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| Title | Date Published | DOI |
| Treatment for Severe Acute Respiratory Distress Syndrome from COVID-19 | 03/20/2020 | 10.1016/S2213-2600(20)30127-2 |
| Treatment of 5 Critically Ill Patients with COVID-19 with Convalescent Plasma | 03/27/2020 | 10.1001/jama.2020.4783 |
| Remdesivir for the Treatment of COVID-19-Preliminary Report | 5/22/2020 | 10.1056/NEJMoa2007764 |
Treatment for Severe Acute Respiratory Distress Syndrome from COVID-19
One of the hallmark complications of COVID-19 is Acute Respiratory Distress Syndrome (ARDS). Patients with ARDS present with respiratory failure – shortness of breath, increased respiratory rate, and decreased oxygen in the blood. The article suggests multiple evidence-based treatment options for patients suffering from severe ARDS due to COVID-19. A previous study recommended the use of extracorporeal membrane oxygenation (ECMO) for severe ARDS due to COVID-19; however, this requires resources and protocols that may be difficult to coordinate on a larger-scale during a pandemic.
Lung protective ventilation strategies may be useful in patients requiring intubation to avoid ventilator associated complications. The authors encourage low tidal volumes, low plateau pressures, low driving pressures, and higher PEEP levels. If a patient is asynchronous with the ventilator, has increasing airway pressures, or worsening hypoxemia, clinicians may want to consider neuromuscular blockade agents. The authors also include prone positioning as a way to potentially improve oxygenation.
Unfortunately, patients may be unresponsive to these measures. Inhaled nitrous oxide (NO), fluid conservative therapy, and renal replacement therapy are mentioned as additional strategies. Previous studies in ARDS patients demonstrated that inhaled NO increases blood flow to well-ventilated areas of the lungs, reduces arterial blood pressure in the lungs, and improves blood oxygen levels. The authors propose combining fluid conservative therapy with renal replacement therapy to reduce pulmonary edema. Of note, the authors recommend antibiotics in cases of secondary bacterial infections, but discourage use of steroids. An interesting consideration is the use of high-dose vitamin C to reduce lung injury. Vitamin C is a well-known attenuator of inflammation and vascular injury.
Treatment of 5 Critically Ill Patients with COVID-19 with Convalescent Plasma
In the absence of a definitive treatment, convalescent plasma has been used as empiric therapy for various infections such as SARS-CoV, Ebola, and MERS-CoV. Convalescent plasma is blood collected from people who have recovered from an infection that contains antibodies against the disease. As the COVID-19 pandemic continues to spread worldwide, numerous management options are being investigated; however, few have proven to be effective to date. This uncontrolled case series conducted in Shenzhen, China explored the use of convalescent plasma in the treatment of critically ill patients suffering from COVID-19 and Acute Respiratory Distress Syndrome (ARDS). Five patients ages 36-65 with confirmed COVID-19 using qRT-PCR were given plasma from five patients who had recovered from the infection. The study defined critically ill COVID-19 patients as those currently on mechanical ventilation with high viral loads, despite at least 10 days of antiviral treatment, and a PAO2/FIO2 < 300. Convalescent plasma transfusions with SARS-CoV-2 IgG with antibody titers greater than 1:1000 were given to patients between day 10-22 of admission. Patients were concurrently given methylprednisolone, in addition to various antivirals. Changes in body temperature, Sequential Organ Failure Assessment (SOFA) scores, PAO2/FIO2 ratio, viral loads, serum antibody titers, ARDS and ventilatory supports, and routine blood indices were analyzed before and after transfusions. Results of this case series showed an improvement in clinical status in all five patients. Body temperatures normalized within three days in 4/5 patients, PAO2/FIO2 ratios increased, viral loads decreased and became negative, and SOFA scores decreased within 12 days of transfusion. ARDS resolved in 4/5 patients within 12 days of transfusion, 3/5 patients were discharged from the hospital, and the other 2 patients were in stable condition at time of publication. Of note, none of the patients were smokers and only one had a pre-existing health condition. The small sample size, lack of controls, and administration of additional medications may have affected results. Given these limitations as well as the positive clinical results from this study, more investigation is necessary to further elucidate the effects of convalescent plasma in the treatment of COVID-19 and ARDS.
Remdesivir for the Treatment of COVID-19: Preliminary Report
To date, no specific therapeutic agent has proven to be efficacious for the treatment of COVID-19. As the virus continues to spread worldwide, the discovery of a safe and effective treatment is paramount. Previous research identified remdesivir’s ability to inhibit COVID-19 in vitro. Remdesivir prevents viral replication by inhibiting the viral RNA-dependent RNA polymerase. In this study, researchers examined the use of intravenous remdesivir to treat adults hospitalized with COVID-19. The paper presents preliminary results from a multicenter, double-blind randomized control trial. Patients in the experimental group were administered intravenous remdesivir with a 200-mg loading dose on day 1, followed by 100-mg maintenance doses for days 2-10. The control group was given a matching placebo on the same schedule. All patients continued to receive supportive care as determined by the standard of care at their respective hospital. If a hospital allowed for other off-label treatments of COVID-19, the patient could continue to receive them if the treatment had been initiated prior to enrollment. Patients were followed for 28 days after the first dose. To measure clinical status, a categorized ordinal scale was used ranging from 1, indicating not hospitalized, to 8, denoting death. The primary outcome of interest was time to recovery, defined as the patient’s first day satisfying categories 1, 2, or 3. Results demonstrated that patients receiving remdesivir had a shorter time to recovery compared to the placebo group. When the results were stratified according to baseline ordinal scale, the benefit was greatest in patients with a baseline score of 5. The authors suggest this may be due to the larger sample size in this category. Overall, the odds of improvement were higher in the remdesivir group. Despite improvement in clinical status, there was still a high mortality rate among the remdesivir group, suggesting the need for combination therapy. While the trial is still ongoing, these preliminary findings support use of remdesivir in COVID-19 patients who require supplemental oxygen.
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