Coronavirus Disease 2019 (COVID-19) Follow Up

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.