Coronavirus: Summary to date & insights

Just several weeks ago, I received a chat message from a colleague with a link to the news from the English version of China Daily about a mysterious virus that infected 44 individuals (11 in serious conditions) in Wuhan, Hubei province. It was January 3rd, 2020.

The Beginning

The article read ‘All the patients have been quarantined and are receiving medical treatment in hospitals in Wuhan. A total of 121 people who had close contact with the patients are under medical observation and health authorities are tracking more close contacts, according to the commission.

Epidemiological investigation shows that some patients are vendors in a seafood market in Wuhan. "So far, there is no clear signs of human-to-human transmission, and no medical worker has been infected," the release said.’

Wuhan healthcare authorities started to register first cases in the beginning of December, with the first patient admitted to the local hospital as early as December 8, 2019, presenting with fever-like symptoms from December 1, 2019. Between the first case registered on 8th and 31st of December there were 27 cases, which left no doubts that Wuhan was dealing with a viral pneumonia of unknown etiology (unknown cause). On that day, WHO China Country Office was officially informed of the Wuhan virus.

Later, the cohort of the first 41 patients has become a subject of in-depth analysis aiming to shed some light on the causes and severity of the new disease. The findings of the study were published in The Lancet on January 24, 2019. As we know now, the median age of the first 41 patients was 49 years old. One third had preexisting diseases, such as diabetes, cardiovascular disease and hypertension. The mortality rate among 41 patients constituted 15%, most of the fatalities occurred with elderly patients with secondary diseases. Although the majority of the cases had been associated with the notorious Huanan seafood market, the first three patients had no exposure to the market. Nevertheless, 27 of 41 patients had visited the market within 14 days before being admitted to the hospital.

What caused the virus still remains a mystery. The virus most likely originates from bats, the species that infamously bestowed SARS, Ebola and some diseases to humans. Chinese authorities demonstrated truly phenomenal speed in isolating and sequencing a new pathogen (nCoV-2019), which turned out to be 96% identical at the whole genome level to a bat coronavirus.

Wuhan Crisis

Pic. Wuhan

Wuhan is the world’s 42nd and China’s 7th largest city with 9 million permanent and 5 million temporary citizens. According to Wuhan Mayor, Zhou Xianwang, about 5 million people left the city before the lockdown initiated by the government on 23 January. Twelve other cities in the same province followed suit. In just three weeks of the new year it became clear that the virus was getting out of control and unless unprecedented measures were taken, the pandemic would spread nationwide. Perhaps it was already too late – all regions across China now have registered cases of nCoV-2019 virus. Nevertheless, even if belated, this was the right call. Wuhanhad hundreds of the registered cases in just several days starting from the mid-January.

Virus nCoV-2019

    High Contagiousness

Indeed, if we compare how SARS spread out in 2002-2003, it is hard not to notice how much more contagious nCoV-2019 is compared to SARS. It took SARS three months to reach to the point of 300 cases between November 2002 and February 2003. In the climax of SARS, the daily number of newly registered cases in Mainland China never exceeded 200 cases. In comparison, on 28th January 2020 alone, 1459 new cases of nCoV-2019 were reported nationwide, including 315 cases in Wuhan. In just a week between 20-28 January, the number of patients with nCoV-2019 exceeded the number of all SARS patients confirmed in Mainland China between 2002-2004! Mainland China had just 5327 cases of SARS, but nCoV-2019 already had 5974 registered cases by the end of January 28th, 2020.

       Mortality Rate

Luckily, nCoV-2019 has a relatively low expected fatality rate in comparison with the other two bat coronaviruses that appeared in the last two decades – SARS and MERS (Middle East Respiratory Syndrome). SARS’ mortality level was about 10%, and MERS had more than 30 percent of fatal cases. Despite of the gloomy data on mortality (15%) obtained through the study on the 41 earliest patients, most of the professionals in and out of China agree that the fatality rate of nCoV-2019 should be within 3%. To put this in perspective, common flu has fatality rate of 0.1%.

      Long Incubation Phase

The main concern for nCoV-2019 is relatively extended incubation phase of the virus, which can last from 5 to 14 days, during which a person is contagious. Moreover, there is already evidence of clinically silent cases (no symptoms), which will make prevention even more challenging.

In any case, full-scale quarantine to cope with Wuhan crisis seems to be a legitimate measure, supported both domestically and in the international community. 

     Relatively Low Number of Super-Spreaders

Currently, the Wuhan virus has only one ‘super spreader’ case – a highly virulent carrier who infects large groups of people. So far, there was one patient who allegedly infected more than a dozen of medical staff. As of today, there have been no other cases reported, which is encouraging news.

During SARS time, super spreaders were the main culprits of transforming disease into a nightmare. In Hongkong, for instance, a single spreader was responsible for 321 cases of SARS, which eventually lead to 42 deaths in the Amoy Gardens residential area in Hongkong, which he visited briefly just four times in the end of March, 2003. By the same token, Amoy Gardens’ super spreader was allegedly infected by yet another Hongkong super spreader in Prince of Wales Hospital, who infected 143 individuals, including medical workers, patients in the same ward and visitors. Another highly effective episode of viral transmission occurred onboard China Air’s flight 112 from Hong Kong to Beijing on March 15, 2003, when 22 people from the flight got infected by just a single person. In a similar manner, the transmission chain could be traced back to a single or several super spreaders in other regions across China in 2002-2003. Studies conducted in the wake of the severe acute respiratory syndrome (SARS) pandemic revealed that, in the absence of super-spreading events, most individuals infect few, if any, secondary contacts.

Improved Government’s Efforts

      Communications

During the SARS pandemic in 2002-2003, there was significant room for improvement in the frequency, transparency and speef of government’s communication with the public. This is not the case in 2020. From very early on, the central government has taken a stance of full transparency on the coverage of the nCoV-2019 epidemic. As such, the government has made a centralized informational dashboard available on PC and smartphone with general information about the virus, hourly updates, graphs representing the spread of the virus and other related information.

         Identification of possibly infected people      

Tremendous efforts are being made to trace and isolate all close contact of people who became ill. As an example, every day, dozens of messages are spread via social media with information on train numbers or metro lines taken by people who later were diagnosed with nCoV-2019. The messages encourage people from the same trains to provide their information and whereabouts to the local healthcare authorities. Local healthcare providers visit recent returnees from Wuhan at their permanent residences to check on their health condition. As of 28 January, 59 990 people are under clinical observation. 

To minimize unnecessary exposure of patients with conditions to the hospitals, the government organizes remote consultations with primary care doctors and specialists from patients.

        Quarantine Measures across the country

On the national scale, the government has taken a ‘regional quarantine’ approach by concentrating all the cases of nCoV-2019 in certain regions. Provided that hundreds of millions of people move around the country during the Chinese New Year, extending involuntarily holidays should help to reach this goal. As example, Shanghai holidays have been officially prolonged for 10 days.   

Hopes for relief        

Diagnostic tools

Back in 2002-2003 immunological assays were the primary option for detection of pathogen in a patient’s sample. Today doctors are armed with more precise and sensitive diagnostic tools – molecular diagnostic test kits. Unlike immunological assays that test antibodies produced in response to the SARS coronavirus infection and may not be detectable during the early phase of the disease or in patients with weak immune systems, molecular diagnostics enable very precise and early detection of the virus’s genetic material and amplification of viral RNA via PCR (polymerase chain reaction) technique. PCR technique is highly sensitive and can provide results within just two hours.

After sequencing viral genome in the beginning of January 2020, dozens of local companies rushed into developing PCR diagnostic kits. As of 25 January, several diagnostic kits have already been approved by the Chinese NMPA – BGI, Shanghai Liferiver, Shanghai GeneoDX. The announced daily capacity of Shanghai Liferiver alone is 200 000 kits. Many other companies will soon join with their own PCR diagnostic kits.

Moreover, in the recent years, China has accumulated huge experience in sequencing technology. Many public hospitals are equipped with NGS (next-generation sequencing) instruments. According to the WHO, during the early outbreak stage of the new virus, sequence information should be generated from all positive specimens and shared, to allow comparison with available sequence data. This will help to identify all potential mutations of the new virus early on. 

     Turning point?

It seems that China is well prepared to cope with the crisis. The country’s medical system, although extremely stretched, is equipped with the necessary tools to get epidemics under control. Quarantine measures will help to constrain further spread. Hopefully, we have just witnessed the turning point of the disease spread, as the number of newly registered cases in Wuhan, the heart of the epidemic, has dropped from 892 cases on 27 January to just 321 cases on 28 January. The number of new nationwide cases is still growing from day to day (1459 cases on 28 January as opposed to 1291 cases on 27 January). However, a new spike is likely to happen due to the movements of dozens of millions of travelers returning back home from their Chinese New Year travel. Regardless, the drop in number of cases does offer a glimpse of hope.