“Sometimes the wrong train takes you to the right station”

– an Indian proverb

It’s not often that a Korean telenovela sweeps me off my feet. While most of the shows have original stories and screenplays and exceptional technical work, their predictable endings usually leaves one miserably uncomfortable in the end. On prodding by netizens, and the recent win of “Parasite” as Best Picture at the Oscars (yes, I loved the movie), I needed to see for myself what the buzz was all about over “Crash Landing On You”. After all, even Netflix had been “suggesting” I watch this series as well. [They weren’t wrong when I was overwhelmed at how good the story writings of Sky Castle and Hotel de Luna were.]

Crash Landing On You is the new K drama series that has everyone talking about how good a telenovela this is. After all, it’s not just an ordinary love story. The series takes us into two nations divided by a border, and even living in the 21st century, a sociopolitical cultural gap. The storyline is so well-stitched together that it embraces fate and destiny in the most unusual cross starred lovers – a South Korean businesswoman (Se-ri played by Son Ye-Jin) and a North Korean soldier (Ri Jeong-Hyeok played by Hyun Bin).

It weaves a story of power. Greed. Friendship. Loneliness. Suffering. Corruption. Family. Deception. Grief. Of good triumphing over evil. Of dreams and aspirations. And while there is a hodgepodge of conundrums convoluted in the drama, the most important story of all, told a hundred times each episode was clearly that of love, forgiveness, goodbyes and moving on.

The North Korean angle was a bit confusing for those of us who are not from the two Koreas. We’re told of horror stories of North Korea and while it makes no mention of Kim Jong-Un, it tells of the rigid government of the country. The shuttle back and forth from Pyongyang (the capital of North Korea) and the small village that delineates the border of the Demilitarized Zone (DMZ) between South and North Korea is the central setting for the series. The north is more popularly known for an absolute authoritarian regime, where capital punishment is imposed on many crimes ranging from grand theft to defection, treason, espionage, among a few. Executions are carried out by firing squad or hanging in public. While the series provides us a sneak peak into the lives of North Koreans, such as the disparity in provisions of the higher military officials (from housing to cars), the kind of food that is available to the lower class people and the different degrees and extent of corruption, this angle was subtly hidden away. I couldn’t tell the difference in the accents of Koreans from the South and the North. But that’s because I was an outsider trying to figure out the English subtitle.

Interspersed between some light moments was heavy drama. Sometimes to the point of being impossible. Yet one cannot help but turn a blind eye to that impossibility that even in the movies, anything can happen. But I will leave that to the audience to judge as this is one series that I highly recommend and I won’t spoil it by telling you each episode.

The scenic settings in Korea, Mongolia and Iseltwald, Switzerland was breathtaking and gave justice to the theme of Crash Landing on You.

Then there’s the side story of another kind of love. Between Dan and Seung-Jun. The kind of love that would overcome one’s own destiny and altruism that parallels that of the stars of the show, but would end tragically sans regrets (and a bit of payback to boot).

It’s difficult not to fall in love with the story. After all, the central theme of love and selfless giving revolved around each and every protagonist character in the series. Their darkest and brightest moments.

The most wistful of all is the conversation between Yoon Se-Ri and Ri Jyeong Hyeok where Se-Ri tells Jyeong Hyeok:

There’s an Indian proverb that goes…sometimes the wrong train takes you to the right station. It was like that for me too. Throughout my life, I always felt like I was on the wrong train. One time, I wanted to give up. I didn’t want to go anywhere. So I thought about jumping off the train. Look where I am now. I took the wrong train again, and a very wrong one at that. It even got me across the 38th parallel. Still, you should think about the future, even if things don’t always go as you wish. I wish you could stay happy even after I leave, Jyeong-Hyeok. I want you to arrive at the right station, no matter what train you take.

Those lines alone…they were worth the 16 episodes.

Hope and love will always be a beautiful landing on anyone. This is a series that will long be remembered…because we all hope to arrive at the right station in spite of the wrong train rides in life.

In just two days, the novel coronavirus was christened twice.

COVID-2019 is the official DISEASE name when you get sick with the 2019 novel coronavirus. The virus has a new name as well. It’s called SARS-CoV-2.

The Coronavirus Study Group (CSG) of the International Committee on Taxonomy of Viruses [Gorbalenya, A. “Severe acute respiratory syndrome-related coronavirus – The species and its viruses, a statement of the Coronavirus Study Group”, bioRxiv] had decided to call the virus, severe acute respiratory syndrome coronavirus 2, or SARS-CoV-2.

The naming issues between the World Health Organization and the Coronavirus Study Group had caused a bit of chaos on this matter. As reported in Science, here’s a run down on the name christening event:

Unfortunately, China is reportedly objectionable to the name provided by CSG as it resisted comparisons between the current crisis and the traumatic 2002-03 coronavirus epidemic. And why the two names emerged almost simultaneously is also shrouded in mystery.

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For now, in layman’s terms, SARS-CoV-2 is the name of the virus that causes COVID-2019. And you can get infected with SARS-CoV-2 and be asymptomatic or not get sick at all. But when you do get sick, then you have COVID-2019. It’s like when you get infected with the influenza virus, you can get flu…or something to that effect. [Did we really need to get more confusing than this? Seriously, there are people in media who would pounce at the discombobulated scientists and organizational groups who are leading, or misleading, the confused keyboard warrior who’s desperately trying to get a grasp of all this confusion.]

It’s not as if the “whats-in-a-name” has already caused confusion, health officials in China report more than 14,000 new cases in Hubei Province alone. The reason for the sudden surge in numbers? Changing the diagnostic criteria.

At the epicenter of the novel coronavirus outbreak are many people who are sick and yet have no access to being tested. The various hospitals in Wuhan (the largest city in Hubei Province) have been grappling on how to diagnose infections with “scarce and complicated tests that detect the virus’s genetic signature directly. Other countries, too, have had such issues.” [Roni Caryn Rabin, New York Times, 12 February 2020]

But the issue on the complicated tests and its waterloo wasn’t on China alone. On Wednesday (12 February 2020), the Center for Disease Control in the United States had announced that some of the “coronavirus testing kits sent to state laboratories around the country have flaws and do not work properly…But the failure of the kits means that states that encountered problems with the test should not use it, and would still have to depend on the CDCs central lab, which could cause several days’ delay in getting results.” [Denise Grady, New York Times, Updated 13 February 1:03am ET]

The sudden surge in cases is due to the government including now cases diagnosed in clinical settings including CT scan findings. “The change in reporting is meant to provide a more accurate view of the transmissibility of the virus. The new criteria is intended to give doctors broader discretion to diagnose patients, and more crucially, isolate patients to quickly treat them.”

Some government experts noted that the lack in testing kits in the provinces, its low accuracy of 30-40%, the slow turn around time for the test results, and the overstretched hospitals in the epicenter were enough reasons to look at the clinical diagnosis of the disease instead.

With so much at stake and muddling and befuddling this disease entity, this sudden shift in accounting has become an epidemiologists nightmare as well. How do you now accurately track the cases of SARS-CoV-2 as causing COVID-2019? Like so many diagnostic tests out there, the timing of when to actually take specimens matter. Patients may have no symptoms and yet turn out positive or other patients may be severely ill in the late stage of the infection and turn out negative.

When scientists, the medical community and governments are thrown at the epicenter of panic and chaos and become confused, providing accurate public information becomes a challenging task. Crisis management should always center on the patients who are afflicted.

The secret of crisis management is not good vs. bad. It’s preventing the bad from getting worse.

– Andy Gilman

Call it by any other name, it is still the same. But the World Health Organization announced yesterday the “official” name for the novel Coronavirus that has hogged the recent health headlines. According to WHO Secretary-General Dr. Tedros Adhanom Ghebreyesus, “the name should not refer to a geographical location, an animal, an individual or group of people, and is pronounceable and related to the disease. Having a name matters to prevent the use of other names that can be accurate or stigmatizing. It also gives the WHO a standard format to use for any future coronavirus outbreaks.“

Do numbers matter?

The problem with numbers is how they are interpreted. Or misinterpreted. And the numbers become troubling, as they leave more questions than answers to an already confused public.

As of this writing, there are 45,153 cases and 1,115 deaths. The case fatality rate (CFR) now stands at 2.47%. But that is just an estimate as CFR is the number of known deaths divided by the number of confirmed cases. This does not represent the true CFR as we don’t know the actual number of cases there are (patients who are asymptomatic may be positive and yet not get tested). There are several ways epidemiologists look at the numbers we know. The table below shows the current information regarding COVID-19. Making heads or tails and interpreting the graph can be done positively or negatively.

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The American Journal of Epidemiology [Ghani AC. Donnelly CA, et al. “Methods for Estimating the Case Fatality Ratio for a Novel, Emerging Infectious Disease”, Am J Epidemiol 2005;162:479-486] cites a method that could reasonably work well if the hazards of death and recovery at any time t measured from admission to the hospital, conditional on an event occurring at time t, are proportional, would be to use the formula:

CFR = death/(deaths + recovered)

Using this formula and the data above, the worldwide CFR would be (1,115/[1115+4894]) = 19%. Let’s remove all the cases in mainland China (which are a lot). The total number of deaths outside of China is 2, while the number of recovered is 54. Using the same formula, we now get 2/(2+54) = 3.6% CFR for patients outside of China. The National Health Commission (NHC) of China on the other hand utilizes the simplified formula:

Cumulative current total death/current confirmed cases

Using this formula, we now get 1,113/44,436 = 2.5% (this is based on 44,636 cases confirmed in China, with 1,113 deaths or 99.8% of the mortality is in China). Outside of China, only 2 patients have died as of this writing. There are 517 cases (1.14% of all the cases in the world) outside of China.

How contagious is the COVID19?

Attack rate or transmissibility of a virus is indicated by the symbol Ro (reproductive number, pronounced as R-nought or r-zero). It represents the average number of people to which a single infected person will transmit the virus.

Let’s look at a school as an example. Ro describes how many kids will get sick when one sick kid goes to class (population), based on the assumption that all kids are able to get sick (susceptibility). The disease itself and the interaction with these kids are important factors.

If Ro > 1, then more kids are infected. It doesn’t mean that the higher the Ro is the more dangerous the disease is. Some viral URIs (upper respiratory tract infections) can have a high Ro, while some deadly diseases a low Ro (< 1). If the Ro <1, then not everyone that comes in contact with the sick patient will get infected. If, however, the Ro >1, then the propensity to infect more kids is higher. Let’s say that the Ro ~ 15 (as in measles). This means that for every child diagnosed to have measles, he/she most likely will infect 15 more children. The other sick children would eventually infect other kids and in a short period, all the kids in one community would come down with measles in the shortest duration.

Unfortunately, COVID-19 is a relatively new viral pathogen. Because there is no vaccine or previous exposure by most patients, we are all susceptible to getting the disease (unlike vaccine-preventable diseases). In short, when people have immunity against a disease, people won’t get sick. But that’s not what we are seeing with COVID-19. This gets complicated with ‘super-spreaders’. If we use the school setting again as an example, the ‘super-spreader’ will most probably be the adults in school – teacher, principal, work staff, etc – who work with every child.

The computed Ro for COVID-19 is estimated at 2-3. Meaning for every (+) patient, he/she can potentially infect 2 to 3 people. Pertussis has the highest Ro value at 17-18, measles at 12-15, tuberculosis at 10, smallpox 4-6, Ebola anywhere from 1.34-2, and influenza (common flu) at < 2.

It is important to remember that Ro depends on several factors: contact, how long illness lasts (incubation period), how many contacts the person has encountered even before the symptoms have appeared (which makes asymptomatic cases troublesome because they don’t know they’re sick but they’re transmitting infection), and how often the illness spreads during each contact.

Are we over reacting?

For the moment, perhaps we should be more circumspect because of the lack of information in the diagnosis, treatment and true outcome of this disease. Consider the fact that as of this writing, there have been 1,115 deaths due to the COVID-19. This, however, pales in comparison to the fact that 56,600 people have died from seasonal flu ALONE this year!

Numbers that count should focus on what we know and what we can treat and prevent. For 2020 alone, HIV/AIDS deaths are now at 195,988, malaria at 114,358, smoking related at 582,822, alcohol related deaths at 291,596, and deaths from cancer at 957,528 (based on data as of this writing).

With the total number of communicable disease deaths at 1,513,600 (at 1 death almost per second) to date, note how death due to COVID-19 is at a measly 0.07% of deaths. That means that 99.93% of deaths from communicable diseases are unrelated to COVID-19.

Let’s focus on the ball while making sure we have adequate defense. Remember, panic will always be a bestseller. Let’s not get derailed in our daily lives with data and information that you don’t understand but share. If we get swayed by media and other people who have turned the numbers for personal distraction, we may end up losing the war in communicable diseases.

The author was former professor in biostatistics and research methodologies at the University of Santo Tomas, Faculty of Medicine and UST Graduate School. His undergraduate and graduate studies are in Mathematics.

No one knew them until they started making us sick. Then some died. Like some unknown enemy out of a Hollywood movie, Coronavirus became an overnight sensation.

Coronaviruses are a large family of viruses that are common in many different species of animals, including camels, cattle, cats and bats. Rarely, animal coronaviruses can infect people and then spread between peoples such as with MERS, SARS and now with 2019-nCoV.

http://www.cdc.gov/coronavirus/2019-ncov/summary.html

First isolated in 1937, coronaviruses are the second leading cause of colds (after rhinovirus). There are 4 major categories, and they are known by the greek letters – alpha, beta, delta and gamma. Only alpha and beta cause diseases in humans. The 2019-nCoV is a betacoronavirus. Seven (7) human coronaviruses have been identified so far. This includes SARS-CoV, MERS-CoV and the novel coronavirus.

Coronaviruses are zoonotic. Meaning they are transmissible between humans and animals, but most infect only their specific host. SARS killed about 10% of the people it infected. MERS killed around 35% of those that came down with this viral infection. The good news is that SARS has relatively disappeared from the limelight. MERS on the other hand remains an ongoing viral organism to contend with. Transmission of coronavirus is between people who were in close contact with patients. Hence, post a greater risk to the healthcare worker.

Clinically, this virus can manifest with just a sneeze, a cold, or at worse, become complicated enough to cause pneumonia. Whether patients die because of the virus or complications from the viral infection is another story altogether.

They’re called coronaviruses for a reason. Under electron microscopy, they look like halos. They are part of the RNA (ribonucleic acid) viruses family. Typically they are single stranded, 32 kb (kilobases) long, and is the largest known RNA virus genome. In reality, they’re actually dumb viruses. They cannot last on their own and will need to find hosts in order to replicate. Coronaviruses are promiscuous. They mutate and change at a very high rate. Meaning they are bad when it comes to reproduction. While the virus is dumb, evolution is smart. Mutations are random. Thoughtless. This process makes the organism more suitable to survive. And while most of the other viruses die, the few that survive make the virus more successful quickly take over.

Coronaviruses mutate less rapidly than other RNA viruses because they have a genome that’s 2-3x bigger than other RNA viruses. They are more complex. Accuracy in reproduction is more important for them. They are the only RNA virus family with a ‘proofreading’ capability.

Peter Coy, “The Global Battle to Force the Coronavirus Below It’s Tipping Point”, Bloomberg Businessweek, January 30, 2020

What information can be derived from knowing the enemy?

For one, the fact that the viruses mutate and change at a high rate is a dilemma for both diagnostic detection as well as treatment and development of vaccines against them.

Coronaviruses have an unusual replication process, which involves a 2-step replication mechanism. Many RNA virus genomes contain a single open reading frame (ORF) which is then translated as a single polyprotein that is then catalytically cleaved into smaller functional viral proteins, but coronaviruses can contain up to 10 separate ORFs. Most ribosomes translate the biggest one of these ORFs, called replicase, which alone is twice the size of many other RNA viral genomes. The replicase gene encodes a series of enzymes that use the rest of the genome as a template to produce a set of smaller, overlapping messenger RNA molecules, which are then translated into the structural proteins – the building blocks of new viral particles.

Rodney Rohde, “2019 Novel Coronavirus (2019-nCoV) Update: Uncoating the Virus”, American Society for Microbiology, January 31, 2020

Dr. Mark Denison, director of the division of pediatric infectious diseases at Vanderbilt University School of Medicine points out that the effort at slowing down this virus can only succeed not on what people do, but on how successful science is at addressing the virus. Because Coronavirus are dumb and cannot reproduce on their own, they hijack the reproductive machinery of the cells they attack. Man vs. Microbe scenario.

Remember the ‘proofreading’ capability of coronaviruses? That function seems to be able to be switched off if the virus is under evolutionary pressure. Here is where antiviral drugs theoretically can be useful. The antiviral that targets RNA will allow disruption in proofreading. Locking in that function makes the virus unadaptable, mutate faster, and essentially fall apart. Drug development takes into consideration knowing the enemy in order to eliminate them. An adenosine analogue that incorporates into nascent viral RNA chains resulting in premature termination is Remdesivir. Interesting is the potential of an old friend in Chloroquine. Chloroquine is used for the treatment of malaria and some diseases of the autoimmune system. Some data have shown that it also has potential as a broad-spectrum antiviral agent. The antiviral activity of chloroquine works by increasing endosomal pH for viral/cell fusion and interfering with glycosylation of cellular receptors of SARS-CoV. Chloroquine in addition has immune-modulating activity that can synergistically enhances its antiviral effect in vivo. [Manli Wang, Ruiyuan Can, Leike Zhang, Xinglou Yang, Jia Liu, Mingyue Xu, Zhengli Shi, Zhihong Hu, Wu Zhong, & Gengfu Xiao, “Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro:, Cell Research, 04 February 2020, as Letter to the Editor].

These are difficult times between man and microorganism. Science has come a long way. Technology and modern scientific and laboratory tools have paved the way at treating various infectious diseases using a more scientific approach. Gone are the days of hit and miss. Now we know the enemy, our next move is to destroy it expeditiously and precisely. Because in the end, only one can survive.

The Novel Coronavirus (NCoV) that has caused concern among people and the health experts has overtaken all other causes of global calamity (natural and political).

What started out as a a “potential” SARS-like illness from Wuhan, China in December 2019, has, as of this writing, become a story that looks like it was written for a Netflix series.

Less than a month into the lockdown in Wuhan (and expanded to other cities in the central province of Hubei), the Chinese authorities have now, according to the New York Times, “resorted to increasingly extreme measure on Thursday to try to halt the spread of the deadly coronavirus, ordering house-to-house searches, running up the sick and warehousing them in enormous quarantine centers. The urgent, seemingly improvised steps come amid a worsening humanitarian crisis in Wuhan, one exasperated by tactics that have left this city of 11 million, with a death rate from the coronavirus of 4.1% as of Thursday – staggeringly higher than the rest of the country’s rate of 0.17%”.

In early December, Dr. Li Wenliang, a physician at Wuhan City Central Hospital had warned of the outbreak – but was reportedly silenced by the police for it. In a country whose government is known to be shrouded in secrecy in order to keep social and political norms at bay, public anger is simmering and unrest and disorder at the brink of concern for the Communist Party, who are reportedly trying to stifle news organizations and local social medial platforms on criticisms related to how the government in general and President Xi Jin Ping in particular are handling this medical crisis. The death of Dr Li from this novel coronavirus was likewise shrouded in so many speculations before the news was finally released that he had indeed died from the viral infection.

While there are now 31,481 confirmed cases, 635 deaths, and 28 countries affected (as of this post) giving an overall case fatality rate of 2.01%, the numbers may not reflect the actual case fatality rate of the disease (worldometers.info/coronavirus). That’s because all except for 2 deaths are concentrated in China. The epicenter Wuhan has the most number of cases – 22,112 (72% of all the cases in the world) and the most number of deaths – 470 (of the 633 deaths in China alone, or 74% of all deaths). According to the National Health Commission of China (based on a press conference last February 4, 2020):

1. The national mortality rate is 2.1% of CONFIRMED cases,
2. Mild cases are usually not reported
3. 97% of the total deaths in China were in Hubei Province. Mortality rate in Wuhan was 4.9%, while the fatality rate in other provinces at 0.16%.
4. Most of those affected are males (around 70%) and the elderly with co-morbid conditions have higher fatality rate.
5. Infectivity period can be anywhere between 2-14 days (average is around 5.2 days), ASYMPTOMATIC transmission is possible (hence the rationale for a 14 days quarantine or medical observation period for the pathogen).

While this global medical problem isn’t going to go away anytime. It comes at a time when the cooler temperatures and viral upper respiratory infections are common complaints seen in the various clinics, making managing respiratory problems a more difficult and fearful one.

The graph below shows the data culled from worldometers.info/coronavirus on the trend of daily new cases. While preliminary data is encouraging on the present statistical trend, the health authorities should not keep their guard down on this pathogen.

At the pinnacle of the outbreak is a country whose leadership and culture are being tested and challenged. China should change its paradigm on its approach to novel diseases and outbreaks emanating from a region whose 1.4 Billion people are at the forefront of travel, migration and economy. The SARS story in 2003 must have made China learn its lesson – that diseases like these cannot be swept under the rug. Seventeen years ago, social media and travel driven by advances in technology evolved dynamically into an industry in itself. Not even a highly restricted state media can control how people provide accurate information and react to life and death situations in the real world. We begin to realize that no one individual is worth protecting – even if he is the anointed president for “life”. No one is worth the sacrifice, if only to keep the notion that “business is as usual” and the “economy” of the world’s number 2 nation is at risk. This kind of mindset is archaic and the hierarchical type of governance is detrimental to the health of a nation.

We are not at that point in medicine where man will ever be ready for the microorganisms that roam the same planet we live in. Only fools would make that conclusion. Even as new threats emerge (they’re called emerging diseases in infectious medicine), the old scourges like TB, polio, cholera, the plague, to name a few, are still very much around and flare up with disturbing regularity. Former US adviser on public health emergencies Richard Hatchett nails it in his opinion that “we’ve created an interconnected, dynamically changing world that provides innumerable opportunities to microbes. If there’s weakness anywhere, there’s weakness everywhere.”

The coronavirus (or any infectious disease pathogen for that matter) will not distinguish a head of state from a common citizen. It knows no nationality or boundaries. Hence, it is the mandate of every leader to make sure that none of its citizens suffer or die because he/she prioritized personal, political and economic gains for the lives of a few.

Muhammad Ali Pate, global director for health, nutrition and population at the World Bank, correctly points out that “the foundation for better preparedness is investing in stronger primary health care systems which provide surge capacities that can be mobilized for effective response to contain outbreaks.”

It takes political will to go out in front of an epidemic. Yes. At some point, the outbreak will end. And that’s the problem. We mourn, grieve and bury the dead. And the world will move on. And so will the microbe. They stay quiet. Mutate. Resurge while we’re sleeping.