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August 13, 2022

Clinical Reports

  • Interim Guidance for Prevention and Treatment of Monkeypox in Persons with HIV Infection — United States, August 2022
    A multinational monkeypox outbreak disproportionately affecting men who have sex with men, including persons with HIV infection, is ongoing worldwide. CDC has developed clinical considerations for prevention and treatment of monkeypox in persons with HIV infection, including pre-exposure and postexposure prophylaxis with JYNNEOS vaccine, treatment with tecovirimat, and infection control. Persons with advanced HIV might be at increased risk for severe monkeypox. Postexposure prophylaxis and antiviral treatments are available for persons with HIV infection. Prompt diagnosis and treatment and enhanced prevention efforts might reduce the risk for severe outcomes.
  • Post–COVID-19 Symptoms and Conditions Among Children and Adolescents — United States, March 1, 2020–January 31, 2022
    Compared with patients aged 0–17 years without previous COVID-19, those with previous COVID-19 had higher rates of acute pulmonary embolism (adjusted hazard ratio = 2.01), myocarditis and cardiomyopathy (1.99), venous thromboembolic event (1.87), acute and unspecified renal failure (1.32), and type 1 diabetes (1.23), all of which were rare or uncommon in this study population. COVID-19 prevention strategies, including vaccination for all eligible persons aged ≥6 months, are critical to preventing SARS-CoV-2 infection and subsequent illness, and reducing the public health impact of post-COVID symptoms and conditions among persons aged 0–17 years.
  • Profiling post-COVID syndrome across different variants of SARS-CoV-2
    This study describes post-COVID profiles, and how they relate to different viral variants and vaccination status. In this prospective longitudinal cohort study, researchers analyzed data from 336,652 subjects, with regular health reports through the Covid Symptom Study (CSS) smartphone application. These subjects had reported feeling physically normal for at least 30 days before testing positive for SARS-CoV-2. 9,323 individuals subsequently developed Long-COVID, defined as symptoms lasting longer than 28 days. 1,459 had post-COVID syndrome, defined as more than 12 weeks of symptoms. Clustering analysis of the time-series data was performed to identify distinct symptom profiles for post-COVID patients, across variants of SARS-CoV-2 and vaccination status at the time of infection. Clusters were then characterized based on symptom prevalence, duration, demography, and prior conditions (comorbidities). Using an independent testing sample with additional data (n=140), researchers investigated the impact of post-COVID symptom clusters on the lives of affected individuals. Study authors identified distinct profiles of symptoms for post-COVID syndrome within and across variants: four endotypes were identified for infections due to the wild-type variant; seven for the alpha variant; and five for delta. Across all variants, a cardiorespiratory cluster of symptoms was identified. A second cluster related to central neurological, and a third to cases with the most severe and debilitating multi-organ symptoms. Gastrointestinal symptoms clustered in no more than two specific phenotypes per viral variant. The three main clusters were confirmed in an independent testing sample, and their functional impact was assessed. Unsupervised analysis identified different post-COVID profiles, characterized by differing symptom combinations, durations, and functional outcomes. Phenotypes were at least partially concordant with individuals’ reported experiences. This classification may be useful to understand distinct mechanisms of the post-COVID syndrome, as well as subgroups of individuals at risk of prolonged debilitation.

Antiviral Therapeutics and Vaccines

  • Comparison of lyophilized versus liquid modified vaccinia Ankara (MVA) formulations and subcutaneous versus intradermal routes of administration in healthy vaccinia-naïve subjects
    This study compared the safety and immunogenicity of the standard formulation, dose and route with both a more stable, lyophilized formulation and with an antigen-sparing intradermal (ID) route of administration. 524 subjects were randomized to receive either a full dose of Lyophilized-SC, a full dose of Liquid-SC or 20% (2×10(7) TCID50 in 0.1mL) of a full dose Liquid-ID MVA on Days 0 and 28. Safety and immunogenicity were followed through 180 days post second vaccination. Among the 3 groups, the proportion of subjects with moderate/severe functional local reactions was significantly different (P=0.0013) between the Lyophilized-SC group (30.3%), the Liquid-SC group (13.8%) and Liquid-ID group (22.0%) only after first vaccination; and for moderate/severe measured erythema and/or induration after any vaccination (P=0.0001) between the Lyophilized-SC group (58.2%), the Liquid-SC group (58.1%) and the Liquid-ID group (94.8%) and the reactions lasted longer in the Liquid-ID group. In the ID Group, 36.1% of subjects had mild injection site skin discoloration lasting ≥6 months. After second vaccination Day (42-208), geometric mean of peak neutralization titers were 87.8, 49.5 and 59.5 for the Lyophilized-SC, Liquid-SC and Liquid-ID groups, respectively, and the maximum number of responders based on peak titer in each group was 142/145 (97.9%), 142/149 (95.3%) and 138/146 (94.5%), respectively. At 180 days after the second vaccination, geometric mean neutralization titers declined to 11.7, 10.2 and 10.4 with only 54.3%, 39.2% and 35.2% of subjects remaining seropositive for the Lyophilized-SC, Liquid-SC and Liquid-ID groups, respectively. Both the Lyophilized-SC and Liquid-ID groups were considered non-inferior (primary objective) to the Liquid-SC group. Transitioning to a lyophilized formulation, which has a longer shelf life, will not negatively impact immunogenicity. In a situation where insufficient vaccine is available, ID vaccination could be used, increasing the number of available doses of vaccine in the SNS 5-fold (i.e., from 20 million to 100 million doses).
  • Viral Kinetics of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Omicron Infection in mRNA-Vaccinated Individuals Treated and Not Treated with Nirmatrelvir-Ritonavir
    Researchers measured viral kinetics of SARS-CoV-2 Omicron infection in 36 mRNA-vaccinated individuals, 11 of whom were treated with nirmatrelvir-ritonavir (NMV-r). Study authors found that NMV-r was associated with greater incidence of viral rebound compared to no treatment. For those that did not rebound, NMV-r significantly reduced time to PCR conversion.

Diagnostics

  • Evaluation of the Tetracore Orthopox BioThreat® antigen detection assay using laboratory grown orthopoxviruses and rash illness clinical specimens
    The commercially available Orthopox BioThreat® Alert assay for orthopoxvirus (OPV) detection is piloted. This antibody-based lateral-flow assay labels and captures OPV viral agents to detect their presence. Serial dilutions of cultured Vaccinia virus (VACV) and Monkeypox virus (MPXV) were used to evaluate the sensitivity of the Tetracore assay by visual and quantitative determinations; specificity was assessed using a small but diverse set of diagnostically relevant blinded samples from viral lesions submitted for routine OPV diagnostic testing. The BioThreat® Alert assay reproducibly detected samples at concentrations of 107 pfu/ml for VACV and MPXV and positively identified samples containing 106 pfu/ml in 4 of 7 independent experiments. The assay correctly identified 9 of 11 OPV clinical samples and had only one false positive when testing 11 non-OPV samples. Results suggest applicability for use of the BioThreat® Alert assay as a rapid screening assay and point of care diagnosis for suspect human monkeypox cases.
  • Duration of Symptoms and Association With Positive Home Rapid Antigen Test Results After Infection With SARS-CoV-2
    In this cohort study of individuals newly diagnosed with COVID-19, 75% continued to have positive RAT results, while 35% had culturable virus on day 6. Everyone with a negative day-6 RAT result had a negative viral culture. However, only 50% of those with a positive RAT result had culturable virus. Acknowledging the caveats of a small cohort of mostly young, vaccinated, nonhospitalized individuals with a presumed Omicron variant and potential variation in self-sampling techniques and lab-based culture methods, these data suggest that a negative RAT result in individuals with residual symptoms could provide reassurance about ending isolation. However, a universal requirement of a negative RAT result may unduly extend isolation for those who are no longer infectious. Meanwhile, a recommendation to end isolation based solely on the presence of improving symptoms risks releasing culture-positive, potentially infectious individuals prematurely, underscoring the importance of proper mask wearing and avoidance of high-risk transmission venues through day 10.

Epidemiology

  • Epidemiologic and Clinical Characteristics of Monkeypox Cases — United States, May 17–July 22, 2022
    A global monkeypox outbreak began in 2022. Among U.S. monkeypox cases with available data, 99% occurred in men, 94% of whom reported recent male-to-male sexual or close intimate contact; racial and ethnic minority groups appear to be disproportionately affected. Clinical presentations differed from typical monkeypox, with fewer persons experiencing prodrome and more experiencing genital rashes. Public health efforts should prioritize gay, bisexual, and other men who have sex with men, who are currently disproportionately affected, for prevention and testing, address equity, and minimize stigma, while maintaining vigilance for transmission in other populations. Clinicians should test persons with rash consistent with monkeypox, regardless of whether the rash is disseminated or was preceded by prodrome.
  • Neuropsychiatric sequelae of long COVID-19: Pilot results from the COVID-19 neurological and molecular prospective cohort study in Georgia,
    The COVID-19 Neurological and Molecular Prospective Cohort Study in Georgia (CONGA) was established to investigate the severity and chronicity of these neurologic findings over the five-year period following infection. The CONGA study aims to recruit COVID-19 positive adult patients in Georgia, United States from both the inpatient and outpatient setting, with 50% being African American. This paper reports preliminary results from the baseline visits of the first 200 patients recruited who were on average 125 days since having a positive COVID-19 test. The demographics, self-reported symptoms, comorbidities, and quantitative measures of depression, anxiety, smell, taste, and cognition were analyzed. Cognitive measures were compared to demographically matched controls. Blood and mononuclear cells were drawn and stored for future analysis. Fatigue was the most reported symptom in the study cohort (68.5%). Thirty percent of participants demonstrated hyposmia and 30% of participants demonstrated hypogeusia. Self-reported neurologic dysfunction did not correlate with dysfunction on quantitative neurologic testing. Additionally, self-reported symptoms and comorbidities were associated with depression and anxiety. The study cohort performed worse on cognitive measures compared to demographically matched controls, and African American patients scored lower compared to non-Hispanic White patients on all quantitative cognitive testing. Our results support the growing evidence that there are chronic neuropsychiatric symptoms following COVID-19 infection. Our results suggest that self-reported neurologic symptoms do not appear to correlate with associated quantitative dysfunction, emphasizing the importance of quantitative measurements in the complete assessment of deficits. Self-reported symptoms are associated with depression and anxiety. COVID-19 infection appears to be associated with worse performance on cognitive measures, though the disparity in score between African American patients and non-Hispanic White patients is likely largely due to psychosocial, physical health, and socioeconomic factors.

Situation Dashboards

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World Health Organization (WHO)

Novel Coronavirus (COVID-19) Situation from World Health Organization (WHO)
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Johns Hopkins University (JHU)

Coronavirus COVID-19 Global Cases by the Center for Systems Science and Engineering (CSSE) at JHU
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COVID-19 in US and Canada

1Point3Acres Real-Time Coronavirus (COVID-19) Updates in US and Canada with Credible Sources
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Genomic Epidemiology COVID-19

Genomic Epidemiology of (COVID-19) Maintained by the Nextstrain team, enabled by data from GISAID.

Sources for COVID-19 Information

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World Health Organization (WHO)

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Centers for Disease Control, US

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International Society for Infectious Diseases

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This Week in Virology (TWIV)

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