines have been installed and tracing is done by telephone or Fax follow-ups.
It is worth mentioning that Korea was one of the few countries where the MERS virus was detected in 2009, and perhaps it was this that warned Koreans more than other countries, as by then they had already twice gone through such an epidemic.
In Europe the exit strategy — how to get out of the shutdown — was adopted by several European countries individually to stimulate the economy again. Germany produced an incredible financial umbrella, initially up to 155 billion euros, to protect the economy, but this is constantly increased.
Meanwhile, the pandemic reached India, with 140 million people trying to reach their homes before shutdown. The pandemic has reached the southern hemisphere: it arrived in South Africa, where experience with the HIV/AIDS epidemic was well remembered and led to fast reaction. It has arrived in South America, in Brazil, and even on Easter Island (through tourism?) and has hit isolated indigenous tribes in Brazil. In spite of less health care systems in Africa and South America, it is a hope, that the younger average age of the population may be protective.
Origin of SARS-CoV-2
CoV-2 most probably originates from bats and is a zoonotic disease, meaning that it started in animals before it reached humans. An intermediate was perhaps the pangolin, a scaly ant-eating mammal, sold on the wet market in Wuhan; intermediate hosts are frequently involved. In a paper in the New England Journal of Medicine, G. Gao pointed out that the first infected patients had no link to the market. Perhaps an amplification occurred there or an indirect transmission through latently infected people. The bats are a special kind, the horseshoe bat, which exists in Yunnan (1600 km away), and bats were hibernating at that time.
Bats are the source of many viruses. They have a special immune system: the antiviral interferon system activates another factor, which means almost a doubling of immunity and of protection against viruses. Therefore, bats are often carriers and transmitters of viruses without getting ill themselves. There are about 1500 caves in China where millions of bats live. They rarely infect humans directly, but known viruses, such as Ebola or Marburg disease, and the new coronaviruses originate from bats. Also the SARS outbreak in 2003 was traced back to bats and an intermediate host, the civet cat, which raised the question whether this could happen again.
In 2015, Wuhan’s WIV obtained a high-containment laboratory at the highest biosafety level 4 (BSL-4). This was the first laboratory of this type in mainland China. The construction was already approved in 2003 as a consequence of the SARS outbreak in that year. After this SARS outbreak, intensive research started to understand it and prevent a repeat. The laboratory was designed and constructed with French assistance with the BSL-4 Institute in Lyon as model. A co-operative agreement was made on prevention and control of emerging infectious diseases in 2004. It took until 2014 to finish the construction. Viruses studies there included the Ebola, Lassa, Hendra and Nipah viruses, while SARS does not require BSL-4.
The goal was to study how viruses mutate into new strains and cause diseases, and to develop treatments based on antibodies and small molecules.
A special question was how zoonotic viruses, such as SARS and Ebola, spread among humans. In biosafety laboratories the air is filtered through HEPA filters; the rooms are under low pressure so that viruses will stay inside and do not escape by air flow; researchers have full-body protective suits with their own air supply for breathing; and masks are used. Biosafety labs contain clean benches with hoods, equipped with filters and vertical air flow which acts like an “air curtain” and separate the researcher from his/her work.
In a laboratory at the University of North Carolina in the USA, researchers tried in 2015 to analyze bat viruses, and generated recombinant viruses which could bind to human lung cells. The authors state that such viruses need to be constructed so that one can learn about pandemic viruses. However, the virus became frightening, and the authors mention in their paper that such viral chimeras will no longer be produced. The procedure is called “gain of function” (GOF) for viruses gaining new characteristics. The danger of an epidemic was considered high, and continuation of the experiments was forbidden (Nature Medicine 21, 1508, 2015). The authors are from the USA, China and Switzerland. The main contribution came from the USA, including finances, as stated in a later commentary on the paper. A recent footnote from 2020 states that this synthetic virus could not have contributed to the present pandemic.
I was surprised that SARS-coronaviruses do not require work in BSL-4 but only BSL-3 laboratories. Perhaps the BSL-4 laboratory was used, in spite of this, when it became available. On March 17, 2020 an article in Nature Medicine stated “that the authors do not believe that any type of laboratory-based scenario is plausible” (Nature Medicine 26, 450, 2020). The CoV-2 has an unusual polybasic sequence within the spike protein not found in other coronaviruses. Where did it originate? This basic stretch is a cleavage site for furin proteases, also detected in Influenza where it increases its pathogenicity. Recently a similar sequence was detected in a natural bat virus isolate.
Influenza 1918
The beginning of the Influenza outbreak in