Viral Respiratory Infections: New Tools for a Rapid Diagnosis

Respiratory tract infection is one of the most common diseases in human worldwide. Many viruses are implicated in these infections, including emerging viruses, such as the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Identification of the causative viral pathogens of respiratory tract infections is important to select a correct management of patients, choose an appropriate treatment, and avoid unnecessary antibiotics use. Different diagnostic approaches present variable performance in terms of accuracy, sensitivity, specificity, and time-to-result, that have to be acknowledged to be able to choose the right diagnostic test at the right time, in the right patient. This review describes currently available rapid diagnostic strategies and syndromic approaches for the detection of viruses commonly responsible for respiratory diseases.

The Immune Response to Respiratory Viruses: From Start to Memory

Biomedical research has long strived to improve our understanding of the immune response to respiratory viral infections, an effort that has become all the more important as we live through the consequences of a pandemic. The disease course of these infections is shaped in large part by the actions of various cells of the innate and adaptive immune systems. While these cells are crucial in clearing viral pathogens and establishing long-term immunity, their effector mechanisms may also escalate into excessive, tissue-destructive inflammation detrimental to the host. In this review, we describe the breadth of the immune response to infection with respiratory viruses such as influenza and respiratory syncytial virus. Throughout, we focus on the host rather than the pathogen and try to describe shared patterns in the host response to different viruses. We start with the local cells of the airways, onto the recruitment and activation of innate and adaptive immune cells, followed by the establishment of local and systemic memory cells key in protection against reinfection. We end by exploring how respiratory viral infections can predispose to bacterial superinfection.

Management of Severe Influenza

Influenza infection causes severe illness in 3 to 5 million people annually, with up to an estimated 650,000 deaths per annum. As such, it represents an ongoing burden to health care systems and human health. Severe acute respiratory infection can occur, resulting in respiratory failure requiring intensive care support. Herein we discuss diagnostic approaches, including development of CLIA-waived point of care tests that allow rapid diagnosis and treatment of influenza. Bacterial and fungal coinfections in severe influenza pneumonia are associated with worse outcomes, and we summarize the approach and treatment options for diagnosis and treatment of bacterial and Aspergillus coinfection. We discuss the available drug options for the treatment of severe influenza, and treatments which are no longer supported by the evidence base. Finally, we describe the supportive management and ventilatory approach to patients with respiratory failure as a result of severe influenza in the intensive care unit.

Middle East Respiratory Syndrome Coronavirus

The past two decades have witnessed the emergence of three zoonotic coronaviruses which have jumped species to cause lethal disease in humans: severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2. MERS-CoV emerged in Saudi Arabia in 2012 and the origins of MERS-CoV are not fully understood. Genomic analysis indicates it originated in bats and transmitted to camels. Human-to-human transmission occurs in varying frequency, being highest in healthcare environment and to a lesser degree in the community and among family members. Several nosocomial outbreaks of human-to-human transmission have occurred, the largest in Riyadh and Jeddah in 2014 and South Korea in 2015. MERS-CoV remains a high-threat pathogen identified by World Health Organization as a priority pathogen because it causes severe disease that has a high mortality rate, epidemic potential, and no medical countermeasures. MERS-CoV has been identified in dromedaries in several countries in the Middle East, Africa, and South Asia. MERS-CoV-2 causes a wide range of clinical presentations, although the respiratory system is predominantly affected. There are no specific antiviral treatments, although recent trials indicate that combination antivirals may be useful in severely ill patients. Diagnosing MERS-CoV early and implementation infection control measures are critical to preventing hospital-associated outbreaks. Preventing MERS relies on avoiding unpasteurized or uncooked animal products, practicing safe hygiene habits in health care settings and around dromedaries, community education and awareness training for health workers, as well as implementing effective control measures. Effective vaccines for MERS-COV are urgently needed but still under development.

COVID-19 in Immunocompromised Patients: A Systematic Review

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was first identified as a novel coronavirus in Wuhan, Hubei province, central China, in December 2019, and is responsible for the 2019-to-present pandemic. According to the most recent data released by the World Health Organization, more than 200 million people have been infected by SARS-CoV-2 so far, and more than 4 million people died worldwide. Although our knowledge on SARS-CoV-2 and COVID-19 is constantly growing, data on COVID-19 in immunocompromised patients are still limited. The aim of the present systematic review is to describe clinical picture, disease severity, proposed treatment regimen, and response to vaccination in patients with different types and severity of immunosuppression.

Antiviral Treatments for Influenza

Influenza is an acute respiratory illness caused by the influenza A, B, and C viruses. It can occur in local outbreaks or seasonal epidemics, with possibility to spread worldwide in a pandemic when a novel strain with significant antigenic differences emerges. During the past years, several new drugs have become available, with different accessibility related to specific countries' approval. We have conducted a review of literature, analyzing the most recent data on efficacy and safety of drugs currently available to treat influenza, with a particular attention toward special populations. Efficacy and safety profile of neuraminidase inhibitors (oseltamivir, zanamivir, laninamivir, peramivir) and recently approved cap-dependent endonuclease inhibitor baloxavir marboxil are reported in literature, but still little information is available about special populations such as critically ill patients and patients with a history of chronic respiratory disease. Moreover, the emergence of strains with reduced or no susceptibility to current drugs is a matter of concern, suggesting the need of constant monitoring of viral variants.

Respiratory Syncytial Virus

Human respiratory syncytial virus (RSV) is a negative sense single-stranded RNA virus that can result in epidemics of seasonal respiratory infections. Generally, one of the two genotypes (A and B) predominates in a single season and alternate annually with regional variation. RSV is a known cause of disease and death at both extremes of ages in the pediatric and elderly, as well as immunocompromised populations. The clinical impact of RSV on the hospitalized adults has been recently clarified with the expanded use of multiplex molecular assays. Among adults, RSV can produce a wide range of clinical symptoms due to upper respiratory tract infections potentially leading to severe lower respiratory tract infections, as well as exacerbations of underlying cardiac and lung diseases. While supportive care is the mainstay of therapy, there are currently multiple therapeutic and preventative options under development.

Adenovirus: Epidemiology, Global Spread of Novel Types, and Approach to Treatment

Adenoviruses (AdVs) are DNA viruses that typically cause mild infections involving the upper or lower respiratory tract, gastrointestinal tract, or conjunctiva. Rare manifestations of AdV infections include hemorrhagic cystitis, hepatitis, hemorrhagic colitis, pancreatitis, nephritis, or meningoencephalitis. AdV infections are more common in young children, due to lack of humoral immunity. Epidemics of AdV infection may occur in healthy children or adults in closed or crowded settings (particularly military recruits). The vast majority of cases are self-limited. However, the clinical spectrum is broad and fatalities may occur. Dissemination is more likely in patients with impaired immunity (e.g., organ transplant recipients, human immunodeficiency virus infection). Fatality rates for untreated severe AdV pneumonia or disseminated disease may exceed 50%. More than 100 genotypes and 52 serotypes of AdV have been identified and classified into seven species designated HAdV-A through -G. Different types display different tissue tropisms that correlate with clinical manifestations of infection. The predominant types circulating at a given time differ among countries or regions, and change over time. Transmission of novel strains between countries or across continents and replacement of dominant viruses by new strains may occur. Treatment of AdV infections is controversial, as prospective, randomized therapeutic trials have not been done. Cidofovir has been the drug of choice for severe AdV infections, but not all patients require treatment. Live oral vaccines are highly efficacious in reducing the risk of respiratory AdV infection and are in routine use in the military in the United States but currently are not available to civilians.

Hantavirus

Hantaviruses are tri-segmented lipid-enveloped RNA viruses belonging to the Bunyaviridae family. Human infection corresponds to a zoonosis associated with two different clinical syndromes: hemorrhagic fever with renal syndrome that occurs in Asia and Europe and hantavirus cardiopulmonary syndrome (HCPS) that occurs in the North America, Central America and South America. The major pathogenic mechanisms in HCPS include (1) direct microvascular endothelial injury leading to increased capillary permeability and the development of noncardiogenic pulmonary edema and acute respiratory distress syndrome, and (2) exaggerated host immune response leading to secondary organ damage. The incubation period for this disease is quite long (6–39 days, median: 18 days); however, rapid progression to respiratory failure and shock can occur highlighting the importance of high index of clinical suspicion. Management revolves around high-quality supportive care. Various management and preventative strategies are currently being explored and warrant further examination to improve the overall outlook following infection with hantavirus.