Infectious Disease

Tenforde, M. W., Campbell, A. P., Michaels, M. G., Harrison, C. J., Klein, E. J., Englund, J. A., Selvarangan, R., Halasa, N. B., Stewart, L. S., Weinberg, G. A., Williams, J. V., Szilagyi, P. G., Staat, M. A., Boom, J. A., Sahni, L. C., Singer, M. N., Azimi, P. H., Zimmerman, R. K., McNeal, M. M., Talbot, H. K., Monto, A. S., Martin, E. T., Gaglani, M., Silveira, F. P., Middleton, D. B., Ferdinands, J. M. and Rolfes, M. A. (2022). “Clinical Influenza Testing Practices in Hospitalized Children at United States Medical Centers, 2015-2018.” J Pediatric Infect Dis Soc 11(1): 5-8.

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At nine US hospitals that enrolled children hospitalized with acute respiratory illness (ARI) during 2015-2016 through 2017-2018 influenza seasons, 50% of children with ARI received clinician-initiated testing for influenza and 35% of cases went undiagnosed due to lack of clinician-initiated testing. Marked heterogeneity in testing practice was observed across sites.

Naleway, A. L., Grant, L., Caban-Martinez, A. J., Wesley, M. G., Burgess, J. L., Groover, K., Gaglani, M., Yoon, S. K., Tyner, H. L., Meece, J., Kuntz, J. L., Yoo, Y. M., Schaefer-Solle, N., Olsho, L. E. W., Gerald, J. K., Rose, S., Thiese, M. S., Lundgren, J., Groom, H. C., Mak, J., Louzado Feliciano, P., Edwards, L. J., Lutrick, K., Dunnigan, K., Phillips, A. L., Lamberte, J. M., Noriega, R., Sokol, B. E., Odean, M., Ellingson, K. D., Smith, M., Hegmann, K. T., Respet, K., Dickerson, M., Cruz, A., Fleary, D. E., Murthy, K., Hunt, A., Azziz-Baumgartner, E., Gallimore-Wilson, D., Harder, J. A., Odame-Bamfo, L., Viergutz, J., Arvay, M., Jones, J. M., Mistry, P., Thompson, M. G. and Fowlkes, A. L. (2022). “Incidence of SARS-CoV-2 infection among COVID-19 vaccinated and unvaccinated healthcare personnel, first responders, and other essential and frontline workers: Eight US locations, January-September 2021.” Influenza Other Respir Viruses.

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BACKGROUND: We sought to evaluate the impact of changes in estimates of COVID-19 vaccine effectiveness on the incidence of laboratory-confirmed infection among frontline workers at high risk for SARS-CoV-2. METHODS: We analyzed data from a prospective frontline worker cohort to estimate the incidence of COVID-19 by month as well as the association of COVID-19 vaccination, occupation, demographics, physical distancing, and mask use with infection risk. Participants completed baseline and quarterly surveys, and each week self-collected mid-turbinate nasal swabs and reported symptoms. RESULTS: Among 1018 unvaccinated and 3531 fully vaccinated workers, the monthly incidence of laboratory-confirmed SARS-CoV-2 infection in January 2021 was 13.9 (95% confidence interval [CI]: 10.4-17.4), declining to 0.5 (95% CI -0.4-1.4) per 1000 person-weeks in June. By September 2021, when the Delta variant predominated, incidence had once again risen to 13.6 (95% CI 7.8-19.4) per 1000 person-weeks. In contrast, there was no reportable incidence among fully vaccinated participants at the end of January 2021, and incidence remained low until September 2021 when it rose modestly to 4.1 (95% CI 1.9-3.8) per 1000. Below average facemask use was associated with a higher risk of infection for unvaccinated participants during exposure to persons who may have COVID-19 and vaccinated participants during hours in the community. CONCLUSIONS: COVID-19 vaccination was significantly associated with a lower risk of SARS-CoV-2 infection despite Delta variant predominance. Our data demonstrate the added protective benefit of facemask use among both unvaccinated and vaccinated frontline workers.

Gottlieb, R.L., Vaca, C.E., Paredes, R., Mera, J., Webb, B.J., Perez, G., Oguchi, G., Ryan, P., Nielsen, B.U., Brown, M., Hidalgo, A., Sachdeva, Y., Mittal, S., Osiyemi, O., Skarbinski, J., Juneja, K., Hyland, R.H., Osinusi, A., Chen, S., Camus, G., Abdelghany, M., Davies, S., Behenna-Renton, N., Duff, F., Marty, F.M., Katz, M.J., Ginde, A.A., Brown, S.M., Schiffer, J.T. and Hill, J.A. (2021). “Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients.” N Engl J Med Dec 22. [Epub ahead of print].

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BACKGROUND: Remdesivir improves clinical outcomes in patients hospitalized with moderate-to-severe coronavirus disease 2019 (Covid-19). Whether the use of remdesivir in symptomatic, nonhospitalized patients with Covid-19 who are at high risk for disease progression prevents hospitalization is uncertain. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving nonhospitalized patients with Covid-19 who had symptom onset within the previous 7 days and who had at least one risk factor for disease progression (age ≥60 years, obesity, or certain coexisting medical conditions). Patients were randomly assigned to receive intravenous remdesivir (200 mg on day 1 and 100 mg on days 2 and 3) or placebo. The primary efficacy end point was a composite of Covid-19-related hospitalization or death from any cause by day 28. The primary safety end point was any adverse event. A secondary end point was a composite of a Covid-19-related medically attended visit or death from any cause by day 28. RESULTS: A total of 562 patients who underwent randomization and received at least one dose of remdesivir or placebo were included in the analyses: 279 patients in the remdesivir group and 283 in the placebo group. The mean age was 50 years, 47.9% of the patients were women, and 41.8% were Hispanic or Latinx. The most common coexisting conditions were diabetes mellitus (61.6%), obesity (55.2%), and hypertension (47.7%). Covid-19-related hospitalization or death from any cause occurred in 2 patients (0.7%) in the remdesivir group and in 15 (5.3%) in the placebo group (hazard ratio, 0.13; 95% confidence interval [CI], 0.03 to 0.59; P = 0.008). A total of 4 of 246 patients (1.6%) in the remdesivir group and 21 of 252 (8.3%) in the placebo group had a Covid-19-related medically attended visit by day 28 (hazard ratio, 0.19; 95% CI, 0.07 to 0.56). No patients had died by day 28. Adverse events occurred in 42.3% of the patients in the remdesivir group and in 46.3% of those in the placebo group. CONCLUSIONS: Among nonhospitalized patients who were at high risk for Covid-19 progression, a 3-day course of remdesivir had an acceptable safety profile and resulted in an 87% lower risk of hospitalization or death than placebo. (Funded by Gilead Sciences; PINETREE ClinicalTrials.gov number, NCT04501952; EudraCT number, 2020-003510-12.).

Martits-Chalangari, K., Spak, C.W., Askar, M., Killian, A., Fisher, T.L., Atillasoy, E., Marshall, W.L., McNeel, D., Miller, M.D., Mathai, S.K. and Gottlieb, R.L. (2021). “ALVR109, an off-the-shelf partially HLA matched SARS-CoV-2-specific T cell therapy, to treat refractory severe COVID-19 pneumonia in a heart transplant patient: Case report.” Am J Transplant Dec 15. [Epub ahead of print].

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An unvaccinated adult male heart transplant recipient patient with recalcitrant COVID-19 due to SARS-CoV-2 delta variant with rising nasopharyngeal quantitative viral load was successfully treated with ALVR109, an off-the-shelf SARS-CoV-2-specific T cell therapy. Background immunosuppression included 0.1 mg/kg prednisone, tacrolimus, and mycophenolate mofetil 1 gm twice daily for historical antibody-mediated rejection. Prior therapies included remdesivir, corticosteroids, and tocilizumab, with requirement for high-flow nasal oxygen. Lack of clinical improvement and acutely rising nasopharyngeal viral RNA more than 3 weeks into illness prompted the request of ALVR109 through an emergency IND. The day following the first ALVR109 infusion, the patient’s nasopharyngeal SARS-CoV-2 RNA declined from 7.43 to 5.02 log(10) RNA copies/ml. On post-infusion day 4, the patient transitioned to low-flow oxygen. Two subsequent infusions of ALVR109 were administered 10 and 26 days after the first; nasopharyngeal SARS-CoV-2 RNA became undetectable on Day 11, and he was discharged the following day on low-flow oxygen 5 weeks after the initial diagnosis of COVID-19. The clinical and virologic improvements observed in this patient following administration of ALVR109 suggest a potential benefit that warrants further exploration in clinical trials.

Mozaffari, E., Chandak, A., Zhang, Z., Liang, S., Gayle, J., Thrun, M., Gottlieb, R.L., Kuritzkes, D.R., Sax, P.E., Wohl, D.A., Casciano, R., Hodgkins, P. and Haubrich, R. (2022). “Clinical Management of Hospitalized Coronavirus Disease 2019 Patients in the United States.” Open Forum Infect Dis 9(1): ofab498.

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BACKGROUND: The objective of this study was to characterize hospitalized coronavirus disease 2019 (COVID-19) patients and describe their real-world treatment patterns and outcomes over time. METHODS: Adult patients hospitalized on May 1, 2020-December 31, 2020 with a discharge diagnosis of COVID-19 were identified from the Premier Healthcare Database. Patient and hospital characteristics, treatments, baseline severity based on oxygen support, length of stay (LOS), intensive care unit (ICU) utilization, and mortality were examined. RESULTS: The study included 295657 patients (847 hospitals), with median age of 66 (interquartile range, 54-77) years. Among each set of demographic comparators, the majority were male, white, and over 65. Approximately 85% had no supplemental oxygen charges (NSOc) or low-flow oxygen (LFO) at baseline, whereas 75% received no more than NSOc or LFO as maximal oxygen support at any time during hospitalization. Remdesivir (RDV) and corticosteroid treatment utilization increased over time. By December, 50% were receiving RDV and 80% were receiving corticosteroids. A higher proportion initiated COVID-19 treatments within 2 days of hospitalization in December versus May (RDV, 87% vs 40%; corticosteroids, 93% vs 62%; convalescent plasma, 68% vs 26%). There was a shift toward initiating RDV in patients on NSOc or LFO (68.0% [May] vs 83.1% [December]). Median LOS decreased over time. Overall mortality was 13.5% and it was highest for severe patients (invasive mechanical ventilation/extracorporeal membrane oxygenation [IMV/ECMO], 53.7%; high-flow oxygen/noninvasive ventilation [HFO/NIV], 32.2%; LFO, 11.7%; NSOc, 7.3%). The ICU use decreased, whereas mortality decreased for NSOc and LFO. CONCLUSIONS: Clinical management of COVID-19 is rapidly evolving. This large observational study found that use of evidence-based treatments increased from May to December 2020, whereas improvement in outcomes occurred over this time-period.