Infectious Disease

Tenforde, M. W., W. H. Self, E. A. Naioti, A. A. Ginde, D. J. Douin, S. M. Olson, H. K. Talbot, J. D. Casey, N. M. Mohr, A. Zepeski, M. Gaglani, T. McNeal, S. Ghamande, N. I. Shapiro, K. W. Gibbs, D. C. Files, D. N. Hager, A. Shehu, M. E. Prekker, H. L. Erickson, M. N. Gong, A. Mohamed, D. J. Henning, J. S. Steingrub, I. D. Peltan, S. M. Brown, E. T. Martin, A. S. Monto, A. Khan, C. L. Hough, L. W. Busse, C. C. Ten Lohuis, A. Duggal, J. G. Wilson, A. J. Gordon, N. Qadir, S. Y. Chang, C. Mallow, C. Rivas, H. M. Babcock, J. H. Kwon, M. C. Exline, N. Halasa, J. D. Chappell, A. S. Lauring, C. G. Grijalva, T. W. Rice, I. D. Jones, W. B. Stubblefield, A. Baughman, K. N. Womack, C. J. Lindsell, K. W. Hart, Y. Zhu, M. Stephenson, S. J. Schrag, M. Kobayashi, J. R. Verani and M. M. Patel (2021). “Sustained Effectiveness of Pfizer-BioNTech and Moderna Vaccines Against COVID-19 Associated Hospitalizations Among Adults – United States, March-July 2021.” MMWR Morb Mortal Wkly Rep 70(34): 1156-1162.

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Real-world evaluations have demonstrated high effectiveness of vaccines against COVID-19-associated hospitalizations (1-4) measured shortly after vaccination; longer follow-up is needed to assess durability of protection. In an evaluation at 21 hospitals in 18 states, the duration of mRNA vaccine (Pfizer-BioNTech or Moderna) effectiveness (VE) against COVID-19-associated hospitalizations was assessed among adults aged ≥18 years. Among 3,089 hospitalized adults (including 1,194 COVID-19 case-patients and 1,895 non-COVID-19 control-patients), the median age was 59 years, 48.7% were female, and 21.1% had an immunocompromising condition. Overall, 141 (11.8%) case-patients and 988 (52.1%) controls were fully vaccinated (defined as receipt of the second dose of Pfizer-BioNTech or Moderna mRNA COVID-19 vaccines ≥14 days before illness onset), with a median interval of 65 days (range = 14-166 days) after receipt of second dose. VE against COVID-19-associated hospitalization during the full surveillance period was 86% (95% confidence interval [CI] = 82%-88%) overall and 90% (95% CI = 87%-92%) among adults without immunocompromising conditions. VE against COVID-19- associated hospitalization was 86% (95% CI = 82%-90%) 2-12 weeks and 84% (95% CI = 77%-90%) 13-24 weeks from receipt of the second vaccine dose, with no significant change between these periods (p = 0.854). Whole genome sequencing of 454 case-patient specimens found that 242 (53.3%) belonged to the B.1.1.7 (Alpha) lineage and 74 (16.3%) to the B.1.617.2 (Delta) lineage. Effectiveness of mRNA vaccines against COVID-19-associated hospitalization was sustained over a 24-week period, including among groups at higher risk for severe COVID-19; ongoing monitoring is needed as new SARS-CoV-2 variants emerge. To reduce their risk for hospitalization, all eligible persons should be offered COVID-19 vaccination.

Gill, J., C. A. Hebert and G. B. Colbert (2021). “COVID-19-associated atypical hemolytic uremic syndrome and use of Eculizumab therapy.” J Nephrol Aug 24;1-5. [Epub ahead of print].

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There is a high incidence of acute kidney injury with COVID-19 infections. The etiologies of acute kidney injury could be ischemic acute tubular necrosis or a complex process of complement activation leading to thrombotic microangiopathy. We present a case of 32-year-old Hispanic male with a history of heart transplant, admitted with COVID-19 and atypical hemolytic uremic syndrome, which was successfully treated with Eculizumab.

Thompson, M.G., Burgess, J.L., Naleway, A.L., Tyner, H., Yoon, S.K., Meece, J., Olsho, L.E.W., Caban-Martinez, A.J., Fowlkes, A.L., Lutrick, K., Groom, H.C., Dunnigan, K., Odean, M.J., Hegmann, K., Stefanski, E., Edwards, L.J., Schaefer-Solle, N., Grant, L., Ellingson, K., Kuntz, J.L., Zunie, T., Thiese, M.S., Ivacic, L., Wesley, M.G., Mayo Lamberte, J., Sun, X., Smith, M.E., Phillips, A.L., Groover, K.D., Yoo, Y.M., Gerald, J., Brown, R.T., Herring, M.K., Joseph, G., Beitel, S., Morrill, T.C., Mak, J., Rivers, P., Poe, B.P., Lynch, B., Zhou, Y., Zhang, J., Kelleher, A., Li, Y., Dickerson, M., Hanson, E., Guenther, K., Tong, S., Bateman, A., Reisdorf, E., Barnes, J., Azziz-Baumgartner, E., Hunt, D.R., Arvay, M.L., Kutty, P., Fry, A.M. and Gaglani, M. (2021). “Prevention and Attenuation of Covid-19 with the BNT162b2 and mRNA-1273 Vaccines.” N Engl J Med Jun 30. [Epub ahead of print].

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BACKGROUND: Information is limited regarding the effectiveness of the two-dose messenger RNA (mRNA) vaccines BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) in preventing infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and in attenuating coronavirus disease 2019 (Covid-19) when administered in real-world conditions. METHODS: We conducted a prospective cohort study involving 3975 health care personnel, first responders, and other essential and frontline workers. From December 14, 2020, to April 10, 2021, the participants completed weekly SARS-CoV-2 testing by providing mid-turbinate nasal swabs for qualitative and quantitative reverse-transcriptase-polymerase-chain-reaction (RT-PCR) analysis. The formula for calculating vaccine effectiveness was 100% × (1 - hazard ratio for SARS-CoV-2 infection in vaccinated vs. unvaccinated participants), with adjustments for the propensity to be vaccinated, study site, occupation, and local viral circulation. RESULTS: SARS-CoV-2 was detected in 204 participants (5%), of whom 5 were fully vaccinated (≥14 days after dose 2), 11 partially vaccinated (≥14 days after dose 1 and <14 days after dose 2), and 156 unvaccinated; the 32 participants with indeterminate vaccination status (<14 days after dose 1) were excluded. Adjusted vaccine effectiveness was 91% (95% confidence interval [CI], 76 to 97) with full vaccination and 81% (95% CI, 64 to 90) with partial vaccination. Among participants with SARS-CoV-2 infection, the mean viral RNA load was 40% lower (95% CI, 16 to 57) in partially or fully vaccinated participants than in unvaccinated participants. In addition, the risk of febrile symptoms was 58% lower (relative risk, 0.42; 95% CI, 0.18 to 0.98) and the duration of illness was shorter, with 2.3 fewer days spent sick in bed (95% CI, 0.8 to 3.7). CONCLUSIONS: Authorized mRNA vaccines were highly effective among working-age adults in preventing SARS-CoV-2 infection when administered in real-world conditions, and the vaccines attenuated the viral RNA load, risk of febrile symptoms, and duration of illness among those who had breakthrough infection despite vaccination. (Funded by the National Center for Immunization and Respiratory Diseases and the Centers for Disease Control and Prevention.).

Rolle, C.P., Berhe, M., Singh, T., Ortiz, R., Wurapa, A., Ramgopal, M., Leone, P.A., Matthews, J.E., Dalessandro, M., Underwood, M.R., Angelis, K., Wynne, B.R., Merrill, D., Nguyen, C., van Wyk, J. and Zolopa, A.R. (2021). “Dolutegravir/lamivudine as a first-line regimen in a test-and-treat setting for newly diagnosed people living with HIV.” Aids Jun 9. [Epub ahead of print].

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OBJECTIVES: Dolutegravir/lamivudine (DTG/3TC) is indicated for treatment-naive and experienced people with HIV; however, questions remain about its utility in a test-and-treat setting because of potential transmitted resistance and baseline hepatitis B virus (HBV) co-infection. We present feasibility and efficacy of DTG/3TC in newly diagnosed individuals in a test-and-treat setting. DESIGN: The single-arm STAT study evaluated DTG/3TC in a US test-and-treat setting. METHODS: Eligible adults initiated DTG/3TC ≤14 days after HIV-1 diagnosis without availability of baseline laboratory results. If baseline testing indicated DTG or 3TC resistance, HBV co-infection, or creatinine clearance <30 mL/min/1.73 m2, participants remained on study with treatment modification. Efficacy endpoints included proportions of participants with HIV-1 RNA < 50 copies/mL at Week 24, regardless of antiretroviral regimen, among (1) all participants (intention-to-treat-exposed) and (2) those with available HIV-1 RNA data (observed). RESULTS: Of 131 participants enrolled, 8% were female and 50% were non-white. Through Week 24, treatment was modified in 8 participants (5 with HBV co-infection, 1 with baseline M184 V, 1 for adverse event [AE; rash], 1 participant decision). At Week 24, 78% (102/131) of all participants and 92% (102/111) of those with available data achieved HIV-1 RNA < 50 copies/mL. Incidence of drug-related AEs was low (7%); no drug-related serious AEs occurred. CONCLUSIONS: These data demonstrate the feasibility, efficacy, and safety of using DTG/3TC as a first-line regimen in a test-and-treat setting, with therapy adjustments for baseline resistance or HBV co-infection occurring safely via routine clinical care as needed

Martin, E.T., Cheng, C., Petrie, J.G., Alyanak, E., Gaglani, M., Middleton, D.B., Ghamande, S., Silveira, F.P., Murthy, K., Zimmerman, R.K., Monto, A.S., Trabue, C., Talbot, H.K. and Ferdinands, J.M. (2021). “Low Influenza Vaccine Effectiveness Against A(H3N2)-Associated Hospitalizations in 2016-2017 and 2017-2018 of the Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN).” J Infect Dis 223(12): 2062-2071.

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BACKGROUND: The 2016-2017 and 2017-2018 influenza seasons were notable for the high number of hospitalizations for influenza A(H3N2) despite vaccine and circulating strain match. METHODS: We evaluated vaccine effectiveness (VE) against hospitalization in the test-negative HAIVEN study. Nasal-throat swabs were tested by quantitative reverse transcription polymerase chain reaction (RT-PCR) for influenza and VE was determined based on odds of vaccination by generalized estimating equations. Vaccine-specific antibody was measured in a subset of enrollees. RESULTS: A total of 6129 adults were enrolled from 10 hospitals. Adjusted VE against A(H3N2) was 22.8% (95% confidence interval [CI], 8.3% to 35.0%), pooled across both years and 49.4% (95% CI, 34.3% to 61.1%) against B/Yamagata. In 2017-2018, the A(H3N2) VE point estimate for the cell-based vaccine was 43.0% (95% CI, -36.3% to 76.1%; 56 vaccine recipients) compared to 24.0% (95% CI, 3.9% to 39.9%) for egg-based vaccines. Among 643 with serology data, hemagglutinin antibodies against the egg-based A(H3N2) vaccine strain were increased in influenza-negative individuals. CONCLUSIONS: Low VE for the A/Hong Kong/4801/2014 vaccine virus in both A(H3N2) seasons emphasizes concerns for continued changes in H3N2 antigenic epitopes, including changes that may impact glycosylation and ultimately reduce VE.