Coming to Grips With a Potentially Severe Endemic Viral Respiratory Pathogen in the General Population

Legakis et al1 have reviewed 78 immunocompetent adults hospitalized with adenovirus respiratory infections at a tertiary care academic referral center and 2 affiliated community hospitals over a 2-year period. Viral infections are a common cause of human disease including severe illnesses. Certain viral diseases have long been recognized and some were even targeted with prophylactic strategies centuries ago, for example, smallpox via cutaneous vaccination. However, the minute size of viruses and inability to culture them on artificial media hindered identification compared with bacteria, fungi, and mycobacteria. Eventually viruses were identified as causes of both commonplace troublesome respiratory infections and epidemics with high morbidity and mortality.2 They can also be a component of mixed lung infections.3 Influenza pneumonia may lead to superinfections with specific bacteria4,5 and SARS-CoV-2 infection was found to predispose to certain fungal infections.6 Following introduction of natural product and synthetic antibacterial drugs, antiviral therapy lagged by decades.7 The first antiviral used clinically was topical idoxuridine for herpetic keratitis in 1963.8 Subsequent antiviral agents were often expensive, not very effective and cumbersome to use compared with antibacterial agents such as penicillin and sulfonamides. For example, ribavirin was available starting in 1986 to treat severe respiratory syncytial virus infections in children, but required aerosolized administration and involved risks to pregnant health care workers.9 Therefore, for many years, the focus on viral infections was to achieve a diagnosis allowing avoidance of antibacterial agents and reliance on symptomatic and supportive care of patients, ideally at home. Management of human viral infections improved with better diagnostic testing such as advanced tissue culture techniques. Several decades ago, progress in nucleic acid probes and polymerase chain assays promised identification of pathogens and/or antimicrobial resistance determinants in hours compared with one to several days using traditional cultures.10 This raised the possibility of laboratory diagnoses being made in the middle of the night and resulting problems communicating information to patient-facing health care staff.11 Clinicians were also confronted with proposals for large automated microarrays allowing simultaneous testing for hundreds of pathogens.12 Casting such a wide net triggered the question of what to do if 1 specimen was positive for multiple viruses and bacteria, many just commensal flora or chance bystanders.13 Improvement has continued in the practical application of viral diagnostic testing in outpatient and hospital settings. Respiratory panels for specific groupings of bacteria, mycoplasma, and viral agents are now widely available. However, choices must be made by each practice and institution regarding which pathogens are most likely to be encountered and what would be the cost-benefit of broader testing.14 Artificial intelligence may eventually allow accurate correlation of epidemiologic risk factors, presenting signs and symptoms, and laboratory findings in the real-time diagnosis of acute viral infections.15 However, an accurate and complete database of information on pathogens and illnesses must exist first. Antiviral treatment has also advanced in multiple areas—drugs effective against opportunistic viral pathogens in immunocompromised hosts, therapy focused on severe infections in populations prone to poor outcomes such as young pediatric patients, and agents effective against influenza virus in the general population during flu season.7,8 However, the COVID-19 pandemic due to the SARS-CoV-2 virus was a grim wake up call to clinicians and researchers that viruses remain an existential health threat. It should be recalled that older coronaviruses had been known for years as a cause of infections in healthy individuals that may be severe and persistent.16 Having some knowledge about these coronavirus strains and the availability of rapid diagnostic testing for them helped with a timely response to SARS-CoV-2. Prior published adenovirus case series have focused on limited populations such as children,17 the immunocompromised,18 and outbreaks developing in close quarters. While providing valuable information, the data are narrower in scope than the current study. The patients reviewed by Legakis et al1 were admitted to 3 healthcare facilities over 2 years. This group may be a better approximation of what might be expected in healthcare centers serving a general population. The study also reveals that immunocompetent adults who develop severe adenovirus respiratory infections are more like to have a history of asthma, chronic obstructive pulmonary disease, and smoking. About one-quarter of the study group overall had evidence of possible coinfection. The organisms and sites of isolation suggested a mix of suspected colonizers and significant pathogens. Data were too few to indicate that adenovirus respiratory infection predisposed to specific superinfections. However, presence of a coinfection as well as lack of fever were risk factors for poorer clinical outcome. These observations will help clinicians and health systems decide how to better approach diagnosis of adenovirus respiratory infections, which infected individuals may require more rapid and aggressive therapy, and what role antiviral agents might have in treatment of selected immunocompetent patients.