The first 200 days of COVID-19

A Spanish philosopher, George Santayana, once said, those who cannot remember the past are condemned to repeat it [1]. Santayana forgot to mention that those that do remember are condemned to watch others repeat it.  

 Probably any middle school student will have a fair understanding of the first World War. They might not be aware that the deadliest event in American history in the 20th century was not a war, but the Spanish Flu which lasted from February 1918 to April 1920. The Spanish Flu (which did not originate in Spain), was H1N1 influenza that spread throughout the world and is estimated to have killed 50 million people [3]. This pandemic was the deadliest flu outbreak in the recorded history of the world and was the 2nd single most deadly event in American history after the civil war [4]. As a comparison, the Spanish Flu killed more Americans than all deaths in all battles in the History of the United States combined [5].  

 During the Spanish flu outbreak, 675K Americans died. As a decentralized country, local governments decided to have different public health measures to deal with the pandemic. Two studies published in the Proceedings of the National Academy of Sciences reported that some cities decided to close schools, theaters, churches, banned weddings, and funerals, and ordered everyone to wear face masks [6], [7].  

 The two studies concluded that those cities that imposed social containment measures immediately after the first few cases had cut the death rate by half compared with other cities that waited a few weeks [6], [7]. 

 However, these measures were not that easy to implement. In some parts of the US, where local governments used "controversial" measures forcing people to wear masks, many Americans refused to lose their liberty of not wearing one. Things escalated very quickly, in San Francisco, a group decided to create the Anti-Mask League. An estimated 5,000 citizens attended their first meeting to fight for their rights of not wearing masks [8]. 

 One hundred and two years later, the world is experiencing a new global pandemic. In the last one hundred years, the world has improved in many areas; life expectancy went from 32 years old in 1913 to 71 in 2020[9], and child mortality observed a tenfold reduction (from 32% to 3%)[10]. While the world has become much better in many areas, certain things have not changed.  

 As I write this, countries including New Zealand, Norway, Finland, Greece, Australia, and Iceland, moved fast and controlled the virus, others including Brazil, Mexico, India, and many states in the US, are still struggling to control the growth of the epidemic. California and 15 others states have started enforcing the use of masks, and groups of individuals are already revolting similarly as they did 100 years ago [11]. 

 So, where do we go from here? 

 In the first 200 days, researchers worldwide have learned many things about COVID-19 that can help us understand the future: 

COVID-19 spreads fast 

We know that COVID-19 has an R01 (basic reproductive number) rate of ~3. While this number does not look that big compared to 1.4 from the common flu, the fact is that because of exponential growth, in 10 jumps, an individual with flu will act as a first step to transmit the virus to 29 individuals, while one person with COVID-19 will do it for 59,000. We need to consider that even with a much lower reproductive rate, 9 to 45 million Americans get infected with the FLU every year[12]. 

 Age is one of the main drivers for deaths 

For those patients with COVID-19, the probability of death increases exponentially with age. Those who are 60+ years old have 50 times more chances of dying than 30-year-olds. Deaths of children are very rare. This fact explains in part that we are observing significant mortality in Europe and other developed nations that have a much older age distribution versus some developing countries. 

 Many interventions are not working, but some do 

While the World has made a very fast move for respirators, unfortunately, these have not shown to be that effective. In a study in NY, among the individuals that either died or recovered, 88% of those who received mechanical ventilation respirators in NY died from COVID-19[23]. It is not clear what the counter-factual of not using a respirator would be, but this data does show that respirators might not be having a significant impact. 

 From a treatment point of view, Remdesivir has shown some potential, improving recovery, but there was not a statistically significant difference in the mortality rate as compared to administering a placebo [13]. A recent study showed that Hydroxychloroquine, once considered a possible miracle drug, not only did not work, but was in fact linked to an increase in death in COVID-19 patients[14]. Lastly, for Dexamethasone, early results are showing that this cheap, widely available corticosteroid can significantly reduce deaths of severely sick COVID-19 patients in a major clinical trial[15]. 

 What we still don't know 

 Are there any long-term effects? 

For those COVID-19 patients that recover, we do not know possible long-term effects. In the case of SARS, a study showed that patients after 15 years developed long-term bone and lung consequences[16]. 

 How long will the antibodies last? 

The latest study published this last week in Nature found that antibodies may last only two to three months after an individual is infected and recovers from COVID-19[17]. If this study is correct, the strategy of countries like Sweden to achieve herd immunity might fail. 

 Can we get a vaccine? 

The world hopes to get the first vaccine around December. There are over 100 vaccines in the development pipeline[18]. However, a lot of the vaccines will fail. Even if a successful vaccine is developed, a study claims that just 50% of Americans plan to get it.[19] 

 What to expect for the months ahead? 

 There are currently 14 vaccines under trial in humans [20]. In July, we expect some early results from Moderna and Pfizer. If vaccines are successful, the world might experience a rush to get safe until the vaccine is ready. This might lead to governments being more prudent and increasing protocols of lockdowns/quarantine. If, on the other hand, the vaccine fails, it will not mean that no-vaccine can be developed, but instead that we may need more time. 

 Cases and deaths will continue to rise.  

New estimates by IHME are that we will have 180K death in the US by October[21], the number will likely continue to rise after that. The current prevalence of COVID-19 in the world is still very low, which means that the virus can continue spreading before we see any sign of herd immunity. 

 Not all countries can afford to be in lockdown for so long. For those nations, we expect cases and deaths to continue to increase.  

 Experts estimate that more than 200 million people in the US would have to recover from COVID-19 to get herd immunity and stop the epidemic[22]. It is not clear that if antibodies will only last 2 to 3 months, a country will not be able to get herd immunity and COVID-19 will become endemic. 

 India will soon become the country with more cases 

Even after some lockdown efforts, a country like India has not been able to stop the exponential growth. In the next few weeks, India will probably become the country with the highest number of cases per day. With a population of 1 billion and still very low prevalence of COVID-19, we expect in the next few months for cases to continue to grow. 

 COVID-19-free countries will close their doors to some countries 

For those nations and territories that have successfully suppressed the virus, including Iceland and New Zealand, reopening their borders will be problematic at best. We will probably continue to see countries make safe transit among them, while others with COVID-19 will not be allowed.  

 Similar to what we have observed in South Korea and Israel, countries that had controlled the virus will probably face new waves.  

The world pre-COVID-19 might not return 

 During this lockdown, the world has changed—from the wide adoption of technology, ecommerce, online classes, telemedicine, and working from home—many habits that people have learned might not go back. This will result in positive consequences in some respects and negative in others, but one thing is certain, 2020 will forever be in the history books as the year that changed the world. 

[1] “George Santayana - Wikiquote.” https://en.wikiquote.org/wiki/George_Santayana (accessed Jun. 24, 2020). 

[2] “Why Was It Called the ‘Spanish Flu?’ - HISTORY.” https://www.history.com/news/why-was-it-called-the-spanish-flu (accessed Jul. 03, 2020). 

[3] “1918 Pandemic (H1N1 virus) | Pandemic Influenza (Flu) | CDC,” Jun. 16, 2020. https://www.cdc.gov/flu/pandemic-resources/1918-pandemic-h1n1.html (accessed Jun. 24, 2020). 

[4] G. Gugliotta, “New Estimate Raises Civil War Death Toll,” The New York Times, Apr. 02, 2012. 

[5] “fs_americas_wars.pdf.” Accessed: Jul. 03, 2020. [Online]. Available: https://www.va.gov/opa/publications/factsheets/fs_americas_wars.pdf. 

[6] S. S. Morse, “Pandemic influenza: Studying the lessons of history,” PNAS, vol. 104, no. 18, pp. 7313–7314, May 2007, doi: 10.1073/pnas.0702659104. 

[7] “How they flattened the curve during the 1918 Spanish Flu.” https://www.nationalgeographic.com/history/2020/03/how-cities-flattened-curve-1918-spanish-flu-pandemic-coronavirus/ (accessed Jul. 03, 2020). 

[8] B. Dolan, “Unmasking History: Who Was Behind the Anti-Mask League Protests During the 1918 Influenza Epidemic in San Francisco?,” Perspectives in Medical Humanities, vol. 5, no. 19, May 2020, doi: 10.34947/M7QP4M. 

[9] M. Roser, E. Ortiz-Ospina, and H. Ritchie, “Life Expectancy,” Our World in Data, May 2013, Accessed: Jan. 14, 2020. [Online]. Available: https://ourworldindata.org/life-expectancy. 

[10] “Child and Infant Mortality - Our World in Data.” https://ourworldindata.org/child-mortality (accessed Jun. 24, 2020). 

[11] “People revolt against coronavirus masks as California reopens - Los Angeles Times.” https://www.latimes.com/california/story/2020-06-12/a-revolt-against-wearing-masks-creates-a-new-coronavirus-danger-as-california-reopens (accessed Jun. 24, 2020). 

[12] CDC, “Burden of Influenza,” Centers for Disease Control and Prevention, Apr. 17, 2020. https://www.cdc.gov/flu/about/burden/index.html (accessed Jul. 03, 2020). 

[13] “Covid-19 study details benefits of remdesivir treatment, and also limitations,” STAT, May 23, 2020. https://www.statnews.com/2020/05/22/covid-19-study-details-benefits-of-treatment-with-remdesivir-and-also-its-limitations/ (accessed Jul. 03, 2020). 

[14] “Hydroxychloroquine drug touted by Trump linked to increased risk of death, study says - The Washington Post.” https://www.washingtonpost.com/health/2020/05/22/hydroxychloroquine-coronavirus-study/ (accessed Jul. 03, 2020). 

[15] K. KupferschmidtJun. 16, 2020, and 6:20 Pm, “A cheap steroid is the first drug shown to reduce death in COVID-19 patients,” Science | AAAS, Jun. 16, 2020. https://www.sciencemag.org/news/2020/06/cheap-steroid-first-drug-shown-reduce-death-covid-19-patients (accessed Jul. 03, 2020). 

[16] P. Zhang et al., “Long-term bone and lung consequences associated with hospital-acquired severe acute respiratory syndrome: a 15-year follow-up from a prospective cohort study,” Bone Research, vol. 8, no. 1, Art. no. 1, Feb. 2020, doi: 10.1038/s41413-020-0084-5. 

[17] Q.-X. Long et al., “Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections,” Nature Medicine, pp. 1–5, Jun. 2020, doi: 10.1038/s41591-020-0965-6. 

[18] “Draft landscape of COVID-19 candidate vaccines.” https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines (accessed Jul. 03, 2020). 

[19] W. CornwallJun. 30, 2020, and 4:25 Pm, “Just 50% of Americans plan to get a COVID-19 vaccine. Here’s how to win over the rest,” Science | AAAS, Jun. 30, 2020. https://www.sciencemag.org/news/2020/06/just-50-americans-plan-get-covid-19-vaccine-here-s-how-win-over-rest (accessed Jul. 03, 2020). 

[20] “Covid-19 vaccine from Pfizer and BioNTech shows positive results,” STAT, Jul. 01, 2020. https://www.statnews.com/2020/07/01/covid-19-vaccine-from-pfizer-and-biontech-shows-positive-results/ (accessed Jul. 03, 2020). 

[21] “New IHME COVID-19 Model Projects Nearly 180,000 US Deaths,” Institute for Health Metrics and Evaluation, Jun. 24, 2020. https://www.healthdata.org/news-release/new-ihme-covid-19-model-projects-nearly-180000-us-deaths (accessed Jul. 03, 2020). 

[22] “COVID-19 resources,” Institute for Health Metrics and Evaluation, Mar. 24, 2020. https://www.healthdata.org/covid (accessed Jul. 03, 2020). 

[23] Richardson et al, 2020,  Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area"