Introduction: Hand-foot-mouth disease (HFMD) is a common childhood infectious disease. Atypical skin findings of HFMD, often associated with coxsackievirus A6 (CVA6), were first reported in 2008, with increasing reports worldwide since. Atypical lesions of HFMD often involve sites beyond the palms and soles and tend to have unusual, polymorphic morphology. 
Methods: A systematic review was conducted on clinical features and outcomes of pediatric HFMD with atypical cutaneous manifestations.
Results: Eighty-five studies were included, representing 1,359 cases with mean age 2.4 years and a male predominance of 61%. The most reported morphologies were vesicles (53%), papules (49%), and bullae (36%). Other morphologies included eczema herpeticum-like (19%), purpuric/petechial (7%), and Gianotti Crosti-like (4%). Common atypical sites included the arms and/or legs (47%), face (45%), and trunk (27%). CVA6 was identified in 63% of cases. Symptoms resolved in a mean of 10 days. Overall, 16% of cases received treatment, most commonly with acyclovir, intravenous antibiotics, or topical steroids. The most common complications were nail changes (21%) and desquamation (4%) which occurred a mean of three and two weeks after symptoms, respectively. 
Conclusion: Due to unusual morphologies resembling other conditions, HFMD with atypical cutaneous findings may be misdiagnosed, leading to inappropriate and unnecessary investigations, hospitalization, and treatment. Greater awareness of atypical presentations of HFMD is warranted to improve patient care and counseling on infection control precautions.

Atypical Cutaneous Findings of Hand-Foot-Mouth Disease in Children: A Systematic Review

Background: Life adversities, such as neighborhood disadvantage and lower household incomes, are associated with well-established impairments on language development, which predict academic difficulties throughout school. These language delays are observable by age 2, but it remains unclear if adversities experienced in utero affect neurological underpinnings of language development before delays emerge. Of interest are 3 white matter tracts implicated in early language skills: the corpus callosum (CC), inferior fronto-occipital fasciculus (IFOF), and uncinate (Unc).

Methods: A longitudinal cohort of 160 term-born (>36 weeks gestation) neonates were recruited from the eLABE study at Washington University, which oversampled St. Louis families exposed to poverty. Structural equation modeling was used to create 2 latent constructs of prenatal adversity. The first, “social disadvantage”, aggregates neighborhood disadvantage, family income, insurance status, maternal education, and diet. The second, “maternal psychosocial stress”, models maternal depression, stress, life adversities, and perceived discrimination. At birth, diffusion MRI data were collected, and parameters for white matter tract development were created using probabilistic tractography in FSL. In-person follow-up at age 2 evaluated child language skills. To assess the independent and interactive effects of prenatal adversities and neonatal white matter microstructure on language skills, stepwise linear regression models were conducted after adjustment for child sex, gestational age, and postmenstrual age at scan. 


Results: Prenatal social disadvantage (p=.00) and maternal psychosocial stress (p=.00) predicted significantly lower language scores by age 2. However, in a joint model, only the effects due to social disadvantage remained significant. Lower CC fractional anisotropy predicted significantly lower language scores (p=.02) independently of social disadvantage (p=.00). IFOF and Unc were not predictive of language ( p > .05). To examine the relationship between CC maturation and social disadvantage, a moderation analysis was conducted after dichotomizing families’ income into above and below 200% the federal poverty line (FPL), as most federal assistance programs use this value as a threshold for benefit eligibility. The interaction term was not significant (p= .11), but upon plotting results by income group, the slope for infants above 200% FPL was somewhat stronger. 

Conclusion: This study suggests that prenatal adversity, particularly social disadvantage, and immature CC myelination are strong predictors of language delays by age 2. These data can be used as empirical evidence to advocate for increased funding of federal assistance programs that benefit pregnant people (ex., WIC) and downstream fetal brain development. By continuing to explore the relationship between prenatal adversities on fetal brain development and emerging language skills, future studies will continue to identify specific neurological markers of early language development to allow clinicians to intervene before delays emerge.

The Effects of Prenatal Adversity and Neonatal White Matter Microstructure on Child Language Skills at Age 2

Glioblastoma Multiforme (GBM) is one of the most common and aggressive high-grade primary brain tumors that arises from the glial cells of the central nervous system and occurs most often in the frontal and temporal lobes. Despite current treatment options, long-term prognosis of GBM remains low with no significant improvement rates. Chimeric antigen receptor (CAR)-expressing T cells target the B cell marker CD19 and have shown increased efficacy in B cell lymphomas, and lymphoblastic leukemias suggesting benefits in GBM. This study aims to quantify the persistence of CAR-T cells in the context of GBM tumor volume following neurosurgical debulking procedure. A radiology software known as the mint Lesion was utilized to provide Tumor Response Assessment by Criteria (TRAC) reports that consist of volumetric measurements of the tumor lesions (target enhancing lesions, non-target enhancing lesions, and non-target non-enhancing lesions). Fluorescence-activated cell sorting (FACS) analysis takes a sample mixture of cells and sorts them into different populations based on specific biomarkers and characteristics. B7-H3 CAR-T cell persistence was increased in patients with a larger post-surgical tumor volume (3.04% Subject 001 with 2438 mm² volume and 2.38% Subject 003 with 224 mm² tumor volume). However, the number of CAR-T cells per 1 mm² was significantly reduced in patients with a larger post-surgical tumor volume (0.0012 cells/mm² Subject 001 and 0.010 cells/mm² Subject 003). This study shows that although there is an overall increased CAR-T cell persistence for a larger tumor volume, the number of CAR-T cells per 1 mm² is significantly smaller for larger tumor volumes, while illustrating that a larger post-surgical tumor bulk volume is correlated with an increased CAR-T cell persistence within 1-week post-infusion. These findings provide novel information and complement other correlative studies as part of the Phase 1 interventional clinical trial for glioblastoma patients.

Glioblastoma Multiforme Tumor Volume and Persistence of Chimeric Antigen Receptor T Cells Following Neurosurgical Debulking

Background:
First-line treatment for major depressive disorder (MDD) include cognitive behavioral therapy (CBT) and/or antidepressant medications (ADM). However, these treatments can be highly effective in one patient but ineffective in another. Previous treatment selection biomarker studies using resting state fMRI implicate differential subcallosal connectivity to the left anterior insula, left ventromedial prefrontal, and left periaqueductal gray in CBT and medication remitters (Dunlop AJP 2017). Structural connectivity changes that might mediate these functional connectivity patterns are unknown. Therefore, we evaluated pretreatment White matter (WM) integrity in treatment naïve MDD patients as a function of differential 3-month clinical outcome to monotherapy with CBT or ADM. 
Methods
A retrospective analysis of diffusion-weighted imaging scans (DWI) was performed in 167 treatment naive MDD patients randomized to 12 weeks of CBT or ADM. Subjects were grouped into CBT or ADM remitters (HDRS17 score <7 at 10 and 12 weeks) and CBT or ADM failure (HDRS score change <30%). A Whole brain fractional anisotropy (FA) map was calculated for each subject using Fdt toolbox in FMRIB and Tract-Based Spatial Statistics (TBSS) generated for statistical comparison across outcome groups. A voxel-wise 2 x 2 ANOVA: treatment (CBT/ADM) by outcome (remitter/nonresponder) was performed using the AFNI 3dMVM toolbox. Lastly, regional WM changes were correlated with HDRS score changes with treatment. 
Results
A significant treatment by outcome interaction was identified affecting WM tracts adjacent to the left anterior insula, left supplementary motor area, and left hippocampus (p < 0.001). Post hoc analysis revealed ADM remitters and CBT nonresponders show higher FA values in the left insula and SMA compared to both ADM nonresponders and CBT remitters, similar to the location and differential pattern of functional connectivity. In contrast, ADM remitters and CBT nonresponders show lower FA in the left hippocampus compared to ADM nonresponders and CBT remitters. The left SMA and hippocampus showed significant correlation (R2=0.05 p<0.005) with HDRS score improvement in all groups. The VMPFC and SMA showed similar results within the ADM group. The CBT group showed significant correlation with the DLPFC (R2=0.17 p<0.005).
Conclusion
These findings identify differential WM integrity in WM tracts adjacent to the insula, SMA, and hippocampus in remitters and failures to CBT and ADM. These structural and functional connectivity patterns may define imaging biotypes that guide optimal first line MDD treatment selection. Finally, these findings implicate WM connectivity in differential predictive outcomes in MDD treatment success by treatment.

White matter markers for treatment outcomes in major depressive disorder

Background: SARS-CoV-2 or (CoV2) utilizes the receptor binding domain (RBD) of its surface SPIKE protein to infect human cells that express ACE2 receptor. Infected persons can be asymptomatic or progress to a potentially fatal pneumonia-associated illness. Antibodies that prevent SPIKE/RBD/ACE2 interaction can result from infection or vaccination. However, their quantity, function, and cross-reactive protection requires serological testing. We obtained 50 deidentified serum samples, and were blinded to CoV2 vaccination (Vax+; Vax-) or CoV2 positive test (CoV2+; CoV2-). Serum IgG antibodies to SPIKE and RBD were quantified and efficacy in preventing CoV2 infection in vitro determined. We hypothesized that high titer RBD IgG would be efficient at preventing viral infection and be effective against a later CoV2 variant.

Methods: ELISA was used to quantify SPIKE and RBD antibodies in sera. Neutralizing capability of antibodies was determined by mixing sera with a firefly luciferase lentivirus psuedotyped with Wuhan CoV2 SPIKE. The mixture was applied to ACE2 expressing cells and luciferase activity used to calculate infection rates. Samples were unblinded to determine correlation between in vitro results and CoV2 exposure or vaccination. Cross-protection was determined by repeating neutralization assays with the Omicron BA.2 variant.

Results Thirteen participants reported no CoV2 vaccine or CoV2 positive test (Vax-/CoV2-) yet 7 had anti-SPIKE and -RBD titers and neutralizing function suggesting prior asymptomatic CoV2 infection. The remaining 37 participants reported Vax-/CoV2+ (n=8), Vax+/CoV2- (n=27), or Vax+/CoV2+ (n=2). Titers to RBD were comparatively lower than titers to SPIKE in most patient samples. Average RBD antibody titers were higher for the Vax+/CoV2- group (1:2600) versus Vax-/CoV2+ cohort (1:900). Highest RBD antibody titers were found in Vax+/CoV2+ patients (1:5400). Finally, sera with RBD titer ≥1:2700 and neutralization capacity had equal neutralizing function on Omicron BA.2, a variant with 28 amino acid changes in SPIKE and 16 in the critical RBD region.

Conclusion High-titer RBD sera correlated with greater viral neutralization activity highlighting the functional importance of this domain in infection. High-titer anti-RBD IgG to the initial Wuhan CoV2 virus also provided potent neutralization activity against the BA.2 variant despite 16 amino acid changes in its RBD region. This information could be used in future vaccination efforts and passive immunization, as well as provide a greater level of confidence to healthcare workers, first responders, and other high-risk populations regardless of the CoV2 strain. Serial immune studies in high risk populations could provide indications for booster vaccines.

Functional Serologic Testing and Cross Reactivity of Serum Antibodies to SARS-CoV-2 SPIKE Protein

Human Immunodeficiency Virus 1 (HIV-1) is a retrovirus that primarily infects human CD4+ T cells, a key cell-type in the adaptive immune system. The virus establishes a latent reservoir in the early phases of infection that persists in people living with HIV-1 (PLWH) despite effective antiretroviral treatment (ART). Designing strategies to target the HIV-1 reservoir is critical to achieve progress towards a cure. In eukaryotic and prokaryotic cells, and in viruses, antisense transcripts have been shown to exist as long, non-coding RNAs (lncRNA) or coding RNAs (mRNA). Some viruses, like Human T-cell Leukemia Virus Type 1, encode antisense genes to regulate viral expression and replication. HIV-1 antisense transcripts (AST) have been detected in in vitro and ex vivo studies and have been shown to induce viral latency through methylation of histone 3 lysine 27 by recruiting the polycomb repressive complex 2 (PRC2). Our previous studies demonstrated the presence of HIV-1 AST in vivo at levels of 1-3 copies in a median of 5% infected peripheral blood mononuclear cells (PBMC), suggesting a potential role in inducing viral latency in vivo. To determine if HIV-1 AST expression affects levels of plasma viremia, we designed an assay to measure AST expression in PLWH with high viral loads (non-controllers, viral load 5,000-200,000 copies/mL), with low viral loads (viremic controllers, 50-2,000 copies/mL), and with undetectable viral loads (elite controllers, <40 copies/mL). The assay is a limited-dilution, digital PCR approach that targets HIV-1 AST in donor blood cells using donor-specific primers. First, nucleic acid is extracted and subjected to thorough DNase treatment. The remaining antisense RNA is reverse transcribed using a primer targeting the AST region. Detection is achieved with a fluorescent probe and reported as the number of HIV-1 AST molecules per 100 infected cells. We measured AST levels using ACH-2 cells (a model of HIV-1 latency) as a positive control with an average of 3.18 copies of AST per 100 infected cells, as expected. Negative controls included no reverse transcriptase and no template to ensure complete DNA digestion and no mis-priming nor contamination. Our preliminary data includes 4 donor samples in which HIV-1 AST was detected at 1-53 per 100 infected cells. Future studies will determine if AST functions to control HIV-1 replication and induce viral latency in vivo.

Investigation of HIV-1 Antisense Expression In Vivo

Background:
Intrahepatic cholangiocarcinoma (iCCA) is an aggressive cancer with few treatment options. Oncolytic viruses (OV) can induce anti-tumor immunity by exploiting immuno-inflammatory responses. Emerging concepts suggest cooperative immune evasion between dsDNA Vaccinia (VACV) and other OVs, like ssRNA Vesicular Stomatitis Virus (VSV) can enhance anti-tumor immunity. This project tests the hypothesis that VACV attenuation of interferon-α/β (IFN) enhances VSV oncolysis and immunogenicity.
Methods: 
To understand iCCA susceptibility to select OVs, we infected iCCA cells with VACV +/- VSV. To elucidate OV efficacy as a function of IFNα/β stimulation, we measured cytotoxicity and viral replication via MTT assay and 50% tissue culture infectious dose (TCID50) +/- IFNα stimulation. To study cooperative immune evasion (VACV-induced IFNα/β suppression enhancing VSV oncolysis), we quantified proteins from pathways that activate IFNα/β. Western blots (WB) of STING (DNA pathogen sensing) & RIG1 (RNA pathogen sensing) were performed to evaluate the impact of infection on IFN-stimulating cell-signaling. 
To assess efficacy of VACV+VSV in vivo as a function of IFNα/β response, we infected patient-derived iCCA xenograft (PDX) with PBS, VACV, VSV, or VACV+VSV. Tumor size and IFNα/β signaling (RIG1/STING) were assessed. Tumor growth abrogation was evaluated with repeated measures, one-way ANOVA, and post hoc multiple comparison was made with Dunnett’s test between groups.
Results: 
In vitro, VACV & VSV both show dose-dependent viral replication and cytotoxicity against iCCA measured through TCID50 and MTT cell viability assays. IFNα pretreated iCCA cells showed significant and robust upregulation of both RIG1/STING following viral infection with VACV (p=0.003/0.03, respectively), slightly less intense upregulation was seen in VACV+VSV combination (p=0.02/0.03, respectively), and no change was seen with VSV infection (p=0.89/0.78, respectively).
In vivo, iCCA PDX growth was significantly abrogated in the VACV group (p=0.007) & combination group (p=0.04) compared to control (figure 1). ANOVA results showed significant effect of treatment on tumor volume changes [F(1.385, 12.46)=11.97, p=0.0025, η²=0.5708]. No significant differences observed between the PBS & VSV groups (p=0.5452). WB quantification showed upregulated RIG1 in the combination group (p=0.03) and no significant difference between groups for STING expression (p=.4304).
Conclusions: 
The VACV and VACV + VSV combination treatments resulted in significant tumor growth abrogation compared to VSV treatment and PBS control. However, the RIG1 and STING signaling suggests that this does not occur via immune evasion or rescue of VSV by VACV in this model. These findings underscore the therapeutic potential of combination OV in iCCA and warrant further investigation to elucidate the underlying mechanism.


Treating intrahepatic cholangiocarcinoma with combination viroimunnotherapy

Background
The reimbursement landscape for infectious diseases is constantly evolving. In recent years, there have been significant changes in Medicare reimbursement for infectious disease procedures. These changes have had a major impact on infectious disease specialists, who may be disproportionately affected by changes in reimbursement in certain regions, which could have implications for access to care. Previous research has not examined these fluctuations especially in different geographic regions. Thus, our study analyzed Medicare reimbursement changes from 2013 to 2023 for all U.S. states and territories. We also explored the relationship between these changes and select social determinants of health (SDOH).
Methods
Medicare Administrative Contractor codes for the top 50 infectious disease procedures were used to identify states using the Centers for Medicare and Medicaid Services’ Physician Fee Schedule. Each price was adjusted for inflation using the consumer price index and weighted using an index of codes. A total percent change was generated for each state or territory. State-based data for various SDOH were used to calculate a correlation coefficient with geographic changes in
reimbursement (statistical significance factored with α of 0.05).
Results
From 2013 to 2023, the inflation-adjusted Medicare reimbursement for the top-grossing infectious disease procedures for U.S. states and territories decreased by a mean and median of 24.8% and 25.0%, respectively. The greatest total decrease was experienced by Illinois (-29.0%), Wyoming (-26.8%), Kansas (-26.8%), and Wisconsin (-26.6%). Massachusetts (-22.5%), New York (-22.3%), Washington (-19.8%), and Puerto Rico (-14.2%) were states that had the lowest change over the ten-year period. Some of the top grossing procedures (Current Procedural Terminology code) and their yearly percent change included critical care for the first 30-74 minutes of instance(99291, -197.2%), debridement of subcutaneous tissue for the first 20 cm2 or less(11042, -197.0%), transitional care management with high medical decision complexity(99496, -197.0%), and removal of central venous catheter without subcutaneous port or pump (36589, -197.0%).
Conclusion
Our findings suggest that over the past ten years, Medicare reimbursement for infectious disease procedures has decreased in many regions of the United States. These findings have important implications for access to care. Decreased reimbursement may make it more difficult for infectious disease specialists to provide care in certain regions, which could lead to longer wait times and decreased
access to care for patients. Policymakers should consider and develop strategies to address these geographic disparities. This could include providing financial assistance to infectious disease practices or expanding access to telehealth services.

The Impact of Geography on Medicare Reimbursement for Infectious Diseases: A 10-Year Analysis

Spalt-Like Transcription Factor 4 (SALL4), a member of the SALL family, is a regulator of embryonic stem cell development that plays a crucial role in cell renewal and proliferation. SALL4 expression is normally repressed in most adult organs but is reactivated in a multitude of solid and blood cancers and upon treatment with hypomethylating agents (HMA). There is outstanding clinical need for the development and validation of a less invasive SALL4 expression assay via peripheral blood, which can be used for monitoring patients on HMA treatment and SALL4-targeting therapy such as molecular glue degraders.

Using the Simoa (Single Molecule Array) platform, a bead-based digital enzyme-linked immunosorbent assay, we cross-tested 5 commercial SALL4 antibodies and 13 antibody pair combinations, using the best antibody pair to test the matrix effects of human plasma, buffy coats, and bone marrow aspirates. Quantitative assay development further included creating recombinant protein standards, antibody pair screening and validation, and pre-analytical optimization. Upon completion of these steps, a retrospective cohort analysis via patient peripheral blood samples is currently being conducted to validate assay accuracy and precision. Additionally, we are aiming to conduct prospective studies to explore the role of the SALL4 protein biomarker in risk stratification and treatment monitoring.

Thus far, for quantitative assay development, we have successfully expressed and purified full-length SALL4 which will be used to calibrate the standard curve and determine the assay’s limit of quantification. We also optimized multiple pre-analytic steps, including our cell lysis protocol, isolation of buffy coats using density gradient separation, and sample collection method comparison. The best antibody pair can detect both SALL4A and SALL4B isoforms, with stronger signal detected with the SALL4A isoform. For the retrospective cohort validation, we have obtained samples for analysis for liver cancer, myelodysplastic syndrome (MDS), and acute myeloid leukemia (AML) with plans to expand to breast cancer and lung cancer.

In conclusion, we have developed an ultrasensitive SALL4 protein expression diagnostic assay for use in monitoring patient treatment response and for guiding targeted therapy by analyzing peripheral blood for both solid and liquid tumors. Future steps include validating the diagnostic assay for specificity and sensitivity in a retrospective cohort analysis and conducting prospective studies to explore the role of the SALL4 protein biomarker for risk stratification, monitoring on HMA treatment, and guiding targeted therapy.

Ultrasensitive detection of SALL4 oncoproteins for the use in therapeutic monitoring

Our study addressed COVID-19 vaccine knowledge and attitudes among medical students at the University of New England College of Osteopathic Medicine (UNECOM). Medical students recruited to complete an anonymous online survey assessed backgrounds, experiences, knowledge, and attitudes toward the COVID-19 vaccine. The correlation analysis utilized gender, physical health rating, close connection to someone with COVID-19, and work in the medical field during March 2020 as potential factors affecting students' attitudes. Respondents included 139 medical students aged 20-39 years old, with 99.3% having received at least one dose of the COVID-19 vaccine under institutional mandate. Every student obtained vaccine information from any combination of medical professionals, scientific journals, or review articles. Almost all correctly identified the components of the vaccine, its benefits, and its potential side effects. We found that 85% of medical students expressed little hesitancy toward receiving the vaccine; about 90% of participants supported a vaccine mandate for students. The marked enthusiasm expressed by UNECOM medical students to receive the vaccine contrasts surveys conducted before any vaccine mandate, although students' accurate knowledge of the vaccine and its potential benefits may have influenced acceptance. Overall, consideration of societal and individual implications is paramount. Access to scientifically validated information is essential when implementing public health policy at both institutional and federal levels.




Medical Students' Attitudes and Knowledge on the COVID-19 Vaccine and Mandate

Background
Pack-year history is an invaluable clinical tool for measuring tobacco-associated disease risk and determining eligibility for lung cancer screening with low-dose computed tomography. Patient-reported measures of smoking history have demonstrated strong test-retest reliability across various survey methods, but the variation between research and clinical settings suggests that non-standardized smoking history interview questions in community practice may not always reveal the true extent of a patient’s tobacco exposure. To date, no study has compared patient responses to differently phrased questions assessing the same measure of smoking history. We hypothesize there is a significant discordance between patient-reported number of years smoked and calculated elapsed time between age at initiation and age at cessation (or present age if current smoker).

Methods
This was a two-month prospective survey-based study conducted at the Western Michigan University Homer Stryker M.D. School of Medicine's Internal Medicine resident clinic in Kalamazoo, Michigan, including patients with a documented smoking history in their electronic medical records. Through verbal interviews, we collected data on number of years smoked, packs per day, and age of smoking initiation/cessation. Primary outcome variables were total years smoked and calculated pack-years. Secondary outcome variables were gender, age, and age of smoking initiation.

Results
There were 124 respondents (36% male, 63% female, 1% non-binary) with an average age of 55 and average smoking history of 1.2 packs per day. Of them, 46% were current and 54% were former smokers. Using a paired sample one-tail t-test, we compared patient-reported years smoked (M=22.06, SD=12.44) to calculated years based on age of initiation/cessation (M=24.03, SD=13.53), which showed a significant mean difference of 1.97 years (95% CI 1.16- 2.78, t=4.05, p<0.001). This discordance translated to a 21.29% increase in pack-years (from 24.32 to 29.50 pack-years) and a mean difference of 5.21 pack-years (95% CI 1.04-9.38, t=2.07, p=0.02).

Conclusion
Our study underscores the importance of critically evaluating the ways in which we gather a patient’s smoking history. When compared to pack-years calculated using age of smoking initiation/cessation, our sample population tended to underestimate their exposure by over 5 pack-years—a clinically significant difference for someone at high risk who might not otherwise receive screening imaging. Often a pivotal moment in adolescence, participants recalled their age of smoking initiation with greater precision compared to their estimations of total exposure. These results call for urgent reevaluation of the tobacco history interview, its notation in electronic medical records, and the methodology of taking a substance abuse history in general.

Rethinking the Smoking History Interview: A Prospective Survey-based Study

Background: The WHO reported 132 million cases and 2.8 million deaths from COVID-19 through 2021, with severe cases resulting in multi-organ failure. The Sequential Organ Failure Assessment (SOFA) score measures multi-system organ failure changes overtime. The ability to predict outcomes of critically ill COVID-19 patients would advance allocating resources, better managing this disease. To combat mortality, many potential therapies were studied to manage COVID-19’s lethal effects, one being Azithromycin. While it is safe as treatment for bacterial infections, its effectiveness as treatment for COVID-19 is controversial. Given risks associated with blanket antibiotic use, we sought to evaluate azithromycin’s effectiveness as treatment for COVID-19.

Methods: This is a retrospective, non-controlled, two-center study of consecutive adult (age >18) COVID-19 positive cases admitted at two hospitals in Ventura, California from March 2020 to March 2021. We aim to determine the effect of Azithromycin therapy on SOFA scores, hospital stay duration, and mortality among ICU COVID-19 patients.

Results: 857 patients were admitted between two hospitals for the study period. 46% (N=392) received treatment for COVID-19. 37.8% received Azithromycin as a therapy exclusively or as combination. In the treatment group (N=148), mean age was 57.58±18.70, mean BMI was 31.75±9.1, mean length of stay was 8.26±7.37 days, mean minimum O2 saturation was 79.44±15.26, and mean peak SOFA score was 3.21±3.80. There were 99 (67%) males and 49 (33%) females (P<0.01). 96 (65%) patients self-identified as Hispanic/Latino (P<.01); 62 (42%) were admitted to the ICU. The mortality rate for the treatment group was higher compared to control, but not significantly (17.6 vs. 10.7, P=0.06). Peak SOFA scores were significantly different in the treatment group between those who survived and those who did not (3.9 vs, 10.7, P<0.01).

Conclusion: Azithromycin’s effectiveness at reducing inflammatory markers made it a prominent treatment contender for tempering the COVID-19 cytokine storm, along with data suggesting azithromycin effects viral integration and replication in vitro(10). We found no significant benefit from use of azithromycin in COVID-19 patients. However, despite the treatment group being smaller than control, mortalities were equal. Though not statistically significant, higher mortality was seen after administration of azithromycin to COVID patients. Like other studies, we found no association between the use of Azithromycin in COVID-19 patients and mortality, length of hospital stay, or need for mechanical ventilation(8, 9). Given risk from antibiotic use in large populations without significant benefit, we recommend against the use of azithromycin in COVID-19 patients.

Azithromycin Therapy and its Correlation to the Sequential Organ Failure Assessment, Intensive Care Admission, and Mortality among Hospitalized COVID Positive Patients

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