Seasonal influenza in adults: Clinical manifestations and diagnosis

INTRODUCTION — Influenza is an acute respiratory illness caused by influenza A or B viruses that occurs in outbreaks and epidemics worldwide, mainly during the winter season [1,2].

Issues related to clinical manifestations and diagnosis of seasonal influenza in adults will be reviewed here. Other issues related to seasonal influenza in adults are discussed separately:

●(See "Influenza: Epidemiology and pathogenesis".)

●(See "Seasonal influenza in nonpregnant adults: Treatment".)

●(See "Seasonal influenza vaccination in adults".)

●(See "Seasonal influenza in adults: Role of antiviral prophylaxis for prevention".)

●(See "Seasonal influenza and pregnancy".)

●(See "Infection control measures for prevention of seasonal influenza".)

Issues related to avian influenza are discussed separately. (See "Avian influenza: Epidemiology and transmission" and "Avian influenza: Clinical manifestations and diagnosis" and "Avian influenza: Treatment and prevention".)

TRANSMISSION — Issues related to influenza virus transmission are discussed separately. (See "Infection control measures for prevention of seasonal influenza", section on 'Transmission'.)

Patients with signs and symptoms of influenza should be queried regarding exposure to birds; in the setting of relevant epidemiologic criteria, evaluation for avian influenza may also be warranted. (See "Avian influenza: Clinical manifestations and diagnosis", section on 'Whom to test'.)

CLINICAL MANIFESTATIONS — Both influenza A and B viruses can cause illnesses ranging from mild to severe.

Uncomplicated illness

●Incubation period − The typical incubation period is one to four days (average two days) [3,4]. The time between onset of illness among household contacts (known as the serial interval) is three to four days [5].

●Typical signs and symptoms − Influenza characteristically begins with the abrupt onset of fever, nonproductive cough, and myalgia. Other common symptoms include including malaise, sore throat, nausea, nasal congestion, and headache [6-9].

In some cases, the onset of illness is so abrupt that patients can recall the precise time at which symptoms began. Fever usually ranges from 37.8 to 40.0°C (100 to 104°F) but can be as high as 41.1°C (106°F) [10,11].

Gastrointestinal symptoms such as vomiting and diarrhea are usually not part of influenza in adults but can occur in 10 to 20 percent of children.

●Subtle findings in adults >65 years and immunosuppressed patients – Patients in these groups may present without fever and with fewer typical symptoms (eg, absence of fever or myalgias) than other patients; however, older adults are more likely to have altered mental status [2,11,12].

Typical findings such as sore throat, myalgias, and fever may be absent, and generalized symptoms such as anorexia, malaise, weakness, and dizziness may predominate.

Other less common presentations of influenza include afebrile respiratory illness (similar to the common cold) or illness with systemic signs and symptoms in the absence of respiratory tract involvement.

●Variability with influenza strain – The spectrum of clinical manifestations and the severity of infection can vary with different influenza strains. As an example, vomiting and diarrhea were common among adults during the H1N1 influenza pandemic (2009 to 2010) [13]. In addition, an unusually high number of cases of parotitis was reported during the 2014 to 2015 influenza season; more than half of patients had positive tests for influenza A H3N2 [14-19].

Among vaccinated individuals, clinical manifestations may be similar but less severe.

●Physical findings − Physical findings generally are few. The patient may appear hot and flushed; oropharyngeal abnormalities other than hyperemia are uncommon, even with complaints of severe sore throat. Mild cervical lymphadenopathy may be present and is more common in younger patients. Physical examination of the lungs is generally unremarkable.

●Laboratory findings − Laboratory findings are generally not helpful in making the diagnosis of influenza. Leukocyte counts are normal or low early in the illness but may become elevated later [11]. White blood cell counts >15,000 cells/microL suggest bacterial superinfection.

●Radiographic findings – Chest radiography is normal in patients with uncomplicated influenza.

●Clinical course − Adults with uncomplicated influenza typically have fever and respiratory symptoms for about three days, after which time most show signs of improvement; complete recovery may take 10 to 14 days (longer in adults ≥65 years); however, some patients have persistent symptoms of weakness or fatigue for several weeks [1].

Complications — Groups at high risk for complications of influenza are summarized in the table (table 1).

Influenza can be associated with exacerbation of underlying conditions, including chronic obstructive pulmonary disease, asthma, coronary artery disease, or heart failure.

Pneumonia — Pneumonia is the most common complication of influenza [20]. Forms include secondary bacterial pneumonia, mixed bacterial and viral pneumonia, or primary influenza pneumonia. Bacterial pneumonia complicates approximately 0.5 percent of influenza cases in healthy young individuals and at least 2.5 percent of cases in older individuals and those with predisposing conditions [21]. Bacterial pneumonia typically occurs within a few days of influenza onset [22].

●Clinical presentation – Signs and symptoms suggestive of pneumonia include cough with dyspnea, tachypnea, hypoxia, and fever.

Primary influenza pneumonia should be suspected in patients with persistent symptoms and signs (including high fever and dyspnea) after three to five days of acute influenza. Patients with secondary bacterial pneumonia often demonstrate initial improvement in influenza symptoms and signs (including abatement of fever), followed by relapse of fever as well as cough productive of purulent sputum. Patients with mixed viral and bacterial pneumonia may have either a gradual progression of symptoms or a transient improvement followed by worsening.

Chest examination findings may include auditory crackles or decreased breath sounds.

●Radiographic imaging – Radiographic manifestations of primary influenza pneumonia include bilateral reticular or reticulonodular opacities, with or without superimposed consolidation (image 1) [23]. Less common manifestations include focal areas of consolidation, particularly in the lower lobes, without reticular or reticulonodular opacities. High-resolution computed tomography may demonstrate multifocal peribronchovascular or subpleural consolidation and/or ground glass opacities (image 2 and image 3) [23,24].

Radiographic findings of bacterial pneumonia are described separately. (See "Clinical evaluation and diagnostic testing for community-acquired pneumonia in adults", section on 'Chest imaging findings'.)

●Microbiology – The organisms most commonly implicated in secondary bacterial pneumonia among patients with influenza are Streptococcus pneumoniae, Staphylococcus aureus (both methicillin sensitive and methicillin resistant), and group A Streptococcus [25]. Less common coinfecting bacteria include Pseudomonas aeruginosa, Haemophilus influenzae, Klebsiella pneumoniae, Moraxella catarrhalis, and Escherichia coli.

The approach to evaluation of patients with influenza and suspected pneumonia is described below. (See 'Additional diagnostic evaluation' below.)

Cardiac complications — Influenza infection has been associated with cardiac complications including myocardial infarction (MI), heart failure, myositis, myocarditis, and pericarditis:

●Transient electrocardiographic (ECG) changes – ECG changes are frequently observed in patients with influenza; such findings are usually attributable to underlying cardiac disease rather than viral infection. However, transient ECG changes have also been observed in patients with acute influenza in the absence of pre-existing cardiovascular disease [26].

●Acute myocardial infarction (MI) – Several studies have shown an association between influenza and acute MI [27-30]:

•In a cross-sectional study including more than 80,000 adults with influenza, nearly 12 percent had an acute cardiovascular event; the most common events were acute heart failure (aHF) and acute ischemic heart disease (aIHD) [27]. Factors associated with increased risk for these events included older age, tobacco use, underlying cardiovascular disease, diabetes, and renal disease. Among study patients hospitalized with influenza, those who were vaccinated were significantly less likely to develop aHF (risk ratio 0.86, 95% CI 0.80-0.92) and aIHD (risk ratio 0.80, 95% CI 0.74-0.87) than those who were unvaccinated. While the study was not designed to assess the effectiveness of influenza vaccination for preventing influenza or associated complications, these findings emphasize the importance of influenza vaccination as secondary prevention for acute cardiovascular events.

•In another study including 364 hospitalizations for acute MI within one year before and one year after a positive test result for influenza, 20 occurred during the ‘risk interval’ (first seven days after respiratory specimen collection) and 344 occurred during the "control interval" (one year before and one year after the risk interval) [28]. The incidence ratio of an admission for acute MI during the risk interval (compared with the control interval) was 6.05 (95% CI 3.86-9.50). No increased incidence was observed after day 7. Incidence ratios for acute MI within seven days after detection of influenza B, influenza A, respiratory syncytial virus, and other viruses were 10.11, 5.17, 3.51, and 2.77, respectively.

●Myocarditis and pericarditis – Myocarditis and pericarditis are rare complications of influenza [29,30]. In one study of fatal cases of influenza B infection, myocardial injury was observed in 20 of 29 patients (69 percent) with cardiac specimens available for histology; 10 of these had unequivocal myocarditis [31]. No viral antigens were detected immunohistochemistry, suggesting that myocardial injury is not a direct effect of the virus.

Central nervous system involvement — Influenza has been associated with a broad range of neurologic complications; these include seizures, encephalopathy, encephalitis, cerebrovascular accident, acute disseminated encephalomyelitis, and Guillain-Barré syndrome (GBS) [32-36].

In a case-control study including of GBS cases recorded in the United Kingdom General Practice Research Database between 1990 and 2005, the relative incidence of GBS within 90 days of an influenza-like illness was 7.35 (95% CI 4.36-12.38); the greatest relative incidence was within 30 days (16.64, 95% CI 9.37-29.54) [37]. In contrast, no evidence of an increased risk for GBS within 90 days after seasonal influenza vaccine was observed (relative incidence 0.76, 95% CI 0.41-1.40).

The pathogenesis of the central nervous system involvement associated with influenza remains poorly understood. (See "Guillain-Barré syndrome in adults: Pathogenesis, clinical features, and diagnosis", section on 'Infection'.)

Myositis and rhabdomyolysis — Musculoskeletal complications of influenza include severe myositis and rhabdomyolysis; these occur more frequently in children than adults [38]. While myalgias are a prominent feature of influenza, true myositis is less common.

The hallmark of acute myositis is extreme muscle tenderness, most commonly involving the lower extremities. In severe cases, muscle swelling and bogginess may be observed.

Laboratory findings may include elevated serum creatine phosphokinase; myoglobinuria with associated renal failure has also been described [39,40]. (See "Rhabdomyolysis: Clinical manifestations and diagnosis".)

The pathogenesis of the myositis is not well understood; isolation of influenza virus from muscle has been described [41]. (See "Overview of viral myositis".)

Multisystem organ failure — Critically ill patients may present with multiorgan failure, shock, and sepsis. Respiratory failure, acute respiratory distress syndrome, and refractory hypoxemia may occur, as well as acute kidney injury and renal failure [1]. Levels of hepatic aminotransferases may be elevated but liver failure is rare.

Concomitant infection — Forms of concomitant infection among patients with influenza include pneumonia, bacteremia, meningitis, and aspergillosis. Evaluation for concomitant infection is warranted for patients with influenza who remain febrile for more than three to five days, develop fever after defervescence, or demonstrate worsening symptoms.

●Issues related to pneumonia are discussed above. (See 'Pneumonia' above.)

●Bacteremia and toxic shock syndrome associated with S. aureus or S. pyogenes infection in the setting of influenza has been described [42]. (See "Staphylococcal toxic shock syndrome" and "Invasive group A streptococcal infection and toxic shock syndrome: Epidemiology, clinical manifestations, and diagnosis".)

●An association between meningococcal meningitis and influenza has been described [43]. (See "Clinical manifestations of meningococcal infection" and "Diagnosis of meningococcal infection".)

●Invasive pulmonary aspergillosis among patients with influenza admitted to the intensive care unit has been reported [44,45]. (See "Epidemiology and clinical manifestations of invasive aspergillosis" and "Diagnosis of invasive aspergillosis" and "Treatment and prevention of invasive aspergillosis".)

Other complications — Other complications of influenza include parotitis, bronchitis, sinusitis, and reactive airway disease [2].

Influenza can also exacerbate underlying conditions, including chronic obstructive pulmonary disease, asthma, coronary artery disease, and heart failure.

DIAGNOSIS — The Infectious Diseases Society of America (IDSA) published updated guidelines on the diagnosis and management of influenza in 2018 [2]. The United States Centers for Disease Control and Prevention (CDC) has also published guidance documents on the diagnosis of influenza [46-48]. Our recommendations are generally in keeping with those of the IDSA and CDC.

Diagnosis of influenza

Clinical approach — − The diagnosis of influenza should be suspected in patients with abrupt onset of fever, cough, and myalgia when influenza virus is circulating. Other symptoms, such as malaise, sore throat, nausea, nasal congestion, and headache, are common in the setting of influenza as well as some other viral illnesses.

Among adults ≥65 years and immunocompromised patients, influenza should also be suspected during an influenza outbreak in the setting of atypical systemic symptoms, with or without fever.

Among adults <65 years with acute febrile respiratory illness who are not at high risk for influenza complications (table 1), do not require hospital admission, and have undergone diagnostic evaluation for coronavirus disease 2019 (COVID-19), a clinical diagnosis of influenza may be made during influenza season based on clinical manifestations; in such cases, influenza testing is not required to confirm a clinical diagnosis [49,50].

For sporadic cases of influenza-like illness, there is more urgency to establish a definitive diagnosis, especially with the emergence of novel viral pathogens such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Middle East respiratory syndrome coronavirus. Sporadic cases cannot be differentiated from other respiratory virus infections on clinical grounds alone.

Whom to test

●Indications − Testing for influenza is warranted if the results will influence clinical management decisions (such as antiviral or antimicrobial therapy, further diagnostic evaluation, prophylaxis for high-risk contacts, and/or infection control interventions) or public health activity (such as interventions for outbreak management) [2]. (See "Seasonal influenza in nonpregnant adults: Treatment" and "Seasonal influenza in adults: Role of antiviral prophylaxis for prevention".)

Detection of influenza virus can reduce unnecessary testing for other etiologies, reduce inappropriate antibiotic use, improve the effectiveness of infection prevention and control measures, and increase the appropriate use of antiviral medications [2].

However, test results should not delay initiation of empirical antiviral treatment or implementation of infection prevention measures.

The decision of whether to test should not be influenced by influenza vaccination status; the influenza vaccine affords variable protection against influenza virus infection.

●When influenza virus is circulating – During influenza season, individuals who warrant testing include [2]:

•Patients who are immunocompromised or at high risk for complications (table 1) presenting with influenza-like illness, pneumonia, or nonspecific respiratory illness (eg, cough without fever)

•Patients with acute respiratory symptoms (with or without fever), and either exacerbation of a chronic medical condition (such as asthma, chronic obstructive pulmonary disease, or heart failure) or an influenza complication (such as pneumonia)

•Hospitalized patients with either acute respiratory symptoms (with or without fever) or exacerbation of a chronic medical condition (such as asthma, chronic obstructive pulmonary disease, or heart failure)

●When influenza virus is not circulating − When influenza virus is not circulating, testing for the groups outlined above warrants consideration in the setting of relevant epidemiologic exposure (eg, exposure to a person diagnosed with influenza, an influenza outbreak, an outbreak of respiratory illness of uncertain cause, or recent travel in an area with known influenza activity).

Choice of assay — Several assays are available for diagnosis of seasonal influenza (table 2) [2,46-48]:

●Molecular assays − The preferred tool for diagnosis of influenza is a molecular assay (nucleic acid amplification test), given its high sensitivity and specificity.

Conventional reverse transcription polymerase chain reaction (RT-PCR) assays (turnaround time one to eight hours) are preferred, if available; these are the most sensitive and specific test for diagnosis of influenza virus infection. Conventional assays can distinguish between influenza A and B, as well as influenza A subtypes.

Multiplex RT-PCR assays, capable of detecting influenza as well as other pathogens (including SARS-CoV-2 and bacterial pneumonia), are also available. Such assays are especially useful for immunocompromised patients and patients requiring hospitalization or during periods when both influenza and SARS-CoV-2 are circulating. (See "Clinical evaluation and diagnostic testing for community-acquired pneumonia in adults", section on 'Multiplex molecular assays'.)

Rapid molecular tests (turnaround time 15 to 30 minutes, at the point of care) may be used as an alternative to conventional RT-PCR. Rapid molecular assays can distinguish between influenza A and B, but they cannot differentiate among influenza A subtypes.

●Antigen detection assays − An alternative diagnostic test for influenza is an antigen detection assay, which includes rapid tests and immunofluorescence assays. These assays have low to moderate sensitivity but high specificity.

Negative antigen test results should be interpreted with caution; false-negative results are common [47]. For this reason, antigen detection assays should not be used in hospitalized patients unless molecular assays are unavailable [2]. In addition, antiviral therapy should not be discontinued based on negative antigen test results.

Follow-up testing with a molecular assay is warranted in the following circumstances [2,47,48]:

•Patients with a negative antigen test in the setting of high community influenza activity and clinical indication for laboratory confirmation of infection. (See 'Whom to test' above.)

•Patients with a positive antigen test in the setting of low community influenza activity, given the possibility of a false-positive result.

•Patients with recent exposure to pigs or poultry, in the setting of concern for infection with a novel influenza A virus.

●Viral culture − Viral culture is a tool for public health surveillance but does not yield timely results for clinical management.

●Serologic testing − There is no role for routine serologic testing given the need for acute and convalescent serum specimens.

Specimen collection — Specimens should be obtained as soon after illness onset as possible, preferably within four days of symptom onset [2].

Nasopharyngeal specimens are preferred over other specimens to optimize virus detection. A video demonstrating the proper technique for nasopharyngeal specimen collection can be found at the New England Journal of Medicine website.

If nasopharyngeal specimens are not available, nasal and throat swab specimens should be collected and combined for testing. If it is possible to obtain only one specimen, nasal swab is preferred.

Flocked swabs (with fibers projecting outward) should be used rather than nonflocked swabs, to increase diagnostic yield [51]. Swabs should be immersed in antibiotic-containing transport fluid immediately after collection.

For ventilated patients with negative test results from upper respiratory tract specimens, endotracheal aspirate or bronchoalveolar lavage fluid specimens should be obtained for testing. Influenza virus replication in the lower respiratory tract may be greater and more prolonged than in the upper respiratory tract.

Respiratory specimens for influenza virus testing should be transported on ice and then refrigerated.

There is no role for testing from nonrespiratory sites such as serum, urine, stool, or cerebrospinal fluid.

Antiviral resistance — Evaluation for antiviral resistance should be pursued for patients in the following circumstances [2]:

●Patients who develop influenza infection while receiving or immediately following receipt of postexposure prophylaxis with a neuraminidase inhibitor or baloxavir.

●Immunocompromised patients and patients with severe influenza who remain ill despite treatment with a neuraminidase inhibitor or baloxavir, with evidence of persistent influenza virus replication (demonstrated by persistently positive RT-PCR or viral culture results after 7 to 10 days of antiviral therapy).

●Patients with persistent symptoms of influenza who were treated with subtherapeutic dosing of a neuraminidase inhibitor or baloxavir.

In such cases, a respiratory sample should be sent to the state or regional laboratory for resistance testing, where phenotypic and/or genotypic assays are performed.

Issues related to antiviral drug resistance are discussed further separately. (See "Antiviral drugs for influenza: Pharmacology and resistance".)

Additional diagnostic evaluation — Further diagnostic evaluation is warranted in patients with influenza and:

●Signs and symptoms suggestive of pneumonia (cough with dyspnea, tachypnea, hypoxia, and fever)

●Abnormalities on lung auscultation

●Persistent fever for >3 to 5 days

●Development of fever after initial defervescence

●Worsening symptoms

In such patients, we obtain chest radiography, COVID-19 testing, sputum Gram stain and culture, blood cultures (ideally before administration of antibiotics), nasal methicillin-resistant S. aureus PCR, S. pneumoniae urine antigen, and Legionella testing. For patients with severe illness, we obtain bronchoscopic specimens for microbiologic testing when feasible. (See "Clinical evaluation and diagnostic testing for community-acquired pneumonia in adults".)

DIFFERENTIAL DIAGNOSIS

●Respiratory viral infection − Signs and symptoms of influenza frequently overlap with those of other respiratory viral infections and may be clinically indistinguishable in the absence of diagnostic testing.

•Severe acute respiratory syndrome coronavirus 2/COVID-19 – It can be difficult to distinguish between influenza and COVID-19 based on clinical manifestations alone [52,53]. Fatigue, headache, diarrhea, olfactory disorders (such as anosmia or hyposmia), and taste disorders (such as ageusia or hypogeusia) are more common with COVID-19 than with influenza [54]. The diagnosis of COVID-19 is established via nucleic acid amplification testing or antigen testing. A positive test result for either influenza or COVID-19 does not rule out coinfection when both viruses are circulating. (See "COVID-19: Clinical features" and "COVID-19: Diagnosis".)

•Respiratory syncytial virus (RSV) – RSV causes seasonal outbreaks of respiratory tract illness throughout the world, usually during the winter season. It is common among children but is also an important and often unrecognized cause of respiratory tract infection in older adults and immunocompromised patients. The diagnosis is established via a polymerase chain reaction-based assay. (See "Respiratory syncytial virus infection: Clinical features and diagnosis in infants and children".)

•Common cold − The common cold can be caused by several different viruses, including rhinoviruses, parainfluenza, and common cold coronaviruses. In general, compared with influenza, cold symptoms are usually milder, nasal congestion is more common, and colds rarely result in serious health problems or complications. The diagnosis is based on clinical manifestations. (See "The common cold in adults: Diagnosis and clinical features" and "Epidemiology, clinical manifestations, and pathogenesis of rhinovirus infections" and "Parainfluenza viruses in adults".)

•Adenovirus – Adenoviruses are a cause of febrile illness; manifestations include upper and lower respiratory tract infection. In immunocompromised hosts, disease due to adenovirus can be severe or fatal. (See "Pathogenesis, epidemiology, and clinical manifestations of adenovirus infection".)

•Middle East respiratory syndrome coronavirus (MERS-CoV) − MERS-CoV is a coronavirus causing severe respiratory illness that emerged in 2012 in Saudi Arabia and continues to cause infections, primarily on the Arabian Peninsula. The diagnosis is established via nucleic acid amplification testing. (See "Middle East respiratory syndrome coronavirus: Clinical manifestations and diagnosis".)

●Novel influenza A virus infection − Novel influenza A viruses often originate among animals but may cause human infection. They warrant particular consideration in the setting of exposure to poultry (among whom avian influenza viruses may be circulating), to pigs (among whom swine influenza viruses may be circulating), or to an ill person with animal-associated influenza. They also warrant consideration in the setting of travel to regions with local transmission of such viruses (for example, H7N9 transmission has been associated with travel to China; H5N1 transmission has been associated with travel to Asia and the Middle East) [1]. (See "Avian influenza: Epidemiology and transmission".)

Disease severity in animals does not necessarily correlate with severity in humans. A broad spectrum of clinical manifestations has been described, including asymptomatic infection, conjunctivitis, upper respiratory tract illness, pneumonia, encephalopathy, encephalitis, and multisystem organ failure.

Novel influenza A virus infection cannot be distinguished from seasonal influenza A virus infection by clinical findings or commercially available tests; it must be diagnosed by specific influenza A molecular assays at public health laboratories.

●Bacterial pneumonia − Bacterial pneumonia may present as a complication of influenza, or independently. Patients with bacterial pneumonia typically present with fever, dyspnea, cough, and sputum production. (See "Clinical evaluation and diagnostic testing for community-acquired pneumonia in adults".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Treatment and prevention of seasonal influenza with antivirals".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Flu (The Basics)")

●Beyond the Basics topic (see "Patient education: Influenza symptoms and treatment (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Uncomplicated illness (see 'Uncomplicated illness' above):

•Typical signs and symptoms − Influenza is an acute viral respiratory illness with incubation period of one to four days. It characteristically presents with abrupt onset of fever, nonproductive cough, and myalgia. Other common symptoms include including malaise, sore throat, nausea, nasal congestion, and headache.

•Subtle findings in adults >65 years and immunocompromised patients − Patients in these groups may present without fever and with fewer typical symptoms (eg, absence of fever or myalgias) than other patients; however, older adults are more likely to have altered mental status.

Typical findings such as sore throat, myalgias, and fever may be absent, and generalized symptoms such as anorexia, malaise, weakness, and dizziness may predominate.

•Lung findings − Physical examination of the lungs is generally unremarkable, and chest radiography is normal in patients with uncomplicated influenza.

●Complicated illness − Groups at high risk for influenza complications are summarized in the table (table 1). (See 'Complications' above.)

•Pneumonia − Bacterial pneumonia typically occurs within a few days of influenza onset. Such patients often demonstrate initial clinical improvement (including abatement of fever), followed by relapse of fever and development of productive cough with purulent sputum. In contrast, patients with persistent symptoms and signs (including high fever and dyspnea) after three to five days of acute influenza are more likely to have primary viral pneumonia or mixed viral and bacterial pneumonia.

•Other complications − Other complications of influenza include cardiac complications (myocardial infarction, myocarditis, pericarditis), central nervous system complications, or myositis.

Influenza can also exacerbate underlying conditions, including chronic obstructive pulmonary disease, asthma, coronary artery disease, and heart failure.

●Diagnosis

•Clinical approach (see 'Clinical approach' above)–

-The diagnosis of influenza should be suspected in patients with abrupt onset of fever, cough, and myalgia when influenza virus is circulating (in the Northern hemisphere: October to March; in the Southern hemisphere: April to September).

-Among adults ≥65 years and immunocompromised patients, influenza should also be suspected during an influenza outbreak in the setting of atypical systemic symptoms, with or without fever.

•Indications for testing − Testing for influenza is warranted if the results will influence management decisions (such as antiviral or antimicrobial therapy, further diagnostic evaluation, prophylaxis for high-risk contacts, or infection control interventions).

During influenza season, individuals who warrant testing include (see 'Whom to test' above):

-Patients who are immunocompromised or at high risk for complications (table 1) presenting with influenza-like illness, pneumonia, or nonspecific respiratory illness (eg, cough without fever).

-Patients with acute respiratory symptoms (with or without fever), and either exacerbation of a chronic medical condition (such as chronic obstructive pulmonary disease, asthma, coronary artery disease, or heart failure) or an influenza complication (such as pneumonia).

-Hospitalized patients with either acute respiratory symptoms (with or without fever) or exacerbation of a chronic medical condition.

Test results should not delay initiation of empiric antiviral treatment or implementation of infection prevention measures.

•Choice of assay − Several assays are available for diagnosis of seasonal influenza (table 2). The preferred diagnostic tool is a molecular assay (nucleic acid amplification test), given high sensitivity and specificity. (See 'Choice of assay' above.)

•Additional evaluation – Further diagnostic evaluation is warranted in patients with influenza and:

-Signs and symptoms suggestive of pneumonia (cough with dyspnea, tachypnea, hypoxia, and fever)

-Abnormalities on lung auscultation

-Persistent fever for >3 to 5 days

-Development of fever after initial defervescence

-Worsening symptoms

In such patients, we obtain chest radiography, COVID-19 testing, sputum Gram stain and culture, blood cultures, nasal methicillin-resistant Staphylococcus aureus PCR, Streptococcus pneumoniae urine antigen, and Legionella testing. (See 'Additional diagnostic evaluation' above.)