Infectious Disease

Van Der Pol, B., A. Rao, M. B. Nye, S. Chavoustie, A. Ermel, C. Kaplan, D. Eisenberg, P. A. Chan, L. Mena, S. Pacheco, K. B. Waites, L. Xiao, S. Krishnamurthy, R. Mohan, R. Bertuzis, C. L. McGowin, R. Arcenas, E. M. Marlowe and S. N. Taylor (2021). “Trichomonas vaginalis Detection in Urogenital Specimens from Symptomatic and Asymptomatic Men and Women by Use of the cobas TV/MG Test.” J Clin Microbiol 59(10): e0026421.

Full text of this article.

Trichomonas vaginalis is a prevalent sexually transmitted infection (STI). Diagnosis has historically relied on either microscopic analysis or culture, the latter being the previous gold standard. However, these tests are not readily available for male diagnosis, generally only perform well for symptomatic women, and are not as sensitive as nucleic acid amplification tests (NAATs). Men are largely asymptomatic but carry the organism and transmit to their sexual partners. This multicenter, prospective study evaluated the performance of the cobas T. vaginalis/Mycoplasma genitalium (TV/MG) assay for detection of T. vaginalis DNA compared with patient infection status (PIS) defined by a combination of commercially available NAATs and culture using urogenital specimens. A total of 2,064 subjects (984 men and 1,080 women, 940 [45.5%] symptomatic, 1,124 [54.5%] asymptomatic) were evaluable. In women, sensitivity ranged from 99.4% (95% confidence interval [CI] 96.8 to 99.9%) using vaginal samples to 94.7% (95% CI 90.2 to 97.2%) in PreservCyt samples. Specificity ranged from 98.9 to 96.8% (95% CI 95.4 to 97.8%). In men, the cobas TV/MG assay was 100% sensitive for the detection of T. vaginalis in both male urine samples and meatal swabs, with specificity of 98.4% in urine samples and 92.5% in meatal swabs. The cobas TV/MG is a suitable diagnostic test for the detection of T. vaginalis, which could support public health efforts toward infection control and complement existing STI programs.

Mutnal, M. B., S. Johnson, N. Mohamed, R. Abddelgader, L. Morales, M. Volz, K. Walker, A. C. Arroliga and A. Rao (2021). “Surveillance genome sequencing reveals multiple SARS-CoV-2 variants circulating in central Texas, USA, with a predominance of delta variant and review of vaccine breakthrough cases.” J Med Virol.

Full text of this article.

As surges in the COVID-19 pandemic have continued worldwide, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has mutated, spawning several new variants, and impacting, to various degrees, transmission, disease severity, diagnostics, therapeutics, and natural and vaccine-induced immunity. Baylor Scott & White Health has implemented, along with laboratory diagnosis, SARS-CoV-2 sequencing to identify variants in its geographical service area. We analyzed virus sequencing results of specimens collected across Central Texas and found dramatic changes in variant distribution in the first half of 2021. The alpha variant (B 1.1.7) became predominant at week 13 and continued dominance until week 25. A growth rate of 1.20 (R(2)  = 0.92) for the first 15 weeks was noted and this growth gradually declined to -0.55 (R(2)  = 0.99) for the final 13 weeks. Currently, B.1.1.7 is being displaced with B.1.617.2 at a 0.58 growth rate (R(2)  = 0.97). We also investigated vaccine breakthrough cases (VBCs) within our healthcare system and present clinical data on 28 symptomatic patients.

Rosas, I. O., G. Diaz, R. L. Gottlieb, S. M. Lobo, P. Robinson, B. D. Hunter, A. W. Cavalcante, J. S. Overcash, N. A. Hanania, A. Skarbnik, J. Garcia-Diaz, I. Gordeev, J. Carratalà, O. Gordon, E. Graham, N. Lewin-Koh, L. Tsai, K. Tuckwell, H. Cao, D. Brainard and J. K. Olsson (2021). “Tocilizumab and remdesivir in hospitalized patients with severe COVID-19 pneumonia: a randomized clinical trial.” Intensive Care Med: 1-13.

Full text of this article.

PURPOSE: Trials of tocilizumab in patients with severe COVID-19 pneumonia have demonstrated mixed results, and the role of tocilizumab in combination with other treatments is uncertain. Here we evaluated whether tocilizumab plus remdesivir provides greater benefit than remdesivir alone in patients with severe COVID-19 pneumonia. METHODS: This randomized, double-blind, placebo-controlled, multicenter trial included patients hospitalized with severe COVID-19 pneumonia requiring > 6 L/min supplemental oxygen. Patients were randomly assigned (2:1 ratio) to receive tocilizumab 8 mg/kg or placebo intravenously plus ≤ 10 days of remdesivir. The primary outcome was time from randomization to hospital discharge or “ready for discharge” (defined as category 1, assessed by the investigator on a 7-category ordinal scale of clinical status) to day 28. Patients were followed for 60 days. RESULTS: Among 649 enrolled patients, 434 were randomly assigned to tocilizumab plus remdesivir and 215 to placebo plus remdesivir. 566 patients (88.2%) received corticosteroids during the trial to day 28. Median time from randomization to hospital discharge or “ready for discharge” was 14 (95% CI 12-15) days with tocilizumab plus remdesivir and 14 (95% CI 11-16) days with placebo plus remdesivir [log-rank P = 0.74; Cox proportional hazards ratio 0.97 (95% CI 0.78-1.19)]. Serious adverse events occurred in 128 (29.8%) tocilizumab plus remdesivir and 72 (33.8%) placebo plus remdesivir patients; 78 (18.2%) and 42 (19.7%) patients, respectively, died by day 28. CONCLUSIONS: Tocilizumab plus remdesivir did not shorten time to hospital discharge or “ready for discharge” to day 28 compared with placebo plus remdesivir in patients with severe COVID-19 pneumonia.

Mozaffari, E., A. Chandak, Z. Zhang, S. Liang, M. Thrun, R. L. Gottlieb, D. R. Kuritzkes, P. E. Sax, D. A. Wohl, R. Casciano, P. Hodgkins and R. Haubrich (2021). “Remdesivir treatment in hospitalized patients with COVID-19: a comparative analysis of in-hospital all-cause mortality in a large multi-center observational cohort.” Clin Infect Dis. [Epub ahead of print].

Full text of this article.

BACKGROUND: Remdesivir (RDV) improved clinical outcomes among hospitalized COVID-19 patients in randomized trials, but data from clinical practice are limited. METHODS: We examined survival outcomes for US patients hospitalized with COVID-19 between Aug-Nov 2020 and treated with RDV within two-days of hospitalization vs. those not receiving RDV during their hospitalization using the Premier Healthcare Database. Preferential within-hospital propensity score matching with replacement was used. Additionally, patients were also matched on baseline oxygenation level (no supplemental oxygen charges (NSO), low-flow oxygen (LFO), high-flow oxygen/non-invasive ventilation (HFO/NIV) and invasive mechanical ventilation/ECMO (IMV/ECMO) and two-month admission window and excluded if discharged within 3-days of admission (to exclude anticipated discharges/transfers within 72-hrs consistent with ACTT-1 study). Cox Proportional Hazards models were used to assess time to 14-/28-day mortality overall and for patients on NSO, LFO, HFO/NIV and IMV/ECMO. RESULTS: 28,855 RDV patients were matched to 16,687 unique non-RDV patients. Overall, 10.6% and 15.4% RDV patients died within 14- and 28-days, respectively compared with 15.4% and 19.1% non-RDV patients. Overall, RDV was associated with a reduction in mortality at 14-days (HR[95% CI]: 0.76[0.70-0.83]) and 28-days (0.89[0.82-0.96]). This mortality benefit was also seen for NSO, LFO and IMV/ECMO at 14-days (NSO:0.69[0.57-0.83], LFO:0.68[0.80-0.77], IMV/ECMO:0.70[0.58-0.84]) and 28-days (NSO:0.80[0.68-0.94], LFO:0.77[0.68-0.86], IMV/ECMO:0.81[0.69-0.94]). Additionally, HFO/NIV RDV group had a lower risk of mortality at 14-days (0.81[0.70-0.93]) but no statistical significance at 28-days. CONCLUSIONS: RDV initiated upon hospital admission was associated with improved survival among COVID-19 patients. Our findings complement ACTT-1 and support RDV as a foundational treatment for hospitalized COVID-19 patients.

Thompson, M. G., E. Stenehjem, S. Grannis, S. W. Ball, A. L. Naleway, T. C. Ong, M. B. DeSilva, K. Natarajan, C. H. Bozio, N. Lewis, K. Dascomb, B. E. Dixon, R. J. Birch, S. A. Irving, S. Rao, E. Kharbanda, J. Han, S. Reynolds, K. Goddard, N. Grisel, W. F. Fadel, M. E. Levy, J. Ferdinands, B. Fireman, J. Arndorfer, N. R. Valvi, E. A. Rowley, P. Patel, O. Zerbo, E. P. Griggs, R. M. Porter, M. Demarco, L. Blanton, A. Steffens, Y. Zhuang, N. Olson, M. Barron, P. Shifflett, S. J. Schrag, J. R. Verani, A. Fry, M. Gaglani, E. Azziz-Baumgartner and N. P. Klein (2021). “Effectiveness of Covid-19 Vaccines in Ambulatory and Inpatient Care Settings.” N Engl J Med 385(15): 1355-1371.

Full text of this article.

BACKGROUND: There are limited data on the effectiveness of the vaccines against symptomatic coronavirus disease 2019 (Covid-19) currently authorized in the United States with respect to hospitalization, admission to an intensive care unit (ICU), or ambulatory care in an emergency department or urgent care clinic. METHODS: We conducted a study involving adults (≥50 years of age) with Covid-19-like illness who underwent molecular testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We assessed 41,552 admissions to 187 hospitals and 21,522 visits to 221 emergency departments or urgent care clinics during the period from January 1 through June 22, 2021, in multiple states. The patients’ vaccination status was documented in electronic health records and immunization registries. We used a test-negative design to estimate vaccine effectiveness by comparing the odds of a positive test for SARS-CoV-2 infection among vaccinated patients with those among unvaccinated patients. Vaccine effectiveness was adjusted with weights based on propensity-for-vaccination scores and according to age, geographic region, calendar time (days from January 1, 2021, to the index date for each medical visit), and local virus circulation. RESULTS: The effectiveness of full messenger RNA (mRNA) vaccination (≥14 days after the second dose) was 89% (95% confidence interval [CI], 87 to 91) against laboratory-confirmed SARS-CoV-2 infection leading to hospitalization, 90% (95% CI, 86 to 93) against infection leading to an ICU admission, and 91% (95% CI, 89 to 93) against infection leading to an emergency department or urgent care clinic visit. The effectiveness of full vaccination with respect to a Covid-19-associated hospitalization or emergency department or urgent care clinic visit was similar with the BNT162b2 and mRNA-1273 vaccines and ranged from 81% to 95% among adults 85 years of age or older, persons with chronic medical conditions, and Black or Hispanic adults. The effectiveness of the Ad26.COV2.S vaccine was 68% (95% CI, 50 to 79) against laboratory-confirmed SARS-CoV-2 infection leading to hospitalization and 73% (95% CI, 59 to 82) against infection leading to an emergency department or urgent care clinic visit. CONCLUSIONS: Covid-19 vaccines in the United States were highly effective against SARS-CoV-2 infection requiring hospitalization, ICU admission, or an emergency department or urgent care clinic visit. This vaccine effectiveness extended to populations that are disproportionately affected by SARS-CoV-2 infection. (Funded by the Centers for Disease Control and Prevention.).