Correlation of a commercial platform's results with post-vaccination SARS-CoV-2 neutralizing antibody response and clinical host factors.

INTRODUCTION: The objective of this study was to describe the correlation between the commercially available assay for anti-S1/RBD IgG and protective serum neutralizing antibodies (nAb) against SARS-CoV-2 in an adult population after SARS-CoV-2 vaccination, and determine if clinical variables impact this correlation. METHODS: We measured IgG anti-S1/RBD using the IgG-II CMIA assay and nAb IC50 values against SARS-CoV-2 WA-1 in sera serially collected post-mRNA vaccination in veterans and healthcare workers of the Veterans Affairs Connecticut Healthcare System (VACHS) between December 2020 and January 2022. The correlation between IgG and IC50 was measured using Pearson correlation. Clinical variables (age, sex, race, ethnicity, prior COVID infection defined by RT-PCR, history of malignancy, estimated glomerular filtration rate (GFR calculated using CKD-EPI equation) were collected by manual chart review. The impact of these clinical variables on the IgG-nAb correlation was analyzed first with univariable regression. Variables with a significance of p < 0.15 were analyzed with forward stepwise regression analysis. RESULTS: From 127 sera samples in 100 unique subjects (age 20-93 years; mean 63.83; SD 15.63; 29% female; 67% White), we found a robust correlation between IgG anti-S1/RBD and nAb IC50 (R2 = 0.83, R2adj = 0.70, p < 0.0001). Race, ethnicity, and a history of malignancy were not significant on univariable analysis. GFR (p < 0.05) and prior COVID infection (p < 0.001) had a significant impact on the correlation between IgG anti-S1/RBD and nAb IC50. Age (p = 0.06) and sex (p = 0.07) trended towards significance on univariable analysis, but were not significant on multivariable regression. CONCLUSIONS: There was a strong correlation between IgG anti-S1/RBD and nAb IC50 after SARS-CoV-2 vaccination. Clinical comorbidities, such as prior COVID infection and renal function, impacted this correlation. These results may assist the prediction of post-vaccination immune protection in clinical settings using cost-effective commercial platforms.

Serum Neutralizing Antibody Titers 12 Months After Coronavirus Disease 2019 Messenger RNA Vaccination: Correlation to Clinical Variables in an Adult, US Population.

BACKGROUND: We studied whether comorbid conditions affect strength and duration of immune responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA vaccination in a US-based, adult population. METHODS: Sera (before and after BNT162b2 vaccination) were tested serially up to 12 months after 2 doses of vaccine for SARS-CoV-2-anti-Spike neutralizing capacity by pseudotyping assay in 124 individuals; neutralizing titers were correlated to clinical variables with multivariate regression. Postbooster (third dose) effect was measured at 1 and 3 months in 72 and 88 subjects, respectively. RESULTS: After completion of primary vaccine series, neutralizing antibody half maximal inhibitory concentration (IC50) values were high at 1 month (14-fold increase from prevaccination), declined at 6 months (3.3-fold increase), and increased at 1 month postbooster (41.5-fold increase). Three months postbooster, IC50 decreased in coronavirus disease (COVID)-naïve individuals (18-fold increase) and increased in prior COVID 2019 (COVID-19+) individuals (132-fold increase). Age >65 years (ß = -0.94, P = .001) and malignancy (ß = -0.88, P = .002) reduced strength of response at 1 month. Both neutralization strength and durability at 6 months, respectively, were negatively affected by end-stage renal disease ([ß = -1.10, P = .004]; [ß = -0.66, P = .014]), diabetes mellitus ([ß = -0.57, P = .032]; [ß = -0.44, P = .028]), and systemic steroid use ([ß = -0.066, P = .032]; [ß = -0.55, P = .037]). Postbooster IC50 was robust against WA-1 and B.1.617.2. Postbooster neutralization increased with prior COVID-19 (ß = 2.9, P < .0001), and malignancy reduced neutralization response (ß = -0.68, P = .03), regardless of infection status. CONCLUSIONS: Multiple clinical factors affect the strength and duration of neutralization response after primary series vaccination, but not the postbooster dose strength. Malignancy was associated with lower booster-dose response regardless of prior COVID infection, suggesting a need for clinically guided vaccine regimens.

Long-term quantitative assessment of anti-SARS-CoV-2 spike protein immunogenicity (QUASI) after COVID-19 vaccination in older people living with HIV (PWH).

BACKGROUND: The durability of immune responses to COVID-19 vaccines among older people living with HIV (PWH) is clinically important. METHODS: We aimed to assess vaccine-induced humoral immunity and durability in older PWH (≥ 55 years, n = 26) over 6 months (post-initial BNT162b2 series). A secondary and exploratory objective was to assess T-cell response and BNT162b2 booster reactogenicity, respectively. Our Visit 1 (3 weeks post-initial BNT162b2 dose) SARS-CoV-2 humoral immunity results are previously reported; these subjects were recruited for Visit 2 [2 weeks (+ 1 week window) post-second vaccination] and Visit 3 [6 months (± 2 week window) post-initial vaccination] in a single-center longitudinal observational study. Twelve participants had paired Visit 2/3 SARS-CoV-2 Anti-Spike IgG data. At Visit 3, SARS-CoV-2 Anti-Spike IgG testing occurred, and 5 subjects underwent T-cell immune response evaluation. Thereafter, subjects were offered BNT162b2 booster (concurrent day outside our study) per US FDA/CDC guidance; reactogenicity was assessed. The primary study outcome was presence of detectable Visit 3 SARS-CoV-2 Anti-Spike-1-RBD IgG levels. Secondary and exploratory outcomes were T-cell immune response and BNT162b2 booster reactogenicity, respectively. Wilcoxon signed-rank tests analyzed median SARS-CoV-2 Anti-Spike IgG 6-month trends. RESULTS: At Visit 3, 26 subjects underwent primary analysis with demographics noted: Median age 61 years; male n = 16 (62%), female n = 10 (38%); Black n = 13 (50%), White n = 13 (50%). Most subjects (n = 20, 77%) had suppressed HIV viremia on antiretroviral therapy, majority (n = 24, 92%) with CD4 > 200 cells/µL. At Visit 3, 26/26 (100%) had detectable Anti-Spike-1-RBD (≥ 0.8 U/mL). Among 12 subjects presenting to Visit 2/3, median SARS-CoV-2 Anti-Spike 1-RBD was 2087 U/mL at Visit 2, falling to 581.5 U/mL at Visit 3 (p = 0.0923), with a median 3.305-fold decrease over 6 months. Among subjects (n = 5) with 6-month T-cell responses measured, all had detectable cytokine-secreting anti-spike CD4 responses; 3 had detectable CD4 + Activation induced marker (AIM) + cells. Two had detectable cytokine-secreting CD8 responses, but all had positive CD8 + AIM + cells. CONCLUSIONS: Among older PWH, SARS-CoV-2 Anti-Spike IgG and virus-specific T-cell responses are present 6 months post-primary BNT162b2 vaccination, and although waning, suggest retention of some degree of long-term protective immunity.

Development of an efficient reproducible cell-cell transmission assay for rapid quantification of SARS-CoV-2 spike interaction with hACE2.

Efficient quantitative assays for measurement of viral replication and infectivity are indispensable for future endeavors to develop prophylactic or therapeutic antiviral drugs or vaccines against SARS-CoV-2. We developed a SARS-CoV-2 cell-cell transmission assay that provides a rapid and quantitative readout to assess SARS-CoV-2 spike hACE2 interaction in the absence of pseudotyped particles or live virus. We established two well-behaved stable cell lines, which demonstrated a remarkable correlation with standard cell-free viral pseudotyping for inhibition by convalescent sera, small-molecule drugs, and murine anti-spike monoclonal antibodies. The assay is rapid, reliable, and highly reproducible, without a requirement for any specialized research reagents or laboratory equipment and should be easy to adapt for use in most investigative and clinical settings. It can be effectively used or modified for high-throughput screening for compounds and biologics that interfere with virus-cell binding and entry to complement other neutralization assays currently in use.

Clinical and virologic factors associated with outcomes of COVID-19 before and after vaccination among Veterans: Retrospective analysis from six New England states.

We aimed to characterize clinical and demographic factors affecting clinical outcomes of COVID-19 and describe viral epidemiology among unvaccinated Veterans in New England. Veterans infected with COVID-19 in Veterans Administration healthcare systems in six New England states from April 8, 2020, to September 2, 2021, were correlated with outcomes of 30-day mortality, nonpsychiatric hospitalization, and intensive care unit admission (ICU-care). We sequenced 827 viral genomes. Of 3950 Veterans with COVID-19 before full vaccination, 81% were White, 8% were women, and the mean age was 60 years. Overall, 19% of Veterans required hospitalization, 2.8% required ICU care, and 4.9% died. In this largely male and older cohort, poor outcomes correlated with increasing age. Most New England Veterans (>97%) were infected with B.1 sublineages with the D614G mutation in 2020 and early 2021. B.1.617.2 lineage (68%) predominated after July 2021.

Clinical Variables Correlate with Serum Neutralizing Antibody Titers after COVID-19 mRNA Vaccination in an Adult, US-based Population.

Background: We studied whether comorbid conditions impact strength and duration of immune responses after SARS-CoV-2 mRNA vaccination in a US-based, adult population. Methods: Sera (pre-and-post-BNT162b2 vaccination) were tested serially up to 12 months after two doses of vaccine for SARS-CoV-2-anti-Spike neutralizing capacity by pseudotyping assay in 124 individuals; neutralizing titers were correlated to clinical variables with multivariate regression. Post-booster (third dose) effect was measured at 1 and 3 months in 72 and 88 subjects respectively. Results: After completion of primary vaccine series, neutralizing antibody IC50 values were high at one month (14-fold increase from pre-vaccination), declined at six months (3.3-fold increase), and increased at one month post-booster (41.5-fold increase). Three months post-booster, IC50 decreased in COVID-naïve individuals (18-fold increase) and increased in prior COVID-19+ individuals (132-fold increase). Age >65 years (ß=-0.94, p=0.001) and malignancy (ß=-0.88, p=0.002) reduced strength of response at 1 month. Both strength and durability of response at 6 months, respectively, were negatively impacted by end-stage renal disease [(ß=-1.10, p=0.004); (ß=-0.66, p=0.014)], diabetes mellitus [(ß=-0.57, p=0.032); (ß=-0.44, p=0.028)], and systemic steroid use [(ß=-0.066, p=0.032); (ß=-0.55, p=0.037)]. Post-booster IC50 was robust against WA-1 and B.1.617.2, but the immune response decreased with malignancy (ß =-0.68, p=0.03) and increased with prior COVID-19 (p-value < 0.0001). Conclusion: Multiple clinical factors impact the strength and duration of neutralization response post-primary series vaccination, but not the post-booster dose strength. Prior COVID-19 infection enhances the booster-dose response except in individuals with malignancy, suggesting a need for clinically guiding vaccine dosing regimens. Summary: Multiple clinical factors impact the strength and duration of neutralization response post-primary series vaccination. All subjects, irrespective of prior COVID infection, benefited from a third dose. Malignancy decreased response following third dose, suggesting the importance of clinically guided vaccine regimens.

COVID-19 Outcomes and Genomic Characterization of SARS-CoV-2 Isolated From Veterans in New England States: Retrospective Analysis.

BACKGROUND: Clinical and virologic characteristics of COVID-19 infections in veterans in New England have not been described. The average US veteran is a male older than the general US population. SARS-CoV-2 infection is known to cause poorer outcomes among men and older adults, making the veteran population an especially vulnerable group for COVID-19. OBJECTIVE: This study aims to evaluate clinical and virologic factors impacting COVID-19 outcomes. METHODS: This retrospective chart review included 476 veterans in six New England states with confirmed SARS-CoV-2 infection between April and September 2020. Whole genome sequencing was performed on SARS-CoV-2 RNA isolated from these veterans, and the correlation of genomic data to clinical outcomes was evaluated. Clinical and demographic variables were collected by manual chart review and were correlated to the end points of peak disease severity (based on oxygenation requirements), hospitalization, and mortality using multivariate regression analyses. RESULTS: Of 476 veterans, 274 had complete and accessible charts. Of the 274 veterans, 92.7% (n=254) were men and 83.2% (n=228) were White, and the mean age was 63 years. In the multivariate regression, significant predictors of hospitalization (C statistic 0.75) were age (odds ratio [OR] 1.05, 95% CI 1.03-1.08) and non-White race (OR 2.39, 95% CI 1.13-5.01). Peak severity (C statistic 0.70) also varied by age (OR 1.07, 95% CI 1.03-1.11) and O2 requirement on admission (OR 45.7, 95% CI 18.79-111). Mortality (C statistic 0.87) was predicted by age (OR 1.06, 95% CI 1.01-1.11), dementia (OR 3.44, 95% CI 1.07-11.1), and O2 requirement on admission (OR 6.74, 95% CI 1.74-26.1). Most (291/299, 97.3%) of our samples were dominated by the spike protein D614G substitution and were from SARS-CoV-2 B.1 lineage or one of 37 different B.1 sublineages, with none representing more than 8.7% (26/299) of the cases. CONCLUSIONS: In a cohort of veterans from the six New England states with a mean age of 63 years and a high comorbidity burden, age was the largest predictor of hospitalization, peak disease severity, and mortality. Non-White veterans were more likely to be hospitalized, and patients who required oxygen on admission were more likely to have severe disease and higher rates of mortality. Multiple SARS-CoV-2 lineages were distributed in patients in New England early in the COVID-19 era, mostly related to viruses from New York State with D614G mutation.

Advances in rapid diagnostics for bloodstream infections.

Septicemia from bloodstream infections (BSI) is the second largest cause of inpatient mortality and the single most expensive condition for US hospitals to manage. There has been an explosive development of commercial diagnostic systems to accelerate the identification and antimicrobial susceptibility testing (AST) of causative pathogens. Despite adoption of advanced technologies like matrix-assisted laser desorption imaging-time-of-flight mass spectrometry and multiplex polymerase chain reaction for rapid identification, clinical impact has been variable, in part due to the persistent need for conventional AST as well as prescriber understanding of these rapidly evolving platforms. Newer technologies are expanding on rapid detection of genotypic determinants of resistance, but only recently has rapid phenotypic AST been available. Yet, improved outcomes with rapid diagnostic platforms are still most evident in conjunction with active antimicrobial stewardship. This review will outline key advancements in rapid diagnostics for BSI and the role of antimicrobial stewardship in this new era.

SARS-CoV-2 detection in setting of viral swabs scarcity: Are MRSA swabs and viral swabs equivalent?

BACKGROUND: The global pandemic of Severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV2) has resulted in unprecedented challenges for healthcare systems. One barrier to widespread testing has been a paucity of traditional respiratory viral swab collection kits relative to the demand. Whether other sample collection kits, such as widely available MRSA nasal swabs can be used to detect SARS-CoV-2 is unknown. METHODS: We compared simultaneous nasal MRSA swabs (COPAN ESwabs ® 480C flocked nasal swab in 1mL of liquid Amies medium) and virals wabs (BD H192(07) flexible mini-tip flocked nasopharyngeal swabs in 3mL Universal Transport Medium) for SARS-CoV-2 PCR testing using Simplexa COVID-19 Direct assay on patients over a 4-day period. When the results were discordant, the viral swab sample was run again on the Cepheid Xpert Xpress ® SARS-CoV-2 assay. RESULTS: Of the 81 included samples, there were 19 positives and 62 negatives in viral media and 18 positives and 63 negative in the MRSA swabs. Amongst all included samples, there was concordance between the COPAN ESwabs ® 480C and the viral swabs in 78 (96.3%). CONCLUSION: We found a high rate of concordance in test results between COPAN ESwabs ® 480C in Amies solution and BD H192(07) nasopharyngeal swabs in in 3 mL of Universal Viral Transport medium viral media. Clinicians and laboratories should feel better informed and assured using COPAN ESwabs ® 480C to help in the diagnosis of COVID-19.

Hospital preparedness for COVID-19 pandemic: experience from department of medicine at Veterans Affairs Connecticut Healthcare System.

The 2019-2020 pandemic Coronavirus Disease 2019 (COVID-19) has inundated hospital systems globally, as they prepare to accommodate surge of patients requiring advanced levels of care. Pandemic preparedness has not been this urgently and widely needed in the last several decades. According to epidemiologic predictions, the peak of this pandemic has still not been reached, and hospitals everywhere need to ensure readiness to care for more patients than they usually do, and safety for healthcare workers who strive to save lives. We share our hospital-wide rapid preparedness and response to COVID-19 to help provide information to other healthcare systems globally.

Stethoscope hygiene: Using cultures and real-time feedback with bioluminescence-based adenosine triphosphate technology to change behavior.

BACKGROUND: Stethoscope hygiene is rarely done despite guideline recommendations. We wanted to determine whether demonstrating what is growing on the stethoscopes of providers via culture or bioluminescence technology alters perceptions and improves compliance. METHODS: Providers were given the opportunity to (1) culture their stethoscopes before and after disinfection with alcohol pads, alcohol-based hand rub, or hydrogen peroxide disinfectant wipes and (2) swab stethoscopes for bioluminescence-based adenosine triphosphate testing before and after disinfection. Outcomes were observed for hand and stethoscope hygiene rates and before and after intervention survey responses. The bacteria that were isolated, colony-forming units (CFU), and bioluminescence scores were tracked. RESULTS: A total of 1,245 observed hand hygiene opportunities showed that compliance improved from 72.5%-82.3% (P < .001). In addition, 590 observed patient-provider encounters revealed no significant change in stethoscope hygiene rates of 10% initially and 5% afterward (P = .08), although self-reported rates trended from 56%- 67% postintervention (P = .06). Perceptions regarding stethoscope hygiene importance improved (8.5/10 to 9.3/10; P = .04). Disinfection with alcohol pads, alcohol-based hand rub, and hydrogen peroxide disinfectant wipes were equivalent in CFU reduction (P = .21). CONCLUSIONS: Showing providers what is growing on their stethoscopes via cultures and bioluminescence technology before and after disinfection improved "buy in" regarding stethoscope hygiene importance. Both methods were rated as having an equal impact, however, objective observations failed to show improvement.

Native Joint Septic Arthritis: Comparison of Outcomes with Medical and Surgical Management.

OBJECTIVE: To determine whether there are differences in the outcomes of native joint septic arthritis (SA) in adults, based on medical versus surgical management. METHODS: A 10-year retrospective single-center study was conducted of patients admitted to a tertiary care hospital between January 1, 2006 and December 31, 2015 with a diagnosis of SA to compare outcomes based on the management approach taken: medical (bedside closed-needle joint aspiration) versus surgical (arthrotomy/arthroscopy). Evaluated outcomes included joint recovery, time to recovery, length of stay, disposition to home versus rehabilitation unit, recurrence of SA in the same joint, and mortality. RESULTS: Of 118 confirmed cases of SA, 48 were in prosthetic joints and 70 were in native joints, and 61 met our inclusion criteria. Forty-one (67%) patients received surgery, and 20 (33%) received closed-needle aspiration. There was no statistically significant difference in long-term outcomes between the two groups at 12 months. Patients managed medically were more likely to experience full recovery at 3 months and were less likely to need short-term rehabilitation. CONCLUSIONS: Medical management with closed-needle aspiration may be an adequate approach to the treatment of native joint infections.

The "Hand-in" Project: Jump-starting Communication Between Inpatient and Outpatient Providers.

OBJECTIVES: Communication between hospitalists and primary care providers (PCPs) upon discharge has been much discussed, but the transition from outpatient to inpatient has received less attention. We questioned whether a brief, standardized e-mail from the hospitalist to the PCP upon admission could facilitate information exchange, increase communication, elucidate PCP preferences, and improve outcomes. METHODS: This prospective single-center study with a preintervention-to-postintervention design involved 300 inpatient admissions from June 2015 through October 2015 in the Veterans Affairs Connecticut Healthcare System. Hospitalists e-mailed an encrypted notification of admission along with standardized questions to PCPs within 1 day of admission. Measurements included the number of communications between PCPs and hospitalists, length of stay (LOS), 30-day readmissions, 30-day emergency department (ED) utilization rates, PCP preferences with regard to communication, and follow-up. RESULTS: Preintervention data for 94 patients during a 6-week period revealed 0.11 communications per patient, an LOS of 4.18 days, 30-day readmissions of 28.7%, and 30-day ED visits of 32%. Postintervention data on 206 patients during the next 12 weeks showed statistically significant increased communications per patient (0.5), and a nonsignificant decrease in LOS (3.96 days), 30-day readmissions (22.3%), and 30-day ED visits (31%). P values were <0.001, 0.67, 0.4, and 0.79, respectively. PCPs preferred e-mail communication upon discharge (40%) to telephone (25%) or instant messaging (13%), and 39% wanted a follow-up appointment within 2 weeks, regardless of what transpired. CONCLUSIONS: A hospitalist-led transition-of-care intervention designed to improve communication and information exchange between PCPs and hospitalists at the time of admission demonstrated that encrypted e-mail could be used as a tool to obtain useful additional medical and psychosocial information and to better understand PCP attitudes and preferences. The increased level of communication did not yield statistically significant decreases in LOS, 30-day readmission rates, or 30-day post-discharge ED visits, however.

Can education influence stethoscope hygiene?

The importance of stethoscope hygiene has been demonstrated in prior studies, and is acknowledged by guidelines, yet it is rarely done. We implemented a pilot project consisting of provider education, reminder flyers and provision of cleaning supplies at the start of clinical rotations for housestaff, medical students, and attending physicians. Hand hygiene rates did not change significantly with rates between 58% and 63% while stethoscope hygiene remained at zero.

Diagnostic accuracy of methicillin-resistant Staphylococcus aureus nasal colonization to predict methicillin-resistant S aureus soft tissue infections.

Nasal methicillin-resistant Staphylococcus aureus (MRSA) testing at admission to the hospital was found to have a positive likelihood ratio of 8.5 and a negative likelihood ratio of 0.41 for predicting MRSA soft tissue infections. The clinical utility of this test depends on the prevalence of MRSA infection. In high prevalence populations, nasal MRSA is useful to rule in MRSA infections. In low prevalence populations it may be useful to rule out infections.

Clinical characteristics and outcomes of veterans hospitalised with purulent soft tissue infections with and without systemic signs of infection.

Objective To describe the frequency of systemic inflammatory response syndrome (SIRS) criteria in a cohort of patients hospitalised with purulent soft tissue infections and to determine their impact on clinical characteristics, microbiology and outcomes. Methods Retrospective cohort study of adults hospitalised at the West Haven Veteran's Hospital with purulent soft tissue infections between 1 October 2008 and 30 September 2013. Results A total of 173 patients were included with purulent soft tissue infections; 60 patients had no SIRS, 48 had one SIRS and 65 had ≥ 2 SIRS. Most clinical characteristics were similar between the different SIRS groups, although patients with SIRS were more likely to have severe sepsis and acute kidney injury and to already be on antibiotics at the time of hospitalisation. The microbiology of the infections was similar between SIRS groups. All patients received parenteral antibiotics when admitted and the majority of patients in all SIRS categories received antibiotics with broad Gram-negative activity. Outcomes were generally benign for all SIRS groups, although patients with SIRS had a longer length of stay and a trend towards more bacteremia. Conclusions SIRS are common in patients hospitalised with purulent soft tissue infections, although one third had no systemic signs of infection. Severe sepsis and septic shock are rare. Clinical characteristics, microbiology and antibiotic use are similar among patients in different SIRS groups, although the group without SIRS had a shorter hospitalisation and no episodes of bacteremia. Over-use of antibiotics is common in all SIRS categories.

Parvimonas micra: A rare cause of native joint septic arthritis.

Parvimonas micra is a fastidious, anaerobic, gram positive coccus, which is found in normal human oral and gastrointestinal flora. It has also been known as Peptostreptococcus micros and Micromonas micros with its most recent re-classification in 2006. It has been described in association with hematogenous seeding of prosthetic joints [1,2]. Several cases of discitis and osteomyelitis have been described in association with dental procedures and periodontal disease often with a subacute presentation. However, cases of native joint septic arthritis are limited [3-5]. Per our literature review, there is one case of native knee septic arthritis described in 1999, with a prolonged time to diagnosis and treatment due to difficulty culturing P. micra. The previously reported patient experienced significant joint destruction and morbidity [6]. Advances in culture techniques and new methods of organism identification including MALDI-TOF and 16s rRNA sequencing have lead to increased identification of this organism, which may be a more frequent bone and joint pathogen than previously realized.