Monkey Pox Virus Magnified (simulated)

August 27, 2022

Clinical Reports

Clinical presentation and virological assessment of confirmed human monkeypox virus cases in Spain: a prospective observational cohort study

  • This multicenter, prospective, observational cohort study was done in three sexual health clinics in Madrid and Barcelona, Spain. Researchers enrolled all consecutive patients with laboratory-confirmed monkeypox from May 11 to June 29, 2022. Participants were offered lesion, anal, and oropharynx swabs for PCR testing. Clinical outcomes were followed up until July 13, 2022. 181 patients had a confirmed monkeypox diagnosis and were enrolled in the study. 166 (92%) identified as gay men, bisexual men, or other men who have sex with men (MSM) and 15 (8%) identified as heterosexual men or heterosexual women. Median age was 37·0 years (IQR 31·0–42·0). 32 (18%) patients reported previous smallpox vaccination, 72 (40%) were HIV-positive, eight (11%) had a CD4 cell count less than 500 cells per μL, and 31 (17%) were diagnosed with a concurrent sexually transmitted infection. Median incubation was 7·0 days (IQR 5·0–10·0). All participants presented with skin lesions; 141 (78%) participants had lesions in the anogenital region, and 78 (43%) in the oral and perioral region. 70 (39%) participants had complications requiring treatment: 45 (25%) had a proctitis, 19 (10%) had tonsillitis, 15 (8%) had penile oedema, six (3%) an abscess, and eight (4%) had an exanthem. Three (2%) patients required hospital admission. 178 (99%) of 180 swabs from skin lesions collected tested positive, as did 82 (70%) of 117 throat swabs. Viral load was higher in lesion swabs than in pharyngeal specimens (mean cycle threshold value 23 [SD 4] vs32 [6], absolute difference 9 [95% CI 8–10]; p<0·0001). 108 (65%) of 166 MSM reported anal-receptive sex. MSM who engaged in anal-receptive sex presented with proctitis (41 [38%] of 108 vs four [7%] of 58, absolute difference 31% [95% CI 19–44]; p<0·0001) and systemic symptoms before the rash (67 [62%] vs 16 [28%], absolute difference 34% [28–62]; p<0·0001) more frequently than MSM who did not engage in anal-receptive sex. 18 (95%) of 19 participants with tonsillitis reported practicing oral-receptive sex. The median time from onset of lesions to formation of a dry crust was 10 days (IQR 7–13). In this cohort, monkeypox caused genital, perianal, and oral lesions and complications including proctitis and tonsillitis. Because of the variability of presentations, clinicians should have a low threshold for suspicion of monkeypox. Lesion swabs showed the highest viral loads, which, combined with the history of sexual exposure and the distribution of lesions, suggests close contact is probably the dominant transmission route in the current outbreak.

Monkeypox Virus Infection in Humans across 16 Countries — April–June 2022

  • Before April 2022, monkeypox virus infection in humans was seldom reported outside African regions where it is endemic. Currently, cases are occurring worldwide. Transmission, risk factors, clinical presentation, and outcomes of infection are poorly defined. Researchers formed an international collaborative group of clinicians who contributed to an international case series to describe the presentation, clinical course, and outcomes of polymerase-chain-reaction–confirmed monkeypox virus infections. Researchers report 528 infections diagnosed between April 27 and June 24, 2022, at 43 sites in 16 countries. Overall, 98% of the persons with infection were gay or bisexual men, 75% were White, and 41% had human immunodeficiency virus infection; the median age was 38 years. Transmission was suspected to have occurred through sexual activity in 95% of the persons with infection. In this case series, 95% of the persons presented with a rash (with 64% having ≤10 lesions), 73% had anogenital lesions, and 41% had mucosal lesions (with 54 having a single genital lesion). Common systemic features preceding the rash included fever (62%), lethargy (41%), myalgia (31%), and headache (27%); lymphadenopathy was also common (reported in 56%). Concomitant sexually transmitted infections were reported in 109 of 377 persons (29%) who were tested. Among the 23 persons with a clear exposure history, the median incubation period was 7 days (range, 3 to 20). Monkeypox virus DNA was detected in 29 of the 32 persons in whom seminal fluid was analyzed. Antiviral treatment was given to 5% of the persons overall, and 70 (13%) were hospitalized; the reasons for hospitalization were pain management, mostly for severe anorectal pain (21 persons); soft-tissue superinfection (18); pharyngitis limiting oral intake (5); eye lesions (2); acute kidney injury (2); myocarditis (2); and infection-control purposes (13). No deaths were reported. In this case series, monkeypox manifested with a variety of dermatologic and systemic clinical findings. The simultaneous identification of cases outside areas where monkeypox has traditionally been endemic highlights the need for rapid identification and diagnosis of cases to contain further community spread.

Clinical characteristics of ambulatory and hospitalized patients with monkeypox virus infection: an observational cohort study

  • The objectives of this study were to describe the clinical characteristics and complications of patients with a monkeypox infection. All consecutive patients with a PCR-confirmed monkeypox infection seen in a French referral center were included. Between May 21st and July 5th 2022, 264 patients had a PCR-confirmed monkeypox infection. Among them, 262 (262/264, 99%) were men, 245 (245/259, 95%) were men who have sex with men (MSM) and 90 (90/216, 42%) practiced sex in the last 3 months. Seventy-three (73/256, 29%) were living with HIV and 120 (120/169, 71%) were taking pre-exposure prophylaxis against HIV infection. Overall, 112 patients (112/236, 47%) had a contact with a confirmed monkeypox case, of a sexual nature for 95% of the contacts (86/91). Monkeypox PCR was positive on the skin in 252 patients, on oro-pharyngeal sample in 150 patients and in blood in 8 patients. The majority of patients presented with fever (171/253, 68%) and adenopathy (174/251, 69%). Skin lesions mostly affected the genital (135/252, 54%) and perianal (100/251, 40%) areas. Overall, 17 (17/264, 6%) patients were hospitalized, none of them immunocompromised. Complications requiring hospitalization included cellulitis (n=4), paronychia (n=3), severe anal and digestive involvement (n=4), non-cardia angina with dysphagia (n=4), blepharitis (n=1) and keratitis (n=1). Surgical management was required in four patients. The current outbreak of monkeypox infections has specific characteristics: it occurs in the MSM community, known contact is mostly sexual, perineal and anal areas are frequently affected and severe complications include superinfected skin lesions, paronychia, cellulitis, anal and digestive involvement, angina with dysphagia and ocular involvement.

Antiviral Therapeutics and Vaccines

Compassionate Use of Tecovirimat for the Treatment of Monkeypox Infection

  • As of August 13, 2022, 25 patients with confirmed monkeypox infection had completed a course of tecovirimat therapy. All patients were self-reported male and the median age was 40.7 years (range, 26-76). Nine patients had HIV, 1 patient had received the smallpox vaccine more than 25 years prior, and 4 received 1 dose of JYNNEOS vaccination after symptom onset. At the time of treatment, systemic symptoms, lesions, or both were present for a mean of 12 days (range, 6-24). Systemic symptoms included fever in 19 patients (76%), headache in 8 (32%), fatigue in 7 (28%), sore throat in 5 (20%), chills in 5 (20%), backache in 3 (12%), myalgia in 2 (8%), nausea in 1 (4%), and diarrhea in 1 (4%). Almost all patients (23 [92%]) had genital and/or perianal lesions, and 13 (52%) had fewer than 10 lesions over their entire body. All patients had pain associated with lesions. One patient received 21 days of therapy while the remainder were treated for 14 days. Complete resolution of lesions was reported in 10 patients (40%) on day 7 of therapy, while 23 (92%) had resolution of lesions and pain by day 21. Treatment with tecovirimat was generally well tolerated with no patient discontinuing therapy. The most frequently reported adverse events on day 7 of therapy included the following: fatigue in 7 patients (28%), headache in 5 (20%), nausea in 4 (16%), itching in 2 (8%), and diarrhea in 2 (8%). In this preliminary study, oral tecovirimat was well tolerated by all patients with monkeypox infection, with minimal adverse effects. However, adverse effects could not always be differentiated from symptoms related to the infection. No control group was included, limiting conclusions of antiviral efficacy pertaining to duration of symptoms or severity. Time from symptom onset to presentation was variable among patients, and conclusions related to antiviral use vs natural evolution of disease should be made with caution.

Safety Monitoring of Pfizer-BioNTech COVID-19 Vaccine Booster Doses Among Children Aged 5–11 Years — United States, May 17–July 31, 2022

  • A Pfizer-BioNTech COVID-19 vaccine booster dose is recommended for children aged 5–11 years; approximately 657,302 third doses were administered to children in this age group during May–July 2022. Among children aged 5–11 years, local and systemic reactions were reported to v-safe with similar frequency after doses 2 and 3; specific reactions differed in severity. Vaccine administration errors were the most common events reported to the Vaccine Adverse Event Reporting System. No reports of myocarditis or death after receipt of dose 3 were received. Among children aged 5–11 years, serious adverse events after dose 3 are rare. Additional provider education might prevent vaccine administration errors.

Pfizer and BioNTech Announce Updated COVID-19 Vaccine Data Supporting Efficacy in Children 6 Months through 4 Years of Age

  • Updated analysis from 34 cases occurring at least seven days following a three-dose regimen showed 73.2% vaccine efficacy among children ages 6 months through 4 years. The vaccine efficacy remained consistently above 70% in both the 6 through 23 months and the 2 through 4 years age groups. Sequencing of observed COVID-19 cases confirmed majority were caused by Omicron BA.2, broadening the evidence for efficacy across COVID-19 variants.

Pfizer and BioNTech Submit Application to U.S. FDA for Emergency Use Authorization of Omicron BA.4/BA.5-Adapted Bivalent COVID-19 Vaccine

  • Pre-clinical data showed a booster dose of Pfizer and BioNTech's Omicron BA.4/BA.5-adapted bivalent vaccine generated a strong neutralizing antibody response against Omicron BA.1, BA.2 and BA.4/BA.5 variants, as well as the original wild-type strain.

Oral Nirmatrelvir and Ritonavir in Non-hospitalized Vaccinated Patients with Covid-19

  • Treatment of coronavirus disease-2019 (Covid-19) with nirmatrelvir plus ritonavir (NMV-r) in high-risk non-hospitalized unvaccinated patients reduced the risk of progression to severe disease. However, the potential benefits of NMV-r among vaccinated patients are unclear. We conducted a comparative retrospective cohort study using the TriNetX research network. Patients ≥18 years of age who were vaccinated and subsequently developed Covid-19 between December 1, 2021, and April 18, 2022, were included. Cohorts were developed based on the use of NMV-r within five days of diagnosis. The primary composite outcome was all-cause emergency room (ER) visit, hospitalization, or death at a 30-days follow-up. Secondary outcomes included individual components of primary outcomes, multisystem symptoms, Covid-19 associated complications, and diagnostic test utilization. After propensity score matching, 1,130 patients remained in each cohort. A primary composite outcome of all-cause ER visits, hospitalization, or death in 30 days occurred in 89 (7.87%) patients in the NMV-r cohort as compared to 163 (14.4%) patients in the non-NMV-r cohort (OR 0.5, CI 0.39-0.67; p<0.005) consistent with 45% relative risk reduction. A significant reduction in multisystem symptom burden and subsequent complications such as lower respiratory tract infection, cardiac arrhythmia, and diagnostic radiology testing were noted in NMV-r treated patients. There was no apparent increase serious complications between days 10 to 30. Treatment with NMV-r in non-hospitalized vaccinated patients with Covid-19 was associated with a reduced likelihood of emergency room visits, hospitalization, or death. Complications and overall resource utilization were also decreased.

Diagnostics

Cross-Reactive Antibody Responses against Nonpoliovirus Enteroviruses

  • Enteroviruses are among the most common human viral pathogens. Infection with members of a subgroup of viruses within this genus, the nonpoliovirus enteroviruses (NPEVs), can result in a broad spectrum of serious illnesses, including acute flaccid myelitis (AFM), a polio-like childhood paralysis; neonatal sepsis; aseptic meningitis; myocarditis; and hand-foot-mouth disease. Despite the diverse primary sites of virus infection, including the respiratory and alimentary tracts, and an array of diseases associated with these infections, there is significant genetic and antigenic similarity among NPEVs. This conservation results in the induction of cross-reactive antibodies that are either able to bind and neutralize or bind but not neutralize multiple NPEVs. Using plaque reduction and enzyme-linked immunosorbent assay (ELISA)-based binding assays, researchers define the antigenic relationship among poliovirus and NPEVs, including multiple isolates of EV-D68, EV-A71, EV-D70, EV-94, EV-111, Coxsackievirus A24v, and rhinovirus. The results reveal extensive cross-reactivity among EVs that cannot be predicted from phylogenetic analysis. Determining the immunologic relationship among EVs is critical to understanding the humoral response elicited during homologous and heterologous virus infections.

Clinical characteristics and comparison of longitudinal qPCR results from different specimen types in a cohort of ambulatory and hospitalized patients infected with monkeypox virus.

  • The aim of this study was to compare clinical data with longitudinal qPCR results from lesion swabs, oropharyngeal swabs and blood in a well characterized patient cohort. 16 male patients (5 hospitalized, 11 outpatients) were included in the study cohort and serial testing for monkeypox virus-DNA carried out in various materials throughout the course of disease. Laboratory analysis included quantitative PCR, next-generation sequencing, immunofluorescence tests and virus isolation in cell culture. All patients were male, between age 20 and 60, and self-identified as men having sex with men. Two had a known HIV infection, coinciding with an increased number of lesions and viral DNA detectable in blood. In initial- and serial testing, lesion swabs yielded viral DNA-loads at, or above 106cp/ml and only declined during the third week. Oropharyngeal swabs featured lower viral loads and returned repeatedly negative in some cases. Viral culture was successful only from lesion swabs but not from oropharyngeal swabs or plasma. The data presented underscore the reliability of lesion swabs for monkeypox virus-detection, even in later stages of the disease. Oropharyngeal swabs and blood samples alone carry the risk of false negative results, but may hold value in pre-/asymptomatic cases or viral load monitoring, respectively.

Direct capture of neutralized RBD enables rapid point-of-care assessment of SARS-CoV-2 neutralizing antibody titer

  • Neutralizing antibody(NAb) titer is a key biomarker of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but point-of-care methods for assessing NAb titer are not widely available. Here, we present a lateral flow assay that captures SARS-CoV-2 receptor-binding domain (RBD) that has been neutralized from binding angiotensin-converting enzyme 2 (ACE2). Quantification of neutralized RBD in this assay correlates with NAb titer from vaccinated and convalescent patients. This methodology demonstrated superior performance in assessing NAb titer compared with either measurement of total anti-spike immunoglobulin G titer or quantification of the absolute reduction in binding between ACE2 and RBD. Our testing platform has the potential for mass deployment to aid in determining at population scale the degree of protective immunity individuals may have following SARS-CoV-2 vaccination or infection and can enable simple at-home assessment of NAb titer.

Epidemiology

High-Contact Object and Surface Contamination in a Household of Persons with Monkeypox Virus Infection — Utah, June 2022

  • Among the 30 specimens, 21 (70%) yielded positive real-time PCR results, including those from all three porous items (i.e., cloth furniture and blankets), 17 of 25 (68%) nonporous surfaces (e.g., handles and switches), and one of two mixed surface types (i.e., chair). No specimen yielded a positive viral culture result. During the period of isolation both residents of the home reported showering once or twice each day, performing hand hygiene approximately 10 times daily, laundering bedding and clothing weekly, and performing routine household cleaning (e.g., mopping and daily use of a multisurface spray on most high-contact surfaces). The cleaning spray used was not listed on the Environmental Protection Agency’s List of Disinfectants for Emerging Viral Pathogens. Monkeypox virusDNA was detected from many objects and surfaces sampled indicating that some level of contamination occurred in the household environment. However, the inability to detect viable virus suggests that virus viability might have decayed over time or through chemical or environmental inactivation. Although both patients were symptomatic and isolated in their home for >3 weeks, their cleaning and disinfection practices during this period might have limited the level of contamination within the household. These data are limited, and additional studies are needed to assess the presence and degree of surface contamination and investigate the potential for indirect transmission of Monkeypox virus in household environments.

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