Mpox Disease Statistics in US 2026 | Mpox Facts

Mpox Disease in US

Mpox Disease in America 2026

Mpox — the disease formerly known as monkeypox — is not the headline emergency it was at the peak of 2022, but it has not gone away either. As of the CDC’s most recent U.S. case data update on March 2, 2026, the United States continues to see low-level endemic transmission of clade II mpox, while simultaneously managing the first confirmed cases of the more dangerous clade I variant on American soil. According to official CDC figures, the U.S. had recorded more than 34,187 total mpox cases and 60 deaths since the 2022 outbreak began — with the cumulative total climbing steadily through 2024 and into 2025 as clade II continued circulating at a low but persistent baseline of roughly 50 to 70 reported cases per week. Separately, since November 2024, 11 cases of clade I mpox have been reported in the United States, including a landmark cluster of three California cases in October 2025 that represented the first confirmed community transmission of clade Ib mpox in the country — meaning people with no recent international travel history were infected, a significant escalation in the domestic risk picture. The majority of all ongoing U.S. mpox cases, across both years, continue to occur in people who are unvaccinated or have received only one dose of the JYNNEOS vaccine.

What makes mpox in 2026 a story worth following closely — even as case numbers stay relatively low compared to the 2022 outbreak peak — is the dual-front nature of the threat. On one front, clade IIb mpox remains entrenched in the sexual networks of gay, bisexual, and other men who have sex with men (MSM) across the United States, cycling through the large proportion of the at-risk population that remains incompletely vaccinated. On the other front, the globally spreading clade Ib variant — which carries a significantly higher case fatality rate of 1.4% to ~10% compared to clade II’s 0.1% to 3.6%, per CDC — has now established a foothold in American communities. Between January and September 2025, WHO recorded 44,299 confirmed global mpox cases and 180 deaths across 93 countries, and the WHO’s second public health emergency of international concern (PHEIC) for mpox was lifted on September 5, 2025 — not because the outbreak was over, but because the risk profile had shifted enough to move beyond emergency framing. For Americans, the numbers at home are modest but the trajectory of global clade I spread demands sustained attention in 2026 and beyond.

Interesting Facts About Mpox Disease in the US 2026

Before diving section-by-section, here are the most important, fully verified facts about mpox in the United States as of March 2026 — sourced exclusively from CDC, WHO, MMWR, NEJM, CIDRAP, and peer-reviewed research.

#FactData Point
1Total U.S. mpox cases since 2022 outbreak (CDC, October 31, 2024)34,187 cases
2Total U.S. mpox deaths since 2022 outbreak60 deaths
3U.S. mpox cases during 2022–2023 outbreak peak (by May 10, 2023)30,395 cases; 42 deaths
4Peak U.S. outbreak week (week of July 31, 2022)3,274 cases in one week
5U.S. average weekly clade II mpox cases (Oct 2023–Apr 2024)~59 cases per week
655x reduction from peak to Oct 2023–Apr 2024 averageFrom 3,274 → ~59/week
7U.S. clade II cases in 2024 year-to-date (as of November 23, 2024)2,501 cases
8U.S. clade I mpox cases since November 2024 (CDC, February 13, 2026)11 cases
9U.S. clade Ib community transmission cases (California, October 2025)3 cases — no recent travel history
10New York City mpox cases since January 1, 2026 (NYC Health, March 12, 2026)45 cases
11NYC mpox cases in last 30 days (February 8 – March 7, 2026)16 cases
12Majority of U.S. mpox cases — vaccination statusUnvaccinated or only 1 dose of JYNNEOS
13JYNNEOS vaccine effectiveness (2 doses) — multijurisdictional CDC study85.9% (adjusted VE)
14JYNNEOS vaccine effectiveness (1 dose)75.2% (adjusted VE)
15Meta-analysis VE estimate (2-dose series, 32 studies) — Vaccine 202482%
16Breakthrough infections in fully vaccinated persons (May 2022–May 2024)271 cases<1% of fully vaccinated
17U.S. JYNNEOS doses administered (May 2022–May 2023)>1.2 million doses
18At-risk population with 2-dose completed coverage (as of 2024)Only 25% — majority still unvaccinated
19HIV co-infection rate among mpox cases (Oct 2023–Apr 2024, MMWR)48% of those reporting HIV status
20Hospitalization rate for clade II mpox (Oct 2023–Apr 2024)10% of cases
21Share of fatal mpox cases in Black persons (2022–2023 outbreak)87% (33 of 38 deaths)
22Clade I case fatality rate (CFR) vs Clade II CFR1.4%–~10% vs 0.1%–3.6%
23Global confirmed mpox cases (Jan 1 – Sep 30, 2025, WHO)44,299 cases; 180 deaths
24Global total clade I mpox cases (Jan 1, 2024 to Feb 13, 2026, CDC)More than 46,000
25WHO PHEIC #2 for mpox liftedSeptember 5, 2025

Source: CDC U.S. Case Data, March 2, 2026; CDC Current Situation Report, February 13, 2026; NYC Department of Health mpox dashboard, March 12, 2026; CDC MMWR Clade II Surveillance Update (Oct 2023–Apr 2024), May 2024; CDC Domestic Mpox Response 2022–2023, MMWR May 2023; CDC JYNNEOS Vaccine Effectiveness data, MMWR May 2023; NEJM JYNNEOS VE study, June 2023; Lancet Infectious Diseases JYNNEOS meta-analysis, May 2025; WHO Global Mpox Assessment Report, October 30, 2025; CIDRAP/NEJM Evidence Public Health Alert, December 17, 2025; JHU Situation Updates 2024–2025

These 25 facts capture the full arc of mpox in the United States from 2022 through 2026. The story is one of a crisis successfully reduced but not eliminated — and now complicated by a new and more dangerous variant. The 55-fold reduction from the peak outbreak week to the endemic baseline is one of the most dramatic infectious disease turnarounds in recent U.S. public health history, driven by a combination of vaccination, behavioral change, and natural immunity from prior infection. Yet the persistence of ~59 weekly clade II cases through 2023–2024, the 2,501 new clade II cases in 2024 alone, and the 3 California clade Ib community transmission cases in October 2025 serve as consistent reminders that the virus is still circulating and still evolving. The 87% share of fatal 2022–2023 outbreak cases occurring in Black persons is one of the starkest health equity data points in recent American epidemiology — an inequality driven primarily by differential vaccine access, higher rates of HIV co-infection, and structural barriers to care in Black communities.

Recent Mpox Disease Outbreaks in the US 2026 | Key Clusters and Incidents 2022–2026

From the original 2022 national outbreak to the first-ever domestic clade Ib community transmission in 2025, the United States has experienced a series of distinct mpox outbreaks and clusters that have each advanced scientific understanding and tested the limits of the public health response. Here is the complete verified breakdown of every major U.S. mpox outbreak event from the beginning through March 2026.

Outbreak / ClusterPeriodCases / StatesKey Facts
2022–2023 National Clade IIb OutbreakMay 2022 – May 202330,395 cases; 42 deaths — all 50 states + DCLargest mpox outbreak in U.S. history; U.S. Public Health Emergency declared August 4, 2022; lifted January 31, 2023
Peak outbreak weekWeek of July 31, 20223,274 cases in one weekHighest single-week case count ever recorded in the U.S.
New York City peak clusterSummer 2022NYC was #1 city by case countNYC declared its own Public Health Emergency July 29, 2022; largest urban cluster
California 2022 peak clusterSummer–Fall 2022Largest state by case countLargest mpox state burden; California declared State of Emergency August 1, 2022
First tecovirimat-resistant cluster — CaliforniaLate 2022 – Early 2023Cases in California — sublineage B.1.17First reported spread of TPOXX-resistant mpox to people with no prior TPOXX treatment; F13L gene N267del mutation
Endemic phase — low-level ongoing clade II transmissionMay 2023 – ongoing~59 cases/week average (Oct 2023–Apr 2024)55x reduction from peak; persistent baseline despite vaccination efforts
Second tecovirimat-resistant multi-state clusterOct 6, 2023 – Feb 15, 202418 persons; 5 statesIL (8), CA (5), LA (2), TX (2), NY (1) — first interstate TPOXX-resistant outbreak; all had no prior TPOXX treatment; sublineage B.1.20; F13L mutations N267del + A184T
West Africa clade II re-importation / Summer 2025 uptickSummer 2025Multiple U.S. states (number not specified)Linked to clade II outbreak in Sierra Leone and Liberia; CDC tracked uptick across several states; CDC issued vaccination travel advisory for Liberia (as of January 22, 2026)
First U.S. clade I (clade Ib) caseNovember 20241 case — CaliforniaTravel-associated; individual had recently traveled to West Africa; first-ever clade I detection on U.S. soil
U.S. clade Ib travel-associated clusterNov 2024 – Aug 20258 travel-associated clade I casesCases linked to travel to Central/Eastern Africa; some cases linked to people who had traveled from outbreak areas
First U.S. clade Ib community transmission — CaliforniaAug–Oct 20253 community-transmitted cases + 1 travel-linked sourceSymptom onset mid-to-late September 2025; confirmed clade Ib in October 2025; no international travel history for the 3 community cases; all survived; genomically linked to August 2025 travel case; first domestic clade I transmission chain in U.S. history
Total U.S. clade I cases (Nov 2024 – Feb 13, 2026)Nov 2024 – present11 cases totalMix of travel-associated and community-transmitted; CDC risk to general public: Low; CDC risk to MSM: Low to moderate
NYC 2026 ongoing clade II activityJan 1 – Mar 7, 202645 cases (16 in last 30 days)Continuing endemic transmission; NYC Health dashboard, March 12, 2026

Source: CDC U.S. Case Data, March 2, 2026; CDC Current Situation Report, February 13, 2026; CDC Clade II Outbreaks Page, January 22, 2026; CIDRAP/NEJM Evidence Public Health Alert, December 17, 2025; CDC MMWR “Mpox Cluster Caused by Tecovirimat-Resistant Monkeypox Virus — Five States, October 2023–February 2024,” October 10, 2024 (Gigante et al.); CIDRAP “Second U.S. Drug-Resistant Mpox Cluster Identified,” October 11, 2024; CDC Domestic Mpox Response MMWR, May 2023; CDC Risk Assessment for Clade I, October 20, 2025 and February 13, 2026; NYC Department of Health mpox dashboard, March 12, 2026

When you line up every distinct U.S. mpox outbreak event from 2022 through 2026, a clear and sobering pattern emerges. The 2022–2023 national outbreak was the founding event — explosive in scale, concentrated in specific networks, and ultimately brought under control through a combination of emergency vaccination, community mobilization, and behavioral change rather than any single authoritative policy decision. What was not anticipated at the time was how quickly the virus would begin to generate treatment-resistant variants. The first tecovirimat-resistant California cluster in late 2022–early 2023 was a warning shot: a sublineage carrying the F13L N267del mutation had managed to spread between people who had never even taken the drug, meaning the resistance was not emerging from individual treatment courses but being transmitted in the community. The second, larger five-state tecovirimat-resistant cluster spanning October 2023 to February 2024 — covering 18 people across Illinois, California, Louisiana, Texas, and New York — was the escalation that confirmed the first event was not an isolated fluke. Critically, the MMWR authors noted that because not all U.S. mpox cases undergo genetic sequencing, their 18-case count almost certainly underestimates the true prevalence of the drug-resistant variant in circulation.

The 2025 outbreak timeline marks the most consequential shift in U.S. mpox risk since the 2022 peak, for a different reason entirely: the arrival of clade I on domestic soil. The progression from a single November 2024 travel-associated California case to a confirmed August–October 2025 domestic transmission chain — with three California men infected by a source case who had traveled internationally, none of the three having any travel history themselves — followed exactly the scenario that CDC’s own risk assessment models had flagged as the critical threshold event. The CDC’s October 20, 2025 risk assessment confirmed that the three California community cases did not change the overall low risk classification for the U.S. general public, because their modeling had already accounted for the likelihood of limited local spread. However, it upgraded the risk for MSM in the United States to “low to moderate”, given evidence from European clade Ib clusters in Fall 2025 that the virus can sustain transmission in MSM sexual networks in high-income countries. The summer 2025 clade II uptick linked to Sierra Leone and Liberia, running in parallel, underlined once more that global outbreak events translate into domestic case increases — and that the U.S. endemic baseline is never truly stable as long as clade II continues to circulate internationally.

US Mpox Case Count Statistics in 2026 | Total Cases and Trend 2022–2026

Understanding where U.S. mpox stands today requires tracking the full historical progression from the explosive 2022 outbreak through the current endemic phase.

PeriodU.S. Mpox CasesKey Developments
May–Dec 2022 (outbreak launch)~29,000+ casesClade IIb; declared U.S. Public Health Emergency August 4, 2022
Peak week (July 31, 2022)3,274 cases in one weekHighest single-week total
May 10, 2022 – May 10, 202330,395 cases; 42 deathsFirst full outbreak year total
Through October 31, 2024 cumulative34,187 cases; 60 deathsAll cases; CDC/JHU tracker
Oct 2023–Apr 2024 average~59 cases/week55x below peak; low endemic baseline
2024 year-to-date (as of Nov 23, 2024)2,501 clade II casesSteady low-level circulation
Summer 2025 uptickIncrease across multiple statesLinked to clade II West Africa outbreak (Sierra Leone, Liberia)
Clade I U.S. cases since November 2024 (CDC, Feb 13, 2026)11 casesIncluding 3 with no travel history (Oct 2025, California)
Current U.S. case data updateMarch 2, 2026Monthly update cycle; clade II dominant
NYC cases since Jan 1, 202645 casesMarch 12, 2026 NYC dashboard
NYC cases Feb 8 – Mar 7, 202616 cases in 30 daysNYC Health, March 12, 2026

Source: CDC U.S. Case Data update, March 2, 2026; CDC Current Situation, February 13, 2026; CDC Domestic Mpox Response MMWR, May 2023; JHU Situation Update December 3, 2024; NYC Department of Health and Mental Hygiene mpox data, March 12, 2026

The 34,187 cumulative U.S. mpox cases through October 2024 — with steady additional cases accumulating into 2025 and 2026 — place the United States as the country with the highest total clade II mpox case count in the world, a consequence of both the severity of the 2022 outbreak and the diligence of surveillance systems that detect and report cases thoroughly. The current endemic baseline of approximately 50–70 reported cases per week reflects a disease that has not been eliminated but has been substantially suppressed through a combination of vaccination uptake, behavioral adaptation, and the development of natural immunity in the most heavily exposed communities. The summer 2025 uptick of clade II cases across multiple states — several of which were linked to an ongoing clade II outbreak in Sierra Leone and Liberia — was a clear signal that global outbreaks can re-seed domestic transmission and that the U.S. cannot treat its endemic clade II baseline as entirely disconnected from international case counts.

The 11 clade I cases since November 2024, including the landmark California cluster of 3 confirmed clade Ib cases in October 2025 with no international travel history, marks a qualitative shift in the U.S. mpox risk landscape that infectious disease specialists have been watching carefully. CIDRAP’s December 17, 2025 Public Health Alert — co-published with NEJM Evidence — documented those three California cases in detail, noting that all three men had skin-to-skin intimate contact within the 21-day incubation window but no documented sexual contact, and that one was severely immunocompromised but all survived. The CDC’s viral genomic (DNA fingerprint) analysis confirmed these three October 2025 cases were linked to a separate U.S. clade I case detected in August 2025 following travel — establishing a domestic transmission chain from an imported case to community-level spread without further international introduction. That is precisely the epidemiological pattern that health officials flagged as the most critical scenario to prevent.

US Mpox Demographics Statistics in 2026 | Race, Age, HIV Status 2022–2025

The who of mpox in America is as important as the how many. Demographic data from the 2022–2023 outbreak and the ongoing endemic period reveals persistent and deeply troubling health inequities.

Demographic / Category2022–2023 Outbreak DataOct 2023–Apr 2024 Update (MMWR)
Primary affected groupGay, bisexual, other MSM; transgender personsUnchanged
Age range — majority of casesAdults aged 21–55 yearsConsistent
Black or African American (% of cases)33%25% (declined 7 ppts)
Hispanic or Latino (% of cases)31%34% (increased 3 ppts)
White (% of cases)Smaller share32%
Black share of mpox-associated deaths87% (33 of 38 deaths)
HIV co-infection among cases38% of cases48% of those reporting HIV status
Hospitalization rate8%10% (slight increase)
Hospitalized patients who were HIV-positiveHigh68% of hospitalized with known HIV status
Deaths (Oct 2023–Apr 2024)5 deaths (0.3% fatality rate)
Vaccination rate — cases in unvaccinated personsMajority unvaccinated67% of new cases in unvaccinated persons
Cases in those with ≥1 vaccine doseMinority33% had at least 1 dose
Hospitalization rate — vaccinated (≥1 dose)Only 1% of hospitalized
Tecovirimat (TPOXX) treated patients (2022–2023)6,932 patientsAvailable via CDC IND protocol

Source: CDC Domestic Mpox Response 2022–2023, MMWR May 2023; CDC/MMWR Clade II Mpox Surveillance Update, October 2023–April 2024, published May 2024; CDC mpox cases by demographics archive

The demographic portrait of mpox in America is one that public health officials have consistently described as a disease of inequity — not because it inherently discriminates by race, but because structural inequalities in vaccine access, HIV care, and healthcare system engagement translate directly into differential outcomes. The most striking single statistic remains the 87% of fatal mpox cases in 2022–2023 occurring in Black persons, while Black people represented only 33% of total cases. Among the deceased, 94% were immunocompromised due to HIV infection — a finding that directly links the mpox mortality disparity to disparities in HIV care, specifically the higher rates of advanced, untreated, or incompletely treated HIV disease in Black communities in the United States. Undetectable HIV viral load is strongly associated with survival from severe mpox; conversely, CD4 T-cell counts below 200 cells/mm³ — a marker of advanced immunosuppression — have been consistently associated with the most severe and fatal mpox presentations.

The shift in racial demographic data between the peak outbreak and the 2023–2024 endemic period reflects both the success and the limits of vaccine equity efforts. The Black share of cases declined from 33% to 25%, partly reflecting targeted outreach and vaccination efforts by CDC and community partners at HIV conferences, Pride events, and mobile clinics. Conversely, the Hispanic share of cases increased from 31% to 34%, suggesting that vaccine outreach had relatively less penetration in this community during the same period. The 48% HIV co-infection rate among cases in the endemic period — up from 38% in the outbreak — reflects the progressively more concentrated nature of remaining transmission within the most vulnerable, least-vaccinated, often most-medically-complex segments of the at-risk population. The 10% hospitalization rate in the endemic period, with 68% of hospitalized patients being HIV-positive, confirms that mpox has not become a mild inconvenience at the population level: for people with significant immunocompromise, it remains a potentially life-threatening disease.

US Mpox Clade I Statistics in 2026 | Clade Ib Community Transmission 2025–2026

The arrival and limited spread of clade I mpox in the United States is the single most important new development in the domestic mpox situation since the 2022 outbreak was contained.

MetricFigure / DetailSource / Date
First U.S. clade I case detectedNovember 2024 — travel-associatedCDC situation report
Total U.S. clade I cases (since Nov 2024)11 casesCDC, February 13, 2026
Travel-associated clade I casesMajority — travel to Central/Eastern AfricaCDC
Community-transmitted clade Ib cases — California3 cases — confirmed October 2025CIDRAP/NEJM Evidence, Dec 17, 2025
California cases — travel historyNone — no recent international travelCIDRAP/NEJM Evidence, Dec 17, 2025
California cases — transmission routeSkin-to-skin intimate contact (non-sexual reported)CIDRAP/NEJM Evidence, Dec 17, 2025
California cases — link to imported caseLinked via genomics to August 2025 travel-related caseCDC / CIDRAP
Symptom onset for California clusterMid-to-late September 2025CIDRAP, December 2025
Outcomes for California clade Ib patientsAll survived (one severely immunocompromised)CIDRAP, December 2025
CDC risk assessment — clade I to general public (U.S.)LowCDC, February 13, 2026
CDC risk assessment — clade I to MSM in U.S.Low to moderateCDC, February 13, 2026
Clade I CFR in DRC and Africa1.4%–~10% (vs. clade II’s 0.1%–3.6%)CDC / JHU
Global clade I cases (Jan 1, 2024 – Feb 13, 2026)More than 46,000 — Central/Eastern AfricaCDC February 13, 2026
Countries with clade Ib community transmission (Sep 2025+)Italy, Malaysia, Netherlands, Portugal, Spain, United StatesWHO, October 30, 2025
Clade Ib non-travel cases in Europe (Fall 2025)Multiple cases — MSM sexual contact networksWHO/ECDC reports

Source: CDC Clade I Mpox Outbreak/Current Situation, February 13, 2026; CIDRAP/NEJM Evidence Public Health Alert, December 17, 2025; WHO Global Mpox Risk Assessment Report, October 30, 2025; JHU Mpox Situation Updates 2024–2025

The 11 clade I mpox cases in the United States since November 2024, confirmed by CDC’s February 13, 2026 situation report, represent a carefully monitored but genuinely new chapter in U.S. mpox epidemiology. For the first year of the global clade I outbreak — which exploded in Central and Eastern Africa beginning in mid-2023 and prompted WHO’s second PHEIC declaration on August 14, 2024 — the U.S. saw only sporadic, travel-associated clade I cases with no onward transmission. The three California clade Ib cases confirmed in October 2025, published via the pioneering CIDRAP/NEJM Evidence Public Health Alert initiative on December 17, 2025, changed that calculus. Genomic sequencing confirmed these three men — whose symptoms began in mid-to-late September 2025 — were infected from a common source linked to an August 2025 U.S. travel-associated clade I case, meaning clade Ib had completed at least one domestic transmission chain entirely within U.S. borders.

The significance of the clade I vs. clade II severity distinction cannot be overstated for understanding why this matters. While the U.S. has accumulated over 34,000 clade II cases with a case fatality rate of approximately 0.14% (42 deaths per 30,395 cases at the May 2023 tally, adjusted upward to 60 deaths over the full cumulative period), clade I carries a case fatality rate of 1.4% to ~10% depending on the healthcare setting, immunocompromise level, and access to treatment. In the DRC — the global epicenter — clade Ia has historically been associated with ~3% CFR, heavily concentrated in children. Clade Ib, the newer subvariant driving the current global outbreak, has demonstrated a somewhat lower CFR in high-income country cases but still represents a meaningfully more severe disease than the clade II Americans have encountered over the past three years. The WHO’s October 30, 2025 report documented that six countries — Italy, Malaysia, Netherlands, Portugal, Spain, and the United States — had confirmed clade Ib community cases with no travel history, with at least five occurring in MSM sexual contact networks, opening a new transmission pathway that clade Ib had not previously demonstrated outside Africa at scale.

US Mpox JYNNEOS Vaccine Statistics in 2026 | Vaccination Coverage and Effectiveness 2022–2026

The JYNNEOS vaccine is the primary tool in America’s mpox defense, and the data on its real-world effectiveness and coverage coverage is comprehensive and confirmed.

MetricFigureSource / Year
JYNNEOS doses administered (May 2022–May 2023)>1.2 million dosesCDC Domestic Mpox Response, MMWR 2023
First-dose coverage of estimated at-risk population (May 2023)37%CDC MMWR 2023
Completed 2-dose coverage of at-risk population (May 2023)23%CDC MMWR 2023
At-risk population with ≥1 dose (as of 2024)39%MMWR Surveillance Update, May 2024
At-risk population with completed 2-dose series (as of 2024)Only 25%MMWR Surveillance Update, May 2024
Adjusted VE (2 doses) — multijurisdictional case-control85.9% (95% CI: 73.8%–92.4%)CDC MMWR, May 2023
Adjusted VE (1 dose) — multijurisdictional case-control75.2% (95% CI: 61.2%–84.2%)CDC MMWR, May 2023
Adjusted VE (2 doses) — nationwide EHR study (NEJM)66.0% (95% CI: 47.4%–78.1%)NEJM, June 2023
Unadjusted VE (2 doses) — NEJM study77.2% (95% CI: 65.0%–85.1%)NEJM, June 2023
Pooled 2-dose VE (meta-analysis of 32 studies)82%Vaccine journal meta-analysis, 2024
Breakthrough infections (May 2022–May 2024)271 cases<1% of fully vaccinatedCDC MMWR, May 2024
Vaccinated breakthrough infections — disease severityLess severe vs. unvaccinated (p<0.001)CDC MMWR, May 2024
Immunocompromised person VE (2 doses)70.2% (reduced vs immunocompetent)CDC MMWR, May 2023
Hospitalization rate among ≥1 dose recipientsOnly 1% vs 10% overallMMWR Surveillance Update, May 2024
JYNNEOS commercially available in U.S. as ofApril 1, 2024CDC, September 2025
Additional booster doses recommendedNot currently recommended for general populationCDC, September 5, 2025

Source: CDC Domestic Mpox Response 2022–2023, MMWR, May 2023; CDC MMWR Surveillance Update October 2023–April 2024, May 2024; CDC MMWR JYNNEOS Breakthrough Infections May 2022–May 2024, May 2024; NEJM JYNNEOS Vaccine Effectiveness study, June 2023; Vaccine journal meta-analysis 2024 (cited in Lancet Infectious Diseases, May 2025); CDC JYNNEOS Interim Clinical Considerations, updated September 5, 2025

The JYNNEOS vaccine effectiveness data accumulated over three years of real-world use is among the most robustly validated in modern outbreak response. The 85.9% adjusted vaccine effectiveness for 2 doses from the CDC’s multijurisdictional case-control study — covering 309 case-patients matched to 608 controls across 12 U.S. jurisdictions — and the 82% pooled estimate from a 2024 meta-analysis of 32 observational studies provide converging evidence that a completed JYNNEOS series gives substantial real-world protection against clade IIb mpox infection. The finding that only 271 breakthrough infections occurred among all fully vaccinated persons in the United States between May 2022 and May 2024 — representing less than 1% of those vaccinated — is a compelling population-level outcome. Even more clinically significant is that these 271 breakthrough infections were associated with less severe disease compared to unvaccinated cases, confirming that even when vaccination doesn’t prevent infection entirely, it meaningfully attenuates the illness.

The coverage gap, however, remains the central challenge for mpox vaccination in 2026. Despite the deployment of more than 1.2 million JYNNEOS doses in the first year of the outbreak, only 25% of the at-risk population had completed a 2-dose series as of 2024 — meaning three-quarters of at-risk Americans remain without full vaccine protection more than three years after the shots were made available. The 67% rate of new mpox cases occurring in unvaccinated persons in the endemic period (October 2023–April 2024) is a direct consequence of this gap. The April 1, 2024 transition to commercial availability of JYNNEOS — moving it from government-supplied public health doses to the standard pharmacy and healthcare provider distribution system — was intended to improve access, but also introduced new barriers around insurance coverage, out-of-pocket cost for uninsured individuals, and awareness gaps among healthcare providers unfamiliar with mpox risk stratification. As of September 5, 2025, CDC continues to not recommend additional booster doses for the general vaccinated population, citing the absence of evidence for waning immunity at disparate time intervals in the breakthrough infection data.

US Mpox Hospitalization and Mortality Statistics in 2026 | Severity and Deaths 2022–2025

The clinical severity of mpox in the United States — including hospitalization rates, mortality, and the role of HIV co-infection — is documented with unusual precision thanks to robust outbreak surveillance.

Metric2022–2023 OutbreakOct 2023–Apr 2024 (MMWR Update)
Total mpox-associated deaths42 deaths (as of May 2023)5 additional deaths (0.3% case fatality)
Cumulative U.S. deaths through Oct 202460 deathsCDC/JHU
Share of deaths in Black persons87% (33 of 38 with data)
Immunocompromised among deceased94%HIV infection primary cause
Hospitalization rate — overall~8% of cases10% (slight increase)
HIV-positive among hospitalizedHigh proportion68% of those with known status
Patients with severe disseminated mpoxRare but documentedAssociated with advanced HIV
Cases with proctitis symptomsCommon in 2022 outbreakNoted in clinical records
Tecovirimat (TPOXX) administered6,932 patients (through April 2023)Available via CDC IND protocol
Clade II U.S. case fatality rate~0.14% (42/30,395)0.3% in Oct 2023–Apr 2024 period
Clade I case fatality rate (Africa context)1.4%–~10%
Severe mpox risk factor — HIV with CD4 <200Highest severity groupAntiretroviral therapy optimization critical
3 infant casesBorn to mothers with peripartum mpox symptoms2022–2023 outbreak data
Pediatric clade II casesRare in U.S. (unlike DRC, where children = majority)Different household/transmission context

Source: CDC Domestic Mpox Response 2022–2023, MMWR May 2023; CDC MMWR Surveillance Update Oct 2023–Apr 2024, May 2024; JHU Situation Update December 3, 2024; CDC Risk Assessment for Clade I, February 13, 2026; WHO/CDC comparative CFR data

The 60 U.S. mpox deaths accumulated since the 2022 outbreak — while modest against the backdrop of other infectious disease tolls — represent a preventable tragedy concentrated almost entirely in a single intersecting demographic: Black men with advanced HIV disease who were unable to access either adequate HIV treatment or timely mpox vaccination and treatment. The 94% immunocompromised rate among the deceased, and the 87% concentration of deaths in Black persons who represented only 33% of all cases, defines mpox mortality in America as fundamentally a story of healthcare access failure layered on top of an infectious disease. Advanced HIV disease — specifically CD4 counts below 200 cells/mm³ — transforms clade IIb mpox from a self-limiting painful illness into a potentially fatal disseminated infection with involvement of multiple organ systems. Early optimization of antiretroviral therapy has been identified by CDC as the single most important clinical intervention for improving outcomes in mpox patients with advanced HIV, alongside tecovirimat treatment.

The 10% hospitalization rate in the endemic period (October 2023–April 2024) — slightly higher than the 8% during the outbreak peak — reflects the progressive concentration of remaining clade II transmission in the most vulnerable, most medically complex portion of the at-risk population. With higher-risk, more-vaccinated, immunocompetent individuals driving less of the remaining transmission, the cases that do occur are increasingly in people whose immune systems are least able to handle the infection. The tecovirimat (TPOXX) distribution system, available through a CDC Investigational New Drug (IND) protocol to clinicians who request it through CDC for severely ill patients, treated 6,932 people during the 2022–2023 outbreak — a scale of experimental therapeutic deployment with no recent precedent in U.S. public health. The question of tecovirimat’s effectiveness against clade Ib, which has been flagged in some laboratory studies, remains an active area of research and clinical concern for the management of any future domestic clade I cases.

Global Mpox Context for US 2026 | Clade I Africa Outbreak and International Spread 2024–2025

The domestic U.S. mpox situation in 2026 cannot be understood without the global context that drives both import risk and public health policy decisions.

MetricFigureSource / Date
Global clade I cases (Jan 1, 2024 – Feb 13, 2026, CDC)More than 46,000CDC, February 13, 2026
Global clade I deathsMore than 200CDC, February 13, 2026
DRC confirmed cases + deaths (Jan 2024 – Oct 19, 2025)39,799 cases; 178 deathsWHO/Global Biodefense, Oct 30, 2025
Global confirmed mpox cases (Jan–Sep 2025, WHO)44,299 cases; 180 deathsWHO Oct 30, 2025 assessment
September 2025 global cases + deaths3,135 new cases; 12 deaths (0.4% CFR)WHO
WHO PHEIC #1 for mpox (clade IIb)Declared July 23, 2022 — lifted May 2023WHO
WHO PHEIC #2 for mpox (clade I)Declared August 14, 2024 — lifted September 5, 2025WHO
Countries in Central/Eastern Africa with sustained transmissionDRC, Burundi, Ethiopia, Kenya, Malawi, Mozambique, Rwanda, South Sudan, Tanzania, Uganda, Zambia, CAR, Republic of CongoCDC, August 2025
Clade Ib community transmission — outside Africa (Sep 2025+)Italy, Malaysia, Netherlands, Portugal, Spain, USAWHO Oct 30, 2025
Global clade II cases (2022–2023 outbreak total)~97,281 confirmed cases in 118 countries (as of June 2024)PMC review, 2025
Global mpox (all) confirmed Jan 2022–March 2025137,892 confirmed; 317 deaths in 132 countriesWHO/PMC, 2025
West Africa clade II outbreak (2025)Active — Sierra Leone, Liberia; linked to U.S. summer 2025 uptickCDC August 2025
DRC — % of children in clade Ia cases70% of DRC clade Ia cases in children under 15ACDC, August 2024

Source: CDC Current Situation, February 13, 2026; WHO Global Mpox Rapid Risk Assessment, October 30, 2025; WHO Disease Outbreak News DON587, December 5, 2025; NEJM Evolving Epidemiology of Mpox in Africa, January 2025; PMC Mpox 2022–2025 Comprehensive Review, 2025; Global Biodefense, November 3, 2025

The global mpox situation in late 2025 and early 2026 is one of genuine decline from the acute emergency of 2024 but continued concern over new transmission patterns. The WHO’s October 30, 2025 risk assessment found declining trends in four of six WHO regions, with September 2025 recording 3,135 new confirmed cases and 12 deaths — a case fatality ratio of 0.4% across that month’s reported cases. The DRC remains the epicenter, accounting for 39,799 confirmed cases and 178 deaths in the January 2024–October 2025 period alone, though even DRC’s case counts were declining steadily as of the October 2025 assessment. The African continent as a whole accounted for over 80% of all global mpox cases in September 2025 — a stark reminder that this is fundamentally a disease whose heaviest burden falls on African nations, particularly the DRC, even as its spread to non-endemic countries commands most of the global media attention.

What genuinely concerns infectious disease specialists heading into 2026 is the WHO’s December 5, 2025 Disease Outbreak News report documenting local transmission of clade Ib MPXV in countries with no prior endemic mpox — specifically calling out the emergence of sustained local circulation in MSM networks in Europe and the United States. The WHO Strategic Framework for mpox (2024–2027) explicitly acknowledges that clade Ib has now established transmission in both heterosexual networks (through sex worker contacts in Africa) and MSM networks in high-income countries — a dual-pathway epidemiology that makes containment significantly more complex than in the 2022 clade IIb outbreak. For the United States, the implication is clear: the same vaccination infrastructure, community engagement strategies, and surveillance systems built during the 2022 outbreak will need to remain active and adaptive to monitor, contain, and respond to clade Ib — a virus that is clinically more dangerous than anything American emergency rooms have dealt with in the mpox context to date.

Disclaimer: The data reports published on The Global Files are sourced from publicly available materials considered reliable. While efforts are made to ensure accuracy, no guarantees are provided regarding completeness or reliability. The Global Files is not liable for any errors, omissions, or damages resulting from the use of these reports.