The Journal of Infectious Diseases

INVITED PERSPECTIVE

Pandemic Preparedness and Response: Lessons From

COVID-19
Anthony S. Fauci and Gregory K. Folkers
Washington, District of Columbia, USA

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The global experience with COVID-19 holds important lessons for preparing for, and responding to, future emergences of
pathogens with pandemic potential.
Keywords. COVID-19; SARS-CoV-2; emerging diseases; pandemic preparedness; vaccines.

The severe acute respiratory syndrome capacity for evading immunity induced soon becomes exponential. Playing “catch
coronavirus 2 (SARS-CoV-2) and the dis­ by vaccines, prior infection, or monoclo­ up” in a pandemic is bound to be a losing
ease it causes, coronavirus disease 2019 nal antibodies directed against specific proposition.
(COVID-19), are responsible for the viral epitopes [4]. Another unexpected The third lesson is that global
most catastrophic acute infectious disease and unprecedented element of the out­ information-sharing and collaborations
outbreak that the United States (US) and break is that up to 60% of SARS-CoV-2 are essential for a successful response to
the entire world have experienced since transmissions may occur from a person a pandemic [6]. Sharing of viral isolates,
the historic influenza pandemic of who is asymptomatic [5], which has ne­ viral genomic data, research reagents,
1918–1919. More than 1.1 million gated the syndromic approach to contact variant surveillance data, clinical sam­
COVID-19 deaths have been reported in tracing that has proven effective during ples, and real-world clinical data are es­
the US, and nearly 7 million globally [1]; many previous infectious disease sential to optimally utilize the global
the latter figure is likely a vast underesti­ outbreaks. expertise that exists and is often the gate­
mate [2]. Given the enormous impact of The second lesson is the importance of way to productive international collabo­
this pandemic on virtually every aspect acting early, rapidly, and aggressively in rations. During the height of the
of global society, it is critical that we re­ implementing public health interventions COVID-19 pandemic, considerable ad­
flect on the lessons we have learned (or and countermeasure development. When vantages were realized by information
should have learned) over the past 3 years. dealing with a highly transmissible infec­ made available to US investigators and
Although dozens of lessons could be ad­ tion, especially one spread frequently by public health officials by our British,
dressed [3], we have chosen 10 that are asymptomatic individuals, the epidemic Israeli, and South African colleagues,
noteworthy (Table 1). curve of severe cases or death at any given among others.
The first lesson is inherent to any new­ time reflects transmission that occurred A fourth lesson is the importance of le­
ly emergent infectious pathogen with weeks ago. What is happening now will veraging already existing capabilities
pandemic potential: expect the unexpect­ not be evident in morbidity and mortality such as the extensive domestic and inter­
ed. Within the broad category of “the un­ data until weeks from now. What starts national network of clinical trial infra­
expected,” the COVID-19 pandemic has off as an apparent linear increase in cases structure that had been put in place and
been unprecedented for the evolution
and spread of multiple, successive viral Table 1. Ten Lessons From COVID-19 for Pandemic Preparedness
variants with progressively greater
1. Expect the unexpected.
2. Early, rapid, and aggressive action is critical in implementing public health interventions and
countermeasure development.
Received 03 April 2023; editorial decision 03 April 2023; ac­ 3. Global information sharing and collaborations are essential for a successful response to a pandemic.
cepted 04 April 2023; published online 10 April 2023 4. Already existing infrastructure should be leveraged for the rapid and effective performance of clinical
Correspondence: Gregory K. Folkers, MS, MPH, 4409 trials.
Garrison Street, NW, Washington, DC 20016 (gregfolkers@ 5. Years of investment in basic and clinical research are critical for the rapid development of effective
outlook.com). countermeasures.
6. The prototype pathogen approach to pandemic preparedness and response should be implemented.
The Journal of Infectious Diseases® 2023;228:422–5
© The Author(s) 2023. Published by Oxford University Press on 7. Attention must be paid to perturbations of the animal–human interface.
8. Long-standing systemic health and social inequities that drive pandemic-related disparities must be
behalf of Infectious Diseases Society of America. All rights re­
served. For permissions, please e-mail: journals.permissions@ addressed.
oup.com 9. Misinformation and disinformation are the enemy of public health and pandemic control.
https://doi.org/10.1093/infdis/jiad095 10. Emerging infections are forever.

422 • JID 2023:228 (15 August) • INVITED PERSPECTIVE

fine-tuned over decades for the conduct HIV vaccine [12], respiratory syncytial Administration [11]. Thus, in less than
of clinical trials for human immunodefi­ virus (RSV) vaccines (in late-stage clini­ 12 months from the recognition of this
ciency virus (HIV) therapeutics, preven­ cal development) [13], and investigation­ new virus, vaccine doses were ready to
tion, and vaccines [7]. Well-established al Middle East respiratory syndrome go into the arms of individuals. This sci­
clinical research networks including the (MERS) vaccines [14]. This structure- entific accomplishment, along with the
HIV Prevention Trials Network, the based approach to SARS-CoV-2 immu­ billions of dollars invested by Operation
HIV Vaccine Trials Network, the AIDS nogen design led to the mutationally sta­ Warp Speed [17] that allowed mass pro­
Clinical Trials Group, and the bilized and ultimately highly effective duction of vaccine doses prior to the
Infectious Diseases Clinical Research S-2P immunogen employed in the most proof of efficacy, led to an unprecedented
Consortium were united to form the widely used COVID-19 vaccines [15]. accomplishment—a safe and highly ef­

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COVID-19 Prevention Network [8]. For COVID-19 mRNA vaccines, the fective vaccine available in less than 1
Thousands of volunteers passed through timeline from the identification of a year from the identification of a novel
this consolidated network in clinical tri­ pathogen to the development of a safe and deadly pathogen. This never could
als that demonstrated the safety and and effective vaccine was the shortest in have been accomplished without decades
high degree of efficacy of several the history of vaccinology (Figure 1) of investment in basic and clinical
COVID-19 vaccine candidates. [11]. On 10 January 2020, the genomic research.
The fifth, and arguably most impor­ sequence of SARS-CoV-2 was posted to To sustain the basic and clinical re­
tant, lesson from the COVID-19 pan­ a public database [16]. Within 5 days, search enterprise critical for pandemic
demic is that sustained investments in the development of the Moderna preparedness, a commitment to the vital­
basic and clinical research are critical COVID-19 vaccine began (the Pfizer ity and renewal of the biomedical work­
for the rapid development of effective product was on a similar timeline). force is essential. To meet the varied
countermeasures essential for an optimal Within 65 days a phase 1 trial of the vac­ microbial threats that will no doubt
pandemic response [9]. The most cogent cine was initiated; within 139 days a emerge, we must train the next cadre of
example relates to decades of investment phase 2 clinical trial was begun; and with­ clinicians and scientists in the fields tra­
in basic research that led to the ground­ in 198 days a phase 3 trial began. An in­ ditionally associated with infectious dis­
breaking messenger RNA (mRNA) vac­ terim analysis of the data from the eases, such as microbiology, virology,
cine platform [10, 11]. In parallel, many clinical trials found evidence of prelimi­ immunology, epidemiology, and public
years were devoted by multiple groups nary efficacy at day 311, and at day 325 health. Also essential to pandemic pre­
to perfecting structure-based immuno­ an Emergency Use Authorization was paredness are individuals trained in the
gen design for an (as-yet unsuccessful) submitted to the US Food and Drug physical, chemical, mathematical, and

Figure 1. Severe acute respiratory syndrome coronavirus 2 vaccine development: mRNA-1273 (see text for details). Abbreviations: EUA, Emergency Use Authorization;
GMP, Good Manufacturing Practice.

INVITED PERSPECTIVE • JID 2023:228 (15 August) • 423

computational sciences whose expertise from an animal reservoir to humans. documented result of avoidable suffering
is essential for complex biological chal­ Examples include HIV, influenza, and death. There is no easy solution to
lenges, including vaccine development. Ebola, SARS, MERS, Nipah, and many countering this disturbing wave of misin­
In addition, a new generation of scien­ others. COVID-19 has taught us again formation and disinformation except for
tists with expertise in ecology and evolu­ that we must work harder to reduce the all of us to continue to articulate science-
tionary biology is needed to better risk of pathogen spillover from animals and evidence-based information as
understand the human–microbe inter­ to humans with approaches such as ex­ proactively as those who spread the
face, as well as individuals from the veter­ panding pathogen surveillance at inter­ opposite.
inary sciences to help illuminate the flow faces between humans, domestic The tenth lesson is that emerging in­
of microbes between animals and animals, and wildlife; strictly limiting fections will be with us forever. They al­

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humans. We also need skilled individuals the clearing and degradation of tropical ways have occurred throughout history;
in social science disciplines such as an­ and subtropical forests; improving the in our lifetime we have experienced
thropology, human geography, and health and economic security of commu­ many infectious disease emergences,
sociology. nities living in emerging infectious dis­ and they surely will occur again in the fu­
The sixth lesson is the utility of the pro­ ease hotspots; enhancing biosecurity in ture [25]. The emergence of new infec­
totype pathogen approach to pandemic animal husbandry; and shutting down tions may be impossible to prevent;
preparedness and response. This strategy or strictly regulating wildlife markets however, stopping their evolution into
involves selecting families of viruses with and trade [22]. pandemics is within our control if proper
a high potential of being the source of a The eighth lesson is that longstanding pandemic preparedness and response are
pandemic outbreak. Such families include systemic health and social inequities implemented.
Coronaviridae (SARS-CoV-1, MERS, drive pandemic-related disparities, and The entire world has experienced un­
SARS-CoV-2), Orthomyxoviridae (influ­ these must be addressed [23]. imaginable suffering over the past 3 years
enza), and Paramyxoviridae (Nipah, COVID-19 has shed a bright light on with COVID-19. It is critical that we
RSV), among others [18–20]. The goal is how the social determinants of health commit ourselves to ensuring that a pan­
to intensively study a prototype virus in lead to disparities in incidence and se­ demic of this magnitude will never hap­
each family in anticipation of the emer­ verity of disease. Economic disparities pen again. Hopefully, a consideration of
gence of a novel and potentially pandemic of minority populations such as African these 10 lessons will help us—and those
pathogen from within that family. Prior Americans and Hispanics result in an who follow us—to achieve that goal.
experience with a prototype virus within overrepresentation in occupations in es­
a given family of viruses regarding basic sential work settings where remote Notes
virology, diagnostic assays, animal mod­ work or physical distancing is difficult
Acknowledgments. A. S. F. is the for­
els, antigenic targets, optimal vaccine or impossible. Underlying conditions
mer Director of the National Institute
platforms, and potential immune corre­ such as diabetes, hypertension, obesity,
of Allergy and Infectious Diseases
lates of protection would be informative and chronic lung and heart disease,
(NIAID) at the US National Institutes
in the event of the emergence of a poten­ among others, lead to an increased se­
of Health. G. K. F. formerly was Chief
tially pandemic virus within that family. verity of disease once a person is infected.
of Staff to the NIAID Director.
During the COVID-19 pandemic, our These social determinants of health will
Potential conflicts of interest. Both au­
prior experience with SARS-CoV-1 and not disappear in weeks or months or
thors: No reported conflicts.
MERS greatly informed and facilitated even years; however, they will never dis­
Both authors have submitted the
our response to SARS-CoV-2 [11]. We appear unless we commit now to the pro­
ICMJE Form for Disclosure of Potential
fully expect that baseline studies of proto­ cess of addressing them.
Conflicts of Interest. Conflicts that the
type pathogens in the “higher risk” fami­ The ninth lesson comes through loud
editors consider relevant to the content
lies of viruses will prove extremely useful and clear. Misinformation and disinfor­
of the manuscript have been disclosed.
in allowing a rapid and effective response mation are the enemy of public health
to the emergence of pathogens of pan­ and pandemic control [24]. There are
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