559. A Nationwide Survey of COVID-19 Management in the Dominican Republic Over the Course of the Pandemic

Abstract Background COVID-19 was declared a global Public Health Emergency by the WHO in January 2020. Limited treatment options existed early in the pandemic. As COVID-19 spread across the globe and new therapeutics emerged, different interpretations of the literature grew, and major societies relayed conflictive recommendations. There is a paucity of data on COVID-19 management in low- and middle-income countries. As a result, we performed a nationwide survey of local treatment practices in the Dominican Republic (DR). Methods We performed an anonymous survey of infectious diseases specialists in the DR and US. The survey collected hospital characteristics and COVID-19 management protocols during different quarters of 2020-21. Management was categorized by drug and disease severity based on supplemental oxygen requirements. A convenience sample in the US representing community and academic sites was surveyed for point comparison between the US and DR. Results The survey was completed by physicians from a total of 11 sites located in 4 cities of the DR: Santo Domingo (3), Santiago (4), La Vega (2) and San Francisco (2). These cities were representative of all regions in the country. The survey included 7 (64%) hospitals with < 200 beds, 3 (27%) with 201-300 beds, and 1 (9%) with >400 beds. Seven (47%) were private, 2 (13%) public, and 6 (40%) were teaching hospitals. In the US, 2 academic hospitals with >400 beds and 2 community hospitals with < 200 beds in a major city were surveyed. Management of COVID-19 at sites in the DR and US throughout the pandemic is plotted in Figure 1. Remdesivir use by disease severity is plotted in Figure 2. Figure 1. Management of COVID-19 at sites in the US and DR throughout the COVID-19 pandemic FIgure 2. Remdesivir use by disease severity at sites in the US and DR throughout the COVID-19 pandemic Conclusion Throughout the pandemic, as therapeutic options evolved, hospitals and physicians had to adapt to changing guidelines and availability of novel drugs. Variability between countries and sites emerged. The use of hydroxychloroquine and convalescent plasma waned more rapidly in the US. Dexamethasone was widely used at all sites. Tocilizumab and remdesivir were used more liberally in the DR. Antimicrobial stewardship limited these agents at US sites to more narrow therapeutic windows which could explain the discrepancies seen between the US and DR. Uncertainty of benefit in certain disease states, limited availability, and cost may also play a role. Disclosures All Authors: No reported disclosures


Session: P-24. COVID-19 Treatment
Background. COVID-19 was declared a global Public Health Emergency by the WHO in January 2020. Limited treatment options existed early in the pandemic. As COVID-19 spread across the globe and new therapeutics emerged, different interpretations of the literature grew, and major societies relayed conflictive recommendations. There is a paucity of data on COVID-19 management in low-and middle-income countries. As a result, we performed a nationwide survey of local treatment practices in the Dominican Republic (DR).
Methods. We performed an anonymous survey of infectious diseases specialists in the DR and US. The survey collected hospital characteristics and COVID-19 management protocols during different quarters of 2020-21. Management was categorized by drug and disease severity based on supplemental oxygen requirements. A convenience sample in the US representing community and academic sites was surveyed for point comparison between the US and DR.
Results. The survey was completed by physicians from a total of 11 sites located in 4 cities of the DR: Santo Domingo (3), Santiago (4), La Vega (2) and San Francisco (2). These cities were representative of all regions in the country. The survey included 7 (64%) hospitals with < 200 beds, 3 (27%) with 201-300 beds, and 1 (9%) with >400 beds. Seven (47%) were private, 2 (13%) public, and 6 (40%) were teaching hospitals. In the US, 2 academic hospitals with >400 beds and 2 community hospitals with < 200 beds in a major city were surveyed. Management of COVID-19 at sites in the DR and US throughout the pandemic is plotted in Figure 1. Remdesivir use by disease severity is plotted in Figure 2.  Conclusion. Throughout the pandemic, as therapeutic options evolved, hospitals and physicians had to adapt to changing guidelines and availability of novel drugs. Variability between countries and sites emerged. The use of hydroxychloroquine and convalescent plasma waned more rapidly in the US. Dexamethasone was widely used at all sites. Tocilizumab and remdesivir were used more liberally in the DR. Antimicrobial stewardship limited these agents at US sites to more narrow therapeutic windows which could explain the discrepancies seen between the US and DR. Uncertainty of benefit in certain disease states, limited availability, and cost may also play a role.
Disclosures. Background. Optimal dose of methylprednisolone in patients with moderate or severe COVID-19 is unclear. In our hospital, the use of 250-500 mg/day of methylprednisolone was frequent in the first wave of the pandemic. Lower dose were recommended in our protocol since September 2020. The aim was to evaluate the impact of methylprednisolone dose in the outcome of patients with moderate or severe COVID-19.
Methods. This is a retrospective and observational study. Inclusion criteria: SARS-CoV-2 infection diagnosed by PCR, admission to our hospital between March 2020 and February 2021, SatO2 < 94% or SatO2/FiO2 < 447. Two treatment groups were compared: patients treated with 0.5-1.5 mg/kg/day (group 1) and patients treated with more than 1.5 mg/kg/day (group 2). The primary outcome analyzed was orotracheal intubation (OTI) or death from any cause at 28 days after admission. Differences in demographic, clinical and laboratory characteristics between treatment groups were analyzed. Variables with P < 0.1 were included in a binary logistic regression model, calculating a propensity score for assigning each patient to group 1 treatment. Bivariate analysis was performed to identify variables associated with worst outcome. Finally, Cox regression was performed including treatment group, propensity score as covariate and all the variables with P< 0.05 in the bivariate analysis.
Conclusion. The use of high dose of methylprednisolone compared with intermediate dose is not associated with a better outcome in patients with moderate or severe COVID-19.
Disclosures. All Authors: No reported disclosures Background. Key pathologies in severe COVID-19 include immune cell activation, inflammatory cytokine release, and neutrophil extracellular trap release (NETosis), which are mediated by spleen tyrosine kinase (SYK) ( Figure  1). Fostamatinib, an oral SYK inhibitor approved for chronic immune thrombocytopenia, has shown activity in vitro using plasma from patients with severe COVID-19, by abrogating the hyperimmune response triggered by anti-spike IgG; 1 inhibiting hyperactivation in platelets; 2 and blocking NETosis in neutrophils. 3 R406, active metabolite of fostamatinib, protected against LPS-induced acute lung injury and thrombosis in mice. 4,5 In clinical studies, fostamatinib reduced IL-6 in patients with rheumatoid arthritis. 6 Therefore, a phase 2 study (NCT04579393) evaluated fostamatinib vs. placebo plus standard of care (SOC) in 59 hospitalized COVID-19 patients (manuscript pending). We initiated a phase 3 clinical study (NCT04629703) of fostamatinib for the treatment of COVID-19.

Methods.
A double-blind, randomized, placebo-controlled, adaptive design, multi-center, Phase 3 study (NCT04629703) is underway to evaluate the safety and efficacy of fostamatinib in 308 adult patients with COVID-19 ( Figure 2). Hospitalized patients without respiratory failure (with or without supplemental oxygen) were included. Patients with ARDS or using extracorporeal membrane oxygenation (ECMO) were excluded. Patients will receive fostamatinib 150 mg BID or placebo for 14 days; both arms receive SOC. The primary outcome will be progression to severe/critical disease (worsening in clinical status score on the 8-point ordinal scale) within 29 days of the first dose of study drug. Fostamatinib is investigational for COVID-19.
Results. Blinded update of trial in progress as of 28 April 2021. 12 patients have been randomized in North and South America. The clinical status score at Baseline was 5 (Hospitalized, requiring supplemental oxygen) in all 12 patients. Five patients had 8 adverse events (AE) (Fig 3). One AE (PE) was serious and is resolving. No deaths have been reported. At least two patients have been discharged (Day 5, Day 13) with continued dosing at home.