Research Spotlight

van Zyl, J.S., Felius, J., Alam, A., Hall, S.A., Jamil, A.K., Spak, C.W. and Gottlieb, R.L. (2021). “Dynamic albumin values as clinical surrogate for COVID-19 therapeutics.” J Investig Med May 28;jim-2021-001895. [Epub ahead of print].

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We studied patients admitted for management of COVID-19. Thus, dynamic changes clearly reflect COVID-19 disease. We posited that albumin levels fall dynamically due to the hyperinflammatory pathophysiology of COVID-19, with attendant capillary leak.2 We are delighted that the author of the above letter shares our burning question: does the dynamic fall of serum albumin track the hyperinflammatory markers of C-reactive protein, ferritin, and interleukin 6 (IL-6), and do immunomodulators such as glucocorticoids or anti-IL-6 receptor or anti-IL-6 cytokine monoclonal antibody therapies reverse this? This is an important avenue for future investigation. As IL-6 values are not routinely measured, that question can only be addressed prospectively.[No abstract; excerpt from article].

Taylor, P.C., Adams, A.C., Hufford, M.M., de la Torre, I., Winthrop, K. and Gottlieb, R.L. (2021). “Neutralizing monoclonal antibodies for treatment of COVID-19.” Nat Rev Immunol 21(6): 382-393.

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Several neutralizing monoclonal antibodies (mAbs) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed and are now under evaluation in clinical trials. With the US Food and Drug Administration recently granting emergency use authorizations for neutralizing mAbs in non-hospitalized patients with mild-to-moderate COVID-19, there is an urgent need to discuss the broader potential of these novel therapies and to develop strategies to deploy them effectively in clinical practice, given limited initial availability. Here, we review the precedent for passive immunization and lessons learned from using antibody therapies for viral infections such as respiratory syncytial virus, Ebola virus and SARS-CoV infections. We then focus on the deployment of convalescent plasma and neutralizing mAbs for treatment of SARS-CoV-2. We review specific clinical questions, including the rationale for stratification of patients, potential biomarkers, known risk factors and temporal considerations for optimal clinical use. To answer these questions, there is a need to understand factors such as the kinetics of viral load and its correlation with clinical outcomes, endogenous antibody responses, pharmacokinetic properties of neutralizing mAbs and the potential benefit of combining antibodies to defend against emerging viral variants.

Tenforde, M.W., Olson, S.M., Self, W.H., Talbot, H.K., Lindsell, C.J., Steingrub, J.S., Shapiro, N.I., Ginde, A.A., Douin, D.J., Prekker, M.E., Brown, S.M., Peltan, I.D., Gong, M.N., Mohamed, A., Khan, A., Exline, M.C., Files, D.C., Gibbs, K.W., Stubblefield, W.B., Casey, J.D., Rice, T.W., Grijalva, C.G., Hager, D.N., Shehu, A., Qadir, N., Chang, S.Y., Wilson, J.G., Gaglani, M., Murthy, K., Calhoun, N., Monto, A.S., Martin, E.T., Malani, A., Zimmerman, R.K., Silveira, F.P., Middleton, D.B., Zhu, Y., Wyatt, D., Stephenson, M., Baughman, A., Womack, K.N., Hart, K.W., Kobayashi, M., Verani, J.R. and Patel, M.M. (2021). “Effectiveness of Pfizer-BioNTech and Moderna Vaccines Against COVID-19 Among Hospitalized Adults Aged ≥65 Years – United States, January-March 2021.” MMWR Morb Mortal Wkly Rep 70(18): 674-679.

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Adults aged ≥65 years are at increased risk for severe outcomes from COVID-19 and were identified as a priority group to receive the first COVID-19 vaccines approved for use under an Emergency Use Authorization (EUA) in the United States (1-3). In an evaluation at 24 hospitals in 14 states,* the effectiveness of partial or full vaccination(†) with Pfizer-BioNTech or Moderna vaccines against COVID-19-associated hospitalization was assessed among adults aged ≥65 years. Among 417 hospitalized adults aged ≥65 years (including 187 case-patients and 230 controls), the median age was 73 years, 48% were female, 73% were non-Hispanic White, 17% were non-Hispanic Black, 6% were Hispanic, and 4% lived in a long-term care facility. Adjusted vaccine effectiveness (VE) against COVID-19-associated hospitalization among adults aged ≥65 years was estimated to be 94% (95% confidence interval [CI] = 49%-99%) for full vaccination and 64% (95% CI = 28%-82%) for partial vaccination. These findings are consistent with efficacy determined from clinical trials in the subgroup of adults aged ≥65 years (4,5). This multisite U.S. evaluation under real-world conditions suggests that vaccination provided protection against COVID-19-associated hospitalization among adults aged ≥65 years. Vaccination is a critical tool for reducing severe COVID-19 in groups at high risk.

Talbot, H.K., Martin, E.T., Gaglani, M., Middleton, D.B., Ghamande, S., Silveira, F.P., Murthy, K., Zimmerman, R.K., Trabue, C.H., Olson, S.M., Petrie, J.G., Ferdinands, J.M., Patel, M.M. and Monto, A.S. (2021). “Coronavirus disease 2019 (COVID-19) Versus Influenza in Hospitalized Adult Patients in the United States: Differences in Demographic and Severity Indicators.” Clin Infect Dis May 29;ciab123. [Epub ahead of print].

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BACKGROUND: Novel coronavirus disease 2019 (COVID-19) is frequently compared with influenza. The Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) conducts studies on the etiology and characteristics of U.S. hospitalized adults with influenza. It began enrolling patients with COVID-19 hospitalizations in March 2020. Patients with influenza were compared with those with COVID-19 in the first months of the U.S. epidemic. METHODS: Adults aged ≥ 18 years admitted to hospitals in 4 sites with acute respiratory illness were tested by real-time reverse transcription polymerase chain reaction for influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing COVID-19. Demographic and illness characteristics were collected for influenza illnesses during 3 seasons 2016-2019. Similar data were collected on COVID-19 cases admitted before June 19, 2020. RESULTS: Age groups hospitalized with COVID-19 (n = 914) were similar to those admitted with influenza (n = 1937); 80% of patients with influenza and 75% of patients with COVID-19 were aged ≥50 years. Deaths from COVID-19 that occurred in younger patients were less often related to underlying conditions. White non-Hispanic persons were overrepresented in influenza (64%) compared with COVID-19 hospitalizations (37%). Greater severity and complications occurred with COVID-19 including more ICU admissions (AOR = 15.3 [95% CI: 11.6, 20.3]), ventilator use (AOR = 15.6 [95% CI: 10.7, 22.8]), 7 additional days of hospital stay in those discharged alive, and death during hospitalization (AOR = 19.8 [95% CI: 12.0, 32.7]). CONCLUSIONS: While COVID-19 can cause a respiratory illness like influenza, it is associated with significantly greater severity of illness, longer hospital stays, and higher in-hospital deaths.

Chung, J.R., Flannery, B., Kim, S.S., Gaglani, M., Raiyani, C., Belongia, E.A., McLean, H.Q., Nowalk, M.P., Zimmerman, R.K., Jackson, M.L., Jackson, L.A., Martin, E.T., Monto, A.S. and Patel, M. (2021). “Sample size considerations for mid-season estimates from a large influenza vaccine effectiveness network in the United States.” Vaccine 39(25): 3324-3328.

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INTRODUCTION: Mid-season influenza vaccine effectiveness (VE) estimates are a useful tool to help guide annual influenza vaccine strain selection, vaccine policy, and public health messaging. We propose using a sample size-driven approach with data-driven inputs for publication of mid-season influenza VE. METHODS: We used pooled inputs for VE by (sub)type and average vaccine coverage by age groups using data from eight seasons of the US Influenza VE Network to calculate sample sizes needed to estimate mid-season VE. RESULTS: We estimate that 135 influenza-positive cases would be needed to detect an overall VE of 40% with 55% vaccine coverage among test-negative controls. Larger sample sizes would be required to produce reliable estimates specifically against influenza A/H3N2 and for older age groups. CONCLUSION: Using an existing network, most of the recent influenza seasons in the US would facilitate valid mid-season VE estimates using the proposed sample sizes for broad age groupings.