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This article was originally published on Aug. 19, 2022, and has since been updated by the author.

As COVID-19 continues to circulate, another viral disease has captured the world's attention: mpox (formerly called monkeypox). Since Jan. 2023, the Democratic Republic of the Congo (DRC) has reported more than —the largest number of suspected cases of clade I monkeypox virus (MPXV) ever annually on record. Additional cases have been confirmed in neighboring nations and prompted the World Health Organization (WHO) to designate the disease as a . This understandably sparks the question: do global mpox outbreaks mark the beginning of another full-blown pandemic? While there are similarities between mpox and COVID-19 (e.g., both are zoonotic diseases), there are also distinguishing features with important implications for disease transmission and outbreak dynamics. This article summarizes the similarities and differences between COVID-19 and mpox, and the viruses that cause them.

Reservoirs

Mpox and COVID-19 are both , meaning they are transmitted from animals to humans. SARS-CoV-2 (the cause of COVID-19) , potentially hopping to an intermediate host before making the leap into humans. However, direct evidence supporting this chain of transmission events is still lacking. 

 is endemic to countries in central and western Africa. Although MPXV was first discovered in monkeys kept for research in the DRC, they are not the main, or only, reservoir of the virus. Rodents, including rope squirrels and Gambian pouch rats, are believed to be reservoirs of MPXV. Yet, MPXV has only been isolated from wild animals on 2 occasions, including  in the DRC and a  in Côte d’Ivoire in 2012. As with SARS-CoV-2, more research is needed to understand the origins, reservoirs and circulation of MPXV among animal populations. 

Transmission

SARS-CoV-2 is a respiratory virus—it spreads through virus-laden aerosols (teeny droplets released during breathing) that can be suspended in the air for minutes to hours. If someone else inhales these aerosols, the exposed individual can become infected. Because SARS-CoV-2 spreads efficiently through the air, it is particularly challenging to control—a single person has the potential to infect many others just by breathing. Moreover, people can spread COVID-19, even if they are asymptomatic. 

While MPXV can be transmitted through saliva and respiratory secretions, it is not a respiratory virus. Rather, it  through direct contact with mpox rash, scabs or body fluids from someone who is infected. It can also be spread congenitally, or by using objects and surfaces that have been used by someone with mpox. Bumping up against someone or , however, pose a low risk—an individual would need to have  to increase their risk of infection. This is more likely when living with a person with a confirmed case of mpox, where contact may be regular and prolonged. MPXV can also be transmitted through sexual contact, which played a paramount role in its spread during the 2022-2023 outbreak and continues to be in ongoing outbreaks in Africa.  

Ultimately, because MPXV spreads primarily through close, prolonged contact, mpox is far less transmissible than COVID-19. 

Symptoms and Disease Severity

 appear anywhere from 2-14 days after exposure to SARS-CoV-2. They can include fever, chills, headache, sore throat, congestion or runny nose and loss of taste or smell, among others. People usually feel better after a few days to a few weeks, though develop prolonged symptoms that continue for 3+ months (i.e., Long COVID). COVID-19 can be fatal. Since the beginning of 2020, COVID-19 has caused , though the death rate has declined, in part due to the availability of vaccines and treatments.  on several factors, including the SARS-CoV-2 variant causing the infection, how many times someone has been infected, vaccination status, age and whether a person has underlying conditions. 

, it can take up to 3 weeks after exposure to MPXV for symptoms to develop. Though it varies on a case-by-case basis, symptoms may mirror those of COVID-19 during the early stages of infection (e.g., fever, headache, chills). Clinically speaking, mpox differs from COVID-19 in that it is characterized by the development of a rash, which can be painful and itchy, and tends to be distributed on the face, extremities and genitals. 

Most people recover from mpox after 2-4 weeks, though it can be severe, even fatal. The disease severity is tied, in part, to the strain of MPXV causing infection (clade I viruses, like the strain circulating in Africa, are more deadly than clade II viruses). Mpox severity  on age (young children are more likely to develop severe disease), access to medical care and vaccines and health status (e.g., people with  have a higher risk of severe mpox). 

Diagnosis

People can  at home using rapid antigen tests. Nucleic acid amplification tests (NAAT), such as polymerase change reaction (PCR), are more sensitive than antigen tests for diagnosing COVID-19. These methods may be performed in laboratories or point-of-care facilities (e.g., pharmacies) and involve isolating and amplifying the genetic material from patient specimens to detect SARS-CoV-2 RNA. are also available.  

Currently, there are fewer options for diagnosing mpox. Confirmatory testing is only conducted via PCR on fluid from pustules or dry crust from scabbed lesions. Moreover, samples must be sent to a public health laboratory or a properly equipped commercial lab for analysis.—there are currently no options for testing at home or at point-of-care facilities. As mpox outbreaks evolve, may be developed that promote the ease, accessibility and/or diagnostic capabilities of mpox testing. 

Prevention and Treatment

There were no vaccines for COVID-19 at the beginning of the pandemic because SARS-CoV-2 was a novel virus when it was discovered in late 2019. Now, various vaccines have been approved for use in the U.S. , which protects against severe disease and hospitalization, is approved by the U.S. Food and Drug Administration (FDA) for people 6 months of age and older. There are also  (e.g., Paxlovid) available to treat COVID-19, though they must be administered within 5 days after symptoms begin. 

Unlike the early days of 2020, when COVID-19 first came onto the scene, there are already vaccines that protect against mpox. A live-attenuated vaccine, trademarked , is the most widely used. JYNNEOS was developed to prevent smallpox and is also protective against mpox in adults 18 years and older. Bavarian Nordic, the company that makes JYNNEOS, is the safety and efficacy of the vaccine for use in children (2-12 years old) and adolescents (12-17 years old).  

Mpox vaccination efforts people who have been exposed to mpox or who are more likely to get mpox. Right now, there are no specific treatments for the disease. , a drug that treats smallpox, is being studied for its potential use for mpox; treatment via tecovirimat is primarily available through enrollment in the National Institute of Health’s   

For both and , taking certain behavioral steps are important for preventing and slowing the spread of infection. These include (but are not limited to) isolating infected individuals and maintaining proper hygiene and disinfection practices.  

SARS-CoV-2 and Mpox Virus: Structure and Evolution

Structure and Genome

Structurally speaking, SARS-CoV-2 and MPXV are very different. , like all coronaviruses, is an enveloped single-stranded RNA virus. It is small (), spherical and decorated with a porcupine-like sheath of spike (S) proteins. S proteins bind to host cells via angiotensin-converting enzyme 2 (ACE2), a protein ubiquitously expressed by organs throughout the human body, to initiate infection. 

 is a member of the Poxviridiae family—the virus is enveloped, brick shaped and large (). Its double-stranded DNA genome is encapsulated in a core containing enzymes needed for replication and evasion of host immune defenses. Like SARS-CoV-2, MPXV has surface proteins that facilitate its entry into host cells. However, rather than a single protein, poxviruses use 11-12 transmembrane proteins to fuse with host cells,  glycosaminoglycans or laminin on the cell surface. 

Evolution and Variants

The differences in the genomes of SARS-CoV-2 and MPXV have important evolutionary ramifications.  

RNA viruses, like SARS-CoV-2, can be sloppy replicators. RNA polymerase, which copies the viral genome, . Unlike other RNA viruses,  (i.e., an exoribonuclease) with some proofreading ability. However, while this may slow the acquisition of mutations in SARS-CoV-2, it does not stop them altogether. As a result, random mutations develop that can, if beneficial for viral fitness, quickly become widespread. This has been apparent throughout the COVID-19 pandemic. In 2021, the SARS-CoV-2 Delta variant . When 2022 rolled around, Omicron, which spreads easier from person-to-person, replaced Delta as the most dominant variant; are all derivatives of Omicron. The increased transmissibility of Omicron is tied to a slew of S protein . 

There are 2 known clades (groups that share a common ancestor based on their genome) of MPXV: clade I and clade II. Whereas a clade II virus was responsible for the multi-country 2022-2023 mpox outbreak, current outbreaks in Africa are tied to a clade I strain.  

DNA viruses, like MPXV, do not mutate as freely as RNA viruses. The enzymes involved in DNA viral replication (i.e., DNA polymerase) are better at proofreading and fixing errors than those in RNA viral replication (i.e., RNA polymerase). Poxviruses typically acquire . However, the MPXV strain circulating in 2022   compared to strains detected in 2018-2019. The mutations suggested the virus had been spreading within human populations in Africa and Europe for several years before the influx of cases in 2022-2023. This differs from mutation patterns in SARS-CoV-2, which are  replication errors that may or may not become fixed in a population. 

Mpox Outbreaks vs. The COVID-19 Pandemic

There are several important differences between mpox outbreaks and the COVID-19 pandemic. For one, SARS-CoV-2 was a novel virus when it emerged in late 2019, meaning it had never been seen before. As a result, the world didn’t have vaccines or immunity to the virus, which allowed it to spread like wildfire. The rise of new SARS-CoV-2 variants, coupled with the virus’s ability to transmit efficiently from person to person through the air, only fueled (and continues to fuel) this fire. 

Mpox is not a new disease. Scientists know more about MPXV than they did about SARS-CoV-2 at the beginning of the COVID-19 pandemic. Importantly, given that MPXV spreads primarily through close contact, it , and transmission is unlikely to reach pandemic scale. Vaccines are also already available, though the key is getting the vaccines to those who need them. Vaccination of at-risk populations in places like the U.S. and Europe was critical for controlling the 2022-2023 mpox outbreak. However, vaccine distribution to and accessibility in African countries (e.g. the DRC), where mpox has continued to rage, . to these regions is important for minimizing disease burden.  

Mpox is not COVID-19, but the world must remain vigilant and put the lessons learned from the COVID-19 pandemic to good use. Ensuring adequate and equitable distribution of mpox diagnostics, vaccines and treatments, educating communities about disease spread and prevention, and bolstering public health infrastructure to allow for effective disease control measures are all critical for limiting devastation caused by mpox.