A Propensity-Matched Cohort Assessing Impact of a Neutralizing Monoclonal Antibody in Mild-to-Moderate Coronavirus Disease 2019.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoaV-2) is responsible for the coronavirus disease 2019 (COVID-19) pandemic. In randomized clinical trials, patients who were treated with the anti-spike monoclonal antibody bamlanivimab had fewer COVID-19-related hospitalizations or emergency department (ED) visits than the control group. Methods: A retrospective cohort was assembled across a multisite healthcare system between November 20, 2020 and March 31, 2021. Ambulatory COVID-19 patients treated with bamlanivimab (n = 209) were propensity score matched without replacement (1:1) to a pool of 1024 eligible control patients who received similar care without bamlanivimab. The primary endpoint was all-cause mortality or admission at 30 days. Secondary endpoints included hospitalization, critical care admission, oxygenation requirements, and infusion-related reactions. Propensity score matching (PSM) analysis was used to assess the effect of bamlanivimab infusion on the composite endpoint and secondary endpoints. Results: A total of n = 209 matched patients were included in each arm of the study. The absolute standardized difference (stddiff) was calculated and indicated a balance between the groups. Almost all variables had a stddiff of less than 0.10, except for respiratory rate (RR) (stddiff = -0.11). For the primary composite endpoint of the matched cohort, 10.1% (n = 21) of patients in the intervention group were hospitalized or deceased within 30-day postbamlanivimab infusion versus 27.8% (n = 58) in the control group (adjusted odds ratio [aOR]: 0.29, 95% confidence interval [CI]: 0.17 to 0.51, P < .001). Conclusion: Patients with ambulatory COVID-19 who received bamlanivimab in the outpatient setting had a statistically significant reduction on the odds of admission postinfusion. Despite bamlanivimab's lack of efficacy on newer SARS-CoV-2 variants, this study demonstrates that neutralizing monoclonal antibodies can be effective against specific variants. If variant identification becomes a more accessible tool in outpatient centers or EDs, more targeted therapeutic options may be considered.

Dried blood spots are a valid alternative to venipuncture for COVID-19 antibody testing.

BACKGROUND: Serologic analysis is an important tool towards assessing the humoral response to COVID-19 infection and vaccination. Numerous serologic tests and platforms are currently available to support this line of testing. Two broad antibody testing categories are point-of-care lateral flow immunoassays and semi-quantitative immunoassays performed in clinical laboratories, which typically require blood collected from a finger-stick and a standard venipuncture blood draw, respectively. This study evaluated the use of dried blood spot (DBS) collections as a sample source for COVID-19 antibody testing using an automated clinical laboratory test system. METHODS: Two hundred and ninety-four participants in the BLAST COVID-19 seroprevalence study (NCT04349202) were recruited at the time of a scheduled blood draw to have an additional sample taken via finger stick as a DBS collection. Using the EUROIMMUN assay to assess SARS-CoV-2 anti-spike IgG status, DBS specimens were tested on 7, 14, 21, and 28 days post- collection and compared to the reference serum sample obtained from a blood draw for the BLAST COVID-19 study. RESULTS: SARS-CoV-2 anti-spike IgG status from DBS collections demonstrated high concordance with serum across all time points (7-28 days). However, the semi-quantitative value from DBS collections was lower on average than that from serum, resulting in increased uncertainty around the equivocal-to-positive analytical decision point. CONCLUSIONS: DBS collections can be substituted for venipuncture when assaying for COVID-19 IgG antibody, with samples being stable for at least 28 days at room temperature. Finger-stick sampling can therefore be advantageous for testing large populations for SARS-CoV-2 antibodies without the need for phlebotomists or immediate processing of samples. We have high confidence in serostaus determination from DBS collections, although the reduced semi-quantitative value may cause some low-level positives to fall into the equivocal or even negative range.

Prognostic Value of SARS-CoV-2 Anti-RBD IgG Antibody Quantitation on Clinical Outcomes in Hospitalized COVID-19 Patients

Background Antibody levels against SARS-CoV-2 can be used as an indicator of recent or past vaccination or infection. However, the prognostic value of antibodies targeting the receptor binding protein (anti-RBD) in hospitalized patients is not widely reported. Purpose Determine prognostic impact of SARS-CoV-2 antibody quantification at the time of admission on clinical outcomes in hospitalized COVID-19 patients. Methods We conducted a pilot observational study on patients hospitalized with SARS-CoV-2 infection to determine the prognostic impact of antibody quantitation within the first two days of admission. Anti-nucleocapsid IgG (anti-N) and Anti-RBD levels were measured. Anti-RBD level of 500 AU/mL was used as a cutoff to stratify patients. Spearman’s rank Coefficient (rs) was used to demonstrate association. Results Of the 26 patients included, those who were vaccinated more frequently tested positive for Anti-RBD (100% vs 46.2%, P = 0.005) with higher median titer level (623 vs 0, P = 0.011) compared to unvaccinated patients. Anti-N positivity was more frequently seen in unvaccinated patients (53.9% vs 7.7%, P = 0.03). Anti-RBD levels >500 were associated with lower overall hospital length of stay (LOS)(5 vs 10 days, P = 0.046). The analysis employing a Spearman Rank coefficient demonstrated a strong negative correlation between anti-S titer and LOS (rs=−.515, p = 0.007) and a moderate negative correlation with oxygen needs (rs =−.401, p = 0.042). Conclusion Anti-RBD IgG levels were associated with lower LOS and oxygen needs during hospitalization. Further studies are needed to determine if levels on admission can be used as a prognostic indicator.

Evolution of prescribing practices and outcomes in the COVID-19 pandemic in metropolitan areas.

Introduction: We wanted to characterize the evolution of the COVID-19 pandemic in a typical metropolitan area. Methods: Data were extracted from the Detroit COVID-19 Consortium database for hospitalized COVID-19 patients treated in Southeast Michigan over the 12-month period from March 2020 to February 2021. Demographic and outcomes data were compared to CDC data. Results: A total of 4,775 patients were enrolled during the study period. We divided the pandemic into three phases: Phase-1 (Spring Surge); Phase-2 (Summer Lull); and Phase-3 (Fall Spike). Changes in hydroxychloroquine, remdesivir, corticosteroid, antibiotic and anticoagulant use closely followed publication of landmark studies. Mortality in critically-ill patients decreased significantly from Phase-1 to Phase-3 (60.3% vs. 47.9%, Chisq p=0.0110). Monthly mortality of all hospitalized patients ranged between 14.8% - 21.5% during Phase-1 and 9.7 to 13.4% during Phase 3 (NS). Discussion: The COVID-19 pandemic presented in three unique phases in Southeast Michigan. Medical systems rapidly modified treatment plans, often preceding CDC and NIH recommendations. Despite improved treatment regimens, intubation rates and mortality for hospitalized patients remained elevated. Conclusion: Preventive measures aimed at reducing hospitalizations for COVID-19 should be emphasized.

SER-109, an Oral Microbiome Therapy for Recurrent Clostridioides difficile Infection.

BACKGROUND: Current therapies for recurrent Clostridioides difficile infection do not address the disrupted microbiome, which supports C. difficile spore germination into toxin-producing bacteria. SER-109 is an investigational microbiome therapeutic composed of purified Firmicutes spores for the treatment of recurrent C. difficile infection. METHODS: We conducted a phase 3, double-blind, randomized, placebo-controlled trial in which patients who had had three or more episodes of C. difficile infection (inclusive of the qualifying acute episode) received SER-109 or placebo (four capsules daily for 3 days) after standard-of-care antibiotic treatment. The primary efficacy objective was to show superiority of SER-109 as compared with placebo in reducing the risk of C. difficile infection recurrence up to 8 weeks after treatment. Diagnosis by toxin testing was performed at trial entry, and randomization was stratified according to age and antibiotic agent received. Analyses of safety, microbiome engraftment, and metabolites were also performed. RESULTS: Among the 281 patients screened, 182 were enrolled. The percentage of patients with recurrence of C. difficile infection was 12% in the SER-109 group and 40% in the placebo group (relative risk, 0.32; 95% confidence interval [CI], 0.18 to 0.58; P<0.001 for a relative risk of <1.0; P<0.001 for a relative risk of <0.833). SER-109 led to less frequent recurrence than placebo in analyses stratified according to age stratum (relative risk, 0.24 [95% CI, 0.07 to 0.78] for patients <65 years of age and 0.36 [95% CI, 0.18 to 0.72] for those ≥65 years) and antibiotic received (relative risk, 0.41 [95% CI, 0.22 to 0.79] with vancomycin and 0.09 [95% CI, 0.01 to 0.63] with fidaxomicin). Most adverse events were mild to moderate and were gastrointestinal in nature, with similar numbers in the two groups. SER-109 dose species were detected as early as week 1 and were associated with bile-acid profiles that are known to inhibit C. difficile spore germination. CONCLUSIONS: In patients with symptom resolution of C. difficile infection after treatment with standard-of-care antibiotics, oral administration of SER-109 was superior to placebo in reducing the risk of recurrent infection. The observed safety profile of SER-109 was similar to that of placebo. (Funded by Seres Therapeutics; ECOSPOR III ClinicalTrials.gov number, NCT03183128.).

Compassionate Use of Remdesivir in Pregnant Women With Severe Coronavirus Disease 2019.

BACKGROUND: Remdesivir is efficacious for severe coronavirus disease 2019 (COVID-19) in adults, but data in pregnant women are limited. We describe outcomes in the first 86 pregnant women with severe COVID-19 who were treated with remdesivir. METHODS: The reported data span 21 March to 16 June 2020 for hospitalized pregnant women with polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 infection and room air oxygen saturation ≤94% whose clinicians requested remdesivir through the compassionate use program. The intended remdesivir treatment course was 10 days (200 mg on day 1, followed by 100 mg for days 2-10, given intravenously). RESULTS: Nineteen of 86 women delivered before their first dose and were reclassified as immediate "postpartum" (median postpartum day 1 [range, 0-3]). At baseline, 40% of pregnant women (median gestational age, 28 weeks) required invasive ventilation, in contrast to 95% of postpartum women (median gestational age at delivery 30 weeks). By day 28 of follow-up, the level of oxygen requirement decreased in 96% and 89% of pregnant and postpartum women, respectively. Among pregnant women, 93% of those on mechanical ventilation were extubated, 93% recovered, and 90% were discharged. Among postpartum women, 89% were extubated, 89% recovered, and 84% were discharged. Remdesivir was well tolerated, with a low incidence of serious adverse events (AEs) (16%). Most AEs were related to pregnancy and underlying disease; most laboratory abnormalities were grade 1 or 2. There was 1 maternal death attributed to underlying disease and no neonatal deaths. CONCLUSIONS: Among 86 pregnant and postpartum women with severe COVID-19 who received compassionate-use remdesivir, recovery rates were high, with a low rate of serious AEs.

Coronavirus Disease 2019 (COVID-19) Seropositivity and Asymptomatic Rates in Healthcare Workers Are Associated with Job Function and Masking.

BACKGROUND: Although the risk of exposure to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is higher for frontline healthcare workers, not all personnel have similar risks. Determining infection rate is difficult due to the limits on testing and the high rate of asymptomatic individuals. Detection of antibodies against SARS-CoV-2 may be useful for determining prior exposure to the virus and assessing mitigation strategies, such as isolation, masks, and other protective equipment. METHODS: An online assessment that included demographic, clinical, and exposure information and a blood sample was collected from 20 614 participants out of ~43 000 total employees at Beaumont Health, which includes 8 hospitals distributed across the Detroit metropolitan area in southeast Michigan. The presence of anti-SARS-CoV-2 IgG was determined using the EUROIMMUN assay. RESULTS: A total of 1818 (8.8%) participants were seropositive between April 13 and May 28, 2020. Among the seropositive individuals, 44% reported that they were asymptomatic during the month prior to blood collection. Healthcare roles such as phlebotomy, respiratory therapy, and nursing/nursing support exhibited significantly higher seropositivity. Among participants reporting direct exposure to a Coronavirus Disease 2019 (COVID-19) positive individual, those wearing an N95/PAPR mask had a significantly lower seropositivity rate (10.2%) compared to surgical/other masks (13.1%) or no mask (17.5%). CONCLUSIONS: Direct contact with COVID-19 patients increased the likelihood of seropositivity among employees but study participants who wore a mask during COVID-19 exposures were less likely to be seropositive. Additionally, a large proportion of seropositive employees self-reported as asymptomatic. (Funded by Beaumont Health and by major donors through the Beaumont Health Foundation). CLINICALTRIALS.GOV NUMBER: NCT04349202.

Asystole During Nasopharyngeal Swab: Is COVID-19 to Blame?

The use of nasopharyngeal (NP) swab sampling for the detection of various respiratory pathogens has been a standard procedure in medicine for many years. While this is a fairly common procedure, there has been a significant increase in utilization recently due to the SARS-CoV-2 pandemic. We describe a case of a 40-year-old SARS-CoV-2 positive patient with no prior cardiac history who developed asystole while an NP swab was being used to obtain a sample for a SARS-CoV-2 assay. Return of normal sinus rhythm was achieved with chest compressions alone. The incident was deemed to have been an exaggerated vagal response to intranasal stimulation; better known as the trigeminocardiac reflex. This is the first reported case describing asystole during use of an NP swab. This case occurred in a patient with no known cardiac disease and highlights the potential importance of the arrhythmogenic nature of COVID-19 that could potentiate the vagal response in susceptible individuals undergoing NP sampling.

Vestibular neuritis caused by severe acute respiratory syndrome coronavirus 2 infection diagnosed by serology: Case report.

Vestibular neuritis is a disorder selectively affecting the vestibular portion of the eighth cranial nerve generally considered to be inflammatory in nature. There have been no reports of severe acute respiratory syndrome coronavirus 2 causing vestibular neuritis. We present the case of a 42-year-old Caucasian male physician, providing care to COVID-19 patients, with no significant past medical history, who developed acute vestibular neuritis, 2 weeks following a mild respiratory illness, later diagnosed as COVID-19. Physicians should keep severe acute respiratory syndrome coronavirus 2 high on the list as a possible etiology when suspecting vestibular neuritis, given the extent and implications of the current pandemic and the high contagiousness potential.