Life in the Time of COVID-19 (2020)

COVID-19: COVID-19The COVID-19 (Coronavirus Disease-2019) world pandemic is still in the mid-phases in most of the world. It may persist for several months, or even longer. In some geographies that ignored its early threat (Spain, Italy), COVID-19 spread rapidly and overwhelmed medical infrastructures: hospital beds, ICU beds, respirators, dialysis machines, personal protective equipment (PPE), and health care workers. This extended to areas with COVID-19 spread-enhancing features: cosmopolitan, high influx of tourism, dense populations, mass transit, poorer neighborhoods with close quarters and multigenerational families, large events (Mardi Gras in New Orleans; soccer game with 40,000 attendance in Lombardy, Italy). In these epicenters, COVID-19 has been associated with higher mortality rates (10-12% in Spain and Italy), and high infection rates among health care workers (10-20%). COVID-19 continues to infect millions and cause the deaths of tens of thousands. These figures may be underestimations because of lack of widespread testing, autopsies, and reporting. The virus is weakening world economies and large and small industries, particularly in the sectors of oil, services, tourism, transportation, sports, and the arts. It is also rapidly changing our social habits and norms into what might become a “new normal” life. As of April 17, 2020, the COVID-19 pandemic had infected 2.2+ million people worldwide and caused the death of 147,000+. In the United States, 672,000+ people had been infected, with 33,000 deaths. In the early phases of the pandemic, the prevalence of the infection (total number of infected people) increased by 33% daily, which means it doubled every 3 days.1 By mid-April, the doubling rate had increased to 7 days, confirming the benefits of COVID-19 preventive measures: enhanced hygiene, PPE, social distancing; geographic lock-downs; and COVID-19 testing, contact tracing, and isolation. This also suggests that, rather than causing widespread and overwhelming COVID-19 surges, the disease may simmer in a “slow-motion” waxing and waning status until we develop safe and effective anti-COVID-19 vaccines and treatments. This is unless we are happily surprised by one of the following: 1) the virus gradually undergoes mutations that make it less infective (as with influenza); 2) the viral spread is suppressed by warmer, humid weather (seasonal spread); or 3) “herd immunity” develops faster than expected (as measured by blood testing for COVID-19 neutralizing antibodies). This will be discussed later. Still important but as yet unknown parameters that influence the final toll of COVID-19 are: 1) Will it recur in waves? 2) Will it then become more or less virulent? 3) Will COVID-19 IgG neutralizing antibodies provide durable immunity? Recent estimates from other coronaviruses suggest protection for months to 2 years. And 4) how quickly will safe and effective vaccines and treatments become available? On a personal note, one of the authors (H.K.) had discussions with medical oncology colleagues in several countries in the Middle East (Lebanon, Jordan, Israel, Saudi Arabia, and Iran). It is their impression that COVID-19, with social restrictions but minimal testing, is less common and less fatal in this part of the world. This simply may be due to insufficient testing or reporting, but there is also the possibility that COVID-19 is not thriving in these geographies (warmer, humid weather), or that it has mutated to a less virulent form. Time will tell. The Spread of COVID-19 The first cases of COVID-19 were found in China in mid-November 2019, but not reported until later. The disease abated there in early March, after severe social restrictions and wide COVID-19 screening, isolation, and prevention.2 Some experts criticized China for its early delays and lack of transparency/data sharing, and are questioning its reported cases, particularly the number of deaths, which may be higher. Some countries had experience with previous regional epidemics like severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS).3 They took the threat seriously, developing early COVID testing and wide screening, contact tracing and isolation, and social distancing. They were able to contain the COVID-19 spread earlier and more effectively. These include South Korea, Australia, Hong Kong, Japan, Singapore, and Taiwan. However, COVID-19 started spreading again once protective measures were eased. Countries that had no prior experiences with viral epidemics, and that delayed testing and protective measures, experienced significantly higher infection and mortality rates (Spain, Italy, France, and England). The United States did not appreciate the potential COVID-19 threat early on, had significant delays (about 6-8 weeks) in wide testing due to development and manufacturing issues,4 and delayed implementing social distancing and restrictions. We are still mid-pandemic, and testing and protective measures will definitely reduce the final toll of COVID-19, as has been observed in the past week in several cities and regions. What Can We Learn From Previous Viral Epidemics? COVID-19 is not “like influenza,” as has been suggested. The influenza season of 2017-2018 infected 45 million Americans and caused the death of 61,000, a mortality rate of about 0.13%.5 The estimated mortality rate from COVID-19 is so far about 5%, 30-40 times higher than that of influenza. The difference in mortality rates in different geographies may relate to several factors: extent of testing; protection measures; effect of warmer, humid weather (still in question); medical infrastructure capacities; number and prevalence of preexisting conditions; viral genetic variations; reporting; and others. For example, about 25-50% of COVID-19 infected patients may be asymptomatic. Therefore, wide COVID-19 testing increases the incidence of reported COVID-19 clinical infections. This results in a lower reported mortality rate. Limited screening (e.g., by the Centers for Disease Control & Prevention criteria) would only capture more symptomatic and severe cases, producing a higher reported mortality rate. In addition, the mortality rate may be significantly higher among patients with cancer due to their immunocompromised state. Small cohort studies suggest one as high as 30+%.6 The “Spanish influenza” pandemic of 1918-1920 was the most devastating on record. It recurred in 3 waves, the second being the most virulent, infected a third of the world population (500 million of 1.5 billion), and resulted in an estimated 50 million deaths (mortality rate 10% over the 3 waves).7 However, there were no vaccines or drugs then to mitigate the spread of the virus, no antibiotics to treat secondary infections, little understanding of the pathophysiology of diseases, and nothing to compare with the incredible research resources and medical infrastructures that exist today. The swine flu of 2009 infected 60 million Americans and caused the death of about 12,500 (mortality rate 0.02%). A safe and effective vaccine available then mitigated the viral spread and reduced mortality.9 COVID-19 is highly contagious, airborne, and survives on inert surfaces for a few hours to several days, depending on the ambient temperatures and conditions.10-13 Seasonal influenza transmits from 1 person to 1.2 others; COVID-19 transmits from 1 person to 6-7 without precautions, and to 2-3 with precautions. It is important to note that infectivity actually may be highest before the onset of symptoms. This explains why COVID-19 is difficult to control without wide testing by nasal swabs and blood serology for COVID-19 neutralizing IgG (discussed below), and if social protective measures are relaxed before herd immunity develops from viral exposure or vaccines.11,12 The long-term health care impact of the COVID-19 pandemic will probably be significantly less severe than that of the 1918-1920 Spanish influenza. The health care and economic effects of the 1918-20 Spanish influenza were closely intertwined with the post-World War 1 consequences (infrastructure destruction, poor nutrition, poor medical support, vast migrations). In contrast, only 4 months into the COVID-19 pandemic, millions of researchers and most large health care companies and public health care infrastructures worldwide are investing huge amounts of time and resources, and billions of dollars to investigate hundreds of potential vaccines and treatments. Even as of mid-April, many hopeful leads are coming through. Also the benefits of wide testing and protective social measures are already showing positive trends for COVID-19 suppression in many geographies. Herd Immunity & Importance of Wide Testing From historical data, we know that viral spread can be controlled once a proportion of a population becomes immune, through either exposure to the virus or vaccination. This percent depends on the infectivity of a particular virus and availability of an effective vaccine. For COVID-19, it is estimated that 60% of a particular population needs to be exposed and/or vaccinated. With regard to testing, a distinction should be made between COVID-19 “exposure,” measured by blood IgG serology, and “clinical infection,” measured by nasal swabs, since up to 50% of exposed people may never exhibit symptoms. From the existing data (with very limited testing by nasal swabs and even less serologic testing), it is estimated that less that 1-2% of the world population has been clinically infected. To get a precise estimate of “exposure” and how long herd immunity will take to develop, we need wide serology testing to detect the virus-specific IgG antibody. This is not just a simple epidemiologic exercise. It will help identify different “COVID-19 immunologic profiles,” protect lives, reduce mortality, and revive economies faster (discussed later). Ending the COVID-19 pandemic and seeing light at the end of the COVID-19 tunnel will happen if any of these conditions are met: 1) Herd immunity through exposure to COVID-19 that covers 60% of people.14 2) Development of effective and safe vaccines. Short of a vaccine, the development of effective anti-COVID-19 treatments, as with AIDS, where a vaccine could not be developed, but highly effective drugs exist. 3) Any of the following happy “black swans” occur—COVID-19 virus develops mutations that weaken and eliminate it (as happens with influenza); it is suppressed by warmer humid weathers (seasonal, giving enough time to develop vaccines); serology testing shows exposure and herd immunity developing much faster than expected; or exposure results in many years (rather than months) of immunity. COVID-19 Testing Nasal swab testing (PCR testing) identifies people with an active SARS-CoV-2 infection, the virus that causes COVID-19. This test gives results in 5 minutes, using small portable devices that can be deployed widely in all health care facilities. COVID-19 testing in the blood (serology test) involves measuring the immune response of the body to the viral exposure. An early non-specific IgM immune response develops about 5 days after exposure. A second more selective COVID-19 neutralizing IgG antibody immune response develops 2-4 weeks later. Based on the COVID-19 testing, individuals may fall into different “COVID-19 immunity profile” groups. The first are those who are COVID-19 negative by both nasal and serologic tests. These are still at risk. The second are those with positive PCR nasal swabs. These are infected and can infect others, and they must be isolated to avoid the viral spread. The third are those who have recovered from a COVID-19 infection and have developed COVID-19 IgG antibodies (positive serology). These individuals are probably resistant to a reinfection. They protect others as buffers in crowds. They may be able to donate plasma (rich with anti-COVID–specific IgG) to treat severely ill patients. They can also return safely to work and, if they are health care workers, they can be deployed preferentially to treat infected patients. Defining different COVID-19 risk groups can be used to prevent the COVID-19 spread, protect and treat patients, reinvigorate industries and work places, and reopen and normalize societal venues. However, there may be unintended consequences. For example, poorer and out-of-work Americans without income or resources may potentially take a risk and purposefully infect themselves to become immune and be able to work again. During high-risk COVID-19 periods, capacities should be scaled to enable testing any individual with any symptoms, and to conduct COVID-19 serology testing on all individuals at the start, then periodically (every month). COVID-19 testing may become routine, like measuring the blood pressure, the temperature, or blood sugar and chemistry levels. At least a million nasal swabs and blood serologies may need to be done daily, and be easily available across all health care facilities. As happened in some nursing homes, health care facilities may be easy venues for COVID-19 spread (mini-epicenters), because of the presence of dense populations of vulnerable patients, and frequent contacts with health care workers. Testing and social protective measures in medical facilities should be even more intense. Summary Life in the time of COVID-19 will certainly be different from the past. In high-risk COVID-19 periods, testing should be widespread, as discussed. In addition, the new normal in our lives will include: 1) Better hygiene and social distancing. This will not only prevent COVID-19, but may also reduce mortality for other viral infections, such as influenza. 2) Fewer physical gatherings, more virtual communications, and enhanced telecommuting capabilities. 3) Universal health care and better-prepared health care facilities. This will provide equal and optimal access to medical care for all Americans in such stressful times, without fears of lack of insurance, catastrophic medical bills, rejection of care, etc. 4) Elimination of unnecessary bureaucracies that have accumulated over decades across multiple disciplines, for example in health care and medical research. These bureaucracies have not improved quality of care, research, or patient safety. They have, however, slowed progress, added multiple layers of administrative burdens, and increased costs 3- to 10-fold. Some of the above measures have already demonstrated favorable trends towards reducing global warming. Finally, enhanced capacity for preparedness is essential to be able to effectively face new viral pandemics and other potential catastrophes. HAGOP KANTARJIAN, MD, is a medical oncologist and a Special Fellow of Health Policies at the Baker Institute, Rice University. MARY ALMA WELCH, MMSC, is a physician assistant in Houston. STEVEN KORNBLAU, MD, is a medical oncologist in Houston. ANDREW DINARDO, MD, is an infectious disease specialist in Houston. NADIM AJAMI, PHD, is a virologist and microbiologist who specializes in virome and microbiome research. The opinions of the authors do not reflect those of the institutions with which they are affiliated.Hagop Kantarjian, MD: Hagop Kantarjian, MDMary Alma Welch, MMSc: Mary Alma Welch, MMScSteven Kornblau, MD: Steven Kornblau, MDAndrew Dinardo, MD: Andrew Dinardo, MDNadim Ajami, PhD: Nadim Ajami, PhD