Respiratory Virus Testing and Treatment for Healthcare Professionals

While respiratory infections have unique characteristics, it is often difficult to identify respiratory viruses based on symptoms alone. Only testing for these viruses can confirm the diagnosis. In patients with signs and symptoms of respiratory virus illness, especially those who are at risk for severe disease, act fast to test for flu, RSV, and COVID-19 and discuss treatment options.

Page Contents

Testing

Therapeutics

Influenza

Treatment
Chemoprophylaxis
Recommended Dosage and Duration of Influenza Antiviral Medications for Treatment or Chemoprophylaxis (table)

COVID-19

Treatment
Chemoprophylaxis
Outpatient Treatment Agents (For active COVID-19 infection) (table)
Prevention Agents (Not for active COVID-19 infection treatment) (table)

RSV

Cost and Coverage

Resources

Testing

Because respiratory symptoms can indicate multiple viral and bacterial etiologies, diagnostic testing for respiratory pathogens can guide clinical management, antimicrobial treatment when appropriate, and infection prevention and control measures.

Clinical testing when multiple respiratory viruses are co-circulating

While COVID-19 is common during the summer and early fall months, influenza and RSV activity typically starts increasing in the fall and peaks during winter months. When respiratory viruses are co-circulating, clinicians should test using multiplex panels (molecular assays that can detect multiple seasonal respiratory viruses) for influenza, RSV, and COVID-19. If patients test negative for influenza, RSV, and COVID-19, additional testing for other respiratory viruses with broader multiplex panels can be performed if clinically indicated.

Rapid molecular tests are recommended over rapid antigen tests due to their higher sensitivities to detect respiratory viruses. However, rapid antigen tests for influenza and COVID-19 are available for over-the-counter purchase. Rapid antigen tests can be used if molecular testing is unavailable. A positive result from an at-home antigen test is likely to be a true positive. If negative, consider in-clinic testing if indicated.

Influenza testing by rRT-PCR is recommended in situations where subtyping or sequencing may be needed, including:

Severe cases, including hospitalized, intensive care unit (ICU), and/or fatal cases, even if patients have already reported positive results from at-home tests.
Acute respiratory illness outbreaks of public health concern.
Persons with recent close contact or exposures within 10 days of symptom onset that are concerning for avian, variant, or novel influenza infection (e.g., variant influenza A (H3N2)v, (H1N2)v, or (H1N1)v, or avian influenza H5N1 or H7N9).

Specimens should be collected within 24–72 hours of symptom onset and no later than 5 days (or up to 10 days when avian, variant, or novel influenza is suspected). Specimens from ICU or hospitalized patients should be sent to a public health laboratory (PHL) as soon as possible, preferably within 24-48 hours of collection. Influenza rRT‑PCR testing and subtyping are available at CDPH‑VRDL and 24 PHLs. Providers should contact their local PHL for submission instructions. PHLs can contact CDPH‑VRDL for additional assistance when needed.

Information to assist healthcare providers about when to consider respiratory virus testing is available at Clinical Guidance for Hospitalized and Non-Hospitalized Patients When SARS-CoV-2 and Influenza Viruses are Co-Circulating | Influenza (Flu) | CDC, Information for Clinicians on Influenza Virus Testing, Respiratory Syncytial Virus for Healthcare Professionals, and Overview of Testing for SARS-CoV-2.

Therapeutics

Influenza and COVID-19 antiviral treatment can decrease the risk of serious illness and hospitalization in those at higher risk for severe disease. The greatest benefits are observed when starting antivirals as soon as possible. For disease specific information, please see the following on Influenza, COVID-19, and RSV:

Influenza:

Treatment

Antiviral medications can be used to treat influenza, and some can be used to prevent influenza. Influenza antivirals are recommended in hospitalized patients, outpatients at higher risk for severe disease, and patients who may transmit the virus to high-risk contacts.

Do not delay treatment while waiting for test results if influenza is suspected. Treat immediately with oseltamivir (available orally as a generic version or under the trade name Tamiflu®) or single-dose baloxavir (available orally as a generic version or under the trade name Xofluza®) if indicated; consider in-clinic administration where possible.

See the Don't Delay, Start Antiviral for Suspected Influenza Immediately in Outpatients clinical flow chart below for when to start oseltamivir or baloxavir antivirals for suspected or confirmed influenza cases in the outpatient setting.

For outpatients:

At increased risk for severe disease: oseltamivir* or baloxavir^†, as soon as possible and ideally within 48 hours of symptom onset.
With progressive or severe disease (such as pneumonia or exacerbation of chronic underlying medical conditions): oseltamivir, regardless of time since onset
Not at increased risk for severe disease: treatment within 48 hours of symptom onset may be considered for symptomatic outpatients.

Treatment regardless of symptom duration may be considered for symptomatic outpatients who are close contacts of individuals at high risk for severe disease.

For hospitalized patients: oseltamivir, as soon as possible, regardless of symptom onset. See IDSA guidelines for recommendations in hospitalized patients.

There are two additional FDA approved antivirals for influenza: zanamivir (available inhaled, trade name Relenza®), and peramivir (available IV, trade name Rapivab®). These are largely reserved for more specialized clinical cases. Providers should consider involving an infectious diseases specialist if using these medications.

*Initial doses of oseltamivir may cause nausea and/or emesis. Administer with food if possible.
†Clinical trials demonstrated that one dose of baloxavir is effective at reducing influenza hospitalization risk, symptom duration, hospitalization duration, and household transmission. Baloxavir has fewer side effects than oseltamivir, which is taken twice a day for 5 days, and greater clinical efficacy in influenza B illness. While the upfront cost of baloxavir is higher than that of oseltamivir, modeling studies indicate that it is cost-effective compared with oseltamivir. However, baloxavir has been associated with treatment-emergent antiviral resistance. In addition, baloxavir is not recommended for those under 5 years of age, pregnant or ≤2 week postpartum individuals, breast-feeding individuals, immunocompromised patients, or hospitalized or severe cases; oseltamivir is first line treatment in such patients.

Don't Delay, Start Antiviral for Suspected Influenza Immediately in Outpatients

Chemoprophylaxis

Providers may also consider seasonal influenza pre-exposure prophylaxis (PrEP) with oseltamivir or zanamivir and post-exposure prophylaxis (PEP) with oseltamivir or baloxavir in:

Select noninstitutionalized individuals at very high risk for infection who are unvaccinated or in whom vaccination is expected to have low effectiveness
Unvaccinated close contacts of these individuals.

For post-exposure prophylaxis recommendations in institutionalized patients, see Recommendations for Prevention and Control of COVID-19, Influenza, and Other Respiratory Viral Infections in California Skilled Nursing Facilities (PDF) and CDC Influenza Antiviral Medications: Summary for Clinicians.

Recommended Dosage and Duration of Influenza Antiviral Medications for Treatment or Chemoprophylaxis

Antiviral Agent	Use	Children	Adults
Oral Oseltamivir	Treatment (5 days)¹	If younger than 1 yr old²: 3 mg/kg/dose twice daily^3,4 If 1 yr or older, dose varies by child’s weight: 15 kg or less, the dose is 30 mg twice a day >15 to 23 kg, the dose is 45 mg twice a day >23 to 40 kg, the dose is 60 mg twice a day >40 kg, the dose is 75 mg twice a day	75 mg twice daily
	Chemoprophylaxis (7 days)⁵	If child is younger than 3 months old, use of oseltamivir for chemoprophylaxis is not recommended unless situation is judged critical due to limited data in this age group. If child is 3 months or older and younger than 1 yr old²: 3 mg/ kg/dose once daily³ If 1 yr or older, dose varies by child’s weight: 15 kg or less, the dose is 30 mg once a day >15 to 23 kg, the dose is 45 mg once a day >23 to 40 kg, the dose is 60 mg once a day >40 kg, the dose is 75 mg once a day	75 mg once daily
Inhaled Zanamivir⁶	Treatment (5 days)	10 mg (two 5-mg inhalations) twice daily (FDA approved and recommended for use in children 7 yrs or older)	10 mg (two 5-mg inhalations) twice daily
	Chemoprophylaxis (7 days)⁵	10 mg (two 5-mg inhalations) once daily (FDA approved for and recommended for use in children 5 yrs or older)	10 mg (two 5-mg inhalations) once daily
Intravenous Peramivir⁷	Treatment (1 day)¹	(6 months to 12 yrs of age) One 12 mg/kg dose, up to 600 mg maximum, via intravenous infusion for a minimum of 15 minutes (FDA approved and recommended for use in children 6 months or older)	(13 yrs and older) One 600 mg dose, via intravenous infusion for a minimum of 15 minutes
	Chemoprophylaxis⁸	Not recommended	N/A
Oral Baloxavir⁹	Treatment (1 day)	(5 yrs and older weighing <20 kg: single dose of 2 mg/kg by suspension; weighing 20 kg to <80 kg: single dose of 40 mg by tablet or suspension; weighing ≥80 kg: single dose of 80 mg by tablet or suspension) FDA approved and recommended for use in otherwise healthy children 5 yrs and older.	Weight <80 kg: One 40 mg dose; Weight >80 kg: One 80 mg dose⁹
	Chemoprophylaxis⁹	FDA approved for post-exposure prophylaxis for persons aged 5 years and older. Dosage is the same as for treatment.	Dosage is the same as for treatment

Source: Centers for Disease Control and Prevention: Recommended Dosage and Duration of Influenza Antiviral Medications for Treatment or Chemoprophylaxis

Abbreviations: N/A = not approved

1. Longer treatment duration may be needed for severely ill patients.

2. Oral oseltamivir is approved by the FDA for treatment of acute uncomplicated influenza within 2 days of illness onset with twice-daily dosing in people 14 days and older, and for chemoprophylaxis with once-daily dosing in people 1 year and older. Although not part of the FDA-approved indications, use of oral oseltamivir for treatment of influenza in infants less than 14 days old, and for chemoprophylaxis in infants 3 months to 1 year of age, is recommended by CDC and the American Academy of Pediatrics (Recommendations for Prevention and Control of Influenza in Children, 2023–2024).

3. This is the FDA-approved oral oseltamivir treatment dose for infants 14 days and older and less than 1 year old and provides oseltamivir exposure in children similar to that achieved by the approved dose of 75 mg orally twice daily for adults, as shown in two studies of oseltamivir pharmacokinetics in children (Kimberlin, 2013 [CASG 114], EU study WP22849, FDA Clinical Pharmacology Review). The American Academy of Pediatrics has recommended an oseltamivir treatment dose of 3.5 mg/ kg orally twice daily for infants 9-11 months old, on the basis of data which indicated that a higher dose of 3.5 mg/kg was needed to achieve the protocol-defined targeted exposure for this cohort as defined in the CASG 114 study (Kimberlin, 2013). It is unknown whether this higher dose will improve efficacy or prevent the development of antiviral resistance. However, there is no evidence that the 3.5 mg/kg dose is harmful or causes more adverse events to infants in this age group.

4. Current weight-based dosing recommendations are not appropriate for premature infants. Premature infants might have slower clearance of oral oseltamivir because of immature renal function, and doses recommended for full-term infants might lead to very high drug concentrations in this age group. CDC recommends dosing as also recommended by the American Academy of Pediatrics (Recommendations for Prevention and Control of Influenza in Children, 2023–2024): limited data from the National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group provide the basis for dosing preterm infants using their postmenstrual age (gestational age + chronological age): 1.0 mg/kg/dose, orally, twice daily, for those <38 weeks postmenstrual age; 1.5 mg/kg/dose, orally, twice daily, for those 38 through 40 weeks postmenstrual age; 3.0 mg/kg/dose, orally, twice daily, for those >40 weeks postmenstrual age.

5. Does not apply to duration for chemoprophylaxis for outbreaks in institutional settings.

6. Inhaled zanamivir is approved for treatment of acute uncomplicated influenza within 2 days of illness onset with twice-daily dosing in people aged ≥7 years, and for chemoprophylaxis with once-daily dosing in people aged ≥5 years.

7. Intravenous peramivir is approved for treatment of acute uncomplicated influenza within 2 days of illness onset with a single dose in people aged ≥6 months. Daily dosing for a minimum of 5 days was used in clinical trials of hospitalized patients with influenza (de Jong, 2014, Ison, 2014).

8. There are no data for use of peramivir for chemoprophylaxis of influenza.

9. Oral baloxavir marboxil is approved by the FDA for treatment of acute uncomplicated influenza within 2 days of illness onset in people aged ≥5 years who are otherwise healthy, or in people aged ≥12 years at high risk of developing influenza-related complications. Baloxavir marboxil (Xofluza) [package insert]. Baloxavir marboxil should not be administered with dairy products, calcium-fortified beverages, polyvalent cation-containing laxatives, antacids or oral supplements (e.g., calcium, iron, magnesium, selenium, or zinc); co-administration with polyvalent cation-containing products may decrease plasma concentrations of baloxavir which may reduce efficacy. There are no available published data from clinical trials for baloxavir treatment of influenza in non-hospitalized patients who are pregnant, immunocompromised, or have severe disease. A randomized clinical trial reported that combination neuraminidase inhibitor (primarily oseltamivir) and baloxavir for treatment of hospitalized influenza patients aged ≥12 years did not result in superior clinical benefit (time to clinical improvement) compared with neuraminidase inhibitor and placebo (Kumar, 2022). Oral baloxavir is approved by the FDA for post-exposure prophylaxis of influenza for persons aged ≥5 years within 48 hours of contact with an individual with influenza.

COVID-19:

Treatment

In individuals who are at high risk for severe disease, prescription COVID-19 antivirals can prevent serious illness including hospitalization and death.
CDPH recommends that providers prescribe nirmatrelvir/ritonavir (available orally, trade name Paxlovid®) as first-line therapy to non-hospitalized, symptomatic, eligible patients at higher risk of disease progression within 5 days of symptom onset.

Nirmatrelvir/ritonavir has extensive drug interactions. Providers should check drug-drug interactions before prescribing.

Remdesivir (available IV, trade name Veklury®), should be considered when nirmatrelvir/ritonavir is clinically contraindicated. Treatment should be started within 7 days of symptom onset.

Outpatient administration requires access to daily infusions in a center capable of providing acute care.

Molnupiravir (available orally, trade name Lagevrio®) may be considered in eligible patients if Paxlovid is clinically contraindicated and remdesivir is impractical. Treatment should be started within 5 days of symptom onset.
Molnupiravir is authorized under an emergency use authorization (EUA) that will be terminated on June 29, 2027.
For inpatient management of COVID see IDSA guidelines.

Chemoprophylaxis

Providers can consider additional preventative therapeutics:

Pemivibart (available IV, trade name Pemgarda®) may be used as COVID-19 pre-exposure prophylaxis for moderately-to-severely immunocompromised individuals ≥12 years of age who may not mount an adequate immune response to COVID-19 vaccination.

Pre-exposure prophylaxis with Pemgarda® is not a substitute for vaccination, and all individuals who can receive vaccination should do so.
Pemivibart is authorized under an emergency use authorization (EUA) that will be terminated on June 29, 2027.

Ensitrelvir (available orally, trade name Xocova®) may be used as post-exposure prophylaxis of COVID-19 within 72 hours of contact with an individual who has COVID-19 in patients ≥12 years of age whether they are high-risk or otherwise healthy.

Ensitrelvir has extensive drug interactions. Providers should check drug-drug interactions before prescribing.
Providers should assess pregnancy status in patients of childbearing potential before prescribing.
Providers should check compatibility with patient insurance plans as financial assistance programs are evolving for this new drug. For some insurance plans, a $0 co-pay card may be available. Contracts with Medi-Cal are pending. Ensitrelvir may not be accessible to all patients.

Outpatient Treatment Agents (For active COVID-19 infection)

	Nirmatrelvir/Ritonavir (Paxlovid®)	Remdesivir (Veklury®)
Who can receive	Adults 18+ with mild-to-moderate COVID-19 at high risk for progression to severe disease, hospitalization, or death. Adolescents 12-17 (40 kg+) eligible under EUA.	Hospitalized patients of any severity, and non-hospitalized adults/pediatric patients (40 kg+ or per weight-based EUA dosing) with mild-to-moderate COVID-19 at high risk for progression.
When to start	Within 5 days of symptom onset; earlier initiation improves outcomes.	Within 7 days of symptom onset.
Dosing	300 mg nirmatrelvir + 100 mg ritonavir twice daily Renal impairment: eGFR≥60: No dosage adjustment eGFR≥30 to <60: 150mg nirmatrelvir + 100mg ritonavir twice daily eGFR<30: Day 1: 300mg nirmatrelvir + 100mg ritonavir x1; Days 2-5: 150mg nirmatrelvir + 100mg ritonavir once daily	Children: <28 days, wt≥1.5kg: 2.5mg/kg day 1, then 1.25 mg/kg daily ≥28 days, wt 1.5 to <3 kg: 2.5mg/kg day 1, then 1.25 mg/kg daily ≥28 days, wt 3 to <40 kg: 5 mg/kg day 1, then 2.5mg/kg daily Wt≥40kg: 200mg day 1, then 100mg daily Adults: 200 mg IV load, then 100mg IV daily
Duration	5 days	3 days
Essential clinical considerations	Significant CYP3A4-mediated drug-drug interactions (boxed warning); screen medication list carefully. Renal dosing adjustment required for moderate impairment; not recommended if eGFR <30 mL/min. Avoid in severe hepatic impairment. Rebound symptoms can occur and do not require retreatment.	Requires infusion capability, which can limit outpatient access. Hepatic labs and prothrombin time should be checked before and during treatment. No renal dose adjustment needed, including on dialysis.

Prevention Agents (Not for active COVID-19 infection)

	Ensitrelvir (Xocova®)	Pemivibart (Pemgarda®)
Who can receive	Adults and adolescents 12+ following known contact with a person who has COVID-19.	Adults and adolescents 12+ (40 kg+) with moderate-to-severe immune compromise who are unlikely to mount an adequate response to COVID-19 vaccination. Must not have current infection or known recent exposure.
When to start	Within 72 hours of exposure.	Not applicable to acute illness; intended before any known exposure (pre-exposure prophylaxis), typically re-dosed periodically per current variant coverage.
Dosing	375mg on day 1, then 125mg daily on days 2-5	4500mg IV infusion
Duration	5 days	Single infusion over 1 hour; may repeat every 3 months
Essential Clinical Considerations	NOT authorized for treatment of active infection, only post-exposure prophylaxis. Should not be used in a symptomatic, confirmed COVID-19 patient. Providers should check compatibility with patient insurance plans.	NOT authorized for treatment of active infection or post-exposure prophylaxis, only pre-exposure prevention. Requires infusion setting due to anaphylaxis risk. Authorization is variant-dependent and subject to change if resistance emerges.

RSV:

While there is no specific treatment for RSV except in specific severely immunocompromised patient populations, there are various therapeutics for RSV prevention, especially in infants and young children, pregnant people, and older adults. For more information, see CDPH's Immunization Recommendations for RSV and AAP recommendations for RSV.

Cost and Coverage

For patients without insurance or those whose insurance plan does not cover the cost of antivirals for influenza or COVID-19, there may be patient assistance programs, discount programs, and other plans to help support access to medications at low cost or no cost.

Offer your patients support programs for covering costs of treatment:

For influenza:

Xofluza® (baloxavir) coupon to cap out-of-pocket expense at $50
Note that generic oseltamivir typically averages about $52.45 for 10 75mg capsules. With discount programs such as GoodRx, prices can drop to approximately $22.06.

For COVID-19:

In addition to vaccination, testing, and treatment, talk to your patients about respiratory virus season and advise patients to continue to follow the additional core prevention strategies found at CDPH's Respiratory Viruses Hub for the public.