Hepatitis B in Heart Transplant Donors and Recipients: A Systematic Review and Meta-Analysis.

INTRODUCTION: Expanding the heart donor pool to include patients with hepatitis B virus (HBV) could help ameliorate the organ shortage in heart transplantation. We performed a systematic review and meta-analysis to evaluate the management and recipient outcomes of D+/R- and D-/R+ heart transplants. METHODS: An electronic search was performed to identify all relevant studies published on heart transplants involving HBV+ donors and/or HBV+ recipients. A comparison was performed between two groups where heart transplants were performed a) D+/R- (n = 98) versus b) D-/R+ (n = 65). RESULTS: Overall, 13 studies were selected, comprising 163 patients. Mean patient age was 55 y (95% CI: 39, 78) and 79% (69, 86) were male. Active post-transplant HBV infection requiring antiviral treatment occurred in 11% (1, 69) of D+/R- recipients and 33% (9, 71) of D-/R+ recipients. Post-transplant antiviral therapy was given to 80% (6, 100) of D+/R- recipients compared to 72% (42, 90) of D-/R+ recipients (P = 0.84). Hepatitis-related mortality was observed in no D+/R- recipients and 7% (2, 27) of D-/R+ recipients. Survival 1-y post-transplant was comparable between both groups at 83% (83, 92) and 81% (61, 92) for D+/R- and D-/R+ transplants, respectively. CONCLUSIONS: Our review found that HBV D+/R- heart transplantation was associated with fewer active hepatitis infections and lower hepatitis-related mortality than D-/R+ transplantation, with comparable survival at 1 y. Additional studies utilizing HBV nucleic acid testing (NAT) to compare outcomes with HBsAg+ and anti-HBc+ donors are crucial to reach more definitive conclusions about the risk of donor-derived infections in this context.

"Saving lives with nirmatrelvir/ritonavir one transplant patient at a time".

BACKGROUND: Solid organ transplant (SOT) recipients are at risk of complications from COVID-19. Nirmatrelvir/ritonavir (Paxlovid) can reduce mortality from COVID-19 but is contraindicated in patients receiving calcineurin inhibitors (CI), which depend on cytochrome p4503A (CY3PA). In this study, we aim to show the feasibility of nirmatrelvir/ritonavir administration to SOT recipients receiving CI with coordination of medication management and limited tacrolimus trough monitoring. METHODS: We reviewed adult SOT recipients treated with nirmatrelvir/ritonavir from 4/14 to 11/1/2022 and assessed for changes in tacrolimus trough and serum creatinine after therapy. RESULTS: Of 47 patients identified, 28 were receiving tacrolimus and had follow-up laboratory testing. Patients had a mean age of 55 years, 17 (61%) received a kidney transplant and 23 (82%) received three or more doses of SARS-CoV-2 mRNA vaccine. Patients had mild-moderate COVID-19 and started nirmatrelvir/ritonavir within 5 days of symptom onset. Median baseline tacrolimus trough concentration was 5.6 ng/mL (Interquartile range 5.1-6.7), while median follow-up tacrolimus trough concentration was 7.8 ng/mL (Interquartile range 5.7-11.5, p = 0.0017). Median baseline and follow-up serum creatinine levels were 1.21 mg/dL (Interquartile range 1.02-1.39) and 1.21 mg/dL (interquartile range 1.02-1.44, p = 0.3162), respectively. One kidney recipient had a follow up creatinine level >1.5 times baseline. No patients were hospitalized or died from COVID-19 in the follow up period. CONCLUSION: While administration of nirmatrelvir/ritonavir resulted in a significant increase in tacrolimus concentration, this did not result in significant nephrotoxicity. Early oral antiviral treatment in SOT recipients is feasible with medication management, even with limited tacrolimus trough monitoring.

Shoulder periprosthetic joint infection is associated with increased mortality.

BACKGROUND: Periprosthetic joint infections (PJIs) are a catastrophic complication after shoulder arthroplasty and may be associated with an increased mortality risk, as seen in hip and knee arthroplasty. Shoulder PJI organisms differ from hip and knee infections, as lower-virulence organisms, such as Cutibacterium acnes, are more commonly encountered. This study evaluated the association between shoulder PJI and mortality. METHODS: We retrospectively identified 411 patients who underwent revision shoulder arthroplasty from 2007 to 2020 at a single institution. 2018 International Consensus Meeting on Musculoskeletal Infection criteria were used to categorize each case as definite, probable, possible, or unlikely PJI. Mortality rate was assessed by performing chart reviews and an obituary search. Revision cases were grouped into a septic cohort (definite and probable PJI) and an aseptic cohort (possible and unlikely PJI). Kaplan-Meier analyses were performed to compare survival between septic and aseptic groups. The log-rank test was used to compare cumulative survival distributions and survival rates at 90 days, 6 months, 1 year, 2 years, and 5 years. Demographic information, Charlson Comorbidity Index (CCI), and culture data were collected. PJI organisms were categorized as virulent or nonvirulent per an infectious disease specialist, and predictors of mortality were determined by performing stepwise logistic regression analyses. RESULTS: The overall mortality rate was significantly greater (P < .001) in the septic group (20.5%) than in the aseptic group (6.6%). When evaluating time from revision surgery to death, patients with PJI had significantly greater mortality compared with those undergoing aseptic revision at 2 years (7.7% vs. 2.1%, P = .01) and 5 years (17% vs. 5.1%, P < .001). Body mass index, CCI, race, sex, and age were not significantly different between groups. Groups differed in utilization of 2-staged procedures (65% septic, 9% aseptic, P < .001). Multivariate regression analysis found that the variables most associated with mortality were septic revision, 2-staged procedures, and CCI. In the septic group, patients with C acnes PJI had a significantly lower mortality rate when compared to PJI from any other offending organism (3.1% vs. 48.4%, P = .001). CONCLUSION: Revision shoulder arthroplasty in the setting of PJI not only carries severe functional consequences for patients but is also associated with an increased mortality risk. Furthermore, C acnes infections are associated with a more favorable survival profile than PJI resulting from other organisms. Continued efforts to decrease shoulder arthroplasty infection rates are warranted and may influence long-term survival.

If, When, and How to Use Rifampin in Acute Staphylococcal Periprosthetic Joint Infections, a Multicentre Observational Study.

BACKGROUND: Rifampin is generally advised in the treatment of acute staphylococcal periprosthetic joint infections (PJI). However, if, when, and how to use rifampin remains a matter of debate. We evaluated the outcome of patients treated with and without rifampin, and analyzed the influence of timing, dose and co-antibiotic. METHODS: Acute staphylococcal PJIs treated with surgical debridement between 1999 and 2017, and a minimal follow-up of 1 year were evaluated. Treatment failure was defined as the need for any further surgical procedure related to infection, PJI-related death or the need for suppressive antimicrobial treatment. RESULTS: A total of 669 patients were analyzed. Treatment failure was 32.2% (131/407) in patients treated with rifampin and 54.2% (142/262) in whom rifampin was withheld (P < .001). The most prominent effect of rifampin was observed in knees (treatment failure 28.6% versus 63.9%, respectively, P < .001). The use of rifampin was an independent predictor of treatment success in the multi-variate analysis (OR 0.30, 95% CI 0.20 - 0.45). In the rifampin group, the use of a co-antibiotic other than a fluoroquinolone or clindamycin (OR 10.1, 95% CI 5.65 - 18.2) and the start of rifampin within 5 days after surgical debridement (OR 1.96, 95% CI 1.08 - 3.65) were predictors of treatment failure. The dosing of rifampin had no effect on outcome. CONCLUSIONS: Our data supports the use of rifampin in acute staphylococcal PJIs treated with surgical debridement, particularly in knees. Immediate start of rifampin after surgical debridement should probably be discouraged, but requires further investigation.

Debridement, Antibiotics, and Implant Retention Is a Viable Treatment Option for Early Periprosthetic Joint Infection Presenting More Than 4 Weeks After Index Arthroplasty.

BACKGROUND: The success of debridement, antibiotics, and implant retention (DAIR) in early periprosthetic joint infection (PJI) largely depends on the presence of a mature biofilm. At what time point DAIR should be disrecommended is unknown. This multicenter study evaluated the outcome of DAIR in relation to the time after index arthroplasty. METHODS: We retrospectively evaluated PJIs occurring within 90 days after surgery and treated with DAIR. Patients with bacteremia, arthroscopic debridements, and a follow-up <1 year were excluded. Treatment failure was defined as (1) any further surgical procedure related to infection; (2) PJI-related death; or (3) use of long-term suppressive antibiotics. RESULTS: We included 769 patients. Treatment failure occurred in 294 patients (38%) and was similar between time intervals from index arthroplasty to DAIR: the failure rate for Week 1-2 was 42% (95/226), the rate for Week 3-4 was 38% (143/378), the rate for Week 5-6 was 29% (29/100), and the rate for Week 7-12 was 42% (27/65). An exchange of modular components was performed to a lesser extent in the early post-surgical course compared with the late course (41% vs 63%, respectively; P < .001). The causative microorganisms, comorbidities, and durations of symptoms were comparable between time intervals. CONCLUSIONS: DAIR is a viable option in patients with early PJI presenting more than 4 weeks after index surgery, as long as DAIR is performed within at least 1 week after the onset of symptoms and modular components can be exchanged.

Tick-borne illness after transplantation: Case and review.

Tick-borne infections in solid organ transplant recipients are an infrequent and difficult diagnostic challenge owing to multiple routes of acquisition and unusual presentations. A 67-year-old male recipient of a combined liver and kidney transplant presented with recurrent fevers following surgery. Standard microbiologic workup was non-diagnostic. Shortness of breath, confusion, lethargy, and hypotension developed along with progressive anemia, requiring multiple blood transfusions. Workup suggested hemolysis and review of the peripheral smear was diagnostic for Babesia microti infection. Tick transmission, transmission via blood products, and/or the transplanted organ were all considered. More extensive questioning revealed a history of intermittent fevers for several months before transplantation. Testing of pre-transplant blood was positive for B. microti antibodies, suggesting infection prior to transplantation. The delayed diagnosis of babesiosis in this patient highlights the need for a detailed exposure history prior to transplantation, as well as considering the potential for atypical presentations of tick-borne infections in immune suppressed solid organ recipients. Furthermore, this case illustrates the importance of early Infectious Disease consultation to meet the challenges exhibited by febrile transplant patients. Infectious Diseases physicians are trained to consider, diagnose, and treat tick-borne infections, contributing to improved clinical outcome.

The Mark Coventry, MD, Award: Oral Antibiotics Reduce Reinfection After Two-Stage Exchange: A Multicenter, Randomized Controlled Trial.

BACKGROUND: Many patients develop recurrent periprosthetic joint infection after two-stage exchange arthroplasty of the hip or knee. One potential but insufficiently tested strategy to decrease the risk of persistent or recurrent infection is to administer additional antibiotics after the second-stage reimplantation. QUESTIONS/PURPOSES: (1) Does a 3-month course of oral antibiotics decrease the risk of failure secondary to infection after a two-stage exchange? (2) Are there any complications related to the administration of oral antibiotics after a two-stage exchange? (3) In those patients who develop a reinfection, is the infecting organism different from the initial infection? METHODS: Patients at seven centers randomized to receive 3 months of oral antibiotics or no further antibiotic treatment after operative cultures after the second-stage reimplantation were negative. Adult patients undergoing two-stage hip or knee revision arthroplasty for a periprosthetic infection who met Musculoskeletal Infection Society (MSIS) criteria for infection at the first stage were included. Oral antibiotic therapy was tailored to the original infecting organism(s) in consultation with an infectious disease specialist. MSIS criteria as used by the treating surgeon defined failure. Surveillance of patients for complications, including reinfection, occurred at 3 weeks, 6 weeks, 3 months, 12 months, and 24 months. If an organism demonstrated the same antibiotic sensitivities as the original organism, it was considered the same organism; no DNA subtyping was performed. Analysis was performed as intent to treat with all randomized patients included in the groups to which they were randomized. A log-rank survival curve was used to analyze the primary outcome of reinfection. At planned interim analysis (enrollment is ongoing), 59 patients were successfully randomized to the antibiotic group and 48 patients to the control group. Fifty-seven patients had an infection after TKA and 50 after a THA. There was no minimum followup for inclusion in this analysis. The mean followup was 14 months in the antibiotic group and 10 months in the control group. RESULTS: Patients treated with oral antibiotics failed secondary to infection less frequently than those not treated with antibiotics (5% [three of 59] versus 19% [nine of 48]; hazard ratio, 4.37; 95% confidence interval, 1.297-19.748; p = 0.016). Three patients had an adverse reaction to the oral antibiotics severe enough to cause them to stop taking the antibiotics early, and four patients who were randomized to that group did not take the antibiotics as directed. With the numbers available, there were no differences between the study groups in terms of the likelihood that an infection after treatment would be with a new organism (eight of nine in the control group versus one of three in the treatment group, p = 0.087). CONCLUSIONS: This multicenter randomized trial suggests that at short-term followup, the addition of 3 months of oral antibiotics appeared to improve infection-free survival. As a planned interim analysis, however, these results may change as the study reaches closure and the safety profile may yet prove risky. Further followup of this cohort of patients will be necessary to determine whether these preliminary results are durable over time. LEVEL OF EVIDENCE: Level I, therapeutic study.

Bacterial Contamination in Tips of Electrocautery Devices During Total Hip Arthroplasty.

Surgical equipment can become contaminated during surgery. It is unknown if electrocautery tips can become contaminated in clean orthopedic procedures despite the produced heat. Therefore, we conducted a prospective study to address this concern. The tips from 25 primary and 25 aseptic revision THAs were collected and an additional 5 sterile tips served as negative controls. Aerobic and anaerobic cultures were incubated for a minimum of 3 days. There were 3 positive cultures (6%); one in primary THA (4%) with Lactobacillus and Enterococcus faecalis; two among revisions (8%), one with E. faecalis and another one with alpha hemolytic streptococci and coagulase negative Staphylococcus. The mean exposure time of the contaminated tips was 132.3 minutes. Patients were followed for 90 days postoperatively and none of them developed surgical site infection. This is the first study to demonstrate that electrosurgical devices can become contaminated during THA in laminar flow equipped operating rooms.

The Association of Asthma and Metabolic Dysfunction With Outcomes of Hospitalized Patients With COVID-19.

BACKGROUND: There have been conflicting results on the association of asthma with the severity of coronavirus disease 2019 (COVID-19). Poor metabolic health has been previously associated with both severe COVID-19 and inflammation in asthma. OBJECTIVES: To examine the association between asthma and COVID-19 outcomes and whether these associations are modified by metabolic syndrome. METHODS: We performed an international, observational cohort study of adult patients hospitalized for COVID-19 from February 2020 through October 2021. The primary outcome was hospital mortality. RESULTS: The study included 27,660 patients from 164 hospitals, 12,114 (44%) female, with a median (interquartile range) age of 63 years (51-75). After adjusting for age, sex, smoking, race, ethnicity, geographic region, and Elixhauser comorbidity index, we found that patients with asthma were not at greater risk of hospital death when compared with patients with no chronic pulmonary disease (controls) (adjusted odds ratio [aOR], 0.97; 95% CI, 0.90-1.04; P = .40). Patients with asthma, when compared with controls, required higher respiratory support identified by the need for supplemental oxygen (aOR, 1.07; 95% CI, 1.01-1.14; P = .02), high-flow nasal cannula or noninvasive mechanical ventilation (aOR, 1.06; 95% CI, 1.00-1.13; P = .04), and invasive mechanical ventilation (aOR, 1.09; 95% CI, 1.03-1.16; P = .003). Metabolic syndrome increased the risk of death in patients with asthma, but the magnitude of observed association was similar to controls in stratified analysis (interaction P value .24). CONCLUSIONS: In this international cohort of hospitalized COVID-19 patients, asthma was not associated with mortality but was associated with increased need for respiratory support. Although metabolic dysfunction was associated with increased risks in COVID-19, these risks were similar for patients with or without asthma.

Skull Base Osteomyelitis: Historical Perspective, Diagnosis and Management Update.

SBO is a life-threatening disease that requires a high index of suspicion based on these patients complex underlying medical co-morbidities and clinician's acumen. Once a diagnosis is made, is it critical to communicate and work closely with other multidisciplinary teams (neuroradiology for appropriate choice of imaging study and interpretation; infectious disease for appropriate medical treatment and duration; internist to properly manage their underlying medical co-morbidities). Despite advances in imaging, the diagnosis is first made based on clinical judgment, appropriate culture, and tissue biopsy.

Should We Use Rifampicin in Periprosthetic Joint Infections Caused by Staphylococci When the Implant Has Been Exchanged? A Multicenter Observational Cohort Study.

Background: Previous studies demonstrated the efficacy of a rifampicin-based regimen in the treatment of acute staphylococcal periprosthetic joint infections (PJIs) treated with surgical debridement. However, evidence is lacking to support the use of rifampicin in cases where the implant is exchanged during revision. Methods: We included all consecutive cases of staphylococcal PJIs treated from January 2013 to December 2018 with revision surgery in this international, retrospective, multicenter observational cohort study. PJI was defined according to the European Bone and Joint Infection Society diagnostic criteria. A relapse or reinfection during follow-up, the need for antibiotic suppressive therapy, the need for implant removal, and PJI-related death were defined as clinical failure. Cases without reimplantation or with follow-up <12 months were excluded. Results: A total of 375 cases were included in the final analysis, including 124 1-stage exchanges (33.1%) and 251 2-stage exchanges (66.9%). Of those, 101 cases failed (26.9%). There was no statistically significant difference in failure of patients receiving rifampicin (22.5%, 42/187) and those not receiving rifampicin (31.4%, 59/188; P = .051). A subanalysis of chronic PJIs treated by 2-stage exchange arthroplasty demonstrated a lower failure rate in cases treated with rifampicin (15%) compared with the no-rifampicin group (35.5%; P = .005). In this subgroup, the use of rifampicin and an antibiotic holiday of >2 weeks were independent predictors of clinical success (odds ratio [OR], 0.36; 95% CI, 0.15-0.88; and OR, 0.19; 95% CI, 0.04-0.90; respectively). Conclusions: Combination treatment with rifampicin increases treatment success in patients with chronic staphylococcal PJI treated with 2-stage exchange arthroplasty.

Validation of automated data abstraction for SCCM discovery VIRUS COVID-19 registry: practical EHR export pathways (VIRUS-PEEP).

Background: The gold standard for gathering data from electronic health records (EHR) has been manual data extraction; however, this requires vast resources and personnel. Automation of this process reduces resource burdens and expands research opportunities. Objective: This study aimed to determine the feasibility and reliability of automated data extraction in a large registry of adult COVID-19 patients. Materials and methods: This observational study included data from sites participating in the SCCM Discovery VIRUS COVID-19 registry. Important demographic, comorbidity, and outcome variables were chosen for manual and automated extraction for the feasibility dataset. We quantified the degree of agreement with Cohen's kappa statistics for categorical variables. The sensitivity and specificity were also assessed. Correlations for continuous variables were assessed with Pearson's correlation coefficient and Bland-Altman plots. The strength of agreement was defined as almost perfect (0.81-1.00), substantial (0.61-0.80), and moderate (0.41-0.60) based on kappa statistics. Pearson correlations were classified as trivial (0.00-0.30), low (0.30-0.50), moderate (0.50-0.70), high (0.70-0.90), and extremely high (0.90-1.00). Measurements and main results: The cohort included 652 patients from 11 sites. The agreement between manual and automated extraction for categorical variables was almost perfect in 13 (72.2%) variables (Race, Ethnicity, Sex, Coronary Artery Disease, Hypertension, Congestive Heart Failure, Asthma, Diabetes Mellitus, ICU admission rate, IMV rate, HFNC rate, ICU and Hospital Discharge Status), and substantial in five (27.8%) (COPD, CKD, Dyslipidemia/Hyperlipidemia, NIMV, and ECMO rate). The correlations were extremely high in three (42.9%) variables (age, weight, and hospital LOS) and high in four (57.1%) of the continuous variables (Height, Days to ICU admission, ICU LOS, and IMV days). The average sensitivity and specificity for the categorical data were 90.7 and 96.9%. Conclusion and relevance: Our study confirms the feasibility and validity of an automated process to gather data from the EHR.

Antibody Response to SARS-CoV-2 Vaccination in Patients With Lymphoproliferative Disorders and Plasma Cell Dyscrasias: Anti-Lymphoma Therapy as a Predictive Biomarker of Response to Vaccination.

We retrospectively analyzed SARS-CoV-2 vaccination antibody responses in a cohort of 273 patients with lymphoproliferative disorders or plasma cell dyscrasias who were seen at a single tertiary cancer center. Semi-quantitative anti-spike protein serologic testing was performed with enzyme immunoassay method. We found that the antibody response rate to SARS-CoV-2 vaccination was 74.7% in our patient cohort with no difference based on gender, age or race. The highest response rate was found in patients with Multiple Myeloma (MM) (95.5%). The response rates found in Diffuse Large B-Cell Lymphoma (DLBCL), Chronic Lymphocytic Leukemia (CLL), and Low-Grade Non-Hodgkin Lymphoma (LG-NHL) were 73.2%, 61.5% and 53% respectively. We also evaluated the effects of receiving active chemo-immunotherapy on SARS-CoV-2 vaccination antibody response. We found that the patients on treatment had lower response than the patients off treatment (62.1% versus 84.4% p<0.001). Thirty-four of 58 LG-NHL patients were receiving anti-lymphoma treatment with a lower SARS-CoV-2 vaccination response as compared to the patients who were not on treatment (29.4% v 87.5% p<0.001). We observed a similar pattern in CLL patients receiving treatment (48.1 v 76.0 p:0.049). We found that only disease type and treatment status (on-treatment vs. off- treatment), but not gender, age or race were significant predictors of non-response in the multivariable logistic regression model. The interaction between disease type and treatment status was not statistically significant by multivariate analysis. In conclusion, receiving anti-cancer treatment was found to play a significant role in decreasing the response to COVID-19 vaccination.

Periprosthetic joint infections of the shoulder: A 10-year retrospective analysis outlining the heterogeneity among these patients.

Background: Diagnosis and treatment of shoulder periprosthetic joint infection is a difficult problem. The purpose of this study was to utilize the 2018 International Consensus Meeting definition of shoulder periprosthetic joint infection to categorize revision shoulder arthroplasty cases and determine variations in clinical presentation by presumed infection classification. Methods: Retrospective review of patients undergoing revision shoulder arthroplasty at a single institution. Likelihood of periprosthetic joint infection was determined based on International Consensus Meeting scoring. All patients classified as definitive or probable periprosthetic joint infection were classified as periprosthetic joint infection. All patients classified as possible or unlikely periprosthetic joint infection were classified as aseptic. The periprosthetic joint infection cohort was subsequently divided into culture-negative, non-virulent microorganism, and virulent microorganism cohorts based on culture results. Results: Four hundred and sixty cases of revision shoulder arthroplasty were reviewed. Eighty (17.4%) patients were diagnosed as definite or probable periprosthetic joint infection, of which 29 (36.3%), 39 (48.8%), and 12 (15.0%) were classified as virulent, non-virulent, or culture-negative periprosthetic joint infection, respectively. There were significant differences among periprosthetic joint infection subgroups with regard to preoperative C-reactive protein (p = 0.020), erythrocyte sedimentation rate (p = 0.051), sinus tract presence (p = 0.008), and intraoperative purulence (p < 0.001). The total International Consensus Meeting criteria scores were also significantly different between the periprosthetic joint infection cohorts (p < 0.001). Discussion: While the diagnosis of shoulder periprosthetic joint infection has improved with the advent of International Consensus Meeting criteria, there remain distinct differences between periprosthetic joint infection classifications that warrant further investigation to determine the accurate diagnosis and optimal treatment.

Pharmacologic Ascorbic Acid as Early Therapy for Hospitalized Patients with COVID-19: A Randomized Clinical Trial.

Despite the widespread availability of effective vaccines, new cases of infection with severe acute respiratory syndrome coronavirus-2, the cause of coronavirus disease 2019 (COVID-19), remain a concern in the settings of vaccine hesitancy and vaccine breakthrough. In this randomized, controlled, phase 2 trial, we hypothesized that high-dose ascorbic acid delivered intravenously to achieve pharmacologic concentrations may target the high viral phase of COVID-19 and thus improve early clinical outcomes. Sixty-six patients admitted with COVID-19 and requiring supplemental oxygen were randomized to receive either escalating doses of intravenous ascorbic acid plus standard of care or standard of care alone. The demographic and clinical characteristics were well-balanced between the two study arms. The primary outcome evaluated in this study was clinical improvement at 72 h after randomization. While the primary outcome was not achieved, point estimates for the composite outcome and its individual components of decreased use of supplemental oxygen, decreased use of bronchodilators, and the time to discharge were all favorable for the treatment arm. Possible favorable effects of ascorbic acid were most apparent during the first 72 h of hospitalization, although these effects disappeared over the course of the entire hospitalization. Future larger trials of intravenous ascorbic acid should be based on our current understanding of COVID-19 with a focus on the potential early benefits of ascorbic in hospitalized patients.