Prospective Cohort Study

Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Infectious Diseases Society of America.

SUMMARYIn recent decades, several new diseases have emerged in different geographical areas, with pathogens including Ebola virus, Zika virus, Nipah virus, and coronaviruses (CoVs). Recently, a new type of viral infection emerged in Wuhan City, China, and initial genomic sequencing data of this virus do not match with previously sequenced CoVs, suggesting a novel CoV strain (2019-nCoV), which has now been termed severe acute respiratory syndrome CoV-2 (SARS-CoV-2). Although coronavirus disease 2019 (COVID-19) is suspected to originate from an animal host (zoonotic origin) followed by human-to-human transmission, the possibility of other routes should not be ruled out. Compared to diseases caused by previously known human CoVs, COVID-19 shows less severe pathogenesis but higher transmission competence, as is evident from the continuously increasing number of confirmed cases globally. Compared to other emerging viruses, such as Ebola virus, avian H7N9, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV-2 has shown relatively low pathogenicity and moderate transmissibility. Codon usage studies suggest that this novel virus has been transferred from an animal source, such as bats. Early diagnosis by real-time PCR and next-generation sequencing has facilitated the identification of the pathogen at an early stage. Since no antiviral drug or vaccine exists to treat or prevent SARS-CoV-2, potential therapeutic strategies that are currently being evaluated predominantly stem from previous experience with treating SARS-CoV, MERS-CoV, and other emerging viral diseases. In this review, we address epidemiological, diagnostic, clinical, and therapeutic aspects, including perspectives of vaccines and preventive measures that have already been globally recommended to counter this pandemic virus.

Coronavirus Disease 2019–COVID-19

Since the first antiviral drug, idoxuridine, was approved in 1963, 90 antiviral drugs categorized into 13 functional groups have been formally approved for the treatment of the following 9 human infectious diseases: (i) HIV infections (protease inhibitors, integrase inhibitors, entry inhibitors, nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, and acyclic nucleoside phosphonate analogues), (ii) hepatitis B virus (HBV) infections (lamivudine, interferons, nucleoside analogues, and acyclic nucleoside phosphonate analogues), (iii) hepatitis C virus (HCV) infections (ribavirin, interferons, NS3/4A protease inhibitors, NS5A inhibitors, and NS5B polymerase inhibitors), (iv) herpesvirus infections (5-substituted 2'-deoxyuridine analogues, entry inhibitors, nucleoside analogues, pyrophosphate analogues, and acyclic guanosine analogues), (v) influenza virus infections (ribavirin, matrix 2 protein inhibitors, RNA polymerase inhibitors, and neuraminidase inhibitors), (vi) human cytomegalovirus infections (acyclic guanosine analogues, acyclic nucleoside phosphonate analogues, pyrophosphate analogues, and oligonucleotides), (vii) varicella-zoster virus infections (acyclic guanosine analogues, nucleoside analogues, 5-substituted 2'-deoxyuridine analogues, and antibodies), (viii) respiratory syncytial virus infections (ribavirin and antibodies), and (ix) external anogenital warts caused by human papillomavirus infections (imiquimod, sinecatechins, and podofilox). Here, we present for the first time a comprehensive overview of antiviral drugs approved over the past 50 years, shedding light on the development of effective antiviral treatments against current and emerging infectious diseases worldwide.

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Approved Antiviral Drugs over the Past 50 Years

Best Practice Statement on Urologic Procedures and Antimicrobial Prophylaxis

This comprehensive review outlines the impact of military-relevant respiratory infections, with special attention to recruit training environments, influenza pandemics in 1918 to 1919 and 2009 to 2010, and peacetime operations and conflicts in the past 25 years. Outbreaks and epidemiologic investigations of viral and bacterial infections among high-risk groups are presented, including (i) experience by recruits at training centers, (ii) impact on advanced trainees in special settings, (iii) morbidity sustained by shipboard personnel at sea, and (iv) experience of deployed personnel. Utilizing a pathogen-by-pathogen approach, we examine (i) epidemiology, (ii) impact in terms of morbidity and operational readiness, (iii) clinical presentation and outbreak potential, (iv) diagnostic modalities, (v) treatment approaches, and (vi) vaccine and other control measures. We also outline military-specific initiatives in (i) surveillance, (ii) vaccine development and policy, (iii) novel influenza and coronavirus diagnostic test development and surveillance methods, (iv) influenza virus transmission and severity prediction modeling efforts, and (v) evaluation and implementation of nonvaccine, nonpharmacologic interventions.

Respiratory Infections in the U.S. Military: Recent Experience and Control

https://www.mayoclinicproceedings.org/article/S0025-6196(16)00148-8/pdf

Zika Virus in the Americas: A Review for Clinicians

The hallmark of human immunodeficiency virus (HIV) infection is progressive loss of CD4+ T cells in peripheral blood (PB) and lymphoid tissues (LTs) that is not fully restored with antiretroviral therapy (ART) [1–4]. HIV infection is also associated with chronic inflammation that is only partially normalized with ART [5, 6]. This chronic inflammatory state is maintained by several factors, including the direct effects of HIV replication [7], coinfections such as cytomegalovirus (and other herpes viruses) [8], and chronic damage to the gut mucosa that causes microbial translocation [9–11]. Acute and chronic inflammation associated with HIV infection leads to upregulation of transforming growth factor β in the LT, where HIV replicates and stimulates local production of collagen [12–14]. Collagen deposition into LT dramatically alters the architecture and function of the LT and ultimately causes progressive loss of naive T cells. This happens because the fibroblastic reticular network that produces interleukin 7 (important for naive T-cell homing and survival) is replaced by collagen [13, 15–17]. Potent and sustained suppression of HIV replication with ART reduces immune activation, but the degree to which LT pathologies are reversed and tissue architecture is restored is unknown.

A subset of HIV-infected individuals called elite controllers have durable control of HIV in the absence of therapy, in that their plasma viral load is maintained at <50 copies/mL [18]. The response by HIV-specific mature CD8+ T cells is an important mechanism contributing to elite control [19–21]; however, virus replication and immune activation persist [18, 22, 23]. Clinical conditions attributable to immune activation and inflammation that are increasing in incidence among ART-treated persons (ie, coagulopathy and vascular disorders [24–26]) are also seen in elite controllers [27, 28]. We hypothesized that individuals exhibiting elite control of virus replication would have inflammatory damage to lymphoid structures but that the degree to which the tissue architecture was damaged would be less, given the lower burden of virus and decreased amount of immune activation, compared with persons without elite control. To test this hypothesis, we obtained a series of rectal tissues from elite controllers, HIV-infected patients requiring ART to control virus replication, HIV-infected persons who were not receiving ART, and people without HIV infection.

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Lymphoid Fibrosis Occurs in Long-Term Nonprogressors and Persists With Antiretroviral Therapy but May Be Reversible With Curative Interventions

https://www.labmed.theclinics.com/article/S0272-2712(15)00103-1/pdf

Joyce L. Sanchez

Papers

Best Practice Statement on Urologic Procedures and Antimicrobial Prophylaxis

Respiratory Infections in the U.S. Military: Recent Experience and Control

Zika Virus in the Americas: A Review for Clinicians

Lymphoid Fibrosis Occurs in Long-Term Nonprogressors and Persists With Antiretroviral Therapy but May Be Reversible With Curative Interventions

Clinical Manifestations and Treatment of Lyme Disease