Infectious Disease

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.

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: 1-12.

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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.

Flannery, B., Meece, J.K., Williams, J.V., Martin, E.T., Gaglani, M., Jackson, M.L. and Talbot, H.K. (2021). “Systematic Testing for Influenza and Coronavirus Disease 2019 Among Patients With Respiratory Illness.” Clin Infect Dis 72(9): e426-e428.

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We recently examined the timing and extent of COVID-19 among patients with acute respiratory illness (ARI) enrolled in 2 US influenza vaccine effectiveness networks [2, 3]. We retrospectively tested specimens collected between late January 2020 and mid-March 2020, a time period during which genomic analyses of SARS-CoV-2 isolates suggested silent community spread in several US locations [4–6]. In the influenza networks, outpatients aged ≥6 months and inpatients aged ≥18 years with ARI (defined as cough or respiratory symptoms with onset ≤10 days earlier) were enrolled during the influenza season at healthcare facilities associated with study sites in 6 states (Michigan, Pennsylvania, Tennessee, Texas, Washington, and Wisconsin) [7]. [no abstract; excerpt from article].

Gaglani, M., Vasudevan, A., Raiyani, C., Murthy, K., Chen, W., Reis, M., Belongia, E.A., McLean, H.Q., Jackson, M.L., Jackson, L.A., Zimmerman, R.K., Nowalk, M.P., Monto, A.S., Martin, E.T., Chung, J.R., Spencer, S., Fry, A.M. and Flannery, B. (2021). “Effectiveness of Trivalent and Quadrivalent Inactivated Vaccines Against Influenza B in the United States, 2011-2012 to 2016-2017.” Clin Infect Dis 72(7): 1147-1157.

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BACKGROUND: Since 2013, quadrivalent influenza vaccines containing 2 B viruses gradually replaced trivalent vaccines in the United States. We compared the vaccine effectiveness of quadrivalent to trivalent inactivated vaccines (IIV4 to IIV3, respectively) against illness due to influenza B during the transition, when IIV4 use increased rapidly. METHODS: The US Influenza Vaccine Effectiveness (Flu VE) Network analyzed 25 019 of 42 600 outpatients aged ≥6 months who enrolled within 7 days of illness onset during 6 seasons from 2011-2012. Upper respiratory specimens were tested for the influenza virus type and B lineage. Using logistic regression, we estimated IIV4 or IIV3 effectiveness by comparing the odds of an influenza B infection overall and the odds of B lineage among vaccinated versus unvaccinated participants. Over 4 seasons from 2013-2014, we compared the relative odds of an influenza B infection among IIV4 versus IIV3 recipients. RESULTS: Trivalent vaccines included the predominantly circulating B lineage in 4 of 6 seasons. During 4 influenza seasons when both IIV4 and IIV3 were widely used, the overall effectiveness against any influenza B was 53% (95% confidence interval [CI], 45-59) for IIV4 versus 45% (95% CI, 34-54) for IIV3. IIV4 was more effective than IIV3 against the B lineage not included in IIV3, but comparative effectiveness against illnesses related to any influenza B favored neither vaccine valency. CONCLUSIONS: The uptake of quadrivalent inactivated influenza vaccines was not associated with increased protection against any influenza B illness, despite the higher effectiveness of quadrivalent vaccines against the added B virus lineage. Public health impact and cost-benefit analyses are needed globally.