This week we have new information on the use of steroids in COVID-19, guidance from the NIH on the use of convalescent serum (which is contrary to the FDA recommendation) and new information on the impact of COVID-19 on community health center visits and on immunizations.
The NIH suggests that convalescent plasma is not standard of care and needs more study. This is despite the endorsement by the FDA. What we know so far: The studies that have looked at convalescent plasma show that it is relatively safe. However, the randomized trials have all been stopped early and have not reached statistical significance (though there is a hint of a benefit). Open label studies have been equivocal with some being positive and others negative. What is new: The NIH suggests that the data is inconclusive, and that convalescent plasma should not be considered the standard of care. The main points are:
“Based on the available evidence, the Panel has determined the following:
- There is insufficient data to recommend either for or against the use of convalescent plasma for the treatment of COVID-19.
- Available data suggest that serious adverse reactions following the administration of COVID-19 convalescent plasma are infrequent and consistent with the risks associated with plasma infusions for other indications.
- The long-term risks of treatment with COVID-19 convalescent plasma [are unknown]. [It is also not clear] whether its use attenuates the immune response to SARS-CoV-2, making patients more susceptible to reinfection.
- Convalescent plasma should not be considered standard of care for the treatment of patients with COVID-19.
- Prospective, well-controlled, adequately powered randomized trials are needed to determine whether convalescent plasma is effective and safe for the treatment of COVID-19. Members of the public and health care providers are encouraged to participate in these prospective clinical trials.” The full statement can be found here.
Other problems include the lack of a standardized dose, how to appropriately determine the antibody levels in convalescent plasma, etc. While more conservative, the NIH statement better reflects the state of the art concerning convalescent plasma in COVID-19.
- The COVID-19 Treatment Guidelines Panel’s Statement on the Emergency Use Authorization of Convalescent Plasma for the Treatment of COVID-19
- FDA Clinical Memorandum, Emergency Use Authorization for COVID-19 convalescent plasma 23 August 2020.
- Ling L. et al. Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19 A Randomized Clinical Trial JAMA. 2020;324(5):460-470. doi:10.1001/jama.2020.10044 (initially published in June, now updated with corrections).
A meta-analysis confirms the value of steroids in critically ill patients with COVID-19. This is a meta-analysis of 7 randomized trials of 1700 patients of whom 37% died. Six of the 7 trials were deemed to have a low risk of bias. Criteria for patient enrollment differed between the trials from 6L/min of oxygen to intubation. Treatments included high or low dose steroids. Outcomes were mortality 28 days after randomization (two studies only reported on 21-day mortality). The absolute risk of mortality in ventilated patients was 30% with steroids vs. 38% with placebo (NNT=8). For those not ventilated the absolute risk of mortality was 23% for corticosteroids vs 42% for usual care or placebo (NNT=5). The full study can be found here.
This study confirms the benefit of corticosteroids in critically ill patients with COVID-19. Based on this meta-analysis, the World Health Organization (WHO) recommends 6 mg of dexamethasone orally or intravenously daily or 50 mg of hydrocortisone intravenously every 8 hours for 7 to 10 days in seriously ill patients.
This does not mean that every patient with COVID-19 should get steroids. But it seems to be helpful in those with “severe” disease.
- The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group. Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis. Published online September 02, 2020. doi:10.1001/jama.2020.17023
Community health centers (CHCs) are a significant locus of COVID-19 testing. Additionally, preventive service visits dropped dramatically between January first and May 1st compared to historical controls. This is a study of CHCs from 21 states comprising 431 unique CHCs that use the same electronic medical record. In that period, 33,226 patients (1.7% of the total seen) were tested for COVID-19. Of these, 28% were positive. Importantly, the number of face-to-face visits as did well child visits, Pap tests, mammograms and hemoglobin A1c testing. The full study is available here. Other studies have documented a steep decline in routine immunizations despite an infrastructure that is adequate to administer said vaccines.
These studies remind us that routine health care may be suffering as a result of COVID-19. We need to redouble our effort to reassure our patients that, properly done, routine visits are safe.
- Heintzman J, O’Malley J, Marino M, et al. SARS-CoV-2 Testing and Changes in Primary Care Services in a Multistate Network of Community Health Centers During the COVID-19 Pandemic. Published online August 31, 2020. doi:10.1001/jama.2020.15891
- Vogt TM, Zhang F, Banks M, et al. Provision of Pediatric Immunization Services During the COVID-19 Pandemic: an Assessment of Capacity Among Pediatric Immunization Providers Participating in the Vaccines for Children Program — United States, May 2020. MMWR Morb Mortal Wkly Rep 2020;69:859–863. DOI: http://dx.doi.org/10.15585/mmwr.mm6927a2external icon.
- Santoli JM, Lindley MC, DeSilva MB, et al. Effects of the COVID-19 Pandemic on Routine Pediatric Vaccine Ordering and Administration — United States, 2020. MMWR Morb Mortal Wkly Rep 2020;69:591–593. DOI: http://dx.doi.org/10.15585/mmwr.mm6919e2