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Complications
Acute
Respiratory Distress Syndrome
Acute respiratory distress syndrome is defined as new
or worsening respiratory symptoms with an onset within a week of known
pneumonia. It is a lung injury that is acute, diffuse, and inflammatory which
is due to a variety of etiologies. Chest imaging may show bilateral opacities (not
fully explained by volume overload) and lobar or lung collapse or nodules.
Classification Based on
Impairment in Oxygenation in Adults
Patients with acute
respiratory distress syndrome may be classified based on the impairment in
oxygenation and are assigned as follows:
- Mild acute respiratory distress syndrome: 200 mmHg <PaO2/FiO2 ≤300 mmHg (with positive end-expiratory pressure [PEEP] or continuous positive airway pressure [CPAP] ≥5 cmH2O, or non-ventilated)
- Moderate acute respiratory distress syndrome: 100 mmHg <PaO2/FiO2 ≤200 mmHg (with PEEP ≥5 cmH2O, or non-ventilated)
- Severe acute respiratory distress syndrome: PaO2/FiO2 ≤100 mmHg (with PEEP ≥5 cmH2O, or non-ventilated)
Management
The management of acute respiratory distress syndrome includes admission to the ICU, observance of airborne precautions, conservative fluid management for patients without tissue hypoperfusion and fluid responsiveness, empiric antimicrobials following the guidelines of pneumonia management, anticoagulation therapy, and consideration of neuromuscular blockade in intubated patients.
Dexamethasone 6 mg/day for 10 days may be given; titrated upwards and the use of Methylprednisolone may be considered when dealing with cytokine storm.
Observe acute respiratory distress syndrome protocol for mechanical ventilation with the initiation of recruitment maneuvers and lung protection strategies (eg PEEP titration). PEEP titration requires consideration of benefits (reducing atelectrauma and improving alveolar recruitment) versus risks (end-inspiratory overdistension leading to lung injury and higher pulmonary vascular resistance).
Sepsis or
Septic Shock
Sepsis
Sepsis
is defined as organ dysfunction that is acute and life-threatening due to a dysregulated
host response to suspected or proven infection. The signs of organ dysfunction
include altered mental status, difficulty or fast breathing, low oxygen
saturation, reduced urine output, fast heart rate, weak pulse, cold extremities
or low blood pressure, skin mottling, laboratory evidence of coagulopathy,
thrombocytopenia, acidosis, high serum lactate level, or hyperbilirubinemia.
Septic Shock
Septic
shock is defined as persistent hypotension despite volume resuscitation that
requires vasopressors to maintain mean arterial pressure of ≥65 mmHg and serum
lactate level of >2 mmol/L. It is important to recognize early the signs of
septic shock and within 1 hour of recognition, administration of antimicrobial
therapy and initiation of fluid bolus and vasopressors for hypotension should
be done. The use of central venous and arterial catheters should be based on
resource availability and individual patient needs.
Crystalloid
fluid (including normal saline and Ringer’s lactate) 250-500 mL should
be given as a rapid bolus in the first 15 to 30 minutes of resuscitation. Fluid
administration should be reduced or discontinued if there is no response to
fluid loading or signs of volume overload appear (eg jugular venous distension,
crackles on lung auscultation, pulmonary edema on imaging, or hepatomegaly).
When
shock persists during or after fluid resuscitation, vasopressors should be
administered. The initial blood pressure target is a mean arterial pressure of
≥65 mmHg in adults and improvement of markers of perfusion. Norepinephrine is
considered the first-line treatment in adult patients; Epinephrine or
Vasopressin can be added to achieve the mean arterial pressure target. Because
of the risk of tachyarrhythmia, Dopamine should be reserved for selected
patients with low risk of tachyarrhythmia or those with bradycardia.
COVID-19-Associated
Pulmonary Aspergillosis (CAPA)
SARS-CoV-2
infection may cause severe damage to the airway epithelium that will enable
aspergillus invasion. There have been reports that this is caused by
azole-resistant Aspergillus. The presence of any of the following
clinical findings warrants diagnostic investigation for CAPA in patients with refractory
respiratory failure for >5 to 14 days despite receiving all therapy for
severe COVID-19 patients:
- Refractory fever for >3 days or new fever after a period of defervescence of >48 hours during appropriate antibiotic therapy in the absence of any other obvious cause
- Worsening respiratory status (eg tachypnea or increasing oxygen requirements)
- Hemoptysis
- Pleural friction rub or chest pain
IV
Voriconazole or Isavuconazole is a recommended treatment while for
azole-resistant Aspergillus, liposomal Amphotericin B is recommended. It
is suggested to have a 6- to 12-week treatment course. Weekly therapeutic drug
monitoring of patients with CAPA is recommended especially in cases of fully
susceptible Aspergillus sp.
COVID-19
and Mental Health
In
early May 2020, the United Nations recommended that actions should be taken in
order to minimize the mental health consequences of the COVID-19 pandemic. Studies
made in Spain and China show an association between the job situation, the
expected negative economic consequences, the perceived worsening of health and habits,
and worries about COVID-19 infection with depressive symptomatology during
confinement.
Depression
and difficulty with thinking and concentration (sometimes referred to as
"brain fog") are among the common long-term symptoms in patients who
have recovered from COVID-19 infection.
Multisystem Inflammatory
Syndrome in Children
Multisystem inflammatory syndrome in children is also
called pediatric multisystem inflammatory syndrome (PMIS), pediatric
inflammatory multisystem syndrome temporally associated with SARS-CoV-2
(PIMS-TS), pediatric hyperinflammatory syndrome, or pediatric hyperinflammatory
shock.
The diagnosis is given to a confirmed COVID-19 patient who is <21
years old or had COVID-19 exposure in the past 4 weeks with no alternative
diagnosis presenting with fever, laboratory evidence of inflammation, clinically
severe illness requiring hospitalization, and multisystem (≥2) organ
involvement (cardiac, renal, respiratory, hematologic, gastrointestinal,
dermatologic, or neurological).
Signs and Symptoms
Patients
with the multisystem inflammatory syndrome in children present with persistent
fever; evidence of organ dysfunction or shock; Kawasaki disease-like symptoms (eg
conjunctivitis, red eyes, red or swollen hands or feet, rash, red cracked lips,
swollen glands); toxic shock syndrome-like features with hemodynamic
instability; cytokine storm or macrophage activation or hyperinflammatory
features; thrombosis, poor heart function, diarrhea, and gastrointestinal
symptoms, acute kidney injury; and shortness of breath suggestive of congestive
heart failure. The respiratory symptoms typically reported in adults with
COVID-19 may not be present in pediatric patients with multisystem inflammatory
syndrome in children.
Laboratory Findings
Laboratory
findings include abnormal levels of inflammatory markers in the blood (eg
elevated erythrocyte sedimentation rate [ESR]/CRP and ferritin, LDH); lymphopenia
of <1,000, thrombocytopenia of <150,000, neutrophilia; and elevated
B-type natriuretic peptide (BNP) or NT-proBNP (pro-BNP), hyponatremia, and elevated
D-dimers.
Treatment
IVIG
1 to 2 g/kg ideal body weight/dose plus low- to moderate-dose
Methylprednisolone with the timing of administration influenced by the patient’s
cardiac function and fluid status may be given. Steroid therapy (ranging from 2
to 30 mg/kg/day of Methylprednisolone depending on the severity of illness) and
biologics (eg Anakinra 2 to 10 mg/kg/day, SC or IV, divided every 6 to 12
hours) may also be given. Patients often go home with a 3-week taper of
steroids and/or biologics.
For
children who did not improve within 24 hours of initial immunomodulatory
therapy, they may start one of the following:
Concurrent
antibiotic therapy has been given due to the need for early intervention and
the need to initiate treatment for multiple possible etiologies. For patients with
Kawasaki-like syndrome and antithrombotic treatment, low-dose Aspirin at a
minimum is given.
- High-dose Anakinra 5 to 10 mg/kg/day IV or SC
- Higher dose glucocorticoid (eg 10 to 30 mg/kg/day IV Methylprednisolone)
- Infliximab 5 to 10 mg/kg IV for 1 dose
Concurrent
antibiotic therapy has been given due to the need for early intervention and
the need to initiate treatment for multiple possible etiologies. For patients with
Kawasaki-like syndrome and antithrombotic treatment, low-dose Aspirin at a
minimum is given.
Prevention
Patients
with suspected multisystem inflammatory syndrome in children who have been
hospitalized should be considered as patients under investigation for COVID-19.
RT-PCR and antibody testing for COVID-19 should be done.
Follow-up
Starting
2 to 3 weeks after discharge, patients diagnosed with multisystem inflammatory
syndrome in children should have close outpatient pediatric cardiology
follow-up. For patients diagnosed with myocarditis, cardiology-directed
restriction and/or release from vigorous activities is recommended.
Long-Term COVID-19 Disease
Long-term COVID-19 disease is an
umbrella term for the wide range of physical and mental health consequences
that are present for ≥4 weeks after infection of SARS-CoV-2. These consequences
include both general complications of prolonged illness as well as
hospitalization and post-acute sequelae of SARS-CoV-2 infection (PASC), which
are more specific to the effects of SARS-CoV-2 infection and cannot be
explained by an alternative diagnosis.
It
is also called long COVID, post-acute COVID-19, long-term effects of COVID,
post-acute COVID-19 syndrome, chronic COVID, long-haul COVID, late sequelae, and
PASC (research term). It can occur in patients who have had varying degrees of
illness during acute infection, including those who had mild or asymptomatic
infections.
Medical
and research communities are still learning about these post-acute symptoms and
clinical findings. It can be considered as a lack of return to the usual state
of health following acute COVID-19 illness. It may also include the development
of new or recurrent symptoms that occur after the symptoms of acute illness
have resolved.
Clinical Case Definitions
The clinical case definitions for COVID-19 disease
are as follows:
- Acute COVID-19: Patient has signs and symptoms of COVID-19 for up to 4 weeks
- Ongoing symptomatic COVID-19: Patient has signs and symptoms of COVID-19 from 4 weeks up to 12 weeks
- Post-COVID-19 syndrome: Patient has signs and symptoms that
developed during or after an infection consistent with COVID-19 which continued
for >12 weeks and are not explained by an alternative diagnosis
- It usually presents with a cluster of symptoms, often overlapping, that can fluctuate and change over time and can affect any system of the body
- This can be considered before 12 weeks while the possibility of an alternative underlying disease is also being assessed
- Long COVID: Commonly called when the signs and symptoms continue or develop after acute COVID-19 and includes both ongoing symptomatic COVID-19 and post-COVID-19 syndrome
Commonly
Reported Symptoms
Common
symptoms of long COVID-19 include tiredness, fatigue, and lack of concentration.
Generalized symptoms include fatigue, fever, and pain. Respiratory symptoms include
breathlessness, cough, and dyspnea or increased respiratory effort. Cardiovascular
symptoms include chest tightness, chest pain, and palpitations. Neurological
symptoms include cognitive impairment (‘brain fog’, loss of concentration or
memory issues), headache, sleep disturbance, peripheral neuropathy symptoms
(pins and needles and numbness), dizziness, delirium (in older populations), mobility
impairment, and visual disturbance. Gastrointestinal symptoms include abdominal
pain, nausea and vomiting, diarrhea, weight loss, and reduced appetite. Musculoskeletal
symptoms include joint and muscle pain. Ear, nose, and throat symptoms include
tinnitus, earache, sore throat, dizziness, loss of taste and/or smell, and nasal
congestion. Dermatological symptoms include skin rashes and hair loss. Psychological
or psychiatric symptoms include symptoms of depression, anxiety, and post-traumatic
stress disorder.
Management
Evidence
of pharmacological treatment of long-term COVID-19 disease is still lacking;
however, there are established treatments for some of the common symptoms of
ongoing long-term COVID-19 disease.
Urgent
referral for psychiatric assessment is advised in patients with severe
psychiatric symptoms or are displaying a high risk of self-harm or suicide.
For
patients with dyspnea, pharmacotherapy for any identified underlying cardiac or
pulmonary disease is optimized. For patients with cough, supportive therapy is
advised. Over-the-counter cough suppressants as needed can be given.
For
patients having persistent and severe chest discomfort, pain or tightness,
nonsteroidal anti-inflammatory drugs (NSAIDs) may be administered in the
absence of renal dysfunction or other contraindications. The lowest effective
dose for the shortest period of time is advised.
For
patients having orthostasis and dysautonomia (eg unexplained sinus tachycardia,
dizziness on standing) following COVID-19, initial conservative therapy of
compression stockings, abdominal binder, hydration, physical therapy, and behavioral
modifications may be advised.
For
patients having moderate-severe cognitive impairment, neuropsychological or
speech-language pathology evaluation and management is advised.
For
patients with fatigue, they are encouraged to have adequate rest, good sleep
hygiene, and specific fatigue management strategies. For the majority of
patients, an individualized and structured, titrated return-to-activity program
based on the level of fatigue is advised.