Over 10% of people infected with the SARS-CoV-2 virus experience acute respiratory distress syndrome (ARDS) and require supportive treatment with oxygen and even mechanical lung ventilation. Multiple COVID-19 complications occur because SARS family coronaviruses can cause extensive heart and lung damage. SARS-CoV-2 viruses can easily penetrate deep into these organs leading to excessive inflammation. People who had COVID-19 and required mechanical ventilation face a long recovery. Based on prior experience with SARS disease and ARDS patients who had other causes of lung disease, exercise limitations, psychological and physical disability persist at 5-year follow-up, despite regaining almost normal lung function. In this summary, we will review how pharmacogenetics can support medication selection during recovery for people suffering from COVID-19 complications. 

Observed COVID-19 complications include:

• ARDS-related lung damage
• Arrhythmias (18%)
• Myocardial infarction (3.6%)
• Stroke/Deep vein thrombosis (3.3%)
• Renal failure (13.3%)
• Anesthesia-induced delirium

Pharmacogenetic guidelines are available for hundreds of medications that may be used by people with COVID-19 complications. Below are the types of coronavirus-induced complications and currently available treatment options.

Long term COVID-19 complications on lung function

COVID-19 induced lung damage is a combination of severe tissue inflammation caused by the virus and secondary infections, as well as ventilator-induced tissue damage. Mechanical ventilation is used to increase oxygen in the body. However, excessive pressure and air volume can cause tissue damage and can even lead to lung collapse. Following COVID-19, scarring and thickening of the tissue between the air sacs can occur within a few weeks. Breathing problems can persist for months, so after COVID-19, some people may need supplemental oxygen at home to compensate for shortness of breath and fatigue. Physiotherapy may help to restore lung function. Most patients will also need puffers. Pillcheck pharmacogenetic testing service assesses response to two different types of bronchodilators used in puffers: salmeterol (Advair Diskus) and indacaterol (Arcapta Neohaler, Utibron Neohaler). These drugs are each metabolized differently and Pillcheck can help to select effective treatment options.

ARDS-related trauma and laboured breathing can lead to the strain of chest muscles and diaphragm, leading to chest pains. Prolonged use of pain killers such as ibuprofen, celecoxib and other NSAIDs may pose a risk of gastrointestinal bleeding and heart complications for people with inherently reduced metabolism of these medications. For people who are recovering from COVID-19 complications, Pillcheck can assess whether it is safe to take NSAIDs over an extended period needed for full physical recovery.

Heart disease

Stiffening of lungs and virus-induced heat inflammation can lead to blood clot formation, stroke and heart attacks. Irregular heartbeat (Long QT syndrome) is one of the most common heart complications in COVID-19 patients in intensive care. Hydroxychloroquine, anesthetics, and other drugs used in intensive care can cause an irregular heartbeat that can lead to heart failure. The severe immune response also leads to excessive blood clotting, strokes and thrombosis. People with pre-existing heart conditions and hypertension have much higher mortality rates.

Patients who experienced a cardiovascular event will probably need prolonged treatment with blood thinners (warfarin, clopidogrel, ticagrelor), antiarrhythmic medications (carvedilol, propafenone, propranolol, ranolazine), antihypertensive medications (irbesartan, losartan), and statins (atorvastatin, rosuvastatin). The Pillcheck report includes all of these drugs. Clinical guidelines are available for pharmacogenetics-based warfarin and statin dosing, determining eligibility for clopidogrel, and selection of blood pressure medications. Pillcheck can help to reduce the risk of secondary stroke and heart attack and minimize adverse drug reactions, thus facilitating recovery from COVID-19 complications.

Mental health concerns after COVID-19 recovery

Based on the analysis of long-term outcomes of ARDS survivors, mental health conditions including, depression, PTSD, and cognitive decline, are a concern. In 95% of patients, at least one mental distress symptom was found, affecting quality of life and physical function. Sedatives and low levels of oxygen in the blood can lead to memory loss and cognitive problems after ARDS in nearly half of patients. Anesthesia-induced delirium may require treatment with antipsychotic medications. The Toronto ARDS outcomes group reports that 58% of ARDS survivors suffered from depression two years after hospital discharge. Depression is treatable, but in most cases requires trial with different antidepressants. Pharmacogenetic testing has been shown to reduce the time needed to find optimal depression medication and reduce depression symptoms—Pillcheck covers over 50 antidepressants and antipsychotic medications.

Muscle weakness and pain

Severe inflammation triggers muscle degradation and wasting. In some cases, “waste” protein can cause kidney damage. Muscle and joint pain may persist for several weeks. The risk of muscle pain is also increased for people with reduced statin metabolism. Statins may also cause drug-drug interactions with several cardiovascular and mental health medications. Reduction in statin dose can minimize the risk of muscle weakness and pain. Pillcheck pharmacists can advise whether statin dose reduction or switch to other cholesterol-lowering drugs is warranted.

Pilllcheck clinical pharmacists will review the patient’s current medications in the context of their inherited drug metabolism (determined by detailed DNA analysis) and will advise how to adjust treatment to reduce the risk of drug-drug and drug-gene interactions. Recommendations may include drug switches or dose adjustments that could improve recovery from COVID-19 complications.

Summary

• Over 10% of COVID-19 patients suffer from long-term complications affecting multiple organs including lungs, heart and brain
• Many medications used to treat lung damage, heart disease, as well as depression and pain have pharmacogenetic prescribing guidelines
• Pillcheck can help to shorten the length of recovery through the personalized treatment of multiple medications

References:

Intermountain Medical Center: ICU patients who survive ARDS may suffer from prolonged post-intensive care syndrome

Papazian L., et al. Formal guidelines: management of acute respiratory distress syndrome  Annals of Intensive Care volume 9, Article number: 69 (2019)

Beitler JR., et al. Ventilator-Induced Lung Injury Clin Chest Med. 2016 Dec; 37(4): 633–646.

Sasannejad C., et al. Long-term cognitive impairment after acute respiratory distress syndrome: a review of clinical impact and pathophysiological mechanisms Critical Care volume 23, Article number: 352 (2019)

Dinglas VD., et al., Perspectives of survivors, families and researchers on key outcomes for research in acute respiratory failure Thorax 2017; 73 i-ii Published Online First: 13 Dec 2017. doi: 10.1136/thoraxjnl-2017-211331

Chiumello D., et al. What’s Next After ARDS: Long-Term Outcomes Respiratory Care May 2016, 61 (5) 689-699

Bein T., et al. Long-term outcome after the acute respiratory distress syndrome: different from general critical illness?  Curr Opin Crit Care. 2018 Feb; 24(1): 35–40.