Monkeypox emergency: Urgent questions and perspectives.

Amidst the COVID-19 pandemic, we now face another public health emergency in the form of monkeypox virus. As of August 1, the Centers for Disease Control and Prevention report over 23,000 cases in 80 countries. An inclusive and global collaborative effort to understand the biology, evolution, and spread of the virus as well as commitment to vaccine equity will be critical toward containing this outbreak. We share the voices of leading experts in this space on what they see as the most pressing questions and directions for the community.

Associations Between HIV and Severe Mpox in an Atlanta Cohort.

BACKGROUND: In the Southeastern United States, the 2022 mpox outbreak disproportionately impacted people who are black and people with HIV (PWH). METHODS: We analyzed a cohort of 395 individuals diagnosed with mpox across 3 health care systems in Atlanta, Georgia between 1 June 2022 and 7 October 2022. We present demographic and clinical characteristics and use multivariable logistic regression analyses to evaluate the association between HIV status and severe mpox (per the US Centers for Disease Control and Prevention definition) and, among PWH, the associations between CD4+ T-cell count and HIV load with severe mpox. RESULTS: Of 395 people diagnosed with mpox, 384 (97.2%) were cisgender men, 335 (84.8%) identified as black, and 324 (82.0%) were PWH. Of 257 PWH with a known HIV load, 90 (35.0%) had > 200 copies/mL. Severe mpox occurred in 77 (19.5%) individuals and there was 1 (0.3%) death. Tecovirimat was prescribed to 112 (28.4%) people, including 56 (72.7%) people with severe mpox. In the multivariable analysis of the total population, PWH had 2.52 times higher odds of severe mpox (95% confidence interval [CI], 1.01-6.27) compared with people without HIV. In the multivariable analysis of PWH, individuals with HIV load > 200 copies/mL had 2.10 (95% CI, 1.00-4.39) times higher odds of severe mpox than PWH who were virologically suppressed. Lower CD4+ T-cell count showed a significant univariate association with severe mpox but was not found to be significantly associated with severe mpox in multivariable analysis. CONCLUSIONS: PWH with nonsuppressed HIV loads had more mpox complications, hospitalizations, and protracted disease courses than people without HIV or PWH with suppressed viral loads. PWH with nonsuppressed HIV loads who are diagnosed with mpox warrant particularly aggressive monitoring and treatment.

Multisite Mpox Infection and Viral Dynamics Among Persons With HIV in Metro Atlanta.

The 2022 mpox outbreak primarily involved sexual transmission among men who have sex with men and disproportionately affected persons with human immunodeficiency virus (HIV). We examined viral dynamics and clinical features in a cohort evaluated for mpox infection at a comprehensive HIV clinic in Atlanta, Georgia. Viral DNA was found in 8 oropharyngeal and 5 anorectal specimens among 10 mpox cases confirmed by lesion swab polymerase chain reaction. Within-participant anatomic site of lowest cycle threshold (Ct) value varied, and lower Ct values were found in oropharyngeal and anorectal swabs when corresponding symptoms were present. This provides insight into mpox infection across multiple anatomic sites among people with HIV.

Monkeypox.

Monkeypox is a zoonotic illness caused by the monkeypox virus, an Orthopoxvirus in the same genus as the variola, vaccinia, and cowpox viruses. Since the detection of the first human case in the Democratic Republic of the Congo in 1970, the disease has caused sporadic infections and outbreaks, mainly restricted to some countries in west and central Africa. In July, 2022, WHO declared monkeypox a Public Health Emergency of International Concern, on account of the unprecedented global spread of the disease outside previously endemic countries in Africa and the need for global solidarity to address this previously neglected disease. The 2022 outbreak has been primarily associated with close intimate contact (including sexual activity) and most cases have been diagnosed among men who have sex with men, who often present with novel epidemiological and clinical characteristics. In the 2022 outbreak, the incubation period ranges from 7 days to 10 days and most patients present with a systemic illness that includes fever and myalgia and a characteristic rash, with papules that evolve to vesicles, pustules, and crusts in the genital, anal, or oral regions and often involve the mucosa. Complications that require medical treatment (eg, antiviral therapy, antibacterials, and pain control) occur in up to 40% of patients and include rectal pain, odynophagia, penile oedema, and skin and anorectal abscesses. Most patients have a self-limited illness; between 1% and 13% require hospital admission (for treatment or isolation), and the case-fatality rate is less than 0·1%. A diagnosis can be made through the presence of Orthopoxvirus DNA in PCRs from lesion swabs or body fluids. Patients with severe manifestations and people at risk of severe disease (eg, immunosuppressed people) could benefit from antiviral treatment (eg, tecovirimat). The current strategy for post-exposure prophylaxis or pre-exposure prophylaxis for people at high risk is vaccination with the non-replicating modified vaccinia Ankara. Antiviral treatment and vaccines are not yet available in endemic countries in Africa.

Inflammatory and Immune Mechanisms for Atherosclerotic Cardiovascular Disease in HIV.

Atherosclerotic vascular disease disproportionately affects persons living with HIV (PLWH) compared to those without. The reasons for the excess risk include dysregulated immune response and inflammation related to HIV infection itself, comorbid conditions, and co-infections. Here, we review an updated understanding of immune and inflammatory pathways underlying atherosclerosis in PLWH, including effects of viral products, soluble mediators and chemokines, innate and adaptive immune cells, and important co-infections. We also present potential therapeutic targets which may reduce cardiovascular risk in PLWH.

Human monkeypox virus infection in women and non-binary individuals during the 2022 outbreaks: a global case series.

BACKGROUND: Between May and November, 2022, global outbreaks of human monkeypox virus infection have been reported in more than 78 000 people worldwide, predominantly in men who have sex with men. We describe the epidemiological and clinical characteristics of monkeypox virus infection in cisgender (cis) and transgender (trans) women and non-binary individuals assigned female sex at birth to improve identification and understanding of risk factors. METHODS: International collaborators in geographical locations with high numbers of diagnoses of monkeypox virus infection were approached and invited to contribute data on women and non-binary individuals with confirmed monkeypox virus infection. Contributing centres completed deidentified structured case-report spreadsheets, adapted and developed by participating clinicians, to include variables of interest relevant to women and non-binary individuals assigned female at birth. We describe the epidemiology and clinical course observed in the reported infections. FINDINGS: Collaborators reported data for a total of 136 individuals with monkeypox virus infection who presented between May 11 and Oct 4, 2022, across 15 countries. Overall median age was 34 years (IQR 28-40; range 19-84). The cohort comprised 62 trans women, 69 cis women, and five non-binary individuals (who were, because of small numbers, grouped with cis women to form a category of people assigned female at birth for the purpose of comparison). 121 (89%) of 136 individuals reported sex with men. 37 (27%) of all individuals were living with HIV, with a higher proportion among trans women (31 [50%] of 62) than among cis women and non-binary individuals (six [8%] of 74). Sexual transmission was suspected in 55 (89%) trans women (with the remainder having an unknown route of transmission) and 45 (61%) cis women and non-binary individuals; non-sexual routes of transmission (including household and occupational exposures) were reported only in cis women and non-binary individuals. 25 (34%) of 74 cis women and non-binary individuals submitted to the case series were initially misdiagnosed. Overall, among individuals with available data, rash was described in 124 (93%) of 134 individuals and described as anogenital in 95 (74%) of 129 and as vesiculopustular in 105 (87%) of 121. Median number of lesions was ten (IQR 5-24; range 1-200). Mucosal lesions involving the vagina, anus, or oropharynx or eye occurred in 65 (55%) of 119 individuals with available data. Vaginal and anal sex were associated with lesions at those sites. Monkeypox virus DNA was detected by PCR from vaginal swab samples in all 14 samples tested. 17 (13%) individuals were hospitalised, predominantly for bacterial superinfection of lesions and pain management. 33 (24%) individuals were treated with tecovirimat and six (4%) received post-exposure vaccinations. No deaths were reported. INTERPRETATION: The clinical features of monkeypox in women and non-binary individuals were similar to those described in men, including the presence of anal and genital lesions with prominent mucosal involvement. Anatomically, anogenital lesions were reflective of sexual practices: vulvovaginal lesions predominated in cis women and non-binary individuals and anorectal features predominated in trans women. The prevalence of HIV co-infection in the cohort was high. FUNDING: None.

Mpox and HIV-Collision of Two Diseases.

PURPOSE OF REVIEW: The global outbreak of mpox has brought renewed attention to a previously neglected disease which is particularly severe in people with underlying untreated HIV co-infection. For this population, the disease is progressive, severe, and often lethal. In this review, we examine the pathogenesis of mpox disease and its collision with co-existent HIV infection and discuss key considerations for management as well as emerging clinical dilemmas and areas for future research. RECENT FINDINGS: Co-existent untreated HIV infection characterized by severe immunocompromise potentiates the nefarious effects of monkeypox virus infection leading to severe manifestations of mpox. Treating mpox in the context of HIV requires mpox-directed therapies, supportive care, and HIV-specific treatment to restore immune function. Preventative measures for PWH are like those in healthy individuals, but the effectiveness and durability of protection conferred by existing vaccines in PWH remain to be fully characterized. Mpox is an important opportunistic infection in PWH. Clinicians should be aware of the unique features of the disease in this population and approaches to care and management of mpox in PWH.

Social Media: Flattening Hierarchies for Women and Black, Indigenous, People Of Color (BIPOC) to Enter the Room Where It Happens.

Social media platforms are widely used to connect people across multiple settings, including country of origin, profession, race/ethnicity, sexual orientation, gender identity, seniority, and training. Groups that have been marginalized or historically excluded from decision-making encounters may lack formal mentors/sponsors because of a lack of representation of women and Black, Indigenous, People Of Color (BIPOC) in senior leadership positions. This can serve as a barrier to professional advancement at all stages of career development. Identifying and connecting with these potential mentors/sponsors outside of one's institutional space can be challenging. For this reason, leveraging social media to develop these professional relationships through flattened hierarchies can allow for professional networking beyond traditional mechanisms. Here we aim to describe how individuals can connect through social media to advance their careers and scientific and clinical expertise, advocate for communities, and provide high-quality communication to the public.

Educational Impact of #IDJClub, a Twitter-Based Infectious Diseases Journal Club.

BACKGROUND: Journal clubs have been an enduring mainstay of medical education, and hosting these on social media platforms can expand accessibility and engagement. We describe the creation and impact of #IDJClub, an infectious diseases (ID) Twitter journal club. METHODS: We launched #IDJClub in October 2019. Using the account @IDJClub, an ID physician leads a 1-hour open-access Twitter discussion of a recent publication. All participants use the hashtag #IDJClub. Sessions started monthly, but increased due to demand during the coronavirus disease 2019 (COVID-19) pandemic. We used Symplur 's Healthcare Hashtag project to track engagement of #IDJClub per 60-minute discussion plus the following 30 minutes to capture ongoing conversations. We also conducted an online anonymous survey using Likert scales and open-ended questions to assess educational impact. RESULTS: In its first 20 months, 31 journal clubs were held, with medians of 42 (interquartile range [IQR], 28.5-60) participants and 312 (IQR, 205-427.5) tweets per session. 134 participants completed the survey, of whom 39% were ID physicians, 19% pharmacists, 13% ID fellows, and 10% medical residents. Most agreed or strongly agreed that #IDJClub provided clinically useful knowledge (95%), increased personal confidence in independent literature appraisal (72%), and was more educational than traditional journal clubs (72%). The format addressed several barriers to traditional journal club participation such as lack of access, subject experts, and time. CONCLUSIONS: #IDJClub is an effective virtual journal club, providing an engaging, open-access tool for critical literature appraisal that overcomes several barriers to traditional journal club participations while fostering connectedness within the global ID community.

#SoMe the Money! Value, Strategy, and Implementation of Social Media Engagement for Infectious Diseases Trainees, Clinicians, and Divisions.

Social media platforms have revolutionized how we consume information, along with how to effectively present communication, education, and advocacy efforts. There is profound value in leveraging social media within these aspects for the field of infectious diseases, for divisions and individual clinicians. Herein, we provide the rationale to incorporate social media as a key competency for infectious diseases training and specific guidance on aspects of education and strategic development of new accounts critical for success.

A Diverse Physician-Scientist Pipeline to Fight Structural Racism.

Translational research plays a pivotal role in leveraging good science to serve humanity. Structural racism and a lack of diversity severely limit our potential as scientists to exert a maximum impact. This moment calls for a renewed commitment to ridding science of racism and bias and promoting diversity, which makes us more effective at innovating and delivering therapeutics to the patients we serve.

Use of Baricitinib in Patients With Moderate to Severe Coronavirus Disease 2019.

Hyperinflammation is associated with increased mortality in coronavirus disease 2019 (COVID-19). In this retrospective, uncontrolled patient cohort with moderate -severe COVID-19, treatment with baricitinib plus hydroxychloroquine was associated with recovery in 11 of 15 patients. Baricitinib for the treatment of COVID-19 should be further investigated in randomized, controlled clinical trials.

Combination antiretroviral therapy and cell-cell spread of wild-type and drug-resistant human immunodeficiency virus-1.

Human immunodeficiency virus-1 (HIV-1) disseminates between T cells either by cell-free infection or by highly efficient direct cell-cell spread. The high local multiplicity that characterizes cell-cell infection causes variability in the effectiveness of antiretroviral drugs applied as single agents. Whereas protease inhibitors (PIs) are effective inhibitors of HIV-1 cell-cell and cell-free infection, some reverse transcriptase inhibitors (RTIs) show reduced potency; however, antiretrovirals are not administered as single agents and are used clinically as combination antiretroviral therapy (cART). Here we explored the efficacy of PI- and RTI-based cART against cell-cell spread of wild-type and drug-resistant HIV-1 strains. Using a quantitative assay to measure cell-cell spread of HIV-1 between T cells, we evaluated the efficacy of different clinically relevant drug combinations. We show that combining PIs and RTIs improves the potency of inhibition of HIV-1 and effectively blocks both cell-free and cell-cell spread. Combining drugs that alone are poor inhibitors of cell-cell spread markedly improves HIV-1 inhibition, demonstrating that clinically relevant combinations of ART can inhibit this mode of HIV-1 spread. Furthermore, comparison of wild-type and drug-resistant viruses reveals that PI- and RTI-resistant viruses have a replicative advantage over wild-type virus when spreading by cell-cell means in the presence of cART, suggesting that in the context of inadequate drug combinations or drug resistance, cell-cell spread could potentially allow for ongoing viral replication.