R ESPIRATORY V IRUSES ARE C OMMON ! Coinfection CAP HAP 5% - - PDF document

RESPIRATORY VIRAL INFECTIONS

Jennifer Babik, MD, PhD Associate Clinical Professor Division of Infectious Diseases, UCSF

Infectious Diseases in Clinical Practice February 2020

DISCLOSURES

• I have no disclosures.

LEARNING OBJECTIVES

By the end of this talk, you will be able to:

• 1. Recognize the key clinical and radiologic features of

influenza and its complications

• 2. Describe the different diagnostic tests and antiviral
• ptions for influenza
• 1. Recognize the salient features and treatment options

for the other common respiratory viruses

ROAD MAP

• Brief Introduction to Respiratory Viruses
• Influenza
• Clinical, Diagnosis, Treatment
• Quick Takes on other Respiratory Viruses
• RSV
• Parainfluenza
• Human metapneumovirus
• Adenovirus
• Rhinovirus

ROAD MAP

• Brief Introduction to Respiratory Viruses
• Influenza
• Clinical, Diagnosis, Treatment
• Quick Takes on other Respiratory Viruses
• RSV
• Parainfluenza
• Human metapneumovirus
• Adenovirus
• Rhinovirus
• Swine Flu

RESPIRATORY VIRUSES ARE COMMON!

Most common viruses isolated (in order): 1. Rhinovirus 2. Influenza, parainfluenza, metapneumovirus, RSV, coronavirus 3. Adenovirus

Jain et al, NEJM 2015, 373:415. Shorr et al, Resp Med 2017, 122:76. Micek et al, Chest 2016, 150:1008.

No pathogen 62% Viral 22% Bacterial 11% Coinfection 5%

CAP

No pathogen 54% Viral 23% Bacterial 23%

HAP

RESPIRATORY VIRUS SEASONALITY

Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec

Influenza RSV Coronavirus Human Metapneumovirus Adenovirus Rhinovirus Parainfluenza‐3

ROAD MAP

• Brief Introduction to Respiratory Viruses
• Influenza
• Clinical, Diagnosis, Treatment
• Quick Takes on other Respiratory Viruses
• RSV
• Parainfluenza
• Human metapneumovirus
• Adenovirus
• Rhinovirus

INFLUENZA

From the Italian word meaning influence because it was thought the stars and planets caused/controlled disease

Fort Riley, Kansas, during the 1918 pandemic

ANNUAL BURDEN OF INFLUENZA

Deaths 12,000‐61,000 Hospitalizations 140,000‐810,000 Illnesses 9 million ‐ 45 million $10 billion in direct medical costs

CDC, Disease Burden of Influenza, 2020.

Mortality rate

• f ~0.1%

INFLUENZA TYPES

Influenza A

• Multiple subtypes (e.g. H1N1)
• Reassortment  drastic

change in H +/‐ N  pandemic

• Currently circulating:
• Seasonal H1N1
• Seasonal H3N2
• Pandemic H1N1

Influenza B

• No subtypes
• No reassortment (b/c few

related viruses in animals)

• ~25% of circulating influenza

but wide annual variation

Su et al, Clin Infect Dis 2014, 59:252. Glezen, Clin Infect Dis 2014, 59:1525.

Influenza A and B are clinically indistinguishable

2019‐20 SEASON: MIX OF VIRUSES SO FAR

https://www.cdc.gov/flu/weekly/index.htm pandemic H1N1 (influenza A) Influenza B

SEASONAL VS PANDEMIC INFLUENZA

Demographics

• Younger
• Obese
• Pregnant
• Have no comorbidities

Lee et al, J Infect Dis 2011, 203:1739. Reed et al, Clin Infect Dis 2014, 59:166.

Complications

• Need ICU admission
• Need intubation
• Have PNA, septic shock
• Have higher mortality?

(conflicting results) Hospitalized patients with pandemic H1N1 are more likely to be:

HOW BAD IS FLU SEASON THIS YEAR (HOSPITALIZATIONS)?

https://www.cdc.gov/flu/weekly/index.htm 2019‐20 10,000 deaths so far (average)

NEW IDSA GUIDELINES FOR INFLUENZA

Uyeki et al, Clin Infect Dis 2018.

CASE #1

96 year old woman with COPD is admitted in March with 1 day of SOB, wheeze. No fevers or myalgias. She had the flu vaccine, and her son has a URI.

• Afebrile, HR 125, BP 90/60. WBC

11, lactate 6.

• What is your suspicion for

influenza given lack of fever?

HOW COMMON IS FEVER IN INFLUENZA IN THE ELDERLY?

• 1. 10%
• 2. 35%
• 3. 60%
• 4. 90%

CLINICAL MANIFESTATIONS OF INFLUENZA

Headache Congestion/rhinorrhea Sore throat/hoarseness Altered mental status (encephalopathy, encephalitis) Myalgia (rhabdo, myositis) Weakness Nonproductive cough Chest pain (myocarditis, pericarditis) Abdominal pain Vomiting, diarrhea Fever Chills Malaise/fatigue

Uyeki et al, Clin Infect Dis 2018.

MAKING A CLINICAL DIAGNOSIS IS HARD!

• Abrupt onset of fever + cough is >70% sensitive for flu

but signs/sx of flu are variable in different populations

Kumar et al, Clin Infect Dis 2018, 67:9 Call et al, JAMA 2005; 293:987. Apewokin et al, OFID 2014. Dugas et al, Am J Emerg Med 2015, 33:770. Miller et al, J Infect Dis 2015, 212:1604.

All Elderly Immunocompromised Fever 75% 35% 35‐70% Cough 90% 70% 50‐90%

• In the ER/inpatient setting, the

sensitivity of a provider’s clinical diagnosis for flu is only ~30‐35%

• Vaccine effectiveness usually 40‐50%, varies

based on predominant subtype

• Influenza B 54%
• Seasonal H1N1 67%
• Pandemic H1N1 61%
• H3N2 33% (good match), 23% (poor match)
• CDC/IDSA: a history of vaccination should not be used

in decision‐making about diagnostics or empiric Rx

BUT SHE GOT THE VACCINE!

CDC, Seasonal Influenza Vaccine Effectiveness, 2005‐2017. Belongia et al, Lancet ID 2016, 16:942. Uyeki et al, Clin Infect Dis 2018.

CASE #1 CONTINUED

• Rapid influenza PCR positive for influenza A H3N2
• Is this severe influenza pneumonia or does she have a

bacterial co‐infection?

• Afebrile, HR 125, BP 90/60
• WBC 11, lactate 6

THIS PATIENT’S SEPSIS IS MOST LIKELY RELATED TO:

• 1. Primary influenza pneumonia
• 2. Secondary bacterial pneumonia
• 3. Could be either

PRIMARY INFLUENZA PNEUMONIA

• Occurs in ~40% of those

hospitalized with influenza

• A severe illness!
• 20% present with sepsis
• 10% present with shock
• 50% admitted to the ICU
• 40% require mechanical ventilation
• 25% develop ARDS
• 20% mortality

Jain et al, Clin Infect Dis 2012, 54:1221. Rice et al, Crit Care Med 2012, 40:1487.

Key Point

• Presentation

indistinguishable from bacterial superinfection

• No difference in

symptoms, CXR, labs

PRIMARY INFLUENZA PNA: RADIOLOGY

• Infiltrates bilateral 60‐70%, unilateral 30‐40%
• Consolidations in 75‐90%
• Interstitial thickening 60%

Jain et al, Clin Infect Dis 2012, 54:1221. Jartti et al, Acta Radiologica 2011, 52: 297. Jain et al, N Engl J Med 2009, 361:1935. Agarwal et al, AJR 2009, 193: 1488. Kang et al, J Comput Assist Tomogr 2012, 36:285

GGO predominant Consolidations + GGO Centrilobular nodules + GGO

SECONDARY BACTERIAL PNEUMONIA

• Likely responsible for most of

the deaths from the 1918 pandemic

• How common is it now?
• <3% of all cases of influenza
• 10% of all inpatients
• 20‐30% of critically ill or deaths

MMWR 2009, 58:1. Jain et al, CID 2012, 54:1221. Jain et al, NEJM 2009, 361:1935. Rice et al, Crit Care Med 2012, 40:1487. Morens et al, J Infect Dis 2008; 198:962.

SECONDARY BACTERIAL PNEUMONIA: ETIOLOGY

• Predominantly colonizers of the nasopharynx:
• S. pneumoniae ~40‐50%
• S. aureus ~30‐40% ( in critically ill)
• Group A Streptococcus 5‐25%
• Others:
• H. influenzae, other GNRs
• Atypicals: Mycoplasma, Legionella

Chertow and Memoli, JAMA 2013, 309:275. MMWR 2009, 58:1. Jain et al, Clin Infect Dis 2012, 54:1221. Jain et al, N Engl J Med 2009, 361:1935. Rice et al, Crit Care Med 2012, 40:1487.

SECONDARY BACTERIAL PNEUMONIA: PRESENTATION

• Classic:
• Period of improvement  recurrence of

symptoms 4‐7 days later

• Reality:
• Present on ~day 5 of illness without a period of

improvement

• Presentation indistinguishable from severe influenza

pneumonia (no difference in symptoms, CXR, labs)

MMWR 2009, 58:1. Jain et al, CID 2012, 54:1221. Jain et al, NEJM 2009, 361:1935. Rice et al, Crit Care Med 2012, 40:1487.

So how can I tell the difference between influenza PNA and bacterial PNA?

WHAT DO THE NEW IDSA GUIDELINES SAY?

• Work‐up and empirically treat bacterial coinfection in

patients with suspected/confirmed influenza who:

• Initially present with severe disease
• Deteriorate after initial improvement, particularly in those

treated with antivirals

• Fail to improve after 3‐5 days of antiviral therapy (consider)

Uyeki et al, Clin Infect Dis 2018.

WHAT ABOUT PROCALCITONIN?

• Multiple RCTs, Cochrane review 2017 of PCT use in LRTI:
• ~2.5 day reduction in Abx
•  Abx side effects
•  mortality (8.6 vs 10.0%)
• ProACT study (RCT of 1664 patients, NEJM 2018):
• No difference in Abx use, adverse effects
• ?due to low baseline Abx use in the study
• Discrimination between viral vs. bacterial infection/coinfection

(cut‐off 0.25): Sensitivity 70‐90%, NPV 80‐90%

Schuets et al, JAMA 2009, 302:1059. Pfister et al, Crit Care 2014, 18:R44. Rodriguez et al, J Infect 2016, 72:143. Self et al, Clin Infect Dis 2017, 65:183. Schuetz et al, Cochrane Database Syst Rev 2017. Huang et al, NEJM 2018, 379:236.

Bottom line: PCT may be a useful adjunct but should not replace clinical suspicion

Should PCT be used to decide if it is safe to withhold empiric antibiotics in a patient with CAP (i.e., can it distinguish viral vs bacterial CAP)?

NEW IDSA CAP GUIDELINES: USE OF PROCALCITONIN

Metlay et al, AJRCCM 2019, 200:e45. Self et al, Clin Infect Dis 2018.

Recommendation NO, if a patient has confirmed CAP you should start antibiotics irrespective of the PCT result

(strong rec, moderate quality of evidence)

Rationale

• Many of the PCT

studies looked at CAP vs URI (not viral vs bacterial CAP)

• No PCT cut‐off can

sufficiently distinguish viral vs bacterial (cut‐

• ff of ≥0.1, PCT only

~80% sensitive for bacteria)

INFLUENZA VS BACTERIAL PNA: SUMMARY

• The problem:
• Severe influenza PNA and secondary bacterial PNA look the

same clinically

• How to approach giving antibacterials?
• If severely ill  empiric ABx while cultures pending
• If mild‐moderate illness  use clinical judgment (PCT can be

adjunct)

• When to stop empiric antibiotics?
• Respiratory cultures negative (before ABx)
• Low suspicion for bacterial infection (negative or minimal

changes on CXR, low PCT)

CASE #1 CONTINUED

• She was treated with oseltamivir and 2 days of Abx
• Tenuous clinically but recovered fully, still doing well as

an outpatient.

CASE #2

A 35 year old man is admitted in January with 3 days of fever, cough and progressive respiratory distress. He is transferred from an OSH where rapid influenza antigen test in the ED was negative.

WHAT IS THE SENSITIVITY OF THE RAPID ANTIGEN TESTS?

• 1. <25%
• 2. 30‐50%
• 3. 50‐70%
• 4. >90%

DIAGNOSTIC TESTS FOR INFLUENZA

Harper et al, Clin Infect Dis 2009, 48:1003. CDC, Influenza Symptoms and the Role of Laboratory Diagnostics, 2011. Uyeki et al, Clin Infect Dis 2018.

Rapid Antigen Testing Rapid Antigen Testing

• POCT in clinics, ERs
• ~50‐70% sensitive, >90%

specific

• Cannot rule out influenza

during flu season Molecular Assays

• Most are ~95% sensitive,

specific

• Some assays can

determine influenza subtypes

• Test of choice (IDSA)

WHICH PATIENTS SHOULD BE TESTED? (IDSA)

Outpatients

• High‐risk patients with ILI,

PNA, or nonspecific resp. illness (with or w/o fever) AND

• Testing will change

management (can also treat based on clinical dx)

Inpatients

• All patients admitted with:
• Acute respiratory illness incl.

PNA (with or without fever)

• Acute worsening of a chronic

cardiopulm disease (COPD, asthma, CAD, CHF)

• ICH with undifferentiated fever
• All inpatients who develop an

acute respiratory illness while hospitalized without an alternative diagnosis

Uyeki et al, Clin Infect Dis 2018.

WHO AND WHAT ARE HIGH RISK GROUPS? (CDC/IDSA)

• High risk = increased risk for severe and fatal influenza

Uyeki et al, Clin Infect Dis 2018.

Who are these patients?

• <5 or ≥65 years old
• Chronic medical, neurologic conditions
• Immunocompromised (*highest risk)
• Pregnant, postpartum (<2wks)
• American Indians/Alaska Natives
• Obesity (BMI ≥ 40)
• Residents of chronic care facilities

CASE #2 CONTINUED

• Nasopharyngeal swab was positive by PCR for influenza A

(H3N2).

• He was treated with oseltamivir and slowly recovered.

CASE #3

A 34 year old woman is admitted in January with 5 days of fever, cough, SOB and now has severe hypoxemic respiratory failure requiring intubation and 100% FiO2.

• Febrile to 38.1˚C, WBC 15
• Nasopharyngeal swab for

influenza PCR is negative

SHOULD YOU STOP EMPIRIC OSELTAMIVIR?

• 1. Yes, the PCR is a great test
• 2. No, wait for a lower tract sample

DIAGNOSIS: SAMPLES

• Upper tract samples:
• NP swab is optimal method
• Note that shedding  after 3‐4 days
• Can be negative in up to 40% of critically ill patients with

positive lower tract samples for influenza

• If critically ill: collect upper and lower tract samples and

do not stop empiric therapy until a lower tract sample is negative (IDSA)

Lopez Roa et al, Am J Crit Care Med 2012, 186:929. Reddy et al, Open Forum Infect Dis 2016. CDC, Information on Collection of Respiratory Specimens for Influenza Virus Testing, 2018. Uyeki et al, Clin Infect Dis 2018.

CASE #3 CONTINUED

• Empiric oseltamivir was continued while awaiting a

lower tract sample

• Trach aspirate was PCR positive for influenza A

(pandemic H1N1)

• But wait, she’s had symptoms for 5 days…should she

still be treated?

WOULD YOU CONTINUE HER ANTIVIRALS?

• 1. No antivirals (she is out of the treatment window)
• 2. Oseltamivir 75mg PO bid x 5 days
• 3. Oseltamivir 150mg PO bid x 10 days
• 4. Zanamavir 10mg inhaled bid x 5 days

M2 Inhibitors

• Amantadine, rimantidine
• Influenza A only
• Widespread resistance

Matrix proteins (M1 and M2)

ANTIVIRALS

Neuraminidase Inhibitors

• Oseltamivir, Zanamivir, Peramivir
• Influenza A and B
• Drugs of choice

X

NEUROMINIDASE INHIBITORS

Drug Adult dosage Contraindications Adverse Effects Oseltamivir 75mg PO bid x 5 d (renally dose) None Nausea/vomiti ng Zanamivir 10mg INH bid x 5 d Resp disease (asthma, COPD), cannot use if intubated Bronchospasm Cough Peramivir 600mg IV x 1 (renally dose) None Diarrhea

*All given same recommendation in IDSA Guidelines but oseltamivir is the drug of choice

OSELTAMIVIR IN OUTPATIENTS

Efficacy

• Decrease in

symptom duration by ~24h

• Decrease in PNA,

hospitalizations

• RCT patients all

have symptom duration ≤ 48h

• The earlier

therapy is started  the greater the effect Cost‐effective assuming a benefit in preventing complications, hospitalizations

Kelley and Cowling, Lancet 2015, 385:1700. Dobson et al, Lancet 2015, 385:9979. Talbird et al, Am J Health‐Syst Pharm. 2009; 66:469.

Timing Cost

OSELTAMIVIR IN INPATIENTS

• Treatment of inpatients at <48hrs of symptoms:
•  mortality by 50‐65%
• But >40% of pts hospitalized with influenza present at >48h
• Multiple studies show a mortality benefit at >48hrs, even
• ut to 5‐7 days
• But earlier is better:
• Earlier treatment  lower mortality
• Earlier treatment in elderly  shorter LOS, less need for SNF

Lee and Ison, Clin Infect Dis 2012, 55:1205. Viasus et al, Chest 2011, 140:1025. Muthuri et al, J Infect Dis 2013, 207:553. Chaves et al, Clin Infect Dis 2015, 61:1807. Katzen et al, Clin Infect Dis 2019, 69:52.

WHO TO TREAT? (IDSA/CDC)

• Outpatients:
• Patients with severe or progressive illness
• Patients at high risk of complications
• Treat irrespective of duration of symptoms
• Can “consider” for healthy outpatients
• Inpatients:
• All inpatients with influenza irrespective of duration of symptoms
• For suspected cases (inpatient + outpatient), treat as early

as possible ‐ do not delay while awaiting lab confirmation

CDC Guidelines 2018. SFDPH guidelines 2018. Uyeki et al, Clin Infect Dis 2018.

PERAMIVIR (IV)

• FDA approved 2014 for adults with uncomplicated

influenza and symptoms <48hrs

• When to use?
• Any concerns for GI absorption of oseltamivir
• Note: limited data that oseltamivir is well absorbed in obese

and critically ill patients including those on CRRT and ECMO

• How to dose?
• FDA approved for a single dose in uncomplicated influenza
• ?extend out to 5 days if treating severe influenza

Whitley et al, Antivir Ther 2014, Oct 15 Epub. Kohno et al, Antimicrob Agents Chemother 2010, 54:4568. de Jong et al, Clin Infect Dis 2014, 59:e172.

BALOXAVIR

• Inhibitor of cap‐dependent flu polymerase (single oral dose)
• Capstone‐1: phase 3 RCT (baloxavir vs oseltamivir vs placebo) in 1064

healthy outpatients (age 12‐64) with influenza, symptoms <48 hours

• Baloxavir  duration of symptoms by ~26h (same as oseltamivir)

but had a more rapid  in viral load than oseltamivir

• Mutations in polymerase gene in 10% (symptom duration)
• Can it be used in patients who are high risk (Capstone‐2yes),

hospitalized patients, symptoms >48 hr, or oseltamivir resistance?

• Synergistic with oseltamivir in mouse model, used in 2 patients on

ECMO (IDWeek 2019 abstract)  this may be its place in therapy

Hayden et al, NEJM 2018, 379:913. Fukao et al JAC 2019. Ison et al, IDWeek 2018. Ntem‐Mensah et al, IDWeek 2019.

CASE #3 CONTINUED

After 5 days she remains critically ill and her influenza PCR is still positive. You decide to treat her for an additional 5 days since she is critically ill. However, even after that she remains critically ill and her PCR continues to be positive.

WHAT IS YOUR NEXT STEP?

• 1. Change to IV oseltamivir
• 2. Start vancomycin and cefepime
• 3. Change to inhaled zanamavir
• 4. Send to the DPH for resistance testing

WHAT IF MY PATIENT DOESN’T GET BETTER?

• Consider oseltamivir resistance
• Critically ill or immunocompromised patients with

persistently positive PCR after 7‐10 days of therapy

• Send to DPH or CDC
• Rare (<1‐2% of isolates over last 2 years)
• If concerned for resistance  IV zanamivir available via

urgent EIND approval from GSK and the FDA, ?baloxavir

• Consider whether PO absorption is adequate  if not,

use IV peramivir

Uyeki et al, Clin Infect Dis 2018.

HOUSEHOLD EXPOSURE CHEMOPROPHYLAXIS (CDC/IDSA)

• Indications
• <48h since exposure AND
• Unvaccinated or <2 wks from vaccination or vaccine expected to

be ineffective AND

• Patients at very high risk for complications (eg severe ICH) or

household contacts of a person at very high risk

• Note: alternative is close monitoring + early therapy
• Regimen (70‐90% effective)
• Oseltamivir or zanamavir
• Half‐dose (eg oseltamivir 75mg PO daily)
• Duration: out to 7 days after last known exposure
• Should also give vaccine

CDC, Influenza Antiviral Medications: Summary for Clinicians, updated February 2018. Fiore et al, MMWR 2011, 60:1. Uyeki et al, Clin Infect Dis 2018.

INFLUENZA TREATMENT SUMMARY

• Who to treat?
• High risk outpatients or those with severe/progressive disease
• All inpatients
• Treat as early as possible, irrespective of symptom duration, and do

not delay Rx while awaiting lab confirmation

• Which drug?
• Oseltamivir: drug of choice for most patients
• Zanamivir: only if no COPD/asthma and not intubated
• Peramivir: if need an IV option
• Baloxavir: maybe as part of combination therapy?
• How long?
• 5 days
• Can consider longer in select cases (critically ill, persistently (+)PCR)

CASE #4

A 75 year old man with no known lung disease is admitted in December for a “COPD exacerbation” due to SOB and wheezing.

• He is afebrile with a normal CXR.
• Steroids and antibiotics are started but he doesn’t

improve after 2 days.

HE MOST LIKELY HAS:

• 1. Adenovirus
• 2. RSV
• 3. Parainfluenza‐3
• 4. Cytomegalovirus

HOW WOULD YOU TREAT RSV IN THIS PATIENT?

• 1. Ribavirin
• 2. Ribavirin + IVIG
• 3. Supportive care
• 4. Prednisone

WHAT IF HE WAS A RENAL TX PATIENT WITH PNA?

• 1. Ribavirin
• 2. Ribavirin + IVIG
• 3. Supportive care
• 4. Prednisone

ROAD MAP

• Brief Introduction to Respiratory Viruses
• Influenza
• Clinical, Diagnosis, Treatment
• Quick Takes on other Respiratory Viruses
• RSV
• Parainfluenza
• Human metapneumovirus
• Adenovirus
• Rhinovirus

RSV IN ADULTS

• Clinical:
• Wheezing and dyspnea more common than flu
• URI accounts for majority of disease overall
• Mortality in elderly can approach 10%

Cesario, Clin Infect Dis 2012, 55:107. Lee et al, Clin Infect Dis 2013, 57:1069. Lee et al, Clin Infect Dis 2013, 57:1069.

RSV IN IMMUNOCOMPROMISED PATIENTS

• Bone marrow transplant:
• 30‐40% of patients with URI progress to LRTI
• Mortality rates of up to 70‐80%
• Late airflow decline, bronchiolitis obliterans
• Solid organ transplant: overall better outcomes
• Lung transplants highest risk
• Up to 20% mortality, up to 60% bronchiolitis obliterans

Cesario, Clin Infect Dis 2012, 55:107. Lee et al, Clin Infect Dis 2013, 57:1069. Lee et al, Clin Infect Dis 2013, 57:1069.

RIBAVIRIN: 3 FORMS

• Aerosolized: previously standard of care
• Toxicity: Bronchospasm, cough, dyspnea
• Isolation: Teratogenic, HCW precautions
• IV: poor outcomes, toxicity
• Oral:
• Similar outcomes as with aerosolized
• Less toxic and less $$
• Watch for hemolytic anemia

Marcelin et al, TID 2014. Foolad et al, CID 2019.

80 50 24 10 20 30 40 50 60 70 80 90

No Rx Ribavirin Ribavirin + IVIG

Mortality (%)

TREATING RSV PNA IN IMMUNOCOMPROMISED

Shah and Chemaly, Blood 2011. Khanna et al, CID 2008. Kim et al Seminars in Respiratory and Critical Care Medicine 2007.

• UCSF protocol:
• Oral ribavirin + IVIG for 2 weeks
• Which syndrome?
• In general we only treat PNA
• We only treat URI in BMT

patients <1 mo from transplant

• Which patients?
• BMT, heme malignancy, SOT
• Extrapolate to other types of

immunocompromise?

PARAINFLUENZA

• PIV‐3 most common in adults

(PIV‐1, PIV‐2  croup in kids)

• Clinical:
• Fever, cough, SOB, wheeze
• URI, bronchiolitis, bronchitis, PNA
• Can be severe in immunocompromised
• No treatment clearly effective
• BMT: No benefit with ribavirin in 2 retrospective studies
• Solid organ transplant: some case reports of success with

ribavirin, but no controls

Marx et al, Clin Infect Dis 1999, 29:134. Ustun Biol BMT 2012; Nichols Blood 2001

HUMAN METAPNEUMOVIRUS

• Clinical:
• 40‐70% are asymptomatic
• URI symptoms, cough, wheeze
• Can be severe, especially in

high risk populations

• Treatment:
• Supportive care
• Case reports of ribavirin + IVIG (like for RSV) in transplant
• But a small retrospective study and a systematic review in

BMT patients showed no benefit

Walsh et al, Arch Intern Med 2008, 168:2489. Renaud et al, Biol Blood Marrow Transplant 2013, 19:1220. Shah et al, Cancer Lett 2016, 379:100.

ADENOVIRUS

• Can cause severe PNA in ICH host,

rarely in immunocompetent

• Classic features of adenovirus infection

(pharyngitis, conjunctivitis, rash, diarrhea) may be absent

Louie et al, Clin Infect Dis 2008, 46:421. Clark et al, J Med Case Rep 2011, 5:259. Pabbaraju et al, J Clin Microbiol 2008, 46:3056.

• Diagnosis:
• Some resp viral PCR assays only ~60% sensitive for adenovirus
• If high suspicion, also send serum PCR ( sensitivity)
• Treatment: can consider cidofovir

RHINOVIRUS

• “Common cold”
• Often detected in CAP/HAP but

pathogenicity unclear

• May predispose to bacterial

superinfection

• HSCT patients with rhinovirus have

similar outcomes as those without

• Treatment: supportive

Jacobs et al, Transpl Infect Dis 2013, 15:474. Abandeh et al, Bone Marrow Transplantation 2013, 1.

TAKE‐HOME POINTS

• 1. Influenza pneumonia is common and can be severe
• 2. Rapid antigen tests cannot rule out influenza given

low sensitivity

• 3. Treat all inpatients with influenza irrespective of time
• f symptom onset
• 4. Other respiratory viruses are common in CAP and HAP

THANK YOU!

• Questions?