Table 1 Etiologies and treatment of viral syndromes in the ICU

RESPIRATORY FAILURE

Hypoxic respiratory failure-pneumonia

Hypoxic respiratory failure: Influenza A and B, RSV A and B, coronavirus, Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome coronavirus, Adenovirus, cytomegalovirus, Varicella, HSV, Parainfluenza 1-4, Metapneumovirus, measles especially in immunocompromised patients

Supportive: adequate oxygen delivery

VAP: HSV, CMV, Mimivirus

Hypercapnic-hypoxic respiratory failure

Hypercapnic-hypoxic respiratory failure: Influenza A and B, coronavirus, rhinovirus, Parainfluenza 1-4, RSV A and B

Antivirals:

Asthma/COPD exacerbation

Neuraminidase inhibitors (NAIs) (Oseltamivir, Zanamivir, peramivir, Laninamivir) [12, 13]. For resistant influenza viruses may consider combination therapy of NAI with ribavirin and/or novel antivirals such as Favipiravir [14, 15]

Adult Respiratory Distress Syndrome (ARDS)

ARDS: Influenza virus, Hantavirus [Hantavirus pulmonary syndrome (HPS)], varicella, herpes simplex virus, SARS, MERS-CoV

Ribavirin for RSV in immunocompromised patients and children [16–18] and may also be considered for other viruses such as in SARS [25] or MERS-CoV - lopinavir in combination regimens has also been used

Without lung disease (restrictive disease): Guillain-Barré syndrome (GBS)

GBS: HSV, VZV, CMV, EBV, Influenza, Hantavirus acute and chronic hepatitis B, Rare causes: West Nile virus, Parvovirus B19, Hantavirus, rubella, dengue

Acyclovir for VZV pneumonitis (limited efficacy it is still widely recommended as early primary therapy) [19]

Ganciclovir for CMV pneumonitis in solid organ transplant patients appears to reduce morbidity [20]

Corticosteroids: For influenza [21–23], SARS[24, 25] and VZV pneumonitis [26] to reduce inflammatory tissue injury in severe pneumonia

Immunotherapies: Palivizumab is approved for high-risk pediatric patients with RSV infection [18]; IVIG for certain respiratory viruses including influenza [27, 28] and GBS, plasma exchange for GBS. Combinations of ganciclovir with immunoglobulin or cytomegalovirus immunoglobulin may be of value in patients with bone marrow transplants and CMV pneumonitis [29, 30]

Others: Vitamin A for severe measles [31]

Neurological syndromes

Encephalitis, meningitis, meningoencephalitis, myelitis, polyradiculo-neuropathy, Guillain-Barré syndrome (GBS) Reyes syndrome, subacute sclerosing panencephalitis, postinfectious acute disseminated encephalomyelitis (ADEM) [32]

HSV (40% to 50% of encephalitis cases where a cause is determined, and 10% to 20% overall [32]VZV (the most common cause of encephalitis among immunocompromised patients and the second most common viral cause of sporadic encephalitis not occurring during an outbreak)

Supportive: Treatment of neurologic (eg, cerebral edema, high intracranial pressure, and seizures) and systemic (eg, hypoxemia, low cerebral perfusion pressure, and fever) complications

Clinical presentation: usually as altered mental status, seizures, coma, neuropathies

Enteroviruses (Enterovirus 71, Coxsackie, Echovirus, poliovirus: as a group, enteroviruses) are collectively the third most common cause of sporadic viral encephalitis and the most common cause of aseptic meningitis

Antivirals:Acyclovir: Early aggressive antiviral therapy with acyclovir for HSV, VZV improves mortality and reduces subsequent cognitive impairment

Arboviruses (JEV, WNV, TBEV, MVEV, LCEV, SLEV, EEEV: the most common pathogens to cause encephalitis that is restricted to certain geographic regions)

Influenza (encephalitis is very uncommon complication of seasonal influenza infections but because influenza itself is common 4-19% of patients with severe or fatal H1N1 reported neurologic complications

Ganciclovir: CMV encephalitis

Other viruses: West Nile virus, CMV, mumps, measles, rubella, rabies, JC virus (PML), acute HIV infection)

Foscarnet: HHV-6, combination therapy with foscarnet and ganciclovir is recommended for CMV encephalitis

Oseltamivir: Severe influenza

Pleconaril: severe Enterovirus infections

Corticosteroids: Complicated HSV encephalitis (data based on retrospective studies), VZV encephalitis (for inflammatory vasculopathy), uncomplicated zoster (variable results), severe influenza, WNV (case report) [33], postinfectious encephalitis

Immunotherapies: Immunomodulatory therapy with either intravenous immune globulin or plasma exchange for patients with postinfectious encephalitis who fail corticosteroid treatment (data based on case series) or for WNV encephalitis (Case reports) [34, 35].

Others: Vitamin A for severe measles [31]

Virus related shock

Cardiogenic shock

Enteroviruses (Enterovirus 71, Coxsackie viruses group A and B, Echovirus), Influenza, Adenovirus, Parvovirus, RSV, CMV, HIV-1, hepatitis A and C viruses, vaccinia virus (after smallpox vaccine)

Supportive

Myocarditis

Antivirals:

Rifampin: For RSV myocarditis [36]

Pleconaril: severe Enterovirus infections

Oseltamivir: Severe influenza

ART: HIV-1

Corticosteroids: do not reduce mortality (data based on small RCT of poor quality) [37]

Immunotherapies: IVIG (data based on in vitro data, case series, limited RCT) [38–40]. Combination therapy of IVIG with rifampin has been described in case series [36]

Others: Herbal medicines [41], mechanical ventricular assist devices until resolution or cardiac transplantation is available, novel therapies e.g pleconaril

Distributive shock-Hemorrhagic fever

Arenaviruses (South American HF-Junin; Lassa Fever), Bunyaviruses (Rift valley fever, Chrimean Congo HF-CCHF), HF with renal syndrome, Hantavirus, Filoviruses (Ebola, Marburg), Flaviviruses (Yellow fever, Dengue HF)

Supportive: adequate oxygen delivery, blood products.

Clinical presentation: Febrile illnesses, headache, myalgia, nausea, vomiting and diarrhea are frequent. Hemorrhagic features, disseminated intravascular coagulopathy (DIC), multiple organ system failure and death ensue.

Passive transfer of antibodies (plasma, IVIG) may be of value in Bunyaviruses [45], Junin virus [42], Lassa virus [43], Hantavirus HF [17, 44], Flaviviruses (Yellow fever, Dengue HF) [45–47]

Antivirals: ribavirin for CCHF [17, 48], Lassa virus [17, 49], Hantavirus HF [17, 44]

Ribavirin plus interferon may be considered for Lassa virus [50]

Hypovolemic/distributive shock in the setting of acute liver failure secondary to viral hepatitis

Hepatitis A, B, C, D, E, G, herpes group (CMV, HSV and Epstein Barr virus), adenovirus and influenza virus

Supportive: hemodynamic management, ventilation, prevention and treatment of hemorrhage, dialysis, therapy of co-existent sepsis and electrolyte disturbance, and management of intracranial pressure

Clinical presentation: Nausea and vomiting with progression to encephalopathy and coma; may be new onset or acute decompensation of chronic liver failure due to viral hepatitis/cirrhosis

Orthotopic liver transplantation

Antivirals (may be used for acute flare up of chronic viral hepatitis e.g. in immunocompromised patients.

Hypovolemic/distributive shock in the setting of acute pancreatitis

Mumps (the most common virus associated with pancreatitis, occurring even in the absence of parotitis), Enteroviruses (Coxsackie B), cytomegalovirus, varicella zoster, HSV-1, Epstein-Barr virus, influenza A, Parainfluenza, adenovirus, measles. In fulminant hepatic failure due to hepatitis A (HAV) or hepatitis E (HEV) pancreatitis occurs in up to 34% of the cases [51]

Supportive

Antivirals

Oseltamivir: Severe influenza

Pleconaril: severe Enterovirus infections

Acyclovir: VZV

Shock in the setting of adrenal insufficiency caused by viral infection (rare)

CMV in HIV-1 infection [52]

Treatment of CMV itself is generally not warranted, unless there is evidence of CMV disease elsewhere. However, it is critical to treat the underlying human immunodeficiency virus infection with antiretroviral agents to attempt immune restitution [52]

Rhabdomyolysis

Influenza A and B, Parainfluenza virus, CMV, EBV, VZV, measles, adenovirus, enteroviruses

Supportive

Antivirals

Oseltamivir: Severe influenza

Pleconaril: Severe Enterovirus infections

Acyclovir: VZV

Ganciclovir: CMV

Special Immunocompromised host

Trauma/Burn

HSV, CMV

Supportive, antivirals, corticosteroids

Pregnancy

HSV, VZV, CMV, Influenza virus

Supportive, antivirals

Transplantation

CMV, EBV [post-transplant lymphoproliferative disorder (PTLD)], VZV, HSV, HHV-6 and HHV-8, RSV, Influenza A and B, BK virus, Adenovirus

Supportive, antivirals, immunotherapies (for example donor lymphocyte infusions and anti-CD20 antibody for PTLD), experimental therapies