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Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2020 Recommendations of the International Antiviral Society–USA Panel

Author/s: 
Saag, Michael S., Gandhi, Rajesh T., Hoy, Jennifer F., Landovitz, Raphael J., Thompson, Melanie A., Sax, Paul E., Smith, Savey M., Benson, Constance A., Buchbinder, Susan P., Del Rio, Carlos, Eron Jr., Joseph J., Fätkenheuer, Gerd, Günthard, Huldrych F., Molina, Jean-Michel, Jacobsen, Donna M., Volberding, Paul A.

Importance  Data on the use of antiretroviral drugs, including new drugs and formulations, for the treatment and prevention of HIV infection continue to guide optimal practices.

Objective  To evaluate new data and incorporate them into current recommendations for initiating HIV therapy, monitoring individuals starting on therapy, changing regimens, preventing HIV infection for those at risk, and special considerations for older people with HIV.

Evidence Review  New evidence was collected since the previous International Antiviral (formerly AIDS) Society–USA recommendations in 2018, including data published or presented at peer-reviewed scientific conferences through August 22, 2020. A volunteer panel of 15 experts in HIV research and patient care considered these data and updated previous recommendations.

Findings  From 5316 citations about antiretroviral drugs identified, 549 were included to form the evidence basis for these recommendations. Antiretroviral therapy is recommended as soon as possible for all individuals with HIV who have detectable viremia. Most patients can start with a 3-drug regimen or now a 2-drug regimen, which includes an integrase strand transfer inhibitor. Effective options are available for patients who may be pregnant, those who have specific clinical conditions, such as kidney, liver, or cardiovascular disease, those who have opportunistic diseases, or those who have health care access issues. Recommended for the first time, a long-acting antiretroviral regimen injected once every 4 weeks for treatment or every 8 weeks pending approval by regulatory bodies and availability. For individuals at risk for HIV, preexposure prophylaxis with an oral regimen is recommended or, pending approval by regulatory bodies and availability, with a long-acting injection given every 8 weeks. Monitoring before and during therapy for effectiveness and safety is recommended. Switching therapy for virological failure is relatively rare at this time, and the recommendations for switching therapies for convenience and for other reasons are included. With the survival benefits provided by therapy, recommendations are made for older individuals with HIV. The current coronavirus disease 2019 pandemic poses particular challenges for HIV research, care, and efforts to end the HIV epidemic.

Conclusion and Relevance  Advances in HIV prevention and management with antiretroviral drugs continue to improve clinical care and outcomes among individuals at risk for and with HIV.

Keywords 
antiretroviral drugs HIV disease COVID-19

School closure and management practices during coronavirus outbreaks including COVID-19: a rapid systematic review

Author/s: 
Viner, RM, Russell, SJ, Croker, H, Packer, J, Ward, J, Stansfield, C, Mytton, O, Bonell, C, Booy, R

In response to the coronavirus disease 2019 (COVID-19) pandemic, 107 countries had implemented national school closures by March 18, 2020. It is unknown whether school measures are effective in coronavirus outbreaks (eg, due to severe acute respiratory syndrome [SARS], Middle East respiratory syndrome, or COVID-19). We undertook a systematic review by searching three electronic databases to identify what is known about the effectiveness of school closures and other school social distancing practices during coronavirus outbreaks. We included 16 of 616 identified articles. School closures were deployed rapidly across mainland China and Hong Kong for COVID-19. However, there are no data on the relative contribution of school closures to transmission control. Data from the SARS outbreak in mainland China, Hong Kong, and Singapore suggest that school closures did not contribute to the control of the epidemic. Modelling studies of SARS produced conflicting results. Recent modelling studies of COVID-19 predict that school closures alone would prevent only 2-4% of deaths, much less than other social distancing interventions. Policy makers need to be aware of the equivocal evidence when considering school closures for COVID-19, and that combinations of social distancing measures should be considered. Other less disruptive social distancing interventions in schools require further consideration if restrictive social distancing policies are implemented for long periods.

Keywords 
COVID-19 school 2019 novel coronavirus 2019-nCOV school management

Coronavirus Disease 2019 in Children — United States, February 12–April 2, 2020

Author/s: 
CDC COVID-19 Response Team

Summary

What is already known about this topic?

Data from China suggest that pediatric coronavirus disease 2019 (COVID-19) cases might be less severe than cases in adults and that children (persons aged <18 years) might experience different symptoms than adults.

What is added by this report?

In this preliminary description of pediatric U.S. COVID-19 cases, relatively few children with COVID-19 are hospitalized, and fewer children than adults experience fever, cough, or shortness of breath. Severe outcomes have been reported in children, including three deaths.

What are the implications for public health practice?

Pediatric COVID-19 patients might not have fever or cough. Social distancing and everyday preventive behaviors remain important for all age groups because patients with less serious illness and those without symptoms likely play an important role in disease transmission.

The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application

Author/s: 
Lauer, S.A., Grantz, K.A, Bi, Q, Jones, F.K., Zheng, Q., Meredith, H.R., Azman, A.S., Reich, N.G., Lessler, J.

Abstract

Background:

A novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in China in December 2019. There is limited support for many of its key epidemiologic features, including the incubation period for clinical disease (coronavirus disease 2019 [COVID-19]), which has important implications for surveillance and control activities.

Objective:

To estimate the length of the incubation period of COVID-19 and describe its public health implications.

Design:

Pooled analysis of confirmed COVID-19 cases reported between 4 January 2020 and 24 February 2020.

Setting:

News reports and press releases from 50 provinces, regions, and countries outside Wuhan, Hubei province, China.

Participants:

Persons with confirmed SARS-CoV-2 infection outside Hubei province, China.

Measurements:

Patient demographic characteristics and dates and times of possible exposure, symptom onset, fever onset, and hospitalization.

Results:

There were 181 confirmed cases with identifiable exposure and symptom onset windows to estimate the incubation period of COVID-19. The median incubation period was estimated to be 5.1 days (95% CI, 4.5 to 5.8 days), and 97.5% of those who develop symptoms will do so within 11.5 days (CI, 8.2 to 15.6 days) of infection. These estimates imply that, under conservative assumptions, 101 out of every 10 000 cases (99th percentile, 482) will develop symptoms after 14 days of active monitoring or quarantine.

Limitation:

Publicly reported cases may overrepresent severe cases, the incubation period for which may differ from that of mild cases.

Conclusion:

This work provides additional evidence for a median incubation period for COVID-19 of approximately 5 days, similar to SARS. Our results support current proposals for the length of quarantine or active monitoring of persons potentially exposed to SARS-CoV-2, although longer monitoring periods might be justified in extreme cases.

Primary Funding Source:

U.S. Centers for Disease Control and Prevention, National Institute of Allergy and Infectious Diseases, National Institute of General Medical Sciences, and Alexander von Humboldt Foundation.

In December 2019, a cluster of severe pneumonia cases of unknown cause was reported in Wuhan, Hubei province, China. The initial cluster was epidemiologically linked to a seafood wholesale market in Wuhan, although many of the initial 41 cases were later reported to have no known exposure to the market (1). A novel strain of coronavirus belonging to the same family of viruses that cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), as well as the 4 human coronaviruses associated with the common cold, was subsequently isolated from lower respiratory tract samples of 4 cases on 7 January 2020 (2). Infection with the virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can be asymptomatic or can result in mild to severe symptomatic disease (coronavirus disease 2019 [COVID-19]) (3). On 30 January 2020, the World Health Organization declared that the SARS-CoV-2 outbreak constituted a Public Health Emergency of International Concern, and more than 80 000 confirmed cases had been reported worldwide as of 28 February 2020 (4, 5). On 31 January 2020, the U.S. Centers for Disease Control and Prevention announced that all citizens returning from Hubei province, China, would be subject to mandatory quarantine for up to 14 days (6).

Our current understanding of the incubation period for COVID-19 is limited. An early analysis based on 88 confirmed cases in Chinese provinces outside Wuhan, using data on known travel to and from Wuhan to estimate the exposure interval, indicated a mean incubation period of 6.4 days (95% CI, 5.6 to 7.7 days), with a range of 2.1 to 11.1 days (7). Another analysis based on 158 confirmed cases outside Wuhan estimated a median incubation period of 5.0 days (CI, 4.4 to 5.6 days), with a range of 2 to 14 days (8). These estimates are generally consistent with estimates from 10 confirmed cases in China (mean incubation period, 5.2 days [CI, 4.1 to 7.0 days] [9]) and from clinical reports of a familial cluster of COVID-19 in which symptom onset occurred 3 to 6 days after assumed exposure in Wuhan (1). These estimates of the incubation period of SARS-CoV-2 are also in line with those of other known human coronaviruses, including SARS (mean, 5 days; range, 2 to 14 days [10]), MERS (mean, 5 to 7 days; range, 2 to 14 days [11]), and non-SARS human coronavirus (mean, 3 days; range, 2 to 5 days [12]).

The incubation period can inform several important public health activities for infectious diseases, including active monitoring, surveillance, control, and modeling. Active monitoring requires potentially exposed persons to contact local health authorities to report their health status every day. Understanding the length of active monitoring needed to limit the risk for missing SARS-CoV-2 infections is necessary for health departments to effectively use limited resources. In this article, we provide estimates of the incubation period of COVID-19 and the number of symptomatic infections missed under different active monitoring scenarios.

Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

Author/s: 
Chen, N, Zhou, M, Dong, X, Qu, J, Gong, F, Han, Y, Qiu, Y, Wang, J, Liu, Y, Wei, Y, Xia, J, Yu, T, Zhang, X, Zhang, L

BACKGROUND:

In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia.

METHODS:

In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020.

FINDINGS:

Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure.

INTERPRETATION:

The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection.

FUNDING:

National Key R&D Program of China.

Keywords 
coronavirus 2019-nCOV 2019 novel coronavirus pneumonia China
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