Society Nov. 24, 2020

How Should We Confront COVID-19?

OSHITANI Hitoshi, Professor, Department of Virology, Tohoku University Graduate School of Medicine

Oshitani Hitoshi, Professor, Department of Virology, Tohoku University Graduate
School of Medicine

This is a republication of Prof. Oshitani’s message as published on the website of the Department of Virology, Tohoku University Graduate School of Medicine during the period February 4–22.

Dr. Oshitani Hitoshi

There is no end in sight to the infectious spread of 2019-nCoV (COVID19) that started in China. The true nature of this virus is gradually coming to light. There still remains much that we do not know, but I would like to consider how Japan and the international society should respond to this virus in light of what we do know.

Firstly, the virus that is causing this was quickly identified by Chinese scientists and its gene sequence has been publicized. As a result, we know that the virus is closely related to SARS-CoV, which caused a global outbreak in 2003. However, being virologically related does not mean that they share epidemiological features. Rather the opposite, we are seeing major differences in epidemiology.

SARS is thought to have appeared in November 2002 and it was on July 5, 2003 that the WHO announced that the spread had been halted and successfully contained globally.

The strategy for achieving this containment involved first thoroughly detecting and swiftly isolating all symptomatic patients as well as finding all persons who had been in contact with those confirmed cases (this is referred to as contact tracing), and if anyone among the contacts develops symptoms, they are to be isolated as quickly as possible. In fact, this same strategy proved successful for containing the Ebola virus.

Yet the following are criteria that absolutely need to be fulfilled for this containment strategy to be successful.

The majority of symptomatic patients should have severe symptoms or display typical symptoms that differ from other infectious diseases.
Mild and asymptomatic cases (persons without symptoms despite being infected) that do not display typical symptoms should not show infectivity.
Infected persons should show no infectivity during the incubation period or early stages of illness.

In the case of SARS, the majority of infected persons developed severe symptoms and a typical viral pneumonia, so it was possible to find most symptomatic patients. COVID-19 now is thought to yield mild and asymptomatic cases to a considerable degree, which makes it impossible to find all infected persons. Furthermore, we cannot rule out the possibility that such mild and asymptomatic cases are infectious and can spread the infection to other people. If so, this means that it is possible for the infection to spread between people who have no travel history to Wuhan or similar locations and who have not been in contact with other persons who have traveled there. That is, there are chains of transmission that cannot be detected using the methods employed by Japan and other countries. In the case of SARS, there was thought to be almost no infectivity during the incubation period and early stages of illness, but only in severe cases. This made it possible to quickly isolate symptomatic patients at adequate medical facilities. Yet we have data suggesting that the current virus shows infectivity also during the incubation period. If so, it is possible that infected persons can infect others even if they are isolated as soon as they become symptomatic, which means that the infection cannot be contained.

There is a strong tendency to criticize China’s slow initial response, but it is likely that they implemented countermeasures like those for SARS when COVID-19 started spreading in Wuhan. However, the epidemiological features of the current virus differ greatly. Thus, I suspect that the reality was an unstoppable spread of “invisible” chains of transmission.

The infectious spread will become uncontrollable after it expands beyond a certain level. The biggest issue is that we currently do not have any means to contain the virus. The advance of “invisible” chains of transmission is becoming a reality also in Japan. It is necessary for each region to promptly consider measures such as enhancing the domestic healthcare capacity in anticipation of infectious spread.

It is probable that the infection is spreading rapidly in Chinese cities other than Wuhan. Countries other than China, such as Japan, have found large numbers of infected people, also including the second wave. We are arriving at a situation where rapid infectious spread cannot be avoided also outside of China.

Since containment is not a realistic goal, the aim of any measures has to be shifted to limiting the impact as much as possible. The international society needs to work together to explore the optimal measures to achieve this aim. China holds the key here.

For example, several Chinese cities are trying to control the current infectious spread about two or three weeks after Wuhan. What is happening in those cities? What measures are effective and what measures are ineffective? Such information is extremely important as Japan and other countries consider their own responses.

This virus is no longer just a domestic issue for China, but is a threat to the entire world. In our response, I want to see the WHO take leadership and the international society work together with China as a key partner. We should not isolate China. Criticizing the responses of China and the WHO now will be of no advantage in our battle against the virus before our eyes.

A domestic infectious spread comes with the possibility of spreading to foreigners staying in the country. Inbound tourism and foreign workers do not simply bring money and manpower. They bring people and we need to provide them with as much support as possible. It is possible that this virus will spread to Asian and African countries with fragile healthcare systems where the impact might be even greater. We need to adopt a perspective of considering how we best can support such countries.

Rather than worrying about how this affects the Tokyo 2020 Olympic and Paralympic Games, we should be thinking about what role Japan can play in the face of this global crisis. I am of the conviction that a country unable to do so is not qualified to host the Olympic and Paralympic Games.

The Battle between COVID-19 and Humanity has Entered a New Phase

It feels like the only COVID-19 topic during the week leading up to February 12 in Japan was the cruise ship (Diamond Princess). A virus is an “invisible” being. COVID-19 is a small particle with a diameter of 100–220 nm that cannot be seen with the naked eye or even with a regular optical microscope; an electron microscope is needed to see these viral particles. Not only can the COVID-19 viral particles not be seen, but another characteristic is that the spread of the virus also cannot be seen, which complicates our fight against the virus.

On February 11, the Ministry of Health, Labor, and Welfare (MHLW) announced that seriously ill patients had appeared among the passengers on the cruise ship. This was a situation that was far from unexpected since many of the passengers on the cruise ship were senior, and we saw cases of rapidly worsening symptoms a week or so after onset also with SARS.

The spread of the virus on the cruise ship should be considered something that happened to take place due to the overlapping of several random factors. This again highlights this virus’s ability to spread from person to person as relatively strong. Simultaneous to the tracing of the “visible” spread around the Wuhan market where it is supposed to have started, there was likely taking place a rapid and uncontrollable “invisible” spread in the former’s shadow.

In Singapore, considerable efforts are currently being made to visualize the chains of transmission, so we are finding out the reality of the spread in the region little by little. This is something that was made possible because of systems developed since the SARS pandemic of 2003. Nearly all hospitals in Singapore have the capacity to test for the virus, which enables more than 2,000 tests a day. A testing system will likely be developed quickly in Japan as well, but Japan currently has limited means to visualize the chains of transmission. Taking that into consideration, we ought to think about how we can visualize the chains of transmission most efficiently.

We cannot allow ourselves to be too focused on the “visible” spread onboard the cruise ship so that we lose sight of the overall picture. Rather, the spread on the cruise ship strongly suggests the possibility that local chains of transmission similar to those in Singapore are also advancing inside Japan. Thus, we need to make preparations, such as thinking about the healthcare capacities in each region, on the assumption that the virus will spread in local areas. We have to learn from the lessons of the failures in Wuhan.

We are currently fighting an extremely difficult virus. I do not think we can take on this virus by simply conveying a message of “staying calm and responding as if it were the influenza.” To begin with, this virus clearly is not the same as the seasonal influenza. Many people, predominantly senior citizens, die from the seasonal influenza every year, also in Japan. Yet most of those deaths are so-called influenza-associated deaths where patients die of a different cause, such as an elderly going into cardiac arrest while bedridden due to an influenza infection or suffering from bacterial pneumonia after influenza infection. This is why the influenza is said to be a disease that extinguishes the last light of life for elderly persons.

However, this COVID-19 is completely different. The proportion of people getting severe symptoms is small, but those who do get viral pneumonia where the virus itself propagates inside the lungs. Severe viral pneumonia is difficult to treat and it is conceivable that we will have cases in Japan as well where the patient’s life cannot be saved. This is obviously a dangerous virus for bedridden senior citizens, but reports from China show that many people in their 50s and 60s and even some in their 30s and 40s have died. This is a virus that we cannot afford to underestimate just because it is like a seasonal influenza for the majority.

This virus is spreading across the world at a rapid pace. So far, our battle with this virus has been an utter defeat for humanity. Humanity is nowhere near catching up with the speed with which the virus is spreading and all responses are one step behind. It is not only China that is lagging, but Japan, the WHO, and international society as well. However, we also must not forget that it was this same humanity that gave this virus this unimaginable speed.

If a similar virus had appeared fifty years ago, it is likely that it would have ended with some people dying from mysterious pneumonia in one Chinese province. We are living in an era that is very different even from 2003 when we had SARS. The first spread of SARS happened in Guangzhou in Guangdong Province and it then developed into a worldwide outbreak by spreading via Hong Kong. SARS fortunately did not spread in Japan, but today there are a great number of direct flights between Guangzhou and Japan every day. If the same thing were to happen in Guangzhou now, then it is very probable that Japan would be hit by the virus first. The ones who carry this virus across the world are not animals but people. It is evident that the speed of this virus, which is beyond human control, is a result of the rapid expansion of travel within China and between many countries, including China and Japan.

There are many who optimistically say that the COVID-19 pandemic is coming to a close. It is impossible for a pandemic of this size to continue in one region for more than a year, so it naturally has to come to an end at some point. We should be careful about asserting that the spread in Wuhan has peaked, but it is likely that it will ease in the not-so-distant future. Yet an end to the spread in Wuhan does not mean an end to our struggle against the virus. The virus started spreading in Chinese cities other than Wuhan with a time lag of about two or three weeks, so we need to carefully observe how these spreads develop in the other cities. Nonetheless, it is a good sign that there do not currently appear to be any cities that have ended up in the same situation as Wuhan did initially.

However, the Chinese epidemiological situation does not necessarily match the Japanese domestic situation. What we need to worry about now is the possibility that chains of transmission from travelers have already made their way into Japan. These chains of transmission that may exist inside Japan are naturally independent from the epidemiological situation in China. We have yet to detect even the start of the domestic spread. We are far from a situation where we can relax, swayed by optimistic information.

If some of the measures employed by the Chinese government prove effective and can prevent developments from what we saw in Wuhan, then that information will be crucial for Japan and for the world. The next phase of our battle against the virus will absolutely require us to learn from the Chinese lessons of what worked and what did not. During the 2003 SARS pandemic, China knew how to deal with SARS by early February 2003 at the very least. China was heavily criticized by the international society for not sharing that information, which is thought to have led to the international spread. That is a mistake China must not repeat.

SARS was successfully contained globally because it was possible to interrupt all human-to-human transmission. Yet this virus has spread to such an extent and the chains of transmission are so difficult to discern, so although the end is in sight for the Chinese spread, it is hard to imagine that all chains of transmission can be interrupted in the next half a year. The initial worst-case scenario was for sites across the world to become like Wuhan and the spread like an influenza pandemic, but the risk of that has decreased significantly. It has likewise become less chance to have an extremely large-scale epidemic like that in Wuhan in Japan. Yet there is still the risk that cities in countries with weak medical and public health systems become a “second Wuhan.” The creation of such new sources of infection will make sure that the virus again spreads across the world from there. It is still possible for cities in Southeast Asia and Africa to become a “second Wuhan.” International society needs to work together to prevent the appearance of a “second Wuhan.”

Humanity was utterly defeated in the first round of our fight against the virus, but the pandemic is now entering a new phase and humanity is quickly discovering ways to resist it. In this sense, I fear that this is not the kind of infectious disease where it is enough to “stay calm and respond as if it were seasonal influenza.” In the case of seasonal influenza, we have tools like vaccines, anti-influenza drugs, and rapid diagnostic test kits, but we currently have no such tools for this virus. Unfortunately, we are currently unable to visualize all chains of transmission and the probability that “invisible” chains of transmissions are spreading in Japan is fairly high. However, it is now becoming possible for us to visualize some of the “invisible” chains of transmission by utilizing the limited tools we do have. There is also growing hope for antiviral drugs and a vaccine. I believe we need to maximize the use of the tools we have to fight the virus as we start the second round.

How Should Japan Act in This New Phase?

The WHO strongly recommends risk management based on the risk assessment as a basic strategy to deal with crises caused by infectious diseases like COVID-19. We do not yet sufficiently possess the means to assess the risks of this crisis that is ongoing as we speak, but I think it is useful to consider it in terms of three scenarios: 1. best-case scenario, 2. most likely scenario, and 3. worst-case scenario.

The risk assessment for the spread in Japan envisioned the following scenarios: 1. “There will be no domestic spread,” 2. “There will be domestic spread and some impact, but no explosive spread,” and 3. “The same kind of explosive spread as in Wuhan will happen in Japan.” Scenario 1 was still plausible right after reports about the spread in Wuhan came in, but once the reality of the spread in Wuhan and nearby areas became known, that possibility quickly took a dive toward zero. My view is that it had clearly become zero by February 13, 2020. Meanwhile, Scenario 3 was considered in the beginning, but it does not really seem plausible right now. The reason for this is that we currently have no reason to believe that any Chinese cities except for Wuhan will see the same kind of uncontrollable spread as in Wuhan and nearby areas as well as that we have clarified the characteristics of the virus and thereby become able to control it to some extent.

If so, the question becomes how Scenario 2 will develop. I have been thinking that chains of transmission already exist inside Japan, just that we do not see them. However, viral pneumonia only happens rarely, so I thought that we would find the chains of transmission in Japan if we were to get a situation with multiple cases of suspect viral pneumonia. We have found infected people across Japan since February 13. It appears that the previously invisible chains of transmission in Japan are now rapidly becoming visible.

The significance of the successive detections of infected people from February 13 to 14 greatly differs from previous cases. Excepting the infections from the cruise ship, most previous cases were detected among people who had a travel history to Wuhan or Hubei Province or people who had a contact with people with a travel history, including those who traveled back to Japan by chartered airplanes. Most of the cases detected during those two days do not fall in that category. They strongly suggest that domestic chains of transmission are already underway.

During the 2003 SARS pandemic, the WHO initially said that any country or region should be considered an “affected area” with local transmission if there are domestic secondary infections. This applies to the bus drivers, bus guides, store staff, and so forth who were infected in Japan. Of course, this criterion is far too broad by itself, so they then announced the patterns of domestic infection A, B, and C as a way to assess the danger of local transmission, defined as follows. A is when secondary infections from persons with local transmission happen in the affected area. B is when infections are more advanced than secondary infections from persons with local transmission but can all be traced back to contacts with already identified infected people. C is when infections are found that cannot be traced back to such contacts. C is obviously most serious and means that local transmission can be assessed as happening. It is still possible that we will find that some of the cases discovered in the past two days (February 13 and 14) fall under A, but this does not likely apply to the majority. I should mention that any cases not falling under A or B at the time of discovery were classified as C in 2003. It goes without saying that other countries view Japan as an affected area based on the objective facts.

I was thinking that it might take a while longer before the chains of transmission in Japan become visible and had not anticipated that they would suddenly become visible through this kind of multiple simultaneous infections. This is clearly thanks to the high ability and awareness of medical doctors at Japanese clinical settings. This seems to show that the doctors at these settings were not distracted by the cruise ship as it was not essential but earnestly engaged with this issue and the patients before their eyes.

Nevertheless, it is quite probable that we are only seeing part of the whole picture. We can easily imagine that similar cases will be found across Japan one after the other. We should also be finding infected people around those cases. At present, besides mainland China, I only know of Singapore and Hong Kong as places where chains of transmission have been visualized to some extent. I believe they are able to visualize them precisely because they are both countries or regions with experiences from the SARS outbreak and have systems that can deal with situations like this. Japan has a population much bigger than Singapore and Hong Kong, so it is possible that Japan will end up having a much larger number of infected people, even if we exclude those on the cruise ship. There exist many more countries where chains of transmission already take place, but they simply cannot see them.

We should not see it as purely negative that many infected people have been found in Japan. This should be taken as a sign that Japan is getting a system that can swiftly visualize chains of transmission as well as quickly respond to them. I think that is something we should explain to other countries as well. In fact, the transparency of Singapore is highly praised as they quickly visualized their chains of transmission and published the information. Our fight against the virus has been consistently one step behind, but it has now finally become possible for us to forestall the virus.

We do not have the luxury of spending time for the media to report that could violate the privacy of people or worrying about damages by misinformation. The media should not repeat their mistake of only reporting about the cruise ship at the expense of the whole picture. There might be dozens or even hundreds of infected people around the infected people who have been found. It is possible that the chains of transmission we are seeing now are only a fraction of the actual numbers. What we are seeing now can happen all over Japan and has likely already happened in many places across Japan.

It was reported that a quarantine officer was infected onboard the cruise ship. It also has been reported that people have been infected because of their own failures, but I do not think that necessarily has been the reason. We do not have any precise information about this virus’s transmission routes at the present time, but we need to consider the possibility that it we cannot fully prevent it using the standard methods. I believe that we need to think more seriously about the fact that a quarantine officer, a professional who has prepared and been trained for this kind of situation, was infected on a cruise ship where new cases of infection were appearing every day and he had to be on his toes. How many others would be able to walk among the crowds of the cruise ship with the same level of care as he did? I would not have been able to do that at all.

Something that currently is as important as enhancing local healthcare capacity is figuring out how we can slow down the infectious spread. I do not think it is possible to contain this virus, but it is possible to control the speed by which it is spreading. Infected people need to have cough etiquette and wash their hands. We absolutely have to avoid situations where people with a fever and coughing force themselves to go to work and spread the infection at their workplace. We have to maximize efforts to keep the infection from spreading from people who are potentially infected. We need measures to keep the infection from spreading to the elderly and people with underlying conditions. Pandemic influenza is often spread in local areas primarily by children, so school closures ought to be an effective measure in the early stages of the pandemic, but COVID-19 had not infected many children, which makes it hard to imagine that school closures are useful for controlling the speed of infectious spread.

Lockdown of cities and onboard quarantines like the one that was conducted on the cruise ship are measures reminiscent of the 19th century. As people living in the 21st century, we must find smarter ways to slow down the spread. An obvious approach is to move forward the telecommuting, web and phone meetings, and staggered work hours that was planned for the Tokyo Olympics. It might also be possible to use the home delivery systems to deliver daily necessities to senior citizens and people with underlying conditions. We need to implement various measures locally to slow down the spread without stopping social functions. These measures should not be implemented after the spread has come to light but need to be implemented now. We must not forget that preventing one infection now may prevent chains of transmission leading to 100 or 1,000 people.

Our Imagination as a Weapon

I wrote this on February 21, 2020, which was an extremely important day with regard to the international spread of SARS in 2003. Exactly seventeen years ago, a doctor infected by a patient in Guangzhou, Guangdong Province was staying at a hotel in Hong Kong. Many guests on the 9th floor of that hotel were infected from that one person and then traveled to places like Hanoi, Singapore, and Toronto with the virus inside their bodies, which led to a global outbreak. Without this one spread at that hotel, it is possible that the global SARS outbreak would not have happened.

Seventeen years later, we are facing an issue far more difficult than the one we had seventeen years ago. This virus has a pathogenicity far lower than the virus seventeen years ago and that is what is making it far more difficult to detect all infected people. The advance of globalization has also imbued this virus with a speed of spreading that is uncontrollable.

It was pointed out in the 1990s that this kind of new infectious diseases, meaning emerging infectious diseases, would become a threat to all of humanity. The first spread of an emerging infectious disease in the 21st century was SARS. It was followed by the successive spreads of the avian influenza H5N1, the pandemic influenza H1N1, the avian influenza H7N9, MERS, the Ebola virus, and the Zica virus. Humanity should have considered this warning from nature more humbly and prepared systems to deal with such infectious diseases.

I believe that imagination to care for others is what is most important as we are taking on this issue in the 21st century. There were reports of a young doctor who died after postponing his own wedding to care for patients. How many Japanese can imagine his selflessness?

The number of deaths from this virus in Hubei Province and the rest of China is increasing by the day and it has already exceeded 2,000 by a wide margin. On the day that the WHO declared a Public Health Emergency of International Concern (PHEIC), WHO Director-General Dr. Tedros Adhanom Ghebreyesus spoke about the increasing number of deaths and said that “these are people, not numbers.” I believe that something we need in this fight against the virus is the imagination to be able to see that these are not merely numbers but lives of people who would have lived longer if it were not for the virus.

Japan is now entering a key phase in the battle against this virus. Japan had a major handicap when starting this fight against the virus due to something that was not a domestic problem, namely the inevitable cruise ship problem. Since February 13, we have started finding the chains of transmission in Japan that went out of sight for a while. Normally, the medical institutions would have responded to the gradually rising numbers of infected people little by little, but they were now forced to instantly deal with a large number of infected people from among the passengers and crew of the cruise ship. That also included severely ill patients requiring intensive care.

If we allow the infection to spread now, then we will face the very real risk of medical institutions, especially in the Greater Tokyo Area, going over capacity all at once. If that happens, we might face a situation where lives that Japanese healthcare should be able to save cannot be saved.

I am certain that most people in general until this point have been thinking about what they can do to avoid being infected by this virus. Government and media information has also largely been about that. We do not actually know how effective washing one’s hands or wearing a face mask is in individual prevention. Yet, there are ways that individuals can definitely contribute to our fight against this virus. It is to make our utmost efforts to stop it from spreading from those infected or maybe infected to others.

The majority of people infected with the virus will probably feel that it is no more than a somewhat persistent influenza or even lighter. If a chain of transmissions is started from that person infecting another, then there will definitely appear someone with severe symptoms further down. It is also possible that someone will die. I believe we need to have the imagination to see that the person dying is not just “a woman in her 60s” but a woman who could have seen the face of her first grandchild to be born next month.

The data we have gathered so far very much support the idea that even people with light symptoms can infect others. With seasonal influenza, most people stay home from work or school to recuperate. Yet with this virus, it is absolutely necessary to stay at home, not just to recuperate but to stop it from spreading to others, even if it feels like just a cold. We also need to promptly create an environment where people with light symptoms can work or study online.

This virus is extremely stubborn. It is quite possible that harsh times await Japan too. Yet we are also finding out the virus’s weak points little by little, so there is hope. I am now thinking that it is completely feasible that we can control this virus at an early stage in Japan. In order to make this hope a reality, each and every one living in Japan needs to think seriously about what we can do.

Translated from “Koyo-iji dakedewa genkai ga kuru!: Sengo saidai no kyugyoshasu—Rodoshijo ni naniga okottaka? (We Are Approaching the Limits of Having Only Policies that Preserve Employment!: The Largest Number of People Taking a Leave of Absence Since World War II—What Has Happened in the Labor Market?),” Chuokoron, August 2020, pp. 106-113. (Courtesy of Chuo Koron Shinsha) [November 2020]

DR. OSHITANI Hitoshi

Professor, Department of Virology, Tohoku University Graduate School of Medicine, member of Novel Coronavirus Expert Meeting, New Coronavirus Infectious Disease Control Headquarters, member of the COVID-19 Advisory Committee on Basic Action Policies and member of the Covid-19 Cluster Response Taskforce, Ministry of Health, Labour and Welfare. He has also served as an expert at Japan International Cooperation Agency (JICA) (1991-1994 in Zambia) and the Regional Advisor for Communicable Diseases, WHO Regional Office for the Western Pacific from 1999 to 2006. His publications include Pandemikku to Tatakau (Fight pandemic) and Shingata Infuruenza wa naze osoroshiinoka (Why is the Novel influenza scary?) (both co-authored).