Abstract
Determining exactly what the next pandemic will be is complex, However, by studying some common characteristics of previous viral pandemics, we can predict the general characteristics of the next pandemic. Here, we will explore next pandemic features, reviewing the past pandemics that have afflicted humanity and the factors that might make one viral pathogen more likely than others to cause a future pandemic. There are many factors that accelerate the occurrence of pandemics, including climate change, intensive human interaction in our modern world, and the threat to natural environments of viral reservoirs. By studying a set of requirements, the most important of which is that the virus be transmitted through respiration and air, and that it be able to be transmitted between humans, as well as its ability to undergo genetic mutations, we have identified a specific set of viruses that could potentially turn into future pandemics.
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Keywords: Climate change; Humans; Mutation; Pandemics; Respiration; Viruses
Introduction
The World Health Organization (WHO) uses the term Disease X to denote the possibility that a serious international epidemic could be caused by a pathogen not currently known to cause human disease [
1]. This concept implies 3 major unknowns: the nature of the pathogen, the timing of its emergence, and its geographic origin. These questions remain unanswered, including by the WHO, which introduced the term Disease X. The purpose of the concept is to acknowledge that a future pandemic is considered likely, although its cause, location, and timing remain uncertain. However, some characteristics of a future pandemic can be anticipated, and projections can be developed using available research tools and existing data.
In this paper, we discuss the possible characteristics of Disease X by reviewing past pandemics and the factors that might make some pathogens more likely than others to cause a future pandemic. We limit the scope to viral agents and exclude bacterial and other pathogens, which require separate analysis.
The pathogen that could cause Disease X can be considered in 2 broad categories: a newly emerging pathogen or a known pathogen that re-emerges. If the pathogen is newly emerging, the danger may be greater because knowledge of its biology, transmission route, clinical effects, and public health implications would initially be limited, as occurred during the early phase of the coronavirus disease 2019 (COVID-19) pandemic.
For a viral agent to cause a global pandemic, 2 conditions appear especially important in the present analysis. First, it must be highly transmissible, preferably through respiratory aerosols or droplets. This does not necessarily mean that it must primarily infect the respiratory system, although respiratory infection is possible. Second, it must be capable of sustained human-to-human transmission. These 2 conditions have been met by most viruses that have caused major pandemics in recent history.
Expected Time of the Next Pandemic
The median interval between major viral pandemics since 1900, including human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), is approximately 13 years. This estimate is based on the start years of 6 major viral pandemics: Spanish flu (H1N1) in 1918, Asian flu (H2N2) in 1957, Hong Kong flu (H3N2) in 1968, HIV/AIDS in 1981, swine flu (H1N1pdm09) in 2009, and COVID-19 in 2019.
A 13-year interval should not be interpreted as a fixed periodic pattern. Rather, it provides a reasonable starting point for discussion. This estimate also excludes regional outbreaks, such as Ebola virus disease and Lassa fever, because the present analysis focuses only on global pandemics.
However, several factors suggest that this timeframe may be shorter than 13 years. The most important is the increased speed and volume of human movement between countries and continents. Daily travel and traffic continue to increase, creating more opportunities for rapid international spread.
A second factor is the increasing pressure exerted by climate anomalies, particularly through their effects on animal vectors and reservoirs, as discussed later in this paper. For these reasons, estimating a 5–10-year timeframe for the emergence of the next pandemic does not seem unduly pessimistic. In this review, increased human movement and climate-change-related effects are considered “accelerators” of the next pandemic.
Pandemic Accelerators
One of the main accelerating factors is climate anomalies. Precisely estimating temperature and precipitation anomalies at the origins of previous pandemics is difficult because historical meteorological data are limited, especially for early 20th-century events. Nevertheless, research has identified large-scale climate anomalies that coincided with, or immediately preceded, the emergence and early spread of several major viral events. Research suggests that the 4 major influenza pandemics since 1900—those in 1918, 1957, 1968, and 2009—were all preceded by a La Niña climate pattern [
2]. La Niña is characterized by cooler-than-normal sea surface temperatures in the equatorial Pacific and can drive large-scale atmospheric changes worldwide.
During the 1918 Spanish flu pandemic, temperatures were cooler than normal, and heavy precipitation was reported [
3]. Similarly, during the 1957 Asian flu (H2N2), 1968 Hong Kong flu (H3N2), and 2009 swine flu (H1N1pdm09) pandemics, temperatures were likely cooler because of preceding La Niña conditions [
4]. The mean land surface temperature in Wuhan during the emergence period of COVID-19, from December 2019 to March 2020, was lower than the average land surface temperature during the same period in the previous 3 years [
5]. More broadly, several studies reported a negative correlation between temperature and COVID-19 spread, suggesting that colder winter conditions may have favored transmission [
6]. For influenza, climate-related changes may affect the migratory patterns of wild birds, which serve as animal reservoirs, potentially bringing different species into contact and facilitating the genetic mixing needed for a new pandemic strain to emerge [
7]. Predicting the exact timing and duration of La Niña events more than 1 year in advance is not currently possible with climate models because the phenomenon is fundamentally irregular [
8]. However, long-term climate-change models provide 2 broad predictions regarding El Niño–Southern Oscillation cycles: extreme events may become more frequent and intense, but irregularity and variability are expected to persist [
9]. Thus, the next 2 decades may include an uncertain number of events, with a higher likelihood that some will be more intense than historical averages [
10]. La Niña patterns have also been linked to changes in the abundance, distribution, and behavior of birds and bats, principally through effects on food resources [
11].
Among pandemic accelerators, military conflict should also be considered. Its occurrence is inconsistent across pandemics, but its potential influence on the emergence and spread of infectious disease is plausible, particularly through population displacement, crowding, disrupted health systems, and large-scale troop movement.
Several major viral pandemics since 1900 temporally overlapped with major military conflicts. Spanish flu (H1N1) emerged in 1918, near the end of World War I (1914–November 1918). Asian flu (H2N2) emerged in 1957 during the Vietnam War (1955–1975), and Hong Kong flu (H3N2) emerged in 1968 during the Vietnam War and the War of Attrition (1967–1970). Military movement and conflict may contribute more to the spread of influenza viruses than to their initial emergence [
12].
However, military conflict remains only a possible contributing factor. Among the major pandemics reviewed here, 4 were caused by influenza viruses, a pattern that should be considered when predicting the nature of the next pandemic pathogen. Although the accelerated development of influenza vaccines may reduce the likelihood that influenza will re-emerge as a pandemic threat, influenza viruses cannot be disregarded.
The availability of treatment or vaccination for the anticipated virus is another critical factor. In the absence of an effective treatment or vaccine, infection can spread rapidly while countermeasures are being developed. During a rapidly spreading pandemic, treatment is often limited initially to symptom management and supportive care. The COVID-19 pandemic provides a clear example: effective vaccines required time to develop and deploy, while the infection spread quickly, causing millions of infections and deaths before vaccines became widely available. In addition, COVID-19 was associated with psychological, neurological, and mental health effects among infected individuals, including symptoms that persisted after apparent recovery. These effects also extended to people who were not infected or who remained asymptomatic, reflecting the broader psychological burden of the pandemic. The 1918 Spanish flu pandemic provides another striking example, causing millions of deaths in the absence of a successful treatment or effective vaccine. In general, the major pandemics discussed here were shaped substantially by the lack of effective treatments or vaccines. Vaccines against other viral diseases have also been instrumental in preventing large-scale pandemics. Because ready-made vaccines cannot be developed in advance for all viruses, studies that identify viruses with pandemic potential are important for guiding early treatment and vaccine-development efforts. The mutagenic capacity of viral agents plays a pivotal role in the emergence and rapid spread of pandemics. RNA viruses, including influenza viruses and coronaviruses, have high mutation rates because their replication mechanisms often lack efficient proofreading. These mutations can alter viral proteins, enabling viruses to adapt to new hosts, evade immune responses, and increase transmissibility. As a result, viral evolution can drive the initiation of outbreaks that may eventually develop into global pandemics. In some cases, genetic changes allow viruses that originally circulated in animal reservoirs or vectors to cross species barriers and infect humans, a process known as zoonotic spillover. Once human transmission is established, additional mutations may improve the virus’s capacity for human-to-human spread. The COVID-19 pandemic demonstrated how emerging variants with modified spike proteins could spread more efficiently and reduce the effectiveness of existing immunity, thereby accelerating the global impact of the disease. Another important aspect of viral mutagenesis is its effect on resistance to antiviral drugs and vaccine-induced immunity. Continuous genetic change may reduce the effectiveness of treatment and immunization strategies, making disease control more difficult. Influenza viruses, for example, undergo frequent antigenic drift, which requires annual vaccine updates. Similarly, rapidly mutating viruses can develop resistance to antiviral medications, limiting therapeutic options during outbreaks. These evolutionary adaptations influence the persistence and recurrence of infectious diseases worldwide. Understanding the mutational behavior of viral agents is therefore essential for pandemic preparedness and prevention. Advances in genomic surveillance, molecular biology, and epidemiology allow scientists to monitor viral mutations in real time and identify potential threats before they spread widely. Early detection of high-risk variants can support rapid vaccine development, targeted therapies, and public health interventions. Characterizing viral mutation mechanisms can inform genomic surveillance, vaccine updates, antiviral development, and early public health response.
Best Transmission Route
Based on data from the major viral pandemics since 1900, the respiratory route has been the most common mode of transmission. Five of the 6 pandemics discussed here—Spanish flu (H1N1, 1918), Asian flu (H2N2, 1957), Hong Kong flu (H3N2, 1968), swine flu (H1N1pdm09, 2009), and COVID-19 (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2], 2019)—were transmitted mainly through respiratory droplets and aerosols. This route involves inhalation of the pathogen after an infected person coughs, sneezes, speaks, or breathes, as well as possible transmission after contact with contaminated surfaces. The next viral pandemic pathogen may share this transmission profile. Biologically, respiratory transmission is among the most efficient routes of viral spread [
13]. Although this criterion cannot identify the exact viral pathogen, it can help guide preparedness plans for pathogens transmitted through this route.
Fastest and Deadliest Common Viral Infections
The following section reviews common viral infections worldwide, with particular attention to those with short minimum incubation periods and high case fatality rates, especially infections transmitted by respiratory droplets or aerosols. Each region is considered separately, followed by an attempt to identify broader patterns where possible. The basic reproduction number, R₀, is considered only after the shortlist of respiratory infections is developed from the broader list of rapid and high-fatality infections. Although R₀ is an important indicator of transmission potential, it is not fixed; it varies across time, location, population, and pathogen context [
14].
In Africa, the fastest and deadliest viral infections are typically viral hemorrhagic fevers, which can have rapid onset and high case fatality rates. In this region, Marburg virus disease and Ebola virus disease, both caused by filoviruses, rank highest, with maximum reported case fatality rates approaching 90% and minimum incubation periods of approximately 2 days [
15].
Yellow fever, caused by a flavivirus, ranks second, with case fatality rates of up to 50% in severe untreated cases and a minimum incubation period of 5 days [
16]. Crimean-Congo hemorrhagic fever, caused by a nairovirus, ranks third, with case fatality rates of up to 40% and a minimum incubation period of 1 day after a tick bite [
17]. Lassa fever, caused by an arenavirus, has reported case fatality rates of up to 15%–25% among hospitalized patients and a minimum incubation period of 6 days [
18]. Marburg virus disease, Ebola virus disease, Crimean-Congo hemorrhagic fever, and Lassa fever are viral hemorrhagic fevers that are transmitted mainly through direct contact with bodily fluids [
19].
In contrast, yellow fever is transmitted by Aedes mosquitoes, a route that can allow rapid geographic spread compared with viruses transmitted only through direct human-to-human contact, such as Ebola virus [
20]. However, yellow fever and the other infections listed above are not transmitted primarily through the respiratory route, which is the route emphasized in this analysis.
In South America, yellow fever again ranks among the fastest and deadliest viral infections. It is followed by South American hemorrhagic fevers, which have high but variable case fatality rates depending on the virus strain and incubation periods of approximately 7–14 days. Dengue virus, a flavivirus, ranks third, with a comparatively low case fatality rate (20%), although severe dengue can be fatal [
21].
In North America, hantavirus pulmonary syndrome is among the deadliest and fastest-onset viral infections and has respiratory manifestations, with a high case fatality rate of approximately 35%–40% and rapid progression to severe illness [
22]. Hantavirus is a potential pandemic candidate because it has some features relevant to pandemic emergence. In addition, no curative treatment or effective vaccine is currently available for hantavirus pulmonary syndrome. COVID-19, particularly infections caused by recent Omicron subvariants, remains important because of its rapid spread.
In the Caribbean, yellow fever ranks first among the fastest and deadliest viral infections considered here. Dengue virus follows, and chikungunya virus, an alphavirus transmitted to humans by Aedes mosquitoes, is also relevant; it has a low case fatality rate and an incubation period of approximately 3–7 days [
23].
In Asia, Nipah virus, a paramyxovirus, ranks first among recurrent viral threats considered here. It has a case fatality rate of approximately 40%–75%, an average incubation period of 5 days, and can be transmitted through exposure to respiratory droplets, including droplets produced by coughing or sneezing [
24].
Nipah virus is consistent with the initial assumptions of this analysis: it can cause rapidly progressive disease, has a high fatality rate, and can involve respiratory transmission. Therefore, Nipah virus has characteristics that could make it a global health threat. Middle East respiratory syndrome coronavirus ranks second in this regional assessment because it has a high case fatality rate and a minimum incubation period of 2 days, although sustained human-to-human transmission is limited [
25]. Japanese encephalitis virus, a flavivirus, ranks third, with a case fatality rate of 20%–30% and a 5-day minimum incubation period; however, it is mosquito-borne rather than primarily respiratory [
26]. SARS-CoV-2, COVID-19, and dengue fever may also be considered in this region.
In Europe, Crimean-Congo hemorrhagic fever is among the fastest and deadliest common viral infections considered here, followed by tick-borne encephalitis, a flaviviral infection, and measles, a paramyxoviral infection with very high transmissibility. This ranking also highlights the relevance of recent measles outbreaks in the United States.
Animal Reservoirs and Vectors
Fruit bats, particularly
Pteropus species, or flying foxes, are reservoirs for many viruses, including Nipah virus [
27]. The preferred geographic habitat of
Pteropus species includes tropical and subtropical forests in South and Southeast Asia, especially areas near human agricultural activity, such as fruit orchards and palm groves, that attract bats [
28].
In addition to Nipah virus, fruit bats are natural reservoirs for filoviruses such as Ebola virus and Marburg virus. They can also transmit Australian bat lyssavirus, rabies virus, and Hendra virus, which belongs to the family Paramyxoviridae, the same family as Nipah virus [
29]. Other animal reservoirs that require attention include New World rodents. The deer mouse, genus
Peromyscus, is associated with hantavirus transmission [
30]. The rice rat (
Oryzomys palustris) can also carry hantaviruses and is a reservoir for related viruses, such as Catacamas virus and Playa de Oro virus, as well as possibly arenaviruses [
31]. These rodents are commonly found in rural, forested, and agricultural areas. Human structures such as barns, sheds, and cabins can provide year-round shelter and access to food, increasing opportunities for human exposure [
32].
Influenza
Influenza remains a persistent pandemic candidate despite successful annual vaccine-development efforts. Discussion of influenza must also consider the animals that can be infected by influenza viruses, because animal infection provides opportunities for mutation and reassortment, allowing viruses to return to humans as new strains that may be either less severe or more severe. The likelihood that a mammal will contract an influenza virus is determined primarily by 2 factors: exposure frequency, including close contact with other hosts such as humans, birds, or livestock, and receptor compatibility, particularly the presence of suitable sialic acid receptors in the respiratory tract [
33,
34].
Based on known circulation patterns, epidemic frequency, and documented susceptibility to influenza A, B, C, and D viruses, mammals can be arranged in descending order according to their likelihood of contracting influenza. Humans (
Homo sapiens) have the highest frequency and susceptibility because all seasonal influenza strains, including H1N1, H3N2, and influenza B, circulate endemically in humans. Dense populations and global travel create frequent opportunities for exposure [
35].
Pigs (
Sus scrofa domesticus) are often considered an important “mixing vessel” for influenza viruses because they possess receptors for both avian influenza viruses with α2,3-linked sialic acid preference and human or swine influenza viruses with α2,6-linked sialic acid preference. They can be infected by both human and avian strains, creating opportunities for reassortment and spillover [
36].
Cattle (
Bos taurus) are an important reservoir for influenza D virus and are also susceptible to certain influenza A strains, as demonstrated by recent H5N1 outbreaks in dairy herds [
37]. Cats (
Felis catus) are highly susceptible to some highly pathogenic avian influenza strains, such as H5N1, often through predation on infected birds or consumption of infected raw animal products [
38]. Ferrets (
Mustela putorius furo) are widely used as animal models for human seasonal influenza because their receptor distribution and transmission dynamics, including coughing and sneezing, resemble those of humans [
39].
Dogs (
Canis familiaris) are susceptible to multiple influenza strains, including endemic canine influenza strains, H3N8 and H3N2, that circulate within dog populations. They are also susceptible to some human and avian strains [
40]. Equids, including horses, donkeys, and mules, are regularly affected by equine influenza virus strains, such as H3N8 and H7N7, that circulate endemically in horse populations [
41]. Marine mammals, including seals, sea lions, and whales, can be infected by avian influenza strains, sometimes leading to mass mortality events, such as H10N7 or H5N1 outbreaks in seals and sea lions. Infection may occur through exposure to virus shed by infected birds into aquatic environments [
42]. Finally, bats (order Chiroptera), carry 2 unique influenza A subtypes, H17N10 and H18N11, that circulate only within bat populations. There is no evidence that these strains have been transmitted to humans or other mammals [
43].
By the same rationale, birds that can contract influenza can also be arranged in descending order of likelihood. Wild aquatic birds, including ducks, geese, gulls, and shorebirds, are the primary natural hosts and reservoirs for influenza A viruses. These viruses often circulate enzootically in the gastrointestinal tracts of these birds without causing severe symptoms [
44]. Gallinaceous domestic poultry, including chickens and turkeys, have high susceptibility and exposure risk because of contact with wild-bird feces or contaminated water, high population density, and genetic susceptibility to infection. Domestic waterfowl, including farm ducks and geese, are highly exposed to viruses from wild birds and often serve as a bridge between wild and domestic flocks. They may carry the virus without severe illness, allowing further spread [
45].
Monitoring should focus on influenza virus mutations in both humans and animals infected during each season, especially animals in direct contact with humans, such as those encountered by livestock and poultry farm workers. Perching birds and scavengers, including crows, raptors, ravens, magpies, and sparrows, are susceptible to infection, often after feeding on sick or dead infected poultry or wild birds; highly pathogenic avian influenza H5N1 has been detected in many of these species [
46]. Finally, pigeons and doves, order Columbiformes, are generally considered highly resistant to most avian influenza strains. Although they are often investigated during outbreaks, they are rarely found to be major sources of transmission or morbidity [
47].
Outlook
After this brief overview of the deadliest and fastest-spreading viral diseases worldwide, several points should be emphasized. First, The regional organization is used only to structure the discussion; a pandemic could begin anywhere and spread globally. Second, among the diseases reviewed, viral hemorrhagic fevers appear less likely to become pandemics because most have limited human-to-human transmission and do not spread primarily through respiratory droplets, a key criterion in this analysis for identifying viruses with pandemic potential.
Table 1 summarizes known viral respiratory infections, associated symptoms, and deaths from 2015 to 2025 [
48–
60].
Coronavirus diseases remain a concern despite their reduced impact in populations with effective vaccines. However, 4 other pathogens or pathogen groups stand out: yellow fever virus, measles virus, Nipah virus, and hantaviruses. Yellow fever, which is prevalent in parts of Africa, the Americas, and the Caribbean, is potentially severe, but its mosquito-borne transmission limits direct human-to-human spread. Global efforts to maintain and develop measles vaccines reduce the likelihood that measles will cause a pandemic. For Nipah virus infection and hantavirus pulmonary syndrome, however, the possibility of wider spread remains a concern, particularly because no effective vaccines are currently available for these viral pathogens [
61–
63].
When R₀ is added to the assessment of these respiratory viral infections, measles is the most contagious, with an R₀ of approximately 12–18. COVID-19 follows, with an estimated R₀ of approximately 2–3 for early SARS-CoV-2 lineages, although transmissibility varies by variant. Influenza viruses generally have R₀ values of approximately 2, depending on the year and subtype. Nipah virus has an average R₀ slightly above 1. Hantavirus has an R₀ below the threshold for sustained transmission in most contexts, reflecting the absence of sustained human-to-human spread. However, this does not exclude the possibility that future viral adaptation or specific outbreak conditions could increase transmission.
This raises an important question: if viruses such as hantaviruses or Nipah virus emerged many years ago, why did they not cause pandemics early in their development, as SARS-CoV-2 did, or at least in the recent past? One explanation is that some dangerous viruses, including hantaviruses and Nipah virus, have lacked key pandemic-enabling characteristics, particularly consistent human-to-human transmission. For example, substantial human-to-human transmission of hantavirus was not recognized until the 2019 outbreak in Argentina [
63].
Previously, hantaviruses were believed to be transmitted mainly through exposure to infected rodents or their excreta. In addition, infected individuals often developed clinically apparent disease, which facilitated control and contact tracing by health authorities. This contrasts with COVID-19, in which numerous asymptomatic infections occurred and contributed substantially to transmission during the early phase of the pandemic [
64].
Other reasons relate to 2 main factors: the interaction between the virus and its host, and the possibility of asymptomatic infection. If asymptomatic infection occurs, spread can become more difficult to control, particularly when combined with efficient human-to-human transmission. Under such conditions, new variants of the original virus may emerge that differ in severity and environmental stability, including stability under different humidity conditions [
65].
The second factor is the human environment, particularly population density [
66]. Hantaviruses are now known to be capable of human-to-human transmission in specific circumstances; if such transmission occurred in densely populated areas, spread could be more difficult to control. The consequences would be worse in settings with structural weaknesses in healthcare systems and inadequate surveillance, tracking, and monitoring, especially if the virus had a high case fatality rate.
Conclusion
In this Viewpoint, we adopted an inductive approach by reviewing recent historical pandemics and identifying factors that could contribute to the emergence or development of the next pandemic. The analysis focused on 3 questions: what viral pathogen might cause the next pandemic, when it might occur, and where it might originate. The timing of the next pandemic can be addressed through preparedness, early warning systems, and lessons from the COVID-19 pandemic, which began approximately 5 years before this study was written. The geographic origin is less important from a global preparedness perspective because a pandemic, once established, can affect populations worldwide, including through physiological and mental health effects [
67–
71]. The primary question addressed here was therefore the likely identity of the pathogen.
If the pathogen is entirely new, its initial effects will be difficult to reduce because little will be known about its transmission, clinical manifestations, or control measures. Therefore, this analysis emphasized the identification of dangerous animal reservoirs and vectors that warrant close research attention. If the next viral pandemic is caused by a re-emerging pathogen, the most likely candidates identified here are influenza viruses, other viral respiratory infections, hantaviruses, Nipah virus, measles virus, and coronaviruses. Human history shows that pandemics recur. Research that anticipates, monitors, and prepares for these threats can contribute to protecting human lives through earlier detection, improved prediction, and treatment development.
This study aimed to anticipate the nature of the next viral pandemic in the context of global efforts to strengthen early warning systems and reduce the potentially devastating effects of future outbreaks. The study used an exploratory approach to predict the nature of the next pandemic by collecting data on potential viral threats according to 2 primary assumptions: that the virus would be easily transmissible between humans or have the potential to mutate and spread rapidly between humans, and that it would be transmitted through the air by respiratory droplets or aerosols. The study also considered factors that may accelerate pandemic emergence or spread, including animal-reservoir effects and climate anomalies. These findings are relevant because they identify viral infections with characteristics that may increase their probability of developing into major pandemics.
Future work should include mathematical modeling studies and expert-led analyses that identify a limited number of viral pathogen candidates with pandemic potential. Such work should also support the search for effective treatments and the development of vaccine platforms or implementation plans for groups of viruses most likely to cause pandemics. In addition, factors that accelerate the emergence and spread of viral infections should be addressed. Climate change is particularly important, as is intensified research and monitoring of animal reservoirs and vectors. Routine measures such as quarantine and disinfection, although important, should not be the sole response to initial outbreaks because they may be insufficient against rapidly spreading viral pathogens.
HIGHLIGHTS
• Predicting exactly what the next pandemic will be is complex, but some of its characteristics can be predicted.
• Respiratory and airborne transmission is the most common way pandemics have spread throughout history.
• Several factors can accelerate the occurrence of the next pandemic, including climate change, increased human contact, and human encroachment on natural environments of virus reservoirs.
Article information
Ethics Approval
Not applicable.
Conflicts of Interest
The authors have no conflicts of interest to declare.
Availability of Data
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Acknowledgements
The authors thank the Deanship of Scientific Research staff at Al-Ahliyya Amman University for their continued encouragement and support.
Table 1.Respiratory viral infections, by virus family, virus genus/type, associated respiratory disease, and estimated global deaths (2015–2025)
Table 1.
| Virus family |
Virus genus/type |
Associated respiratory diseases |
Estimated global deaths, 2015–2025 |
Notes on data |
| Coronaviridae |
SARS-CoV-2 |
COVID-19, ranging from mild illness to severe pneumonia |
Approximately 7 million+ |
Dominant cause; figure based on cumulative confirmed deaths, 2020–2025 [48,49]. |
|
MERS-CoV |
Middle East respiratory syndrome |
Approximately 350–400 |
Highly lethal, with an approximate case fatality rate of 36%, but well contained. Cumulative deaths since 2012 have been approximately 960 [50]. |
|
SARS-CoV |
Severe acute respiratory syndrome |
0 |
Contained globally since 2004; no deaths were reported during this decade. |
|
HCoV-229E, HCoV-NL63, HCoV-OC43, and HCoV-HKU1 |
Common cold and mild to severe respiratory disease |
Contributes to acute lower respiratory infection burden |
Specific mortality data are not tracked. Deaths are rare and are attributed to the overall burden of acute lower respiratory infections. |
| Orthomyxoviridae |
Influenza A and B viruses |
Seasonal influenza and severe respiratory illness |
Approximately 2.9–6.5 million |
WHO estimates 290,000–650,000 respiratory deaths annually. The total is a cumulative estimate for the decade [51]. |
|
Influenza C and D viruses |
Mild illness; influenza D primarily affects livestock |
Negligible/not tracked |
Deaths are rare and are not separately tracked in global surveillance. |
| Paramyxoviridae |
Respiratory syncytial virus |
Bronchiolitis and pneumonia |
Approximately 1.5 million |
Global Burden of Disease studies estimate approximately 150,000 deaths annually, primarily among children younger than 5 years [52]. |
|
Measles virus |
Rubeola and respiratory complications |
Approximately 700,000 |
Mortality varies substantially because of vaccination gaps and outbreaks. This value is a cumulative estimate for the decade [53]. |
|
Human metapneumovirus and human parainfluenza viruses 1–4 |
Common cold, bronchiolitis, and pneumonia |
Contributes to acute lower respiratory infection burden |
Contributes to the same acute lower respiratory infection burden as human coronaviruses, estimated at approximately 2.2–2.5 million deaths globally per year from all lower respiratory infections [54]. |
|
Nipah virus |
Nipah virus infection and pneumonia |
350–500 |
High fatality rate [55]. |
| Picornaviridae |
Rhinoviruses A, B, and C |
Most frequent cause of the common cold |
Contributes to acute lower respiratory infection burden |
Deaths are typically recorded only when secondary bacterial infection leads to severe pneumonia. Mortality is not tracked by specific virus [56]. |
|
Enteroviruses, such as EV-D68 |
Cold-like symptoms and pneumonia |
Low/sporadic |
Deaths are rare but occur, often in association with severe neurological complications, such as acute flaccid myelitis [57]. |
| Hantaviridae |
Orthohantaviruses, including Andes virus and Sin Nombre virus |
Hantavirus pulmonary syndrome |
Unknown |
Approximately 200 cases are documented annually worldwide. The average case fatality rate is high, ranging from 30% to 60% [58]. |
| Adenoviridae |
Adenoviruses |
Pharyngitis, common cold, and pneumonia |
Contributes to acute lower respiratory infection burden |
Mortality is low among healthy adults, but adenoviruses are major contributors to severe respiratory disease in children and immunocompromised people [59]. |
| Herpesviridae |
Cytomegalovirus, Epstein-Barr virus, and varicella-zoster virus |
Viral pneumonia, especially in transplant recipients |
Low/immune status–dependent |
Deaths are highly conditional on immune status and are not tracked as a primary cause of global respiratory mortality [60]. |
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