Multisystem Processes & Disorders

Acute viral syndromes: diagnosis and supportive care

Clinical Overview and When to Suspect Acute Viral Syndrome

— Respiratory: influenza A/B, SARS-CoV-2, RSV, rhinovirus, adenovirus, parainfluenza, hMPV

— Systemic/mononucleosis-like: EBV, CMV, acute HIV, primary HSV

— Enteric: norovirus, rotavirus (peds), enteric adenovirus

— Arboviral (travel/seasonal): dengue, Zika, chikungunya, West Nile

— Gradual prodrome with diffuse symptoms (myalgia, coryza, conjunctivitis, diarrhea)

— Absence of focal bacterial findings (no exudative tonsils with anterior nodes meeting Centor, no consolidation, no leukocytosis with left shift)

— Community outbreak context, classroom/household clustering, travel history

— Symptom evolution consistent with self-limited course over days

— Triage severity (vitals, hydration, oxygenation, mental status)

— Identify high-risk hosts (age ≥65, pregnancy, immunocompromise, chronic cardiopulmonary/renal disease, BMI ≥40)

— Decide on point-of-care testing only when result changes management

— Provide return precautions and follow-up cadence

Board pearl: On Step 3, the right answer for an uncomplicated viral URI in a healthy adult is almost always symptomatic care + reassurance + return precautions, NOT empiric antibiotics, chest imaging, or routine viral PCR panels. Reserve testing for outcomes-changing decisions (antiviral eligibility, infection control, pregnancy, immunocompromise).

Definition: Acute viral syndromes are self-limited, systemic illnesses caused by respiratory, enteric, or arboviral pathogens producing fever, malaise, myalgia, headache, GI upset, or upper respiratory symptoms — typically lasting 3–10 days.

Epidemiology and high-yield agents in US ambulatory practice:

When to suspect a viral (versus bacterial) etiology in clinic:

Why this matters at Step 3: The exam tests judicious testing and antibiotic stewardship — recognizing a viral pattern means avoiding unnecessary antibiotics, CT scans, and admissions, and instead delivering targeted antivirals (oseltamivir, nirmatrelvir-ritonavir) plus supportive care.

Initial outpatient framework:

Presentation Patterns and Key History

— Vaccination status (influenza, COVID, RSV in eligible ≥60, MMR, varicella)

— Exposures: school, healthcare, daycare, sick contacts, sexual contacts, IVDU

— Travel within 30 days (mosquito, food/water, animal exposures)

— Immunocompromise, pregnancy, chronic disease, splenectomy

— Time course — abrupt vs gradual, biphasic, dominant symptom

Key distinction: Influenza = abrupt + systemic prostration; common cold = gradual + nasal-predominant + well-appearing. This single discrimination drives whether to test for and treat with oseltamivir within the 48-hour window.

Influenza: Abrupt onset of high fever (often >39°C), severe myalgias, headache, dry cough, and prostration during winter months. Patients "hit a wall." Incubation 1–4 days; contagious 1 day before to 5–7 days after symptom onset.

COVID-19: Variable — fever, cough, fatigue, anosmia/ageusia (less common with newer variants), sore throat, GI symptoms. Day 5–10 deterioration window is classic for hypoxemia in severe cases.

RSV (adults): Wheezing, prolonged cough, low-grade fever; severe in elderly, COPD, CHF, immunocompromised.

Common cold (rhino/corona/parainfluenza): Gradual onset, sneezing, rhinorrhea, sore throat, low/no fever, intact energy.

Mononucleosis (EBV/CMV): Adolescent/young adult with prolonged sore throat >1 week, posterior cervical lymphadenopathy, fatigue lasting weeks, splenomegaly.

Acute retroviral syndrome (HIV): 2–4 weeks post-exposure — fever, pharyngitis, rash (mucocutaneous), lymphadenopathy, mouth ulcers; HIV antibody often negative, but HIV RNA viral load very high.

Viral gastroenteritis: Vomiting predominant (norovirus) or watery diarrhea, low fever, cramps, 24–72 hours; outbreaks on cruise ships, nursing homes.

Arboviral (dengue): Returning traveler, retro-orbital pain, biphasic fever, thrombocytopenia, hemoconcentration on day 4–7 (warning signs phase).

High-yield history elements:

Physical Exam Findings and Hemodynamic Assessment

— Temperature trend (sustained >39°C or hypothermia in elderly is concerning)

— HR-to-temp ratio: relative bradycardia suggests typhoid, dengue, drug fever, or factitious

— Respiratory rate >24 and SpO2 <94% room air → escalate

— Orthostatic vitals if volume-depleted (gastroenteritis, prolonged fever)

— Capillary refill, mucous membranes, skin turgor, urine output by history

— Conjunctival injection without exudate → adenovirus, measles, leptospirosis

— Koplik spots → measles (reportable!)

— Exudative pharyngitis + posterior cervical LAD → mononucleosis

— Vesicles on soft palate → enterovirus (herpangina), HSV

— Strawberry tongue, perioral pallor → consider scarlet fever (bacterial)

— Posterior cervical/generalized → EBV, CMV, HIV, rubella

— Anterior cervical tender → bacterial pharyngitis

— Maculopapular rash on trunk → measles, rubella, acute HIV, dengue, parvovirus

— Slapped cheek + lacy reticular rash → parvovirus B19

— Vesicular dermatomal → zoster; diffuse vesicles in crops → varicella

— Petechiae/purpura → dengue hemorrhagic, meningococcemia (NOT viral — escalate)

Step 3 management: Any febrile patient with petechiae below the nipple line, neck stiffness, or hemodynamic instability gets immediate IV access, blood cultures, and empiric ceftriaxone — do NOT anchor on "viral syndrome." Reassess after fluids and labs.

General appearance and vitals first — drives disposition more than any single finding:

HEENT:

Lymph nodes:

Lungs: Wheezing (RSV, influenza), crackles raise concern for secondary bacterial pneumonia or viral pneumonitis (COVID, influenza).

Abdomen: Splenomegaly (mono, CMV, acute HIV, dengue) — counsel contact sport avoidance in mono x 3–4 weeks.

Skin:

Hemodynamic red flags: Tachycardia disproportionate to fever, hypotension, narrowed pulse pressure (dengue plasma leak), altered mentation, hypoxemia, oliguria.

Diagnostic Workup — Initial Labs, Imaging, Point-of-Care Tests

— Influenza: RIDT or PCR/NAAT during influenza season for hospitalized, high-risk outpatients within 48h symptom onset, pregnancy, or when antiviral decision pending. PCR is gold standard.

— SARS-CoV-2: PCR or antigen — antigen test is rapid but lower sensitivity early; repeat in 48h if negative and high suspicion. Required for nirmatrelvir-ritonavir eligibility decision.

— RSV PCR: Hospitalized adults ≥60 or infants with bronchiolitis when result changes infection control or palivizumab/nirsevimab considerations.

— Multiplex respiratory PCR: Reserve for immunocompromised, ICU, or diagnostic uncertainty.

— CBC with differential: lymphocyte-predominant lymphocytosis with atypical lymphocytes → EBV/CMV; lymphopenia → influenza, COVID, HIV; thrombocytopenia → dengue, severe COVID, HIV.

— CMP: dehydration, transaminitis (EBV, CMV, dengue, COVID), AKI

— CRP/procalcitonin: high procalcitonin suggests bacterial superinfection; low procalcitonin supports viral

— Monospot (heterophile): use after week 1; false-negative in first week and in young children — order EBV VCA IgM/IgG if needed

— UA: dehydration assessment

Board pearl: A returning traveler with fever, myalgia, retro-orbital pain, and platelets <100K with rising hematocrit → think dengue with warning signs. Avoid NSAIDs and aspirin; admit for IV crystalloid and serial hematocrit/platelet monitoring.

Most acute viral syndromes in well-appearing outpatients need NO testing. Test only when the result will change management (antiviral eligibility, isolation, pregnancy decisions, immunocompromise risk).

When to test and what to order:

Targeted labs when systemic illness or comorbidity:

Chest imaging: Only with hypoxemia, focal exam findings, tachypnea, or persistent fever — do not routinely image viral URIs. Bilateral peripheral ground-glass on CT → COVID/viral pneumonitis pattern.

HIV testing: 4th-generation Ag/Ab + HIV RNA if acute retroviral syndrome suspected (window period).

Diagnostic Workup — Advanced or Confirmatory Studies

— Early in illness (<7 days): NAAT/PCR or antigen detection is highest yield (influenza, COVID, dengue NS1 antigen, HIV RNA viral load).

— Convalescent phase: serology shines — EBV VCA IgM (acute) vs IgG and EBNA (past), CMV IgM, dengue IgM, measles IgM, hepatitis A IgM.

— EBV serology interpretation:

· Acute: VCA IgM (+), VCA IgG (+), EBNA (−)

· Past: VCA IgG (+), EBNA (+), VCA IgM (−)

— 4th-gen HIV-1/2 Ag/Ab combination immunoassay first

— If reactive → HIV-1/2 antibody differentiation

— If indeterminate/negative but high suspicion → HIV-1 RNA quantitative PCR (will be positive in acute infection before antibody seroconversion)

Key distinction: Mononucleosis with negative monospot in week 1 does not exclude EBV — order EBV-specific serologies. If EBV serologies are negative and clinical syndrome persists → test for CMV, acute HIV, and toxoplasmosis (heterophile-negative mononucleosis differential).

Serologies vs nucleic acid testing — choose by timing:

Acute HIV workup algorithm:

Liver and spleen evaluation in mononucleosis-like illness: AST/ALT, abdominal ultrasound if marked splenomegaly or trauma risk.

Arbovirus confirmation: Send to state health department/CDC for dengue NS1 + IgM, Zika RT-PCR (urine yields longer), chikungunya PCR/IgM. Zika in pregnancy → mandatory reporting and OB ultrasound surveillance.

CSF analysis: When meningitis/encephalitis features develop (headache + neck stiffness + altered mental status + fever) — LP with HSV PCR, enterovirus PCR, West Nile IgM, VZV PCR, opening pressure, cell count, glucose, protein.

Cardiac evaluation: Troponin and ECG when chest pain, dyspnea, or HF symptoms accompany viral illness — viral myocarditis (coxsackie B, parvovirus B19, HHV-6, SARS-CoV-2) is a "don't miss" diagnosis. Echo if troponin or ECG abnormal.

Repeat testing logic: A negative rapid antigen does not exclude COVID or influenza in high-pretest cases — confirm with PCR or repeat antigen in 48h.

Risk Stratification and First-Line Management Logic

— Outpatient: stable vitals, tolerating PO, SpO2 ≥94%, normal mentation, reliable follow-up

— Observation/ED: dehydration not correcting with PO, borderline vitals, comorbidity flare

— Admit: hypoxemia, hemodynamic instability, sepsis physiology, end-organ dysfunction, inability to maintain hydration

— ICU: respiratory failure, vasopressor need, encephalopathy, multiorgan failure

— Age ≥65, age <2

— Pregnancy and ≤2 weeks postpartum

— Chronic pulmonary (asthma, COPD), cardiac, renal, hepatic, hematologic, neurologic disease

— Immunocompromise (HIV, transplant, chemotherapy, high-dose steroids, biologics)

— BMI ≥40

— Nursing home/long-term care residents

— American Indian/Alaska Native populations (CDC influenza guidance)

— Influenza: oseltamivir within 48h symptoms (any earlier = better); offer regardless of timing to hospitalized or severely ill

— COVID-19 in high-risk outpatients within 5 days: nirmatrelvir-ritonavir (preferred) or remdesivir 3-day course

— RSV in adults: supportive; no approved antiviral

— Herpesvirus reactivations: acyclovir/valacyclovir for severe HSV/VZV

— Hydration (oral preferred), antipyretics (acetaminophen first-line), rest

— Cough suppression with honey (adults, children >1y), dextromethorphan PRN

— Saline nasal irrigation, humidified air

— Strict return precautions

Step 3 management: For a pregnant patient with influenza-like illness during flu season, start empiric oseltamivir 75 mg BID x 5 days while awaiting testing — do not delay. Influenza in pregnancy carries substantial maternal mortality risk; treatment benefit outweighs theoretical fetal risk.

Step 1 — Triage severity and disposition:

Step 2 — Identify high-risk hosts who benefit most from antiviral therapy and closer follow-up:

Step 3 — Decide on antiviral therapy based on pathogen, timing, and host:

Step 4 — Supportive care backbone for all:

Pharmacotherapy — First-Line Drug Regimens

— Oseltamivir 75 mg PO BID x 5 days (adult); weight-based pediatric dosing; renal adjustment for CrCl <60

— Baloxavir marboxil single oral dose for uncomplicated influenza in age ≥5, not pregnant, not breastfeeding; avoid co-administration with dairy/calcium

— Zanamivir inhaled — avoid in asthma/COPD (bronchospasm risk)

— Peramivir IV single dose if oral not feasible

— Nirmatrelvir-ritonavir (Paxlovid) 300/100 mg BID x 5 days — preferred; check drug-drug interactions (statins, calcineurin inhibitors, amiodarone, rivaroxaban, many psychotropics); renal dose for eGFR 30–60; avoid eGFR <30

— Remdesivir IV daily x 3 days — alternative when Paxlovid contraindicated or pregnancy

— Molnupiravir — last-line; avoid in pregnancy and age <18

— Acetaminophen 650–1000 mg q6h (max 3 g/day in most adults, 2 g/day with liver disease or chronic ETOH)

— Ibuprofen 400 mg q6h — avoid in dehydration, CKD, dengue, pregnancy ≥20 weeks, peptic ulcer

— Guaifenesin for productive cough, dextromethorphan for dry cough

— Pseudoephedrine — avoid in HTN, BPH, glaucoma, CAD

— Intranasal ipratropium for rhinorrhea

— Antihistamines (1st-gen) sedating — use sparingly in elderly (Beers criteria)

— Antibiotics without bacterial indication

— Aspirin in children/adolescents (Reye syndrome with influenza/varicella)

— Codeine in children <12

Board pearl: Paxlovid + simvastatin/lovastatin = rhabdomyolysis risk via CYP3A4 inhibition. Hold the statin during Paxlovid course and resume 3 days after completion. Similarly, hold most direct oral anticoagulants or substitute — always run a DDI check before prescribing.

Influenza antivirals (start within 48h ideally; consider later if severe/hospitalized):

COVID-19 outpatient antivirals (high-risk, within 5 days of symptoms):

Symptomatic management universal:

Avoid in viral illness:

Procedures and Expanded Pharmacology — Inpatient Management

— Supplemental O2 to maintain SpO2 92–96% (88–92% in COPD)

— Escalate: nasal cannula → high-flow nasal cannula (HFNC) → NIV → intubation

— Awake proning in moderate COVID hypoxemia

— Conservative IV fluids — avoid overresuscitation in viral pneumonitis (ARDS risk)

— Dexamethasone 6 mg IV/PO daily x up to 10 days for any supplemental O2 requirement

— Remdesivir 200 mg load then 100 mg daily x 5 days (not if eGFR <30, caution with LFTs >5x ULN)

— Baricitinib or tocilizumab added for rapidly escalating O2 needs/ICU

— VTE prophylaxis — therapeutic-dose heparin in moderately ill non-ICU per NIH guidance (selected), prophylactic in critically ill

— Empiric antibiotics only with clinical/radiographic evidence of bacterial superinfection

— Oseltamivir 75 mg BID (consider doubling dose in severe disease per some protocols)

— Treat secondary bacterial pneumonia (S. aureus including MRSA, S. pneumoniae) — empiric vancomycin + ceftriaxone if cavitary or rapidly progressive

— IV crystalloid balanced solutions for dehydration (LR or plasmalyte)

— Antiemetics: ondansetron 4 mg IV/ODT (check QTc)

— DVT prophylaxis on all admitted patients without contraindication

— Droplet + contact: influenza, RSV, COVID (add airborne for aerosol-generating procedures)

— Airborne: measles, varicella, disseminated zoster

— Contact: norovirus (soap-and-water handwashing, not alcohol gel alone)

CCS pearl: For admitted influenza pneumonia, the order set is isolation (droplet), oseltamivir, IV fluids, O2 titration, VTE prophylaxis, acetaminophen, blood/sputum cultures, CXR, CBC/CMP, and continuous pulse oximetry — then advance clock and reassess at 6, 12, 24 hours.

Hospitalized viral pneumonia (influenza or COVID) management ladder:

COVID-19 inpatient pharmacology:

Influenza inpatient pharmacology:

Supportive procedures:

Isolation precautions:

Special Populations — Elderly and Renal/Hepatic Impairment

— Fever may be absent or blunted; delirium, falls, anorexia, functional decline may be the presenting features of influenza, RSV, or COVID

— Lower threshold for chest imaging and admission

— Dehydration and electrolyte derangements develop faster

— Higher risk of secondary bacterial pneumonia (especially post-influenza S. aureus, S. pneumoniae)

— Polypharmacy → check Paxlovid DDIs meticulously (warfarin, DOACs, statins, amiodarone, immunosuppressants)

— Beers criteria: avoid first-generation antihistamines, sedating cough/cold combinations

— Annual influenza (high-dose or adjuvanted preferred ≥65)

— COVID-19 updated formulation

— RSV vaccine (single dose, ≥75 universally, 60–74 with risk factors via shared decision-making)

— Pneumococcal (PCV15+PPSV23 or PCV20)

— Tdap, zoster (Shingrix x 2 doses ≥50)

— Oseltamivir: CrCl 30–60 → 30 mg BID; CrCl 10–30 → 30 mg daily; hemodialysis → 30 mg after each session

— Nirmatrelvir-ritonavir: eGFR 30–59 → reduce to 150/100 mg BID; eGFR <30 → avoid

— Remdesivir: historically avoided eGFR <30; recent data suggest safe with monitoring

— Acyclovir/valacyclovir: renally cleared, adjust to prevent crystal nephropathy and neurotoxicity (myoclonus, confusion)

— Acetaminophen: max 2 g/day in cirrhosis or chronic ETOH; avoid in acute hepatitis

— Nirmatrelvir-ritonavir: avoid in Child-Pugh C

— Monitor LFTs in EBV/CMV/dengue with hepatitis component

Step 3 management: An 82-year-old nursing home resident with new confusion, low-grade fever, and a cough during flu season → get influenza/COVID/RSV testing, CXR, CBC/BMP, UA, and start empiric oseltamivir while awaiting results. Treat presumed delirium with reorientation and reversible-cause workup, not antipsychotics first-line.

Elderly (≥65) — atypical presentations:

Vaccination opportunities at every encounter:

Renal impairment dose adjustments:

Hepatic impairment:

Special Populations — Pregnancy, Pediatrics, and Immunocompromised

— Influenza causes disproportionate maternal morbidity/mortality and preterm labor — empiric oseltamivir without delay for ILI during flu season; do not wait for testing

— COVID-19 in pregnancy: increased ICU admission, preterm birth, stillbirth — vaccination strongly recommended every trimester; remdesivir is preferred antiviral; Paxlovid is considered safe but data limited

— Vaccines in pregnancy: inactivated influenza, COVID-19, Tdap (27–36 wks), RSV maternal vaccine (32–36 wks Sept–Jan)

— Avoid: live vaccines (MMR, varicella, LAIV), ribavirin (teratogen), molnupiravir

— Zika exposure → serial fetal US, microcephaly surveillance; avoid travel to endemic areas

— Parvovirus B19 → fetal hydrops risk, refer MFM for serial Doppler MCA

— Varicella in non-immune pregnant women → VZIG within 10 days of exposure

— Most viral URIs self-limited; avoid OTC cough/cold meds in <6 years (FDA warning)

— Bronchiolitis (RSV): supportive, nasal suction, hydration, oxygen PRN; no routine albuterol, steroids, or antibiotics

— Nirsevimab monoclonal antibody for infants <8 months entering RSV season

— Avoid aspirin (Reye), codeine <12, promethazine <2

— Hand-foot-mouth (coxsackie A): supportive, magic mouthwash

— Croup (parainfluenza): dexamethasone single dose; racemic epinephrine for stridor at rest

— Vaccinate per ACIP schedule; catch-up if behind

— Prolonged viral shedding and atypical/severe disease

— Lower threshold for testing, antivirals, and admission

— Consider CMV reactivation, HSV/VZV reactivation, BK virus in transplant

— Avoid live vaccines in severely immunocompromised

Board pearl: A pregnant patient with confirmed/suspected varicella exposure who is non-immune (negative VZV IgG) should receive VZIG within 10 days of exposure; if active disease develops, treat with IV acyclovir in hospital due to pneumonitis risk.

Pregnancy:

Pediatrics:

Immunocompromised:

Complications and Adverse Outcomes

— Secondary bacterial pneumonia post-influenza: S. pneumoniae most common; S. aureus (including MRSA) causes rapidly cavitary, necrotizing pneumonia with high mortality

— Acute respiratory distress syndrome (ARDS) — COVID, severe influenza

— Exacerbation of asthma/COPD

— Persistent post-viral cough lasting weeks (post-infectious bronchial hyperreactivity)

— Viral myocarditis (coxsackie B, parvovirus B19, HHV-6, SARS-CoV-2) — chest pain, dyspnea, troponin elevation, arrhythmia, new HF

— Pericarditis

— Acute MI risk elevated in week after influenza/COVID — vaccination reduces this

— Stroke risk increased post-acute COVID

— Thrombocytopenia (dengue, EBV, HIV, COVID)

— Hemolytic anemia (cold agglutinins with EBV, mycoplasma)

— Hemophagocytic lymphohistiocytosis (HLH) — rare, severe, EBV-associated

— VTE risk elevated with COVID and severe influenza

— Encephalitis (HSV-1 — temporal lobe, do not miss; West Nile, enterovirus)

— Guillain-Barré syndrome post-Campylobacter, CMV, EBV, Zika, COVID

— Post-infectious cerebellar ataxia (varicella in children)

— Bell palsy (HSV reactivation, Lyme also possible)

— Hepatitis (EBV, CMV, dengue, hepatitis A)

— Acute kidney injury (dehydration, rhabdomyolysis with influenza, COVID-associated)

— Long COVID/PASC: persistent fatigue, dyspnea, cognitive dysfunction, POTS, exertional intolerance >12 weeks

— Post-viral fatigue syndromes generally

Key distinction: Patient with influenza who initially improves then returns at day 5–7 with worsening fever, productive cough, and focal consolidation → secondary bacterial pneumonia, treat with vancomycin + ceftriaxone empirically pending cultures. Continue oseltamivir.

Respiratory complications:

Cardiovascular:

Hematologic:

Neurologic:

Hepatic/renal:

Splenic rupture: Mononucleosis — counsel contact sport avoidance x 3–4 weeks minimum

Post-acute syndromes:

When to Escalate Care — ICU, Consult, or Inpatient Triage

— Hypoxemia (SpO2 <94% room air or new O2 requirement)

— Tachypnea >24, accessory muscle use

— Inability to maintain hydration despite ED trial of oral/IV fluids

— Sepsis-range vitals not improving with fluids

— High-risk host with progressive symptoms (immunocompromise, frail elderly, pregnancy with deterioration)

— Bilateral infiltrates on CXR

— Significant comorbidity decompensation (HF, COPD, DM with DKA, sickle cell crisis triggered by virus)

— Need for HFNC ≥40 L/min or FiO2 >0.6

— Need for NIV or intubation

— Hemodynamic instability requiring vasopressors

— Altered mental status, encephalopathy

— Multiorgan dysfunction (AKI, hepatic failure, DIC)

— Cardiac involvement (myocarditis with arrhythmia or HF)

— Infectious disease: atypical presentations, returning traveler with fever, immunocompromised hosts, severe/complicated disease, suspected emerging pathogen

— Pulmonology: persistent hypoxemia, suspected ARDS, complicated post-viral cough

— Cardiology: suspected myocarditis (troponin, ECG changes, new HF), echo

— Neurology: encephalitis, GBS, new neurologic deficit

— Hematology: profound cytopenias, suspected HLH

— OB/MFM: any pregnant patient requiring antiviral or admission

— Public health/state health department: measles, mumps, rubella, pertussis, novel respiratory pathogens, arboviral disease, foodborne outbreaks

— ECMO candidacy for refractory ARDS — transfer early to ECMO-capable center

— Pediatric viral myocarditis → pediatric cardiac ICU

CCS pearl: When CCS clock advances and the patient on HFNC is worsening (rising RR, falling SpO2, increasing FiO2 demand), the right next move is early intubation in a controlled setting + ICU transfer, not waiting for crash intubation. Order ABG, repeat CXR, and notify pulmonary/critical care.

Admit to floor for:

ICU triage criteria:

Specialty consultations:

Inter-facility transfer considerations:

Key Differentials — Same-Category (Viral and Viral-Mimicking) Causes

— Influenza A/B — abrupt onset, high fever, myalgia, dry cough

— COVID-19 — anosmia, GI symptoms, day 5–10 deterioration

— RSV — wheezing, prolonged cough, elderly/peds

— hMPV — RSV-like in adults and children

— Parainfluenza — croup in kids, URI in adults

— Adenovirus — pharyngoconjunctival fever, pneumonia outbreaks (military)

— Rhinovirus/coronavirus (endemic) — common cold pattern

— EBV — heterophile-positive after week 1, posterior cervical LAD, splenomegaly

— CMV — milder pharyngitis, more hepatitis, heterophile-negative

— Acute HIV — rash, mucocutaneous ulcers, recent risk exposure

— Acute toxoplasmosis — heterophile-negative, lymphadenopathy (technically parasite, but tested in this differential)

— HHV-6 — roseola in children; mono-like in adults rare

— Varicella — crops of vesicles, generalized

— Zoster — dermatomal

— HSV — grouped vesicles

— Hand-foot-mouth (coxsackie A) — palms, soles, mouth

— Measles — Koplik spots → cephalocaudal maculopapular rash

— Rubella — milder rash, postauricular LAD

— Parvovirus B19 — slapped cheek, lacy rash

— Roseola (HHV-6) — high fever breaks, then rash

— Dengue, chikungunya, Zika

— Yellow fever

— Viral hemorrhagic fevers (Ebola, Lassa) — strict isolation

— Hantavirus (rodent exposure)

Board pearl: A young adult with fever, sore throat, lymphadenopathy, and negative monospot in week 2 → check EBV-specific serologies AND HIV RNA viral load. Missing acute HIV is a sentinel diagnostic error and a recurring exam trap.

Influenza-like illness differential (all overlap clinically):

Mononucleosis-like syndrome differential:

Vesicular/rash viral differential:

Returning traveler febrile illness:

Key Differentials — Other-Category (Non-Viral) Causes

— Group A strep pharyngitis — Centor criteria (fever, exudate, anterior cervical LAD, no cough) → rapid antigen ± culture

— Atypical pneumonia (Mycoplasma, Chlamydophila, Legionella) — gradual onset, dry cough, extrapulmonary features

— Early sepsis/bacteremia

— Typhoid fever in returning traveler (relative bradycardia, rose spots)

— Leptospirosis — biphasic fever, conjunctival suffusion, jaundice (water exposure)

— Rickettsial disease (RMSF) — fever, headache, rash spreading centrally, recent tick exposure → empiric doxycycline regardless of age

— Endocarditis with embolic phenomena

— Pertussis — paroxysmal cough, posttussive emesis, whoop

— Malaria — any febrile returning traveler from endemic region → thick and thin smears x 3, rapid antigen — do not miss

— Babesiosis — tick exposure, hemolysis, fever

— Acute schistosomiasis (Katayama fever) — freshwater exposure

— Drug fever, serum sickness, hypersensitivity reactions

— Thyroid storm

— Adrenal insufficiency

— Pulmonary embolism — pleuritic chest pain, hypoxemia, tachycardia (can mimic viral pneumonia)

— Acute leukemia — fatigue, fever, lymphadenopathy, cytopenias

— Lymphoma — B symptoms, lymphadenopathy

— Autoimmune (SLE flare, adult-onset Still disease, vasculitis)

— Acute HIV-associated opportunistic infection in known HIV (PJP, disseminated MAC)

— Substance withdrawal mimicking fever/diaphoresis

— Acute MI with atypical (viral-like) presentation in women, elderly, diabetics

— Pericarditis post-viral

Key distinction: A returning traveler with fever from sub-Saharan Africa is malaria until proven otherwise — order thick/thin smears x 3 and rapid antigen testing immediately. Do not anchor on "viral syndrome" even when the patient looks well between fever spikes.

Bacterial mimics of viral syndrome:

Parasitic/protozoal:

Non-infectious mimics:

Cardiac mimics:

Secondary Prevention, Discharge, and Long-Term Plan

— Annual influenza vaccine for everyone ≥6 months (high-dose or adjuvanted preferred ≥65)

— COVID-19 updated formulation for ≥6 months

— RSV vaccine: ≥75 universally; 60–74 with risk factors (shared decision-making); maternal vaccine 32–36 weeks gestation Sept–Jan; nirsevimab for infants <8 months

— Pneumococcal: PCV20 alone OR PCV15 followed by PPSV23 — adults ≥65 and high-risk adults 19–64

— Tdap booster q10y, Tdap each pregnancy

— Zoster (Shingrix) 2-dose series ≥50, immunocompromised ≥19

— MMR, varicella catch-up for non-immune adults (not in pregnancy/severe immunocompromise)

— HPV through age 26, shared decision-making 27–45

— Hepatitis A, B for at-risk and universally for adults 19–59 per ACIP for hep B

— Hand hygiene (alcohol-based gel; soap and water for norovirus and C. diff)

— Respiratory etiquette, mask use during illness

— Stay home from work/school until afebrile ≥24 hours without antipyretics

— Avoid sharing utensils, drinking glasses

— Complete antiviral course as prescribed

— Antipyretic/analgesic PRN with max daily dose education

— Hydration goals (urine pale yellow)

— When to return: dyspnea, chest pain, persistent fever >5 days, dehydration, altered mentation

— Telephone/video check at 48–72 hours for high-risk patients

— Primary care visit at 1–2 weeks

— Pulse oximeter teaching if relevant

— Pulmonary rehab referral if post-viral deconditioning

Step 3 management: At discharge after influenza pneumonia hospitalization, administer influenza vaccine before leaving the hospital (if not contraindicated and not already given this season) — inpatient vaccination opportunities are an emphasized quality measure and a tested Step 3 concept.

Vaccination — the highest-yield secondary prevention:

Behavioral and household prevention:

Discharge medications and counseling for viral illness:

Post-discharge follow-up:

Follow-Up, Monitoring Parameters, and Rehab/Counseling

— Uncomplicated viral URI in low-risk adult: PRN follow-up; return if worsening or symptoms >10 days

— Influenza/COVID outpatient on antivirals: telehealth at 48–72 hours to confirm improvement

— Post-hospitalization for viral pneumonia: PCP visit within 7–14 days; check resolution, vaccinations, function, mental health

— Post-COVID: assess for persistent symptoms at 4 and 12 weeks; refer to long COVID clinic if ≥3 months symptoms

— Mononucleosis: 2–4 week recheck for splenomegaly resolution before clearing contact sports

— Oxygen saturation (home pulse oximeter) for high-risk discharged patients with respiratory virus

— Hydration and weight in elderly post-gastroenteritis

— LFT recheck if transaminitis on initial labs (EBV, CMV, dengue)

— Platelet count trend in dengue (until clearly recovering)

— Repeat HIV testing if acute retroviral syndrome was suspected with initially negative serology

— Cardiac follow-up with echo at 3–6 months if viral myocarditis

— Graduated return to activity post-viral fatigue — start with light activity, increase as tolerated

— Post-myocarditis: exercise restriction x 3–6 months with cardiology clearance

— Pulmonary rehab for persistent dyspnea after viral pneumonia

— Cognitive rehab and pacing strategies for long COVID

— Mental health screening (PHQ-9, GAD-7) — post-viral depression is common

— Tobacco cessation (worsens viral respiratory illness severity)

— Alcohol moderation

— Sleep hygiene

— Update vaccinations

— Advance care planning if elderly/frail after serious illness

Board pearl: A 17-year-old with EBV mononucleosis cleared to return to football at week 2 because "he feels great" is the wrong answer — minimum 3–4 weeks AND documented absence of splenomegaly by exam (some centers require ultrasound) before contact sports, due to splenic rupture risk.

Outpatient follow-up cadence:

Specific monitoring parameters:

Rehab and recovery counseling:

Counseling topics universal at follow-up:

Ethical, Legal, and Patient Safety Considerations

— Measles, mumps, rubella, pertussis

— Novel/pandemic respiratory pathogens (novel influenza, SARS-CoV-2 in many states early on, MERS)

— Hepatitis A, B, C

— HIV, AIDS

— Arboviral disease (dengue, Zika, West Nile, chikungunya, yellow fever)

— Foodborne outbreaks (norovirus clusters in food service)

— Viral hemorrhagic fevers — immediate notification to state and CDC

— Acute HIV diagnosis → partner services notification (anonymous public health–facilitated) is standard; patient encouraged but public health has authority

— STIs identified during acute viral workup (acute HIV is also an STI) trigger same partner notification framework

— Confidentiality protected even from family/employers without consent — exception is public health reporting

— Vaccination is voluntary; document vaccine hesitancy discussions using motivational interviewing

— Antiviral therapy: discuss risks/benefits/DDIs (especially Paxlovid)

— Off-label use disclosure when applicable

— Medication reconciliation at discharge after viral illness hospitalization — antivirals stopped, prophylactic anticoagulation continued or stopped, statins/DOACs resumed after Paxlovid course

— Clear handoff to PCP within 7–14 days

— Pending culture/viral results responsibility — explicit ownership documented

— Pulse oximeter teaching with return parameters in writing

— Language-concordant discharge instructions and certified interpreters (not family) for limited-English-proficiency patients

— Healthcare workers with confirmed influenza/COVID/RSV — return per institutional policy and CDC, generally afebrile 24h

— Food handlers with norovirus — exclude until 48h asymptomatic

— Pediatric daycare exclusion criteria

Step 3 management: A patient discharged on nirmatrelvir-ritonavir who is on warfarin must have a clear written plan for INR monitoring during and after the course, with explicit communication to the anticoagulation clinic — failure to do so is a tested transition-of-care safety lapse.

Mandatory reporting (jurisdiction-dependent but broadly required):

Confidentiality and partner notification:

Informed consent and shared decision-making:

Patient safety and transition-of-care risks (high-yield Step 3 theme):

Occupational and school exclusion:

High-Yield Associations and Rapid-Fire Clinical Facts

— Koplik spots → measles

— Slapped cheek + lacy rash → parvovirus B19

— Posterior cervical LAD + splenomegaly + heterophile-positive → EBV

— Heterophile-negative mono → CMV, acute HIV, toxoplasmosis

— Retro-orbital pain + thrombocytopenia + traveler → dengue

— Temporal lobe encephalitis → HSV-1

— Hand-foot-mouth → coxsackie A

— Croup (barky cough) → parainfluenza

— Bronchiolitis in infants → RSV

— Roseola (high fever → rash after defervescence) → HHV-6

— Pharyngoconjunctival fever → adenovirus

— Reye syndrome trigger → aspirin + varicella/influenza

— Oseltamivir → within 48h, renal dose

— Paxlovid → CYP3A4 DDIs (statins, DOACs, calcineurin inhibitors)

— Acyclovir → hydrate to prevent crystal nephropathy

— Ribavirin → teratogen, hemolytic anemia

— Aspirin in kids with viral illness → never (Reye)

— Live vaccines (MMR, varicella, LAIV, yellow fever, zoster Zostavax — discontinued): avoid in pregnancy and severe immunocompromise

— Shingrix (recombinant zoster) is safe in immunocompromised

— Maternal RSV vaccine 32–36 weeks during Sept–Jan

— Nirsevimab for infants <8 months

— Atypical lymphocytes → EBV/CMV

— Lymphopenia → HIV, COVID, influenza

— Thrombocytopenia + transaminitis + traveler → dengue

— Eosinophilia → not viral (think helminths, drug reaction)

— Procalcitonin elevation → suggests bacterial superinfection

— Malaria, acute HIV, meningococcemia, RMSF, endocarditis, leukemia/lymphoma, myocarditis, PE

Board pearl: "Bilateral parotitis in an unvaccinated young adult" = mumps until proven otherwise — order mumps IgM, isolate (droplet precautions x 5 days from onset of parotitis), and report to public health.

Pathogen → buzzword:

Drug → key pearl:

Vaccine pearls:

Lab pattern recognition:

Don't miss diagnoses behind a "viral" presentation:

Board Question Stem Patterns

Key distinction: When the stem emphasizes timing, host risk, or transition-of-care steps, the answer is usually a Step 3 systems-level action (vaccinate before discharge, schedule 7-day follow-up, medication reconciliation), not another diagnostic test.

Stem 1 — The flu-shot opportunity: 68-year-old with COPD admitted in October for influenza pneumonia, improving on oseltamivir. The "next best step" before discharge is administer influenza vaccine (if not already given this season) and pneumococcal vaccine if due — not "schedule follow-up in 2 weeks alone."

Stem 2 — The pregnant patient with ILI: 28-year-old at 22 weeks gestation with fever, myalgias, dry cough during flu season. The right answer is start empiric oseltamivir now, do not wait for testing, and do not select acetaminophen alone or "reassure and discharge."

Stem 3 — Heterophile-negative mononucleosis: 24-year-old MSM with 3 weeks of fever, sore throat, lymphadenopathy, maculopapular rash, mouth ulcers, negative monospot. Best next test = HIV RNA viral load (4th-gen Ag/Ab combo also acceptable as first step), not "repeat monospot" or "EBV serology alone."

Stem 4 — Returning traveler: Patient back from Southeast Asia with fever, retro-orbital pain, petechiae, platelets 70K, rising hematocrit. Diagnosis = dengue with warning signs. Management = admit, IV crystalloid, serial hematocrit/platelets, avoid NSAIDs/aspirin.

Stem 5 — Post-influenza decompensation: Patient improving from influenza, then day 6 returns with worsening fever, productive purulent sputum, focal lobar consolidation. Diagnosis = secondary bacterial pneumonia (S. aureus or S. pneumoniae). Treatment = vancomycin + ceftriaxone empirically; continue oseltamivir.

Stem 6 — Paxlovid DDI trap: 70-year-old on simvastatin and apixaban diagnosed with COVID-19, eligible for Paxlovid. Best action = hold simvastatin during and 3 days after course; consult pharmacy regarding apixaban (or substitute), do not simply prescribe Paxlovid.

Stem 7 — Mono and contact sports: 16-year-old football player with EBV mononucleosis wants to return to play at 2 weeks. Right answer = defer at least 3–4 weeks AND document absence of splenomegaly before clearance.

Stem 8 — Reye syndrome: Child with varicella given aspirin develops vomiting, encephalopathy, hepatic dysfunction → Reye syndrome; counsel never to use aspirin in children/adolescents with viral illness.

Stem 9 — Acute HIV partner notification: Patient diagnosed with acute HIV asks that no one be informed. Right approach = maintain confidentiality but utilize public-health-facilitated partner services; encourage but do not coerce direct disclosure.

One-Line Recap

Acute viral syndromes in family medicine are diagnosed clinically with selective testing, treated with supportive care plus targeted antivirals in high-risk hosts within the therapeutic window, and managed longitudinally with vaccination, transition-of-care planning, and vigilant identification of dangerous mimics.

Board pearl: When in doubt on Step 3 — supportive care + vaccinate + schedule the follow-up + reconcile the medications beats reflexive antibiotics, panels, and admissions every time.

Three-pillar framework: Triage severity → identify high-risk host → decide antiviral (oseltamivir within 48h for influenza; nirmatrelvir-ritonavir within 5 days for high-risk COVID; supportive otherwise) + universal supportive care.

Never miss the mimic: Acute HIV behind heterophile-negative mono, malaria behind any returning-traveler fever, secondary bacterial pneumonia behind post-influenza relapse, meningococcemia/RMSF behind petechial "viral" rash, myocarditis behind viral chest pain.

Vaccinate at every opportunity: Annual influenza, updated COVID, RSV (≥75 universal and 60–74 high-risk), pneumococcal, Tdap, zoster ≥50, and inpatient vaccination before discharge is a tested quality measure.

Transition-of-care safety: Medication reconciliation (especially Paxlovid DDIs with statins and DOACs), explicit follow-up cadence within 7–14 days, pending-result ownership, language-concordant discharge instructions, mandatory reporting for measles/mumps/HIV/arboviral disease.

Special populations rules: Empiric oseltamivir in pregnant ILI without waiting; remdesivir preferred for pregnant COVID; renal dosing for oseltamivir and avoidance of Paxlovid at eGFR <30; nirsevimab for infants and maternal RSV vaccine for the perinatal window; contact-sport restriction x 3–4 weeks with documented splenomegaly resolution in mononucleosis.