Clinical severity scores facilitate comparisons to understand risk factors for severe illness. For the 2022 multinational monkeypox clade IIb virus outbreak, we developed a 7-item Mpox Severity Scoring System (MPOX-SSS) with initial variables refined by data availability and parameter correlation. Application of MPOX-SSS to the first 200 patients diagnosed with mpox revealed higher scores in those treated with tecovirimat, presenting >3 days after symptom onset, and with CD4 counts <200 cells/mm3. For individuals evaluated repeatedly, serial scores were concordant with clinical observations. The pilot MPOX-SSS demonstrated good discrimination, distinguished change over time, and identified higher scores in expected groups.

Orthopoxviruses are complex, large-genome DNA viruses that have repeatedly confounded expectations in terms of the clinical illness they cause and their patterns of spread. Monkeypox virus (MPXV) was originally characterized during outbreaks among captive primates in the late 1950's. Human disease (mpox) has been observed since the 1970's and inter-human spread has largely been associated with non-sexual, close physical contact in endemic areas of west and central Africa. In May 2022, a focus of Clade IIb MPXV transmission was detected, spreading largely by sexual contact through international networks of gay, bisexual, and other men who have sex with men. Despite decades of preparedness for the potential biothreat risk posed by smallpox, the outbreak grew in both size and geographic scope, testing the strength of smallpox preparedness tools and public health science alike. In this article we consider what was known about mpox prior to the 2022 outbreak, what we have learned about mpox and Clade IIb virus during the outbreak, and what outbreak response actions and continued research are needed to ensure the global public health community is equipped to detect and halt the further spread of this disease threat. We focus on how epidemiologic characterization and investigation together with laboratory studies have advanced our understanding of the transmission and pathogenesis of mpox, and describe what work remains to be done to optimize diagnostics, therapeutics, and vaccines. Persistent health inequities challenge our capacity to fully eliminate circulation of the 2022 outbreak strain of MPXV currently in the United States.

In this review, we discuss the history and epidemiology of mpox, prevention strategies, clinical characteristics and management, severity of mpox among persons with advanced HIV, and areas for future research relevant to persons with HIV.

HIV-associated immunosuppression may increase risk of hospitalization with mpox. Among persons diagnosed with mpox in the state of Georgia, we characterized the association between hospitalization with mpox and HIV status. People with HIV and CD4 < 350 cells/mm3 or who were not engaged in HIV care had increased risk of hospitalization.

INTRODUCTION: E-cigarettes emerged in the U.S. market in the late 2000s. In 2017, E-cigarette use among U.S. adults was 2.8%, with higher use among some population groups. Limited studies have assessed E-cigarette use among persons with diagnosed HIV. The purpose of this study is to describe the national prevalence estimates of E-cigarette use among persons with diagnosed HIV by selected sociodemographic, behavioral, and clinical characteristics. METHODS: Data were collected between June 2018 and May 2019 as part of the Medical Monitoring Project, an annual cross-sectional survey that produces nationally representative estimates of behavioral and clinical characteristics of persons with diagnosed HIV in the U.S. Statistically significant differences (p<0.05) were determined using chi-square tests. Data were analyzed in 2021. RESULTS: Among persons with diagnosed HIV, 5.9% reported currently using E-cigarettes, 27.1% had ever used them but were not using them currently, and 72.9% had never used them. Current use of E-cigarettes was highest among persons with diagnosed HIV who currently smoke conventional cigarettes (11.1%), those with major depression (10.8%), those aged 25-34 years (10.5%), those who reported injectable and noninjectable drug use in the past 12 months (9.7%), those diagnosed <5 years ago (9.5%), those who self-reported sexual orientation as other (9.2%), and non-Hispanic White people (8.4%). CONCLUSIONS: Overall, findings suggest that a greater proportion of persons with diagnosed HIV used E-cigarettes than the overall U.S. adult population and that higher rates were observed among certain subgroups, including those who currently smoke cigarettes. E-cigarette use among persons with diagnosed HIV warrants continued attention because of its potential impact on HIV-related morbidity and mortality.

In response to our recent Viewpoint1 on air quality interventions to reduce SARS-CoV-2 transmission, Mr Srikrishna and colleagues note that a clear target for air changes per hour in non–health care settings would be helpful. Although we are not aware of COVID-19 outbreaks resulting from SARS-CoV-2 exposure in spaces ventilated with 5 to 6 air changes per hour or less, there are minimal data available on this association to date.2 Further study is needed to determine the effectiveness of various air changes per hour under different circumstances. For some scenarios, higher air changes per hour might be needed to prevent transmission. For example, the CDC recommends at least 12 air changes per hour for hospital airborne infection isolation rooms and for some other patient care areas in health care settings.3

During the multinational mpox (formerly known as monkeypox) clade IIb outbreak in 2022, the emergence of severe mpox among people with HIV bore a striking resemblance to the emergence of opportunistic infections early in the HIV epidemic of the 1980s. Similar to HIV-associated opportunistic infections, mpox produces substantially greater morbidity and prolonged disease in people with advanced (ie, CD4 <350 cells per mm3) or untreated HIV infection.1, 2, 3 A US report2 of 57 hospitalised patients with severe mpox found that 82% had HIV infection, of whom almost three-quarters had a CD4 count less than 50 cells per mm3. Most patients were Black or African American (68%) and 23% were experiencing homelessness, reflecting inequities in access to resources for the prevention and treatment of HIV infection.2 Approximately a third required intensive care support and 20% died, of whom nearly all had HIV infection.2 Notably, fewer than 10% of the patients who had diagnosed HIV were taking antiretroviral therapy (ART).2 These data support the decision made on Sept 28, 2022, to add mpox to the US Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV.4

During 2019 in the United States, there were an estimated 1.2 million people with HIV and 34 800 new HIV infections, among which people belonging to minority ethnic and racial groups were disproportionally affected: 41% of new HIV diagnoses were among Black/African American people and 29% were among Hispanic/Latino people.1 In February 2019, the US Department of Health and Human Services launched Ending the HIV Epidemic in the US, a multiagency initiative with four key strategies (Diagnose, Treat, Prevent, and Respond), which when implemented together can end the HIV epidemic in the United States by 2030.2 Pharmacists and community pharmacies are and will continue to be an essential part of the public health and medical infrastructure needed to end the HIV epidemic. Pharmacists are positioned to facilitate linkage to mainstream health care by reaching people from racial and ethnic groups that are disproportionately affected by HIV. Durable pharmacist impact hinges on addressing policy and practice barriers to enable expanded pharmacy-based HIV services.3 We call on leaders in public health, state and local health departments, professional organizations dedicated to addressing the needs of people with HIV, and community-based organizations to increase engagement with pharmacists and pharmacy associations within their jurisdiction. This could be accomplished, in part, by including them on HIV planning boards and utilizing their skills and availability to support a status-neutral approach to HIV services. These actions will not only help end the HIV epidemic in the United States, but will also help address the syndemic of HIV, viral hepatitis, sexually transmitted infections, and substance use disorder.

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.

High prevalences of HIV and other sexually transmitted infections (STIs) have been reported in the current global monkeypox outbreak, which has affected primarily gay, bisexual, and other men who have sex with men (MSM) (1-5). In previous monkeypox outbreaks in Nigeria, concurrent HIV infection was associated with poor monkeypox clinical outcomes (6,7). Monkeypox, HIV, and STI surveillance data from eight U.S. jurisdictions* were matched and analyzed to examine HIV and STI diagnoses among persons with monkeypox and assess differences in monkeypox clinical features according to HIV infection status. Among 1,969 persons with monkeypox during May 17-July 22, 2022, HIV prevalence was 38%, and 41% had received a diagnosis of one or more other reportable STIs in the preceding year. Among persons with monkeypox and diagnosed HIV infection, 94% had received HIV care in the preceding year, and 82% had an HIV viral load of <200 copies/mL, indicating HIV viral suppression. Compared with persons without HIV infection, a higher proportion of persons with HIV infection were hospitalized (8% versus 3%). Persons with HIV infection or STIs are disproportionately represented among persons with monkeypox. It is important that public health officials leverage systems for delivering HIV and STI care and prevention to reduce monkeypox incidence in this population. Consideration should be given to prioritizing persons with HIV infection and STIs for vaccination against monkeypox. HIV and STI screening and other recommended preventive care should be routinely offered to persons evaluated for monkeypox, with linkage to HIV care or HIV preexposure prophylaxis (PrEP) as appropriate.

Intradermal vaccination delivers antigen into the space between the epidermis and the dermis. This space is an anatomically favorable site for immune stimulation, enriched in a heterogenous population of dendritic cells, macrophages, and monocytes that endow this tissue with a potent capacity to detect and respond robustly to immunologic stimuli, including those present in vaccines. For these reasons, the role of the dermis in adaptive immunity has been exploited for allergen testing and tuberculosis skin testing. And smallpox vaccination was developed by Jenner using something similar to intradermal administration: variolation, or the practice of scratching immunizing material into the skin.

As SARS-CoV-2, the virus that causes COVID-19, continues to circulate globally, high levels of vaccine- and infection-induced immunity and the availability of effective treatments and prevention tools have substantially reduced the risk for medically significant COVID-19 illness (severe acute illness and post-COVID-19 conditions) and associated hospitalization and death (1). These circumstances now allow public health efforts to minimize the individual and societal health impacts of COVID-19 by focusing on sustainable measures to further reduce medically significant illness as well as to minimize strain on the health care system, while reducing barriers to social, educational, and economic activity (2). Individual risk for medically significant COVID-19 depends on a person's risk for exposure to SARS-CoV-2 and their risk for developing severe illness if infected (3). Exposure risk can be mitigated through nonpharmaceutical interventions, including improving ventilation, use of masks or respirators indoors, and testing (4). The risk for medically significant illness increases with age, disability status, and underlying medical conditions but is considerably reduced by immunity derived from vaccination, previous infection, or both, as well as timely access to effective biomedical prevention measures and treatments (3,5). CDC's public health recommendations change in response to evolving science, the availability of biomedical and public health tools, and changes in context, such as levels of immunity in the population and currently circulating variants. CDC recommends a strategic approach to minimizing the impact of COVID-19 on health and society that relies on vaccination and therapeutics to prevent severe illness; use of multicomponent prevention measures where feasible; and particular emphasis on protecting persons at high risk for severe illness. Efforts to expand access to vaccination and therapeutics, including the use of preexposure prophylaxis for persons who are immunocompromised, antiviral agents, and therapeutic monoclonal antibodies, should be intensified to reduce the risk for medically significant illness and death. Efforts to protect persons at high risk for severe illness must ensure that all persons have access to information to understand their individual risk, as well as efficient and equitable access to vaccination, therapeutics, testing, and other prevention measures. Current priorities for preventing medically significant illness should focus on ensuring that persons 1) understand their risk, 2) take steps to protect themselves and others through vaccines, therapeutics, and nonpharmaceutical interventions when needed, 3) receive testing and wear masks if they have been exposed, and 4) receive testing if they are symptomatic, and isolate for ≥5 days if they are infected.

Monkeypox virus, an orthopoxvirus sharing clinical features with smallpox virus, is endemic in several countries in Central and West Africa. The last reported outbreak in the United States, in 2003, was linked to contact with infected prairie dogs that had been housed or transported with African rodents imported from Ghana (1). Since May 2022, the World Health Organization (WHO) has reported a multinational outbreak of monkeypox centered in Europe and North America, with approximately 25,000 cases reported worldwide; the current outbreak is disproportionately affecting gay, bisexual, and other men who have sex with men (MSM) (2). Monkeypox was declared a public health emergency in the United States on August 4, 2022.(†) Available summary surveillance data from the European Union, England, and the United States indicate that among MSM patients with monkeypox for whom HIV status is known, 28%-51% have HIV infection (3-10). Treatment of monkeypox with tecovirimat as a first-line agent is available through CDC for compassionate use through an investigational drug protocol. No identified drug interactions would preclude coadministration of tecovirimat with antiretroviral therapy (ART) for HIV infection. Pre- and postexposure prophylaxis can be considered with JYNNEOS vaccine, if indicated. Although data are limited for monkeypox in patients with HIV, prompt diagnosis, treatment, and prevention might reduce the risk for adverse outcomes and limit monkeypox spread. Prevention and treatment considerations will be updated as more information becomes available.

In 1988, the human immunodeficiency virus (HIV) was rapidly spreading worldwide and disproportionately devastating certain communities, most notably gay, bisexual, and other men who have sex with men. Even after promising new pharmacologic therapies were finally developed, the existing processes for approving their use in humans were painfully slow. Spurred by the AIDS Coalition to Unleash Power (ACT UP) and other advocacy groups, federal scientists and policymakers worked with affected persons to find a way forward that balanced two ethical imperatives: honoring the right of people with serious illness to access potentially beneficial treatment and upholding the responsibility of the health care and public health communities to ensure that those treatments were safe and effective. The result was improvements to the regulatory process designed to accelerate access to and expedite approvals for drugs that treat a serious disease.

The U.S. Public Health Service (PHS) has periodically published recommendations about reducing the risk for transmission of HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV) through solid organ transplantation (1-4). Updated guidance published in 2020 included the recommendation that all transplant candidates receive HIV, HBV, and HCV testing during hospital admission for transplant surgery to more accurately assess their pretransplant infection status and to better identify donor transmitted infection (4). In 2021, CDC was notified that this recommendation might be unnecessary for pediatric organ transplant candidates because of the low likelihood of infection after the perinatal period and out of concern that the volume of blood drawn for testing could negatively affect critically ill children.* CDC and other partners reviewed surveillance data from CDC on estimates of HIV, HBV, and HCV infection rates in the United States and data from the Organ Procurement & Transplantation Network (OPTN)(†) on age and weight distributions among U.S. transplant recipients. Feedback from the transplant community was also solicited to understand the impact of changes to the existing policy on organ transplantation. The 2020 PHS guideline was accordingly updated to specify that solid organ transplant candidates aged <12 years at the time of transplantation who have received postnatal infectious disease testing are exempt from the recommendation for HIV, HBV, and HCV testing during hospital admission for transplantation.

HIV testing is a core strategy for the Ending the HIV Epidemic in the U.S. (EHE) initiative, which has the aim of reducing new HIV infections by at least 90% by 2030.* During 2016-2017, jurisdictions with the highest HIV diagnosis rates were those with higher prevalences of HIV testing; past-year HIV testing was higher among persons who reported recent HIV risk behaviors compared with those who did not report these risks (1). During 2020-2021, the COVID-19 pandemic disrupted health care delivery, including HIV testing in part because many persons avoided services to comply with COVID-19 risk mitigation efforts (2). In addition, public health departments redirected some sexual health services to COVID-19-related activities.(†) CDC analyzed data from four national data collection systems to assess the numbers of HIV tests performed and HIV infections diagnosed in the United States in the years before (2019) and during (2020) the COVID-19 pandemic. In 2020, HIV diagnoses reported to CDC decreased by 17% compared with those reported in 2019. This decrease was preceded by decreases in HIV testing during the same period, particularly among priority populations including Black or African American (Black) gay men, Hispanic or Latino (Hispanic) gay men, bisexual men, other men who have sex with men (MSM), and transgender persons in CDC-funded jurisdictions. To compensate for testing and diagnoses missed during the COVID-19 pandemic and to accelerate the EHE initiative, CDC encourages partnerships among federal organizations, state and local health departments, community-based organizations, and health care systems to increase access to HIV testing services, including strategies such as self-testing and routine opt-out screening in health care settings.

SARS-CoV-2 replicates in the respiratory tract and spreads through exhalation of infectious respiratory particles. The chances of transmission increase the longer an uninfected person stays in an enclosed space with an infected person. Infection can occur not only through short-range transmission of exhaled respiratory particles from an infectious person resulting in mucous membrane deposition or inhalation of exhaled respiratory particles by an uninfected person. Infection also can occur through long-range transmission from inhalation of infectious respiratory particles that remain suspended in air for longer periods (potentially after the infectious person is no longer present) and across longer distances (greater than a few meters).

Although the availability of effective vaccines raises optimism for the control of SARS-CoV-2 transmission in the USA, public health systems must prepare to respond to all COVID-19 health impacts, particularly post-COVID conditions (PCCs).1,2 PCCs consist of new, returning, or ongoing health problems diagnosed in people with a history of SARS-CoV-2 infection, typically present at least 4 weeks after infection.3 While PCCs are still being defined and characterized, PCCs could potentially affect millions of Americans.1,2

COVID-19 vaccination remains the most effective means to achieve control of the pandemic. In the United States, COVID-19 cases and deaths have markedly declined since their peak in early January 2021, due in part to increased vaccination coverage (1). However, during June 19-July 23, 2021, COVID-19 cases increased approximately 300% nationally, followed by increases in hospitalizations and deaths, driven by the highly transmissible B.1.617.2 (Delta) variant* of SARS-CoV-2, the virus that causes COVID-19. Available data indicate that the vaccines authorized in the United States (Pfizer-BioNTech, Moderna, and Janssen [Johnson & Johnson]) offer high levels of protection against severe illness and death from infection with the Delta variant and other currently circulating variants of the virus (2). Despite widespread availability, vaccine uptake has slowed nationally with wide variation in coverage by state (range = 33.9%-67.2%) and by county (range = 8.8%-89.0%).(†) Unvaccinated persons, as well as persons with certain immunocompromising conditions (3), remain at substantial risk for infection, severe illness, and death, especially in areas where the level of SARS-CoV-2 community transmission is high. The Delta variant is more than two times as transmissible as the original strains circulating at the start of the pandemic and is causing large, rapid increases in infections, which could compromise the capacity of some local and regional health care systems to provide medical care for the communities they serve. Until vaccination coverage is high and community transmission is low, public health practitioners, as well as schools, businesses, and institutions (organizations) need to regularly assess the need for prevention strategies to avoid stressing health care capacity and imperiling adequate care for both COVID-19 and other non-COVID-19 conditions. CDC recommends five critical factors be considered to inform local decision-making: 1) level of SARS-CoV-2 community transmission; 2) health system capacity; 3) COVID-19 vaccination coverage; 4) capacity for early detection of increases in COVID-19 cases; and 5) populations at increased risk for severe outcomes from COVID-19. Among strategies to prevent COVID-19, CDC recommends all unvaccinated persons wear masks in public indoor settings. Based on emerging evidence on the Delta variant (2), CDC also recommends that fully vaccinated persons wear masks in public indoor settings in areas of substantial or high transmission. Fully vaccinated persons might consider wearing a mask in public indoor settings, regardless of transmission level, if they or someone in their household is immunocompromised or is at increased risk for severe disease, or if someone in their household is unvaccinated (including children aged <12 years who are currently ineligible for vaccination).

SARS-CoV-2, the virus that causes COVID-19, can be spread by exposure to droplets and aerosols of respiratory fluids that are released by infected persons when they cough, sing, talk, or exhale. To reduce indoor transmission of SARS-CoV-2 between persons, CDC recommends measures including physical distancing, universal masking (the use of face masks in public places by everyone who is not fully vaccinated), and increased room ventilation (1). Ventilation systems can be supplemented with portable high efficiency particulate air (HEPA) cleaners* to reduce the number of infectious particles in the air and provide enhanced protection from transmission between persons (2); two recent reports found that HEPA air cleaners in classrooms could reduce overall aerosol particle concentrations by ≥80% within 30 minutes (3,4). To investigate the effectiveness of portable HEPA air cleaners and universal masking at reducing exposure to exhaled aerosol particles, the investigation team used respiratory simulators to mimic a person with COVID-19 and other, uninfected persons in a conference room. The addition of two HEPA air cleaners that met the Environmental Protection Agency (EPA)-recommended clean air delivery rate (CADR) (5) reduced overall exposure to simulated exhaled aerosol particles by up to 65% without universal masking. Without the HEPA air cleaners, universal masking reduced the combined mean aerosol concentration by 72%. The combination of the two HEPA air cleaners and universal masking reduced overall exposure by up to 90%. The HEPA air cleaners were most effective when they were close to the aerosol source. These findings suggest that portable HEPA air cleaners can reduce exposure to SARS-CoV-2 aerosols in indoor environments, with greater reductions in exposure occurring when used in combination with universal masking.

The Centers for Disease Control and Prevention (CDC) and state, territorial, and local health departments have expanded efforts to detect and respond to HIV clusters and outbreaks in the United States. In July 2017, CDC created the HIV Outbreak Coordination Unit (OCU) to ensure consistent and collaborative assessment of requests from health departments for consultation or support on possible HIV clusters and outbreaks of elevated concern. The HIV OCU is a multidisciplinary, cross-organization functional unit within CDC's Division of HIV/AIDS Prevention. HIV OCU members have expertise in areas such as outbreak detection and investigation, prevention, laboratory services, surveillance and epidemiology, policy, communication, and operations. HIV OCU discussions facilitate problem solving, coordination, and situational awareness. Between HIV OCU meetings, designated CDC staff members communicate regularly with health departments to provide support and assessment. During July 2017-December 2019, the HIV OCU reviewed 31 possible HIV clusters and outbreaks (ie, events) in 22 states that were detected by CDC, health departments, or local partners; 17 events involved HIV transmission associated with injection drug use, and other events typically involved sexual transmission or overall increases in HIV diagnoses. CDC supported health departments remotely or on site with planning and prioritization; data collection, management, and analysis; communications; laboratory support; multistate coordination; and expansion of HIV prevention services. The HIV OCU has augmented CDC's support of HIV cluster and outbreak assessment and response at health departments and had important internal organizational benefits. Health departments may benefit from developing or strengthening similar units to coordinate detection and response efforts within and across public health agencies and advance the national Ending the HIV Epidemic initiative.

Universal masking is one of the prevention strategies recommended by CDC to slow the spread of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (1). As of February 1, 2021, 38 states and the District of Columbia had universal masking mandates. Mask wearing has also been mandated by executive order for federal property* as well as on domestic and international transportation conveyances.(†) Masks substantially reduce exhaled respiratory droplets and aerosols from infected wearers and reduce exposure of uninfected wearers to these particles. Cloth masks(§) and medical procedure masks(¶) fit more loosely than do respirators (e.g., N95 facepieces). The effectiveness of cloth and medical procedure masks can be improved by ensuring that they are well fitted to the contours of the face to prevent leakage of air around the masks' edges. During January 2021, CDC conducted experimental simulations using pliable elastomeric source and receiver headforms to assess the extent to which two modifications to medical procedure masks, 1) wearing a cloth mask over a medical procedure mask (double masking) and 2) knotting the ear loops of a medical procedure mask where they attach to the mask's edges and then tucking in and flattening the extra material close to the face (knotted and tucked masks), could improve the fit of these masks and reduce the receiver's exposure to an aerosol of simulated respiratory droplet particles of the size considered most important for transmitting SARS-CoV-2. The receiver's exposure was maximally reduced (>95%) when the source and receiver were fitted with modified medical procedure masks. These laboratory-based experiments highlight the importance of good fit to optimize mask performance. Until vaccine-induced population immunity is achieved, universal masking is a highly effective means to slow the spread of SARS-CoV-2** when combined with other protective measures, such as physical distancing, avoiding crowds and poorly ventilated indoor spaces, and good hand hygiene. Innovative efforts to improve the fit of cloth and medical procedure masks to enhance their performance merit attention.

Prior to the coronavirus disease 2019 (COVID-19) pandemic, the efficacy of community mask wearing to reduce the spread of respiratory infections was controversial because there were no solid relevant data to support their use. During the pandemic, the scientific evidence has increased. Compelling data now demonstrate that community mask wearing is an effective nonpharmacologic intervention to reduce the spread of this infection, especially as source control to prevent spread from infected persons, but also as protection to reduce wearers’ exposure to infection.

On March 11, 2020, less than 2 weeks after community transmission of the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) was identified in the US, the World Health Organization declared that the novel coronavirus (COVID-19) outbreak was a global pandemic. By March 25, 2020, all kindergarten to grade 12 (K-12) public schools in the US had closed for in-person instruction. After initial closures, many schools pivoted to online education for the remainder of the school year. For the fall 2020 school term, there was tremendous geographic and district-to-district variation in mode of K-12 educational delivery. Among 13 597 of 14 944 districts that provided school reopening plans, 24% were fully online, 51% were using a hybrid model, and 17% were fully open for in-person instruction (some districts included options for parents to opt out); 51% of districts had students participating in school sports programs.1

On December 14, 2020, the United Kingdom reported a SARS-CoV-2 variant of concern (VOC), lineage B.1.1.7, also referred to as VOC 202012/01 or 20I/501Y.V1.* The B.1.1.7 variant is estimated to have emerged in September 2020 and has quickly become the dominant circulating SARS-CoV-2 variant in England (1). B.1.1.7 has been detected in over 30 countries, including the United States. As of January 13, 2021, approximately 76 cases of B.1.1.7 have been detected in 12 U.S. states.(†) Multiple lines of evidence indicate that B.1.1.7 is more efficiently transmitted than are other SARS-CoV-2 variants (1-3). The modeled trajectory of this variant in the U.S. exhibits rapid growth in early 2021, becoming the predominant variant in March. Increased SARS-CoV-2 transmission might threaten strained health care resources, require extended and more rigorous implementation of public health strategies (4), and increase the percentage of population immunity required for pandemic control. Taking measures to reduce transmission now can lessen the potential impact of B.1.1.7 and allow critical time to increase vaccination coverage. Collectively, enhanced genomic surveillance combined with continued compliance with effective public health measures, including vaccination, physical distancing, use of masks, hand hygiene, and isolation and quarantine, will be essential to limiting the spread of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). Strategic testing of persons without symptoms but at higher risk of infection, such as those exposed to SARS-CoV-2 or who have frequent unavoidable contact with the public, provides another opportunity to limit ongoing spread.

BACKGROUND: There is a need for validated and standardized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) quantitative immunoglobulin G (IgG) and neutralization assays that can be used to understand the immunology and pathogenesis of SARS-CoV-2 infection and support the coronavirus disease 2019 (COVID-19) pandemic response. METHODS: Literature searches were conducted to identify English language publications from peer-reviewed journals and preprints from January 2020 through November 6, 2020. Relevant publications were reviewed for mention of IgG or neutralization assays for SARS-CoV-2, or both, and the methods of reporting assay results. RESULTS: Quantitative SARS-CoV-2 IgG results have been reported from a limited number of studies; most studies used in-house laboratory-developed tests in limited settings, and only two semiquantitative tests have received US Food and Drug Administration (FDA) Emergency Use Authorization (EUA). As of November 6, 2020, there is only one SARS-CoV-2 neutralization assay with FDA EUA. Relatively few studies have attempted correlation of quantitative IgG titers with neutralization results to estimate surrogates of protection. The number of individuals tested is small compared with the magnitude of the pandemic, and persons tested are not representative of disproportionately affected populations. Methods of reporting quantitative results are not standardized to enable comparisons and meta-analyses. CONCLUSIONS: Lack of standardized SARS-CoV-2 quantitative IgG and neutralization assays precludes comparison of results from published studies. Interassay and interlaboratory validation and standardization of assays will support efforts to better understand antibody kinetics and longevity of humoral immune responses postillness, surrogates of immune protection, and vaccine immunogenicity and efficacy. Public-private partnerships could facilitate realization of these advances in the United States and worldwide.

IMPORTANCE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiology of coronavirus disease 2019 (COVID-19), is readily transmitted person to person. Optimal control of COVID-19 depends on directing resources and health messaging to mitigation efforts that are most likely to prevent transmission, but the relative importance of such measures has been disputed. OBJECTIVE: To assess the proportion of SARS-CoV-2 transmissions in the community that likely occur from persons without symptoms. DESIGN, SETTING, AND PARTICIPANTS: This decision analytical model assessed the relative amount of transmission from presymptomatic, never symptomatic, and symptomatic individuals across a range of scenarios in which the proportion of transmission from people who never develop symptoms (ie, remain asymptomatic) and the infectious period were varied according to published best estimates. For all estimates, data from a meta-analysis was used to set the incubation period at a median of 5 days. The infectious period duration was maintained at 10 days, and peak infectiousness was varied between 3 and 7 days (-2 and +2 days relative to the median incubation period). The overall proportion of SARS-CoV-2 was varied between 0% and 70% to assess a wide range of possible proportions. MAIN OUTCOMES AND MEASURES: Level of transmission of SARS-CoV-2 from presymptomatic, never symptomatic, and symptomatic individuals. RESULTS: The baseline assumptions for the model were that peak infectiousness occurred at the median of symptom onset and that 30% of individuals with infection never develop symptoms and are 75% as infectious as those who do develop symptoms. Combined, these baseline assumptions imply that persons with infection who never develop symptoms may account for approximately 24% of all transmission. In this base case, 59% of all transmission came from asymptomatic transmission, comprising 35% from presymptomatic individuals and 24% from individuals who never develop symptoms. Under a broad range of values for each of these assumptions, at least 50% of new SARS-CoV-2 infections was estimated to have originated from exposure to individuals with infection but without symptoms. CONCLUSIONS AND RELEVANCE: In this decision analytical model of multiple scenarios of proportions of asymptomatic individuals with COVID-19 and infectious periods, transmission from asymptomatic individuals was estimated to account for more than half of all transmissions. In addition to identification and isolation of persons with symptomatic COVID-19, effective control of spread will require reducing the risk of transmission from people with infection who do not have symptoms. These findings suggest that measures such as wearing masks, hand hygiene, social distancing, and strategic testing of people who are not ill will be foundational to slowing the spread of COVID-19 until safe and effective vaccines are available and widely used.

In the 10 months since the first confirmed case of coronavirus disease 2019 (COVID-19) was reported in the United States on January 20, 2020 (1), approximately 13.8 million cases and 272,525 deaths have been reported in the United States. On October 30, the number of new cases reported in the United States in a single day exceeded 100,000 for the first time, and by December 2 had reached a daily high of 196,227.* With colder weather, more time spent indoors, the ongoing U.S. holiday season, and silent spread of disease, with approximately 50% of transmission from asymptomatic persons (2), the United States has entered a phase of high-level transmission where a multipronged approach to implementing all evidence-based public health strategies at both the individual and community levels is essential. This summary guidance highlights critical evidence-based CDC recommendations and sustainable strategies to reduce COVID-19 transmission. These strategies include 1) universal face mask use, 2) maintaining physical distance from other persons and limiting in-person contacts, 3) avoiding nonessential indoor spaces and crowded outdoor spaces, 4) increasing testing to rapidly identify and isolate infected persons, 5) promptly identifying, quarantining, and testing close contacts of persons with known COVID-19, 6) safeguarding persons most at risk for severe illness or death from infection with SARS-CoV-2, the virus that causes COVID-19, 7) protecting essential workers with provision of adequate personal protective equipment and safe work practices, 8) postponing travel, 9) increasing room air ventilation and enhancing hand hygiene and environmental disinfection, and 10) achieving widespread availability and high community coverage with effective COVID-19 vaccines. In combination, these strategies can reduce SARS-CoV-2 transmission, long-term sequelae or disability, and death, and mitigate the pandemic's economic impact. Consistent implementation of these strategies improves health equity, preserves health care capacity, maintains the function of essential businesses, and supports the availability of in-person instruction for kindergarten through grade 12 schools and preschool. Individual persons, households, and communities should take these actions now to reduce SARS-CoV-2 transmission from its current high level. These actions will provide a bridge to a future with wide availability and high community coverage of effective vaccines, when safe return to more everyday activities in a range of settings will be possible.

Hydroxychloroquine and chloroquine, primarily used to treat autoimmune diseases and to prevent and treat malaria, received national attention in early March 2020, as potential treatment and prophylaxis for coronavirus disease 2019 (COVID-19) (1). On March 20, the Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for chloroquine phosphate and hydroxychloroquine sulfate in the Strategic National Stockpile to be used by licensed health care providers to treat patients hospitalized with COVID-19 when the providers determine the potential benefit outweighs the potential risk to the patient.* Following reports of cardiac and other adverse events in patients receiving hydroxychloroquine for COVID-19 (2), on April 24, 2020, FDA issued a caution against its use(†) and on June 15, rescinded its EUA for hydroxychloroquine from the Strategic National Stockpile.(§) Following the FDA's issuance of caution and EUA rescindment, on May 12 and June 16, the federal COVID-19 Treatment Guidelines Panel issued recommendations against the use of hydroxychloroquine or chloroquine to treat COVID-19; the panel also noted that at that time no medication could be recommended for COVID-19 pre- or postexposure prophylaxis outside the setting of a clinical trial (3). However, public discussion concerning the effectiveness of these drugs on outcomes of COVID-19 (4,5), and clinical trials of hydroxychloroquine for prophylaxis of COVID-19 continue.(¶) In response to recent reports of notable increases in prescriptions for hydroxychloroquine or chloroquine (6), CDC analyzed outpatient retail pharmacy transaction data to identify potential differences in prescriptions dispensed by provider type during January-June 2020 compared with the same period in 2019. Before 2020, primary care providers and specialists who routinely prescribed hydroxychloroquine, such as rheumatologists and dermatologists, accounted for approximately 97% of new prescriptions. New prescriptions by specialists who did not typically prescribe these medications (defined as specialties accounting for ≤2% of new prescriptions before 2020) increased from 1,143 prescriptions in February 2020 to 75,569 in March 2020, an 80-fold increase from March 2019. Although dispensing trends are returning to prepandemic levels, continued adherence to current clinical guidelines for the indicated use of these medications will ensure their availability and benefit to patients for whom their use is indicated (3,4), because current data on treatment and pre- or postexposure prophylaxis for COVID-19 indicate that the potential benefits of these drugs do not appear to outweigh their risks.

Recent epidemiologic, virologic, and modeling reports support the possibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission from persons who are presymptomatic (SARS-CoV-2 detected before symptom onset) or asymptomatic (SARS-CoV-2 detected but symptoms never develop). SARS-CoV-2 transmission in the absence of symptoms reinforces the value of measures that prevent the spread of SARS-CoV-2 by infected persons who may not exhibit illness despite being infectious. Critical knowledge gaps include the relative incidence of asymptomatic and symptomatic SARS-CoV-2 infection, the public health interventions that prevent asymptomatic transmission, and the question of whether asymptomatic SARS-CoV-2 infection confers protective immunity.