Free Vaccinations for All Is, Morally and Economically, the Right Way to Prepare for Pandemic and Seasonal Respiratory Infections

With aging populations, the world’s attention has focused on diseases of aging, yet pandemics have a way of acutely narrowing our attention on infectious disease. Modern society has progressed substantially in the prevention, containment, and treatment of infectious diseases. Despite this, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2),¹ the causative agent of the coronavirus disease 2019 (COVID-19) pandemic, caught the world unprepared. Infectious disease outbreaks have punctuated civilization, and this virus has grabbed our attention more than any since the 1918 influenza pandemic with its estimated 50 million dead and 500 million infected worldwide. In 2005, just over a year after the SARS-coronavirus 1 outbreak ceased, the US Department of Health and Human Services calculated the death toll from a pandemic analogous to 1918 would lead to approximately 1.9 million US deaths. With US COVID-19-related deaths already exceeding 100 000 in less than four months, a total of 1.9 million deaths is certainly possible.

PANDEMICS ARE ALSO IN OUR MORE RECENT PAST

Novel influenza strains have also caused pandemics in 1957, 1968, and as recently as 2009. The 1957, 1968, and 2009 pandemics pale in comparison with 1918, likely because of the introduction of antibiotics and vaccination. A 2008 retrospective analysis of the 1918 flu suggests that bacterial coinfections caused more than half of all deaths.² Early reports out of China, Singapore, and Iran suggested that coinfections during COVID-19 led to worse clinical outcomes.^3–5 This is not surprising; numerous studies have shown that bacterial coinfections result in significantly more morbidity and mortality during seasonal influenza. It remains to be determined how coinfections will influence the overall mortality associated with COVID-19. However, the Chinese cities of Qingdao and Wuhan reported an increase in the percentage of severe COVID-19 cases when associated with coinfections.

COINFECTIONS EXACERBATE DISEASE

Mycobacterium tuberculosis was found to possibly predispose an individual to SARS-CoV-2 as well as increase disease severity. Many patients with COVID-19 and M tuberculosis developed acute respiratory distress syndrome, a severe immune pathology and often fatal outcome of respiratory infections (https://bit.ly/3dynAhP). Another study from China found that bacterial coinfection was the single greatest predictor of disease severity compared with any other singular comorbid condition. Severe cases had a bacterial coinfection rate of 85.7%, whereas mild cases had a coinfection rate of 27.6% (https://bit.ly/2XYShq8). Coinfection with other respiratory viruses, such as influenza, respiratory syncytial virus, parainfluenza, and adenovirus, or with atypical bacteria, including Mycoplasma pneumoniae, Chlamydia pneumophila, and Legionella pneumophila, all increased risk of severe disease.³

The 2009 influenza pandemic had outcomes similar to those in early SARS-CoV-2 reports. Multiple reports identified coinfections as the cause of death in one third of the fatalities during the 2009 pandemic, with those patients developing acute respiratory distress syndrome more likely to have a bacterial coinfection.⁶ Coinfections were not only associated with a large portion of deaths but also highly associated with the most severe outcomes not resulting in death. This occurs during normal respiratory seasons as well when hospital stays for viral-bacterial mixed pneumonias are longer than for viral pneumonia alone. This, of course, identifies only patients who had a detectable coinfection at the time of screening; there is no doubt that many people fall through the testing cracks during every pandemic and respiratory infection season. In 2008, the authors of the 1918 flu retrospective suggested steps the world should take to prepare for the next 1918-like pandemic. Among them was the stockpiling of vaccines against bacterial pathogens in the event mass vaccination is needed.² A simpler solution to this problem is available: vaccinate everyone for vaccine-preventable diseases before a pandemic.

PREVENTIVE PUBLIC HEALTH POLICIES BENEFIT ALL

Adopting this solution as a matter of public health policy would avoid the need for mass vaccinations during a pandemic, a logistically challenging endeavor. This would be minimally more challenging than following the American Academy of Pediatrics vaccine schedule, with a few modifications accounting for any new vaccines. Our experience with the pneumococcal conjugate vaccine should serve as a roadmap. Approved for use in children in 2000, the seven-valent vaccine had an immediate effect on childhood pneumococcal disease, but the effect was soon experienced by the elderly as well. Once children no longer spread the vaccine-included serotypes, pneumococcal disease decreased in all age groups. Because implementing a free vaccination program to everyone all at once is improbable, we must let science and experience guide us and begin with children. Once healthy children no longer carry pathogens asymptomatically, we can proceed with at-risk populations such as the elderly, immunocompromised, and health care workers. This endeavor will take decades, but preparing for the next pandemic requires decades-long dedication, foresight, patience, and perseverance.

Respiratory pathogens do not respect human-created borders; COVID-19 reaffirms that. The United States and the rest of the developed world should quickly implement this strategy in their own countries while planning to expand into developing countries. Morally, free vaccinations make sense because they will save lives, but free vaccinations also make sense as a matter of public health policy. Higher levels of herd immunity result in fewer individuals serving as a pathogen reservoir. This results in fewer coinfections during pandemics and influenza seasons, which means fewer severe cases and more medical resources for everyone. However, free vaccinations also make sense for financial reasons: ultimately, preventing mixed infections through vaccination is substantially less expensive than the cost of hospital intensive care. The cost to vaccinate a child against the childhood respiratory pathogens Streptococcus pneumoniae, Hemophilus influenzae type b, Bordetella pertussis, and diphtheria is approximately $700; yearly flu vaccination costs about $15.

Although we have made great progress in vaccine development for many common respiratory pathogens, numerous needs remain unmet. We must support research and development for vaccines targeting the most common respiratory pathogens, which continue to cause coinfections such as M pneumoniae, respiratory syncytial virus, and tuberculosis. If we assume that these vaccines would cost the average of those listed earlier, then vaccination would range between $900 and $1200 per person. These costs pale in comparison with the average daily cost of either a regular or an intensive care unit hospital stay, which regularly reaches $20 000.

Free vaccinations would deliver returns not only during pandemics. As many as one quarter of all deaths during seasonal influenza are estimated to be the result of a bacterial coinfection. Rapid diagnostic testing has shed light on the true burden of coinfections during influenza, and current estimates are that mixed pneumonia occurs in 30% to 50% of patients and that 20% to 30% of bacterial sepsis cases involve a viral coinfection.

In 2009, the University of Michigan estimated the cost of stockpiling antibiotics for 11 500 patients—the number they would expect to see during a serious pandemic—at $600 000.⁷ A 2016 report from the Healthcare Cost and Utilization Project estimated an average hospital stay for pneumonia to be $9500, meaning that the cost of hospitalizing 11 500 patients would be about $109 250 000 (https://bit.ly/3dA7rsm). Moreover, the average cost of stay for septicemia, a common complication of mixed pneumonias, is $23 663; that cost more than doubles the previously mentioned $100 million total cost. The cost of vaccinating that many people: $8 050 000.

Once the dust settles on this pandemic and thorough studies have been done, coinfections will likely be one of the greatest, if not the single greatest, risk factors for severe disease, death, and cost expenditure. Therefore, regardless of your desired metric—moral or economic—free vaccinations for all passes each one.