Weekly Update: October 7th-October 13th
Welcome to the COVID-19 Channel. This week we have updated guidelines for management of COVID-19 from the NIH, information about cytokine levels in COVID-19 compared to levels in other critically ill patients, and the peer reviewed results of the RECOVERY trial of hydroxychloroquine and the “Remdesivir for the Treatment of COVID-19” trial, both of which were released previously before peer-review.
The NIH has released updated management guidelines for COVID-19. Some of the highlights:
- There are specific recommendations for the use of of dexamethasone and remdesivir.
- There is insufficient data regarding are the use of convalescent serum or monoclonal antibodies.
- A recommendation against mesenchymal stem cells.
- Neither hydroxychloroquine nor azithromycin are recommended.
- HIV: Continue ART and prophylaxis for opportunistic infections in those with HIV.
- Shock: “The Panel recommends norepinephrine as the first-choice vasopressor (AII).”
- Shock: “For adults with COVID-19 and refractory septic shock who are not receiving corticosteroids to treat their COVID-19, the Panel recommends using low-dose corticosteroid therapy (“shock-reversal”) over no corticosteroid therapy (BII).”
- Prone Positioning: “For patients with persistent hypoxemia despite increasing supplemental oxygen requirements in whom endotracheal intubation is not otherwise indicated, the Panel recommends considering a trial of awake prone positioning to improve oxygenation (CIII).”
- Prone Positioning: “The Panel recommends against using awake prone positioning as a rescue therapy for refractory hypoxemia to avoid intubation in patients who otherwise require intubation and mechanical ventilation (AIII).”
- There are also specific recommendations about the use of prophylactic anticoagulation, other immune therapies, etc.
Anyone caring for patients with COVID-19 should review these guidelines. They cannot be easily summarized. The complete document can be found here.
Cytokine levels are higher in critical patients with sepsis and ARDS than they are in critical patients with COVID-19 and ARDS. This calls into question the relevance of “cytokine storm” in the pathophysiology of critical COVID-19. This is a study of 46 patients with COVID-19 related ARDS. They measured tumor necrosis factor (TNF), IL-6 and IL-8 levels and compared these to levels in historical patients who were critically ill with septic shock plus ARDS (51 patients), septic shock and no ARDS (15 patients), 62 multi-trauma patients and 30 patients who had out of hospital cardiac arrest. The data was collected between 2010 and 2020.
Patients with septic shock, with or without ARDS, had statistically significantly higher levels of TNF, IL-6 and IL-8 when compared to the patients with COVID-19 with ARDS.
The results of the other comparisons were variable, but levels of the three markers in trauma and cardiac arrest were either higher or the same as in COVID-19.
This suggests that “cytokine storm” may not be unduly responsible for the clinical condition of patients with COVID-19. The study is limited by the different assays that may have been used over the 10-year period. As with most things COVID-19, additional data would be welcome. The full study can be found here.
- Kox M, Waalders NJB, Kooistra EJ, Gerretsen J, Pickkers P. Cytokine Levels in Critically Ill Patients With COVID-19 and Other Conditions. Published online September 03, 2020. doi:10.1001/jama.2020.17052
Hydroxychloroquine did not help critically ill patients with COVID-19. And, in those not getting mechanical ventilation at baseline, was associated with a higher risk of the combined endpoint of intubation and death. This is the peer-reviewed publication of the RECOVERY trial hydroxychloroquine arm. 1,561 patients were randomized to hydroxychloroquine and 3,155 to usual care. There was no difference in death rates at 28-days in those intubated at baseline versus placebo (27% vs 25%). Of those not being ventilated at baseline, the hydroxychloroquine group had a higher risk of intubation or death (30.7% vs. 26.9%; risk ratio, 1.14; 95% CI, 1.03 to 1.27).
As reflected in the mortality rates, these were sick patients. This study tells us that hydroxychloroquine does not work in those who are critically ill with COVID-19. The full study can be found here.
- The RECOVERY Collaborative Group. Effect of Hydroxychloroquine in Hospitalized Patients with COVID-19. NEJM 8 October 2020 DOI: 10.1056/NEJMoa2022926
Remdesivir shortened the time to recovery in patients hospitalized with COVID-19 who had lower respiratory symptoms. There was no mortality benefit in any group. This is the peer-reviewed publication of the "Remdesivir for the Treatment of COVID-19" trial. This is a double-blind randomized placebo-controlled trial of remdesivir in 541 patients getting active drug and 521 getting placebo. All patients had lower respiratory symptoms and were rated between 4 and 7 in disease severity on a 7-point scale. The recovery time averaged 10 days (CI 95% 9 to 11 days) in those getting remdesivir and 15 days (CI 95% 13-18 days) in those getting placebo. There was no mortality benefit in any group.
The full study can be found here.
- Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the Treatment of COVID-19-final report. NEJM 8 October 2020 DOI: 10.1056/NEJMoa2007764