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COVID-19: Natural History and Spectrum of Disease

OUTLINE Short Comparison of SARS-CoV-2 With SARS-CoV-1 and MERS-CoV, 72 Natural History, 73 Incubation Period, 73 Spectrum of COVID-19, 74 Pathogenicity and Virulence, 74 Asymptomatic Disease and Carrier Status, 75 Asymptomatic Patient Trajectories, 75 Symptomatic Patient Trajectories, 76 Demographics, 76 Pathogenesis, 76 Clinical Characteristics, 76 Respiratory and Pulmonary Manifestations, 76 Cardiovascular Manifestations, 77 Neurological Manifestations, 77 Gastrointestinal Manifestations, 78 Renal Manifestations, 78 Cutaneous Manifestations, 82 Ocular…

Immunology of COVID-19

The extraordinary global spread of SARS-CoV-2 through naïve populations provides compelling evidence of both the strengths and limitations of the human immune response: on the one hand, recognizing and eliminating a novel viral pathogen, while on the other, causing potentially lethal immunopathological conditions ( Fig. 3.1 ). The pandemic also provided a striking opportunity to understand SARS-CoV-2 pathogenesis through a lens offered by multiple clinical trials. COVID-19…

SARS-CoV-2: Structure, Pathogenesis, and Diagnosis

SARS-CoV-2 and Coronaviruses Evolutionary Origins In the last two decades, three coronaviruses have caused outbreaks of varying scales, with the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) representing the most recent threat to human health at a global level. Aside from severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), which were responsible for the first two outbreaks of…

Epidemiology of SARS-CoV-2 and COVID-19

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes a highly contagious disease called CO rona VI rus D isease 2019 (COVID-19). The virus was first reported in Wuhan city, Hubei Province of China in December 2019; in less than 3 months it spread globally and was declared a global pandemic by the World Health Organization (WHO) on March 11, 2020. By March 24, 2020, the novel…

Prevention of Fetal and Early Life Infections Through Maternal−Neonatal Immunization

Overall Principles Vaccination has been the most effective medical intervention in the modern era. Historically, the focus on vaccine development and implementation programs has been on preventing infectious diseases during infancy and early childhood. The current vaccine schedule for early childhood is replete with dozens of inoculations with an array of safe and effective vaccines that have dramatically reduced the incidence of many previously formidable childhood…

Clinical Pharmacology of Antiinfective Drugs

Effective antimicrobial treatment typically begins with empirical therapy at a dose that is most likely to cure the infection with the minimal risk of toxic effects. To select the correct dosage, clinicians need to understand and apply the principles of pharmacokinetics (PK) and pharmacodynamics (PD). This chapter will focus on basic pharmacology and the application of PK and PD principles to the most commonly used antiinfective…

Laboratory Aids for Diagnosis of Neonatal Sepsis

For years, investigators have sought a test or panel of tests able to diagnose neonatal sepsis accurately and more rapidly than is possible with the recovery of microorganisms from specimens of sterile body fluids or tissues. Although results of some studies have been encouraging, microbial isolation from blood, cerebrospinal fluid (CSF), urine, other body fluids (peritoneal, pleural, joint, middle ear), or tissues (bone marrow, liver, spleen)…

Health Care–Associated Infections in the Nursery

Neonates, especially premature neonates who require intensive medical care, are among the patients at highest risk for nosocomial or health care–associated infections (HAIs). Although the rate of HAIs varies with the specific patient population and institution, many institutions have achieved impressive reductions in the incidence of HAI over the past decade. For example, some reports from the early 2000s found that greater than 20% of critically…

Pneumocystis and Other Less Common Fungal Infections

Fungal infections, other than those caused by Candida spp., rarely are considered in the differential diagnosis for an acutely ill newborn infant because disorders of bacterial and viral etiology are vastly more common. Nevertheless, fungal infections do occur in neonates, especially in premature infants and those of very low birth weight (less than 1500 g), and can cause serious and frequently fatal disease. As with any…

Candidiasis

Candida species are important pathogens in the neonate. After a significant increase in the incidence of systemic candidiasis in neonatal intensive care (NICU) patients in the late 1990s, since 2000 the incidence has remained stable or even decreased slightly. However, this has clearly become a disease of the extremely-low-birth-weight (ELBW; birth weight ≤ 1000 g) or medically complex larger infant. Infections range from superficial colonization to…

Malaria and Less Common Protozoan and Helminth Infections

Parasitic infections are highly prevalent in many developing areas of the world and are common among pregnant women in developed countries. They may exacerbate maternal and fetal anemia, and contribute to low birth weight and poor infant survival. The placenta serves as an effective barrier, even in infections such as malaria and schistosomiasis in which systemic involvement and hematogenous spread are common. Although transplacental infections of…

Toxoplasmosis

Toxoplasma gondii is a worldwide, intracellular protozoan parasite that can infect humans and almost all warm-blooded animals. Among the fetal and neonatal pathogens, T. gondii is certainly one of the most: ▪ Widespread, because it affects one third of the world’s human population, although a wide discrepancy is observed between countries (range, 10%-80%), its prevalence is continually evolving, and it is related to regional socioeconomic parameters…

Less Common Viral Infections

Human Papillomavirus Human papillomaviruses (HPV) are the most common cause of sexually transmitted infection in the United States, with approximately 14 million new infections annually, according to the Centers for Disease Control and Prevention (CDC). These DNA viruses are the cause of condyloma acuminata (i.e., genital warts), cervical condylomata, and cervical cancer, but most infections are asymptomatic and resolve spontaneously within 2 years. More than 40…

Rubella

∗ Drs. Louis Cooper and Charles Alford, Jr., previously contributed to this chapter. § References . ‖ References . The impact of rubella virus infection and the progress made toward controlling congenital rubella infection have been well chronicled. Rubella was first recognized in the mid-18th century as a clinical entity by German researchers, who called it Rötheln . They considered it to be a modified form…

Human Parvovirus

The parvoviruses are a family of single-stranded DNA viruses that have a wide cellular tropism and broad host range, causing infection in invertebrate species and vertebrates, from insects to mammals. Although many parvoviruses are important veterinary pathogens, there are only two human pathogens in the family: human parvovirus B19 and the more recently described human bocavirus. Human bocavirus seems to be primarily a respiratory pathogen of…

Herpes Simplex Virus Infections

Neonatal herpes simplex virus infection (HSV) was identified as a distinct disease in the 1930s. The first written descriptions of neonatal HSV were attributed to Hass, who described the histopathologic findings of a fatal case, and to Batignani, who described a newborn child with HSV keratitis, During the initial decades that followed, our understanding of neonatal HSV infections was based on histopathologic descriptions of the disease,…

Hepatitis

Knowledge about the hepatotropic viruses has grown dramatically in the past century, with contributions from clinicians, molecular virologists, immunologists, and pharmacologists. Hepatotropic viruses (hepatitis A through G viruses and torque teno virus [TTV]) are not a common cause of neonatal morbidity and mortality in the developed world. When hepatitis E virus (HEV) is contracted during the second or third trimester, pregnant women are at risk of…

Enterovirus, Parechovirus, and Saffold Virus Infections

The enteroviruses, parechoviruses, and Saffold viruses are all members of the picornavirus family, a group of small, nonenveloped RNA viruses. Enteroviruses, including the polioviruses, coxsackieviruses, echoviruses, and numerically designated types, and parechoviruses constitute two distinct genera among the Picornaviridae, although Saffold viruses are members of the genus Cardiovirus, genetically related to Theiler murine encephalomyelitis virus. The enteroviruses, parechoviruses, and Saffold viruses exhibit clear differences in their…

Cytomegalovirus

Human cytomegaloviruses (HCMV) comprise a group of agents in the herpesvirus family known for their ubiquitous distribution in humans and in numerous other mammals. In vivo and in vitro infections with CMV are highly species specific and result in a characteristic cytopathology of greatly enlarged (cytomegalic) cells containing intranuclear and cytoplasmic inclusions. The strikingly large, inclusion-bearing cells with a typical owl’s eye appearance were first reported by Ribbert…

Varicella, Measles, and Mumps

The viruses that cause varicella, zoster, measles, and mumps may complicate the management of a mother, fetus, or newborn when maternal infection with one of these agents occurs during pregnancy or at term. In the United States and other countries with widespread vaccine use, most women of childbearing years are immune to measles and mumps, and there is little opportunity for exposure to these infections because…