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Morbidity and Mortality Weekly Report (MMWR)
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Morbidity and Mortality Weekly Report (MMWR)
Morbidity and Mortality Weekly Report (MMWR) Home
 1. CDC




SEVERE MONKEYPOX IN HOSPITALIZED PATIENTS — UNITED STATES, AUGUST 10–OCTOBER 10,
2022

Early Release / October 26, 2022 / 71

minus
Related Pages


Maureen J. Miller, MD1,*; Shama Cash-Goldwasser, MD1,2,3,*; Grace E. Marx, MD1;
Caroline A. Schrodt, MD1; Anne Kimball, MD1; Kia Padgett, MPH1; Rebecca S. Noe,
MPH1; David W. McCormick, MD1,2; Joshua M. Wong, MD1,2; Sarah M. Labuda, MD1;
Brian F. Borah, MD1,2,4; Isaac Zulu, MD1; Amimah Asif, MBBS1; Gurpreet Kaur,
MD1,2; Janet M. McNicholl, MD1; Athena Kourtis, MD1; Andrew Tadros, MD, PhD1;
Sarah Reagan-Steiner, MD1; Jana M. Ritter, DVM1; Yon Yu, PharmD1; Patricia Yu,
MPH1; Rachel Clinton, MS1; Corrine Parker, PharmD1; Eleanor S. Click, MD,
PhD1,2; Johanna S. Salzer, DVM1; Andrea M. McCollum, PhD1; Brett Petersen, MD1;
Faisal S. Minhaj, PharmD1,2; Ericka Brown, MD5; Michael P. Fischer, MD6; Robert
L. Atmar, MD7; Andrew R. DiNardo, MD7; Ya Xu, MD, PhD7; Cameron Brown, PhD7;
Jerry Clay Goodman, MD7; Ashley Holloman, MD7; Julia Gallardo, MD7; Hanna
Siatecka, MD7; Georgia Huffman, MD7; John Powell, MD7; Philip Alapat, MD7;
Pralay Sarkar, MD7; Nicola A. Hanania, MD7; Or Bruck, MD7; Steven D. Brass, MD7;
Aneesh Mehta, MD8; Alexandra W. Dretler, MD9; Amanda Feldpausch, DVM10; Jessica
Pavlick, DrPH10; Hillary Spencer, MD2,11; Isaac Ghinai, MBBS11; Stephanie R.
Black, MD11,12; Laura N. Hernandez-Guarin, MD12; Sarah Y. Won, MD12; Shivanjali
Shankaran, MD12; Andrew T. Simms, MD12; Jemma Alarcón, MD2,13; Jesse G. O’Shea,
MD1; John T. Brooks, MD1; Jennifer McQuiston, DVM1; Margaret A. Honein, PhD1;
Siobhán M. O’Connor, MD1; Kevin Chatham-Stephens, MD1; Kevin O’Laughlin, MD1;
Agam K. Rao, MD1; Elliot Raizes, MD1; Jeremy A. W. Gold, MD1,†; Sapna Bamrah
Morris, MD1,†; CDC Severe Monkeypox Investigations Team (View author
affiliations)

View suggested citation

 


SUMMARY

What is already known about this topic?

Severe manifestations of monkeypox in immunocompromised persons have been
observed in previous outbreaks.

What is added by this report?

During August–October 2022, CDC provided clinical consultation for 57
hospitalized patients with severe manifestations of monkeypox, most of whom were
Black men with AIDS. Delays were observed in initiation of monkeypox-directed
therapies. Twelve patients died, and monkeypox was a cause of death or
contributing factor in five patients to date, with several other deaths still
under investigation.

What are the implications for public health practice?

Clinicians should consider early treatment with available therapeutics for those
at risk for severe monkeypox disease, particularly patients with AIDS. Engaging
all persons with HIV in care remains a critical public health priority.

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As of October 21, 2022, a total of 27,884 monkeypox cases (confirmed and
probable) have been reported in the United States.§ Gay, bisexual, and other men
who have sex with men have constituted a majority of cases, and persons with HIV
infection and those from racial and ethnic minority groups have been
disproportionately affected (1,2). During previous monkeypox outbreaks, severe
manifestations of disease and poor outcomes have been reported among persons
with HIV infection, particularly those with AIDS (3–5). This report summarizes
findings from CDC clinical consultations provided for 57 patients aged ≥18 years
who were hospitalized with severe manifestations of monkeypox¶ during August
10–October 10, 2022, and highlights three clinically representative cases.
Overall, 47 (82%) patients had HIV infection, four (9%) of whom were receiving
antiretroviral therapy (ART) before monkeypox diagnosis. Most patients were male
(95%) and 68% were non-Hispanic Black (Black). Overall, 17 (30%) patients
received intensive care unit (ICU)–level care, and 12 (21%) have died. As of
this report, monkeypox was a cause of death or contributing factor in five of
these deaths; six deaths remain under investigation to determine whether
monkeypox was a causal or contributing factor; and in one death, monkeypox was
not a cause or contributing factor.** Health care providers and public health
professionals should be aware that severe morbidity and mortality associated
with monkeypox have been observed during the current outbreak in the United
States (6,7), particularly among highly immunocompromised persons. Providers
should test all sexually active patients with suspected monkeypox for HIV at the
time of monkeypox testing unless a patient is already known to have HIV
infection. Providers should consider early commencement and extended duration of
monkeypox-directed therapy†† in highly immunocompromised patients with suspected
or laboratory-diagnosed monkeypox.§§ Engaging all persons with HIV in sustained
care remains a critical public health priority.

During the ongoing monkeypox outbreak, CDC has provided consultation upon
request to jurisdictions and clinicians treating patients with monkeypox.¶¶ This
report describes the patients from these consultations who were aged ≥18 years
and were hospitalized with probable or confirmed monkeypox during August
10–October 10, 2022; the report includes detailed histories for three patients
who experienced severe manifestations of monkeypox. CDC obtained data on patient
demographic characteristics, clinical course, and outcomes during consultation
with health departments or providers. Patient permission for the use of clinical
images was obtained. This activity was reviewed by CDC and was conducted
consistent with applicable federal law and CDC policy.***

During August 10–October 10, 2022, CDC provided consultation for 57 patients
aged ≥18 years who were hospitalized with severe manifestations of monkeypox
(Table 1). Among 57 patients, 54 (95%) were male, and the median age was 34
years (range = 20–61 years). Forty-seven (82%) had HIV infection; among these
patients, 31 (72%) of 43 with a known CD4 count had <50 CD4 cells/mm3 (Table 2).
Two patients (4%), one of whom had HIV infection, were undergoing chemotherapy
for a hematologic malignancy, three (5%) were solid organ transplant recipients,
and three (5%) were pregnant. Overall, most patients were Black (68%), and 13
(23%) were experiencing homelessness.†††

All patients had severe dermatologic manifestations, and 39 (68%) also had
severe mucosal lesions (Table 1). Some experienced involvement of other organs,
including the lungs (12, 21%), eyes (12, 21%), and brain or spinal cord (four,
7%). Overall, 53 (93%) patients received oral tecovirimat, and 37 (65%) received
intravenous tecovirimat; 29 (51%) patients received vaccinia immune globulin
intravenous (VIGIV),§§§ and 13 (23%) received intravenous cidofovir. All
patients who received cidofovir or VIGIV also received tecovirimat. Seventeen
(30%) patients received ICU-level care and 12 (21%) died: monkeypox was a cause
of death or contributing factor in five of these cases, six deaths remain under
investigation to determine whether monkeypox was a causal or contributing
factor, and in one death, monkeypox was not a cause or contributing factor.

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REPRESENTATIVE CASE DESCRIPTIONS

Patient A. In August 2022, a Hispanic or Latino man in his 20s with no known
past medical history was evaluated at an emergency department for back pain and
a diffuse rash (location not specified). He was prescribed a course of
prednisone for the back pain. Swabs were taken from the lesions to test for
Orthopoxvirus (OPXV) by PCR, and the results were positive two days later. Over
the next week, the patient’s rash progressed to involve his entire body. He was
admitted to a hospital after being evaluated for dyspnea on exertion, dry cough,
persistent back pain, and painful left neck swelling. On admission, he was
febrile (102.8°F [39.3°C]), and he had a diffuse rash with central ulcerations
as well as eschars on his face, trunk, and extremities; oral lesions; and a left
neck mass. Laboratory results indicated a positive test result for HIV (CD4 = 79
cells/mm3, CD4 T-lymphocyte percentage 3%). According to state reporting, the
patient had received a positive HIV test result in 2020 but was subsequently
lost to follow-up. A computed tomography scan of his neck identified a 6.9 x 7.7
x 9.8–cm mass and extensive bilateral cervical lymphadenopathy. On hospital day
2, the patient became somnolent and was transferred to ICU; the next day, he was
intubated for airway protection and received intravenous tecovirimat. He
developed vasopressor-resistant hypotension, experienced a seizure, and went
into kidney failure. During the next several days he was treated with
vasopressors, antiepileptics, antibiotics, and antifungals, and required
cardiopulmonary resuscitation. An extensive evaluation for infectious agents
other than OPXV and HIV was negative. On the second day in ICU, he received 1
dose of VIGIV. Two days later, a brain scan indicated poor perfusion. The family
elected to transition the patient to comfort measures. He was terminally
extubated. An autopsy was conducted, with pathologic findings of necrosis in
multiple tissues consistent with diffuse monkeypox. Immunohistochemistry testing
demonstrated extensive orthopoxviral antigen in multiple tissues.
Cytomegalovirus antigen was also detected in some tissues.¶¶¶

Patient B. In July 2022, a Black man in his 30s with AIDS (CD4 <10 cells/mm3)
and not receiving ART developed a rash on his face, head, back, and genitals. At
multiple subsequent clinic visits, he was tested and treated for gonorrhea,
chlamydia, and syphilis; however, his genital lesions progressed, and he
experienced phimosis and urinary retention for which he was admitted to a
hospital 4 weeks after his rash began. A lesion swab taken the day of admission
tested positive for Monkeypox virus (MPXV) DNA by PCR. The patient was
discharged with a urinary catheter and 14 days of oral tecovirimat
(Supplementary Figure 1; https://stacks.cdc.gov/view/cdc/121838. His skin
lesions initially improved, but then spread, coalesced, and developed central
necrosis (Figure) (Supplementary Figure 2,
https://stacks.cdc.gov/view/cdc/121835). A suprapubic catheter was placed
because of continued need for urinary catheterization. Approximately 10 days
after discharge, the patient was readmitted with malaise, poor appetite, weight
loss, and new hand and penile lesions. During a 15-day hospitalization, the
patient was found to have methicillin-resistant Staphylococcus aureus
bacteremia. He was transferred to ICU because of atrial fibrillation with rapid
ventricular response. In ICU he was treated with intravenous tecovirimat, 2
doses of VIGIV, and antimicrobials. Conjunctivitis developed and was treated
with trifluridine and antibacterial eye drops. The patient was discharged on
oral tecovirimat and ART and with a suprapubic catheter. During week 7 of oral
tecovirimat, he was readmitted because of progressive necrotic lesions with
bacterial superinfection on the left hand, left eyelid lesions with periorbital
swelling, and a right ear canal lesion associated with drainage and decreased
hearing. He was restarted on intravenous tecovirimat and continues this
treatment as of this report.

Patient C. In July 2022, a non-Hispanic White man in his 40s with AIDS (CD4 <10
cells/mm3) and not receiving ART was evaluated for a rash on his face, torso,
hands, feet, and perianal area; lesion swabs tested positive for MPXV DNA by
PCR. He was admitted to a hospital for pain control and received oral
tecovirimat and ART. The patient experienced pain relief and was discharged
after 7 days to complete 14 days of tecovirimat. However, his housing and food
situations were unstable, and absorption of oral tecovirimat is dependent on
concurrent intake of a full, fatty meal. Approximately 3 weeks after discharge,
he was readmitted with coalescing, painful, and necrotic lesions on his hands
and feet. Despite treatment with oral and intravenous tecovirimat for >4 weeks,
2 doses of cidofovir, 1 dose of VIGIV, and multiple antibiotics, progressive
tissue necrosis led to debridement of the soft tissues of the right index finger
and amputation of the right fourth toe. Gradually, the monkeypox lesions
regressed. He was discharged but was readmitted 1 week later for unresolved
lesions and severe pain. He received a second dose of VIGIV and remains
hospitalized on oral tecovirimat and ART as of this report.

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DISCUSSION

Although most monkeypox cases during the ongoing outbreak have been self-limited
(2,8), this report highlights the occurrence of severe manifestations of
monkeypox in the United States, particularly in persons with AIDS. In this
cohort of patients hospitalized with monkeypox and for whom clinicians or
jurisdictions sought consultations with CDC, nearly one third (30%) received
ICU-level care, and 21% of patients died, including several deaths that remain
under investigation to determine the cause of death. Most patients eventually
received tecovirimat, but some experienced delays of up to 4 weeks between
initial care-seeking for monkeypox symptoms and initiation of monkeypox-directed
therapy. For patients with suspected or laboratory-diagnosed monkeypox who are
at risk for severe disease (particularly those with AIDS and other types of
severe immunocompromise), health care providers should consider starting
monkeypox-directed therapy early, potentially before receipt of monkeypox
testing results or before severe manifestations are observed. In patients with
severe disease, or with ongoing disease despite treatment, providers should
consider extending tecovirimat treatment beyond 14 days and escalating therapy
to include cidofovir or VIGIV if clinically indicated (9). For patients with HIV
disease who are not on ART, clinicians should initiate ART as soon as possible,
regardless of CD4 cell count.**** Health care providers should test all sexually
active patients with suspected monkeypox for HIV at the time of testing for
monkeypox unless a patient is already known to have HIV infection.

Most patients in this cohort were Black men, and nearly one quarter of cases
occurred in persons experiencing homelessness. These findings likely reflect
inequities in access to resources for the prevention, early diagnosis, and
treatment of HIV infection, as well as missed opportunities to engage groups
that have been socially or economically marginalized.†††† Public health outreach
should strive to engage all persons with HIV infection in care and to increase
access to monkeypox vaccination, diagnosis, and treatment. To accomplish these
goals, it is critical to leverage existing HIV and sexually transmitted
infection program resources and prioritize communities disproportionately
affected by HIV (1). Collaboration with homeless services providers can help
engage persons who are experiencing homelessness in prevention and treatment
services for HIV and monkeypox.

The findings in this report are subject to at least four limitations. First,
cases were passively identified by CDC through consultations requested by
clinicians or jurisdictions and might not be representative of all patients with
severe monkeypox. Second, this report only included outcomes occurring during
the study period; therefore, deaths occurring after this period were not
included. Third, observed morbidity and mortality might have been related to
factors apart from or in addition to monkeypox, including HIV-related
opportunistic infections. Finally, conclusions about the effectiveness of
monkeypox treatments cannot be inferred from these observational data.

The occurrence of severe manifestations of monkeypox in patients who were most
commonly immunocompromised because of AIDS highlights the importance of engaging
all persons with HIV in sustained care and ending the HIV epidemic. Clinicians
should consider close clinical monitoring, early treatment with available
medical countermeasures, and extension or escalation of therapy as indicated in
patients with or at risk for severe monkeypox. Ensuring equitable access to
resources for the diagnosis, treatment, and prevention of HIV and monkeypox
remains a vital public health priority.

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ACKNOWLEDGMENTS

Inger K. Damon, CDC; David Blythe, Monique Duwell, Haley Farrie, Howard Haft,
Ruth Thompson, Maryland Department of Health; Ulyee Choe, Florida Department of
Health; Johanna X. Segura Restrepo, Reynald Jean, Julio Cesar Pelaez, Edhelene
Rico, Alvaro Mejia-Echeverry, Florida Department of Health in Miami-Dade County;
Rachel Ilic, Alissa Brown, Rebecca Bohinc, Florida Department of Health in
Pinellas County; Katharine Saunders, Epidemic Intelligence Service, CDC, and
Florida Department of Health; Sharon Balter, Moon Kim, Abraar Karan, Lauren
Finn, Kay Hooshmand, Los Angeles County Department of Public Health, California;
Ellen Lee, Mary Foote, Marcia Wong, Maura Lash, Tristan McPherson, New York City
Department of Public Health; Zack Moore, Erica Wilson, North Carolina Department
of Health and Human Services; Erin Ricketts, Epidemic Intelligence Service, CDC,
and North Carolina Department of Health and Human Services; Liz Harris,
Robertson Nash, Pamela Talley, Tennessee Department of Health; Joan Duwve,
Kansas Department of Health and Environment; Maggie Cook-Shimanek, Montana
Department of Public Health and Human Services; Matthew Nichols, Oklahoma State
Department of Health; W. Gina Pang, Atmaram Nambiar, Pennsylvania Department of
Health; Shara Epstein, Lenore Asbel, Dana Perella, Philadelphia Department of
Public Health; Miranda Durham, New Mexico Department of Health; Robyn Weber,
Radhika Ratnabalasuriar, Shannon O’Brien, Alexis Burakoff, Colorado Department
of Public Health and Environment; Amanda Kamali, Akanksha Vaidya, Philip Peters,
Linda S. Lewis, Linda Crebbin, California Department of Public Health; Ellen
Salehi, Kara Tarter, Ohio Department of Health, Courtney Dewart, Center for
Preparedness and Response, CDC and Ohio Department of Health; Amy Forrester,
Dallas County Health and Human Services, Dallas, Texas; Aurelia M. Schmalstieg,
Texas Department of State Health Services, Regions 2 & 3, Arlington, Texas;
Janeana White, Houston Health Department, Houston Texas; Ivy Luong, HCA Houston
Healthcare Medical Center; Lawrence Madoff, Massachusetts Department of Health;
Alexis Page, Virginia Department of Health; Vivian Huang, Maricopa County
Department of Public Health, Arizona; Nick Lehnertz, Sarah Lim, Minnesota
Department of Health; Jennifer Dixon, Washington Department of Health; Kris
Carter, Idaho Department of Health and Welfare; Haley Blake, Kimberly Franich,
Southern Nevada Health District; B. Denise Stokich, Nevada Department of Health
and Human Services; Carla Little, Illinois Department of Health; Ronald J.
Lubelchek, Cook County Health and Human Services, Illinois.


CDC SEVERE MONKEYPOX INVESTIGATIONS TEAM

Shelby Duessel, CDC; Darren Danaie, CDC; Angela Hickman, CDC; Brynn Griffith,
CDC; Haddijatou Sanneh, CDC; Helena Hutchins, CDC; Christine Phyathep, CDC; Ann
Carpenter, CDC; Victoria Shelus, CDC; Julia Petras, CDC; Ian Hennessee, CDC;
Meryl Davis, CDC; Cristin McArdle, CDC; Patrick Dawson, CDC; Bruce Gutelius,
CDC; Kris Bisgard, CDC; Karen Wong, CDC; Romeo R. Galang, CDC; Kiran M. Perkins,
CDC; Thomas D. Filardo, CDC; Whitni Davidson, CDC; Christy Hutson, CDC; David
Lowe, CDC; Jason E. Zucker, Columbia University Irving Medical Center-New York
Presbyterian Hospital, New York, New York; David A. Wheeler, INOVA Fairfax
Hospital, Falls Church, Virginia; Lucy He, INOVA Fairfax Hospital, Falls Church,
Virginia; Aabha K. Jain, INOVA Fairfax Hospital, Falls Church, Virginia;
Oleksandr Semeniuk, INOVA Fairfax Hospital, Falls Church, Virginia; Dev
Chatterji, INOVA Fairfax Hospital, Falls Church, Virginia; Marnie McClure, Johns
Hopkins Hospital, Baltimore, Maryland; Lucy X. Li, Johns Hopkins Hospital,
Baltimore, Maryland; Jona Mata, Johns Hopkins Hospital, Baltimore, Maryland;
Sasha Beselman, Johns Hopkins Hospital, Baltimore, Maryland; Sara L. Cross,
Regional One Health-Memphis; Barbara Menzies, Regional One Health-Memphis,
Memphis, Tennessee; Marina Keller, Westchester Medical Center, Valhalla, New
York; Vishnu Chaturvedi, Westchester Medical Center, Valhalla, New York; Andrea
Thet, Bronxcare Health System New York, New York; Ryan Carroll, The Ohio State
University, Columbus, Ohio; Courtney Hebert, The Ohio State University,
Columbus, Ohio; Gopi Patel, Mount Sinai School of Medicine, New York, New York;
Vani Gandhi, Mount Sinai School of Medicine, New York, New York; Alexandra
Abrams-Downey, Mount Sinai School of Medicine, New York, New York; Mehmood
Nawab, Osceola Regional Medical Center, Kissimmee, Florida; Emily Landon,
University of Chicago School of Medicine, Chicago, Illinois; Gregory Lee, NYC
Health + Hospitals/Bellevue Hospital Center, New York, New York; Emma
Kaplan-Lewis, NYC Health + Hospitals/Elmhurst Hospital Center, New York, New
York; Cyndee Miranda, Cleveland Clinic, Cleveland, Ohio; Anna E. Carmack,
University of Maryland Medical Center, Baltimore, Maryland; Edward C. Traver,
University of Maryland School of Medicine, Baltimore, Maryland; Susana Lazarte,
UT Southwestern Medical Center, Dallas, Texas; Trish M. Perl, UT Southwestern
Medical Center, Dallas, Texas; Jeremy Chow, UT Southwestern Medical Center,
Dallas, Texas; Ellen Kitchell, UT Southwestern Medical Center, Dallas, Texas;
Ank Nijhawan, UT-Southwestern Medical Center and Parkland Hospital and Health
System, Dallas, Texas; Onaizah Habib, Penrose-St. Francis Hospital, Colorado
Springs, Colorado; Allen Bernus, UC Health University of Colorado Hospital,
Aurora, Colorado; Gabriela Andujar, Tufts Medical Center, Boston, Massachusetts;
Kusha Davar, LAC+USC Medical Center, Los Angeles, California; Paul Holtom,
LAC+USC Medical Center, Los Angeles, California; Noah Wald-Dickler, LAC+USC
Medical Center, Los Angeles, California; Marco A. Lorio, Providence St. Patrick
Hospital, Missoula, Montana; Jose Gaviria, Baptist Hospital, Miami, Florida;
Vivian Chu, Duke University School of Medicine, Durham, North Carolina; Cameron
R. Wolfe, Duke University School of Medicine, Durham, North Carolina; Mehri S.
McKellar, Duke University School of Medicine, Durham, North Carolina; Sumaya
Farran, DFW Infectious Diseases, Lewisville, Texas; Roque A. Diaz Wong,
Methodist Hospital, San Antonio, Texas; Tjark Schliep, NYC Health +
Hospitals/Harlem Hospital Center, New York, New York; Raphael Shaw, NYC Health +
Hospitals/Harlem Hospital Center, New York, New York; Pablo Tebas, University of
Pennsylvania, Philadelphia, Pennsylvania; Aaron Richterman, University of
Pennsylvania, Philadelphia, Pennsylvania; Michelle Aurelius, North Carolina
Office of the Chief Medical Examiner; Leah Peterson, Salina Family Healthcare
Center, Salina, Kansas; Ron Trible, Northside Hospital, Atlanta, Georgia; Tyler
Rehman, VA Hospital, Chicago, Illinois; Rabeeya Sabzwari, VA Hospital, Chicago,
Illinois; Edward Hines, Jr., VA Hospital, Chicago, Illinois; Trevor Birkey,
University of Wisconsin Medical Center, Milwaukee, Wisconsin; Jamie King,
University Medical Center of Southern Nevada, Las Vegas, Nevada; Ali Farabi,
University Medical Center of Southern Nevada, Las Vegas, Nevada; Elizabeth
Jenny-Avital, NYC Health + Hospitals/Jacobi Medical Center, New York, New York;
Lauren Touleyrou, Wayne State University, Detroit, Michigan; Avnish Sandhu,
Wayne State University, Detroit, Michigan; Gretchen Newman, Wayne Health,
Detroit, Michigan; Divya Bhamidipati, University of Texas Medical Center,
Austin, Texas; Divya Bhamidipati, McGovern Medical School at UTHealth, Houston,
Texas; Karen Vigil, McGovern Medical School at UT Health, Houston, Texas;
Melissa Caro, HCA Florida Mercy Hospital, Miami, Florida; Koury Banowski, Mercy
Health, Toledo, Ohio; Tanyanyiwa W. Chinyadza, Mercy Health, Toledo, Ohio;
Jaclyn Rosenzweig, Jefferson Health, Philadelphia, Pennsylvania; Michelle S.
Jones, Piedmont Hospital, Atlanta, Georgia; Jose F. Camargo, Miller School of
Medicine, Miami, Florida; Ketzela J. Marsh, University of Minnesota, Minneapolis
and Saint Paul, Minnesota; Eugene W. Liu, Loma Linda University Health, Loma
Linda, California; Richelle Guerrero-Wooley, Loma Linda University Health, Loma
Linda, California; Paul Pottinger, University of Washington, Seattle,
Washington.

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Corresponding author: Maureen J. Miller, yax6@cdc.gov.

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--------------------------------------------------------------------------------

1CDC Monkeypox Emergency Response Team; 2Epidemic Intelligence Service, CDC;
3Minnesota Department of Health; 4Vermont Department of Health; 5Harris County
Public Health, Houston, Texas; 6Texas Department of State Health Services;
7Baylor College of Medicine, Houston, Texas; 8Emory University School of
Medicine, Atlanta, Georgia; 9Infectious Diseases Specialists of Atlanta,
Decatur, Georgia; 10Georgia Department of Public Health; 11Chicago Department of
Public Health, Chicago, Illinois; 12Rush University System for Health, Chicago,
Illinois, 13Los Angeles County Department of Public Health, Los Angeles,
California.

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All authors have completed and submitted the International Committee of Medical
Journal Editors form for disclosure of potential conflicts of interest. Siobhán
M. O’Connor reports US Patent Application #20190212345 and #20150140670 for kits
and methods for determining physiologic levels and ranges of hemoglobin or
disease state. Nicola A. Hanania reports institutional support from GSK, Sanofi,
Genentech, AstraZeneca, and Teva; consulting fees from AstraZeneca, GSK,
Boehringer Ingelheim, Sanofi, Genentech, Teva, and Amgen; and service as editor
in chief of Respiratory Medicine. Jerry Clay Goodman reports payment from the
American Academy of Neurology for a course in neuropathology at the annual
meeting. No other potential conflicts of interest were disclosed.

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* These authors contributed equally to this report.

† These senior authors contributed equally to this report.

§ https://www.cdc.gov/poxvirus/monkeypox/response/2022/us-map.html

¶ A list of severe manifestations of monkeypox can be found at
https://emergency.cdc.gov/han/2022/han00475.asp.

** During the study period and as of October 21, 2022, CDC was notified by state
and local jurisdictions of five decedents whose death certificates included
monkeypox as a cause of death or contributing factor, six decedents whose cause
of death is still under active investigation, and one decedent in whom the death
was not monkeypox-related. Additional monkeypox cases involving severe disease
or death might not be included in this report if CDC has not yet been notified
about the case or if the case occurred outside of the study period
https://www.cdc.gov/poxvirus/monkeypox/response/2022/index.html

†† https://www.cdc.gov/poxvirus/monkeypox/clinicians/treatment.html

§§https://www.cdc.gov/poxvirus/monkeypox/clinicians/case-definition.html

¶¶ CDC offers a monkeypox clinical consultation service for the ongoing
monkeypox outbreak. Health care providers seeking additional clinical guidance
can contact the CDC Emergency Operations by phone (770-488-7100) or by email
(eocevent482@cdc.gov).

*** 45 C.F.R. part 46.102(l)(2), 21 C.F.R. part 56; 42 U.S.C. Sect. 241(d); 5
U.S.C. Sect. 552a; 44 U.S.C. Sect. 3501 et seq.

††† Homelessness was defined by the clinician caring for the patient and
included the experience of both sheltered and unsheltered homelessness.
https://www.cdc.gov/ddid/homelessness/definition.html

§§§ Tecovirimat, an FDA-approved treatment for smallpox, demonstrated efficacy
against monkeypox in animal studies. Interim CDC guidance currently recommends
that tecovirimat be considered in patients with severe monkeypox, those at high
risk for severe disease, or those whose infection involves anatomic areas where
monkeypox virus infection might constitute a special hazard (e.g., the eyes,
pharynx, genitals, or anus). VIGIV has been used to treat complications from
vaccinia vaccination. CDC holds an expanded access investigative new drug
protocol that allows the use of VIGIV for the treatment of orthopoxviruses
(including monkeypox) in an outbreak. https://www.fda.gov/media/78174/download

¶¶¶ Microscopic examination of autopsy tissues at the hospital and CDC showed
findings consistent with diffuse monkeypox in specimens from a foot skin lesion,
abdomen skin lesion, lip, vocal cord, lung, esophagus, mediastinal lymph nodes,
and rectal mass. CDC performed immunohistochemistry testing that demonstrated
extensive orthopoxviral antigen in multiple skin and mucosal tissues and in
liver, pancreas, testis, adrenal gland, lung, and multiple lymph nodes.
Cytomegalovirus antigen was also detected in a subset of skin, mucosal, and
lymph node tissues.

**** https://www.cdc.gov/hiv/clinicians/treatment/treatment-clinicians.html

††††
https://www.hiv.gov/hiv-basics/overview/about-hiv-and-aids/who-is-at-risk-for-hiv

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REFERENCES

 1. Curran KG, Eberly K, Russell OO, et al.; Monkeypox, HIV, and STI Team. HIV
    and sexually transmitted infections among persons with monkeypox—eight U.S.
    jurisdictions, May 17–July 22, 2022. MMWR Morb Mortal Wkly Rep
    2022;71:1141–7. https://doi.org/10.15585/mmwr.mm7136a1 PMID:36074735
 2. Philpott D, Hughes CM, Alroy KA, et al.; CDC Multinational Monkeypox
    Response Team. Epidemiologic and clinical characteristics of monkeypox
    cases—United States, May 17–July 22, 2022. MMWR Morb Mortal Wkly Rep
    2022;71:1018–22. https://doi.org/10.15585/mmwr.mm7132e3 PMID:35951487
 3. Ogoina D, Iroezindu M, James HI, et al. Clinical course and outcome of human
    monkeypox in Nigeria. Clin Infect Dis 2020;71:e210–4.
    https://doi.org/10.1093/cid/ciaa143 PMID:32052029
 4. Yinka-Ogunleye A, Aruna O, Dalhat M, et al.; CDC Monkeypox Outbreak Team.
    Outbreak of human monkeypox in Nigeria in 2017–18: a clinical and
    epidemiological report. Lancet Infect Dis 2019;19:872–9.
    https://doi.org/10.1016/S1473-3099(19)30294-4 PMID:31285143
 5. Selik RM, Mokotoff ED, Branson B, et al. Revised surveillance case
    definition for HIV infection—United States, 2014. MMWR Morb Mortal Wkly Rep
    2014;63(No. RR-3).
 6. Cash-Goldwasser S, Labuda SM, McCormick DW, et al.; CDC Monkeypox Clinical
    Escalations Team. Ocular monkeypox—United States, July–September 2022. MMWR
    Morb Mortal Wkly Rep 2022;71:1343–7. https://doi.org/10.15585/mmwr.mm7142e1
    PMID:36264836
 7. Pastula DM, Copeland MJ, Hannan MC, et al. Two cases of monkeypox-associated
    encephalomyelitis—Colorado and the District of Columbia, July–August 2022.
    MMWR Morb Mortal Wkly Rep 2022;71:1212–5.
    https://doi.org/10.15585/mmwr.mm7138e1 PMID:36136957
 8. Thornhill JP, Barkati S, Walmsley S, et al.; SHARE-net Clinical Group.
    Monkeypox virus infection in humans across 16 countries—April–June 2022. N
    Engl J Med 2022;387:679–91. https://doi.org/10.1056/NEJMoa2207323
    PMID:35866746
 9. CDC. Monkeypox: Information for healthcare providers on obtaining and using
    TPOXX (tecovirimat) for treatment of monkeypox. Atlanta, GA: US Department
    of Health and Human Services, CDC; 2022. (Accessed October 17, 2022).
    https://www.cdc.gov/poxvirus/monkeypox/clinicians/obtaining-tecovirimat.html

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TABLE 1. CHARACTERISTICS OF HOSPITALIZED PATIENTS WITH SEVERE MANIFESTATIONS OF
MONKEYPOX* (N = 57) FOR WHOM CDC PROVIDED CLINICAL CONSULTATION — UNITED STATES,
AUGUST 10–OCTOBER 10, 2022

Characteristic No. (%) Median age, yrs (range) 34 (20–61) Sex Male 54 (94.7)
Race and ethnicity Black or African American, non-Hispanic 39 (68.4) White,
non-Hispanic 8 (14.0) Hispanic or Latino 8 (14.0) Asian, non-Hispanic 1 (1.8)
Multiple races, non-Hispanic 1 (1.8) Experiencing homelessness† 13 (22.8) Any
immunocompromising condition§ 51 (89.5) HIV infection 47 (82.5) History of solid
organ transplantation 3 (5.3) Hematologic malignancy (current chemotherapy) 2
(3.5) Pregnant 3 (5.3) Clinical manifestation¶ Dermatologic 57 (100.0) Mucosal**
39 (68.4) Pulmonary 12 (21.1) Ocular 12 (21.1) Deep tissue (muscle or bone) 5
(8.8) Neurologic 4 (7.0) Monkeypox-directed therapy†† Tecovirimat (oral) 53
(93.0) Tecovirimat (intravenous) 37 (64.9) VIGIV 29 (50.9) Cidofovir†† 13 (22.8)
Received ICU-level care 17 (29.8) STI coinfection§§ 16 (28.1)

Abbreviations: ICU = intensive care unit; STI = sexually transmitted infection,
VIGIV = vaccinia immune globulin intravenous.
* Severe manifestations of monkeypox include, but are not limited to, the
clinical findings listed at https://emergency.cdc.gov/han/2022/han00475.asp.
† Homelessness was defined by the clinician caring for the patient and included
the experience of both sheltered and unsheltered homelessness.
https://www.cdc.gov/ddid/homelessness/definition.html
§ One patient had HIV infection and was receiving chemotherapy for a hematologic
malignancy.
¶ Patients could experience more than one clinical manifestation.
** Mucosal involvement might include oral, urethral, rectal, vaginal, or other
lesions.
†† Patients could receive more than one treatment. All patients who received
VIGIV or cidofovir also received tecovirimat.
§§ STI coinfection included concurrent diagnosis of syphilis, gonorrhea,
chlamydia, herpes simplex virus type 2, or shigellosis.

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TABLE 2. LABORATORY AND TREATMENT CHARACTERISTICS OF HOSPITALIZED PATIENTS WITH
HIV INFECTION AND SEVERE MONKEYPOX* FOR WHOM CDC PROVIDED CLINICAL CONSULTATION
(N = 47) — UNITED STATES, AUGUST 10–OCTOBER 10, 2022

Characteristic (no. with information available) No. (%) HIV CD4, cells/mm3 (43)
<50 31 (72.1) 50–200 9 (20.9) >200 3 (7.0) HIV Treatment (47) On ART at the time
of monkeypox diagnosis 4 (8.5)

Abbreviation: ART = antiretroviral therapy.
* Severe manifestations of monkeypox include, but are not limited to, the
clinical findings listed at https://emergency.cdc.gov/han/2022/han00475.asp

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FIGURE. DISSEMINATED LESIONS ON THE BACK AND HANDS OF A PATIENT* WITH SEVERE
MONKEYPOX — UNITED STATES, AUGUST 10–OCTOBER 10, 2022



Photos/Alexandra Dretler

* Patient has consented to the publication of these photographs.

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Suggested citation for this article: Miller MJ, Cash-Goldwasser S, Marx GE, et
al. Severe Monkeypox in Hospitalized Patients — United States, August 10–October
10, 2022. MMWR Morb Mortal Wkly Rep. ePub: 26 October 2022. DOI:
http://dx.doi.org/10.15585/mmwr.mm7144e1.

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Last Reviewed: October 26, 2022
Source: Centers for Disease Control and Prevention
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