Managing COVID-19 is a work in progress. Multiple treatments have been tried and sometimes adopted without adequate evidence. As trials continue, the evidence changes, the virus continues to evolve, and the pandemic lives on.
“COVID-19 is more than a respiratory illness,” said Bharat Bajantri, MD, Critical Care Pulmonologist, Parkview Health, Fort Wayne, IN. “It is a complex, multisystem disease, and it is a moving target.”
Dr. Bajantri discussed acute treatment of COVID-19 during Plague Version 2020: Acute Management of COVID-19 and Long-term Post COVID-19 Pulmonary Sequelae.
According to Dr. Bajantri, therapeutic recommendations can differ with the severity of COVID symptoms. World Health Organization (WHO) data suggest that about 5% of patients develop critical disease, and maintaining oxygen saturation is an important treatment goal for all patients. WHO recommends supplemental oxygen to maintain 94% SO2 in emergency and resuscitation, 90% for asymptomatic disease, and 92%-95% in pregnancy.
Data for remdesivir is inconclusive, Dr. Bajantri continued, with some trials showing shorter recovery times and others showing little to no effect. Some guidelines recommend remdesivir in severely ill patients not on mechanical ventilation, and most organizations recommend against use in critically ill patients on ventilation. Other antivirals have shown little evidence of benefit.
Antibiotics and antimalarials are generally not recommended, he added. Published randomized trials have not shown efficacy for chloroquine and hydroxychloroquine, and multiple organizations, including WHO, recommend against use.
Similarly, there are no good trial data for antihelminthic agents nor for antiprotozoal agents such as emetine.
Immunomodulation is effective in some patients. A few trials suggest that bamlanivimab-etesevimab or casirivimab-imdevimab may reduce disease progression and rates of hospitalization and mortality, but the data are not robust. Data on postexposure prophylaxis are inconclusive.
Corticosteroids, a 5- to 10-day course of 6-20 mg dexamethasone or equivalent, can reduce mortality, but no benefit was seen in patients without hypoxemia, Dr. Bajantri cautioned. It is not clear if the benefits are a class effect or unique to dexamethasone, nor are the ideal dosing and duration known.
“It is reasonable to follow inflammatory markers and the acuity of clinical illness and adjust dosing,” he said.
Adding IL-6 inhibitors to steroids can improve overall efficacy vs steroids alone, but IL-6 inhibitors alone are less effective as monotherapy than in combination with corticosteroids.
There are promising trial data on steroids plus Janus kinase (JAK) inhibitors but not data on IL-6 inhibitors plus JAK inhibitors.
Overwhelming evidence shows no benefit for convalescent plasma in hospitalized patients, and most guidelines recommend its use only in clinical trials. There are similar trial-only recommendations for sarilumab, thalidomide, bevacizumab, granulocyte-macrophage colony-stimulating factor inhibitors, and multiple other agents.
The data for anticoagulation are mixed, although COVID-19 has a high incidence of macrovascular and microvascular thrombotic events and disseminated intravascular coagulation. Existing evidence does not support high-dose use for routine deep vein thrombosis in hospitalized patients, Dr. Bajantri said, but trials are ongoing. Patients on preexisting anticoagulation should continue treatment.
“COVID-19 is a complex, multisystem disease,” said Damaris Pena Evertz, MD, Pulmonary and Critical Care Specialist, Thomas Jefferson University Hospitals, Philadelphia. “Overall, standard of care prevails with infection protocols in place.”
Four key mechanisms drive the extrapulmonary manifestations of COVID-19: Direct cytotoxic effects, dysregulation of the renin-angiotensin-aldosterone system, endothelial cell damage, and dysregulated immune responses. Treatment intensity increases with disease severity, she said.
About 36% of patients exhibit neurological effects, which may represent a risk for more severe disease. Cardiovascular disease is more common and may be either de novo disease or exacerbation of existing cardiovascular conditions.
“Cardiac damage is likely in patients with severe COVID disease,” Dr. Evertz cautioned.
GI symptoms, particularly diarrhea, are also common, as are liver and kidney damage. About 15% of patients with COVID-19 develop acute kidney injury, which has 60%-90% mortality. The most effective approach seems to be supportive therapy and organ transplantation as appropriate.
About a third of patients exhibit hematologic symptoms, she continued. Standard of care is the most effective approach, including frequent assessment for venous thromboembolism. High-dose anticoagulation does not improve outcomes and is associated with increased adverse events, including death.
Many centers avoided noninvasive ventilation early in the pandemic over fears of virus shedding in aerosols, but high-flow nasal cannulas and helmet oxygenation have become common with greater experience, reported Alaa Abu Sayf, MD, Henry Ford Hospital, Detroit. Noninvasive ventilation is generally successful in non-ICU patients.
Patients with COVID-19 with severe disease nearly always have low lung compliance, complicating mechanical ventilation, said Dr. Sayf. Hypoxia and outcomes are generally worse in patients with COVID-19 and with acute respiratory distress syndrome (ARDS) than in patients without COVID-19 and with ARDS.
ECMO, extracorporeal membrane oxygenation, is currently recommended for patients on mechanical ventilation for more than 7 days, he continued, but about half of patients may have intracranial bleeding. The etiology is unclear, but using low-dose heparin may limit bleeding and vasodilation.
Pulmonary fibrosis is commonly reported, likely the result of aberrant repair after inflammatory response to COVID-related pulmonary injury.
“Timing for lung transplantation is a challenge,” Dr. Sayf added. “Too early and there is a risk for reactivation of COVID-19, and too late, patients may be debilitated with poor rehab potential and increased comorbidities.”
Patients with single-organ injury and adequate nutritional status are more likely to have better outcomes after transplantation, he added. Sixty-day survival is very good, but numbers are limited.
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