Infectious Disease

Domecq, J.P., Lal, A., Sheldrick, C.R., Kumar, V.K., Boman, K., Bolesta, S., Bansal, V., Harhay, M.O., Garcia, M.A., Kaufman, M., Danesh, V., Cheruku, S., Banner-Goodspeed, V.M., Anderson, H.L., 3rd, Milligan, P.S., Denson, J.L., St Hill, C.A., Dodd, K.W., Martin, G.S., Gajic, O., Walkey, A.J. and Kashyap, R. (2021). “Outcomes of Patients With Coronavirus Disease 2019 Receiving Organ Support Therapies: The International Viral Infection and Respiratory Illness Universal Study Registry.” Crit Care Med 49(3): 437-448.

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OBJECTIVES: To describe the outcomes of hospitalized patients in a multicenter, international coronavirus disease 2019 registry. DESIGN: Cross-sectional observational study including coronavirus disease 2019 patients hospitalized with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection between February 15, 2020, and November 30, 2020, according to age and type of organ support therapies. SETTING: About 168 hospitals in 16 countries within the Society of Critical Care Medicine’s Discovery Viral Infection and Respiratory Illness University Study coronavirus disease 2019 registry. PATIENTS: Adult hospitalized coronavirus disease 2019 patients who did and did not require various types and combinations of organ support (mechanical ventilation, renal replacement therapy, vasopressors, and extracorporeal membrane oxygenation). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome was hospital mortality. Secondary outcomes were discharge home with or without assistance and hospital length of stay. Risk-adjusted variation in hospital mortality for patients receiving invasive mechanical ventilation was assessed by using multilevel models with hospitals as a random effect, adjusted for age, race/ethnicity, sex, and comorbidities. Among 20,608 patients with coronavirus disease 2019, the mean (± sd) age was 60.5 (±17), 11,1887 (54.3%) were men, 8,745 (42.4%) were admitted to the ICU, and 3,906 (19%) died in the hospital. Hospital mortality was 8.2% for patients receiving no organ support (n = 15,001). The most common organ support therapy was invasive mechanical ventilation (n = 5,005; 24.3%), with a hospital mortality of 49.8%. Mortality ranged from 40.8% among patients receiving only invasive mechanical ventilation (n =1,749) to 71.6% for patients receiving invasive mechanical ventilation, vasoactive drugs, and new renal replacement therapy (n = 655). Mortality was 39% for patients receiving extracorporeal membrane oxygenation (n = 389). Rates of discharge home ranged from 73.5% for patients who did not require organ support therapies to 29.8% for patients who only received invasive mechanical ventilation, and 8.8% for invasive mechanical ventilation, vasoactive drugs, and renal replacement; 10.8% of patients older than 74 years who received invasive mechanical ventilation were discharged home. Median hospital length of stay for patients on mechanical ventilation was 17.1 days (9.7-28 d). Adjusted interhospital variation in mortality among patients receiving invasive mechanical ventilation was large (median odds ratio 1.69). CONCLUSIONS: Coronavirus disease 2019 prognosis varies by age and level of organ support. Interhospital variation in mortality of mechanically ventilated patients was not explained by patient characteristics and requires further evaluation.

Mutnal, M.B., Lanham, J.A., Walker, K. and Rao, A. (2021). “False positive Influenza rapid tests using newly EUA cleared multiplex assay in a low prevalence setting.” J Med Virol Jan 26. [Epub ahead of print].

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Influenza activity in the United States between September 2020 and mid‐December 2020 was relatively low with laboratory‐confirmed influenza test positivity rate at 0.2%.1 It is very well‐known in the clinical laboratory community that rapid antigen tests lack sensitivity. Studies have shown that the sensitivity of these tests can be less than 60% in a normal Influenza season. It can be speculated that due to very low prevalence of Influenza viruses, rapid antigen tests might be experiencing some assay interference, producing false positive results. When the prevalence of the disease is low, the positive predictive value of the test is low, and false‐positive test results are more likely.2-4 The false‐positive influenza results reported here may have resulted in increased health care costs and potential inappropriate use of antiviral medications. [No abstract; excerpt from Letter].

Palazzuoli, A., Ruocco, G., Tecson, K.M. and McCullough, P.A. (2021). “Screening, detection, and management of heart failure in the SARS-CoV2 (COVID-19) pandemic.” Heart Fail Rev Jan 6;1-7. [ Epub ahead of print]. 1-7.

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Observational studies suggest that a heart failure (HF) diagnosis carries a poor prognosis in subjects with severe SARS-CoV2 (COVID-19) infection, but it is unknown whether this association reflects direct myocardial damage due to COVID-19 or the consequence of preexisting cardiac defects and related cardiovascular disease (CVD) risk burden. Although the close relation between CVD and COVID-19 outcomes is well established, contrasting data exists about the occurrence of HF complications during COVID-19 infection. Therefore, a specific algorithm focused on diagnostic differentiation in acute patients distinguishing between acute HF and acute respiratory distress syndrome related to COVID-19 is needed. Further, several concerns exist for the management of patients with an uncertain diagnosis and acute dyspnea, the exact relationship existing between COVID-19 and HF. Therefore, the treatment for subjects with both COVID-19 and HF and which criteria may be defined for domiciliary or hospital management, remain poorly defined. Herein, we describe practices to be adopted in order to address these concerns and avoid further virus spread among patients, l and their familiars involved in such patients’ care.

van Zyl, J.S., Alam, A., Felius, J., Youssef, R.M., Bhakta, D., Jack, C., Jamil, A.K., Hall, S.A., Klintmalm, G.B., Spak, C.W. and Gottlieb, R.L. (2021). “ALLY in fighting COVID-19: magnitude of albumin decline and lymphopenia (ALLY) predict progression to critical disease.” J Investig Med Jan 11;jim-2020-001525. [Epub ahead of print].

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The global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic leading to coronavirus disease 2019 (COVID-19) is straining hospitals. Judicious resource allocation is paramount but difficult due to the unpredictable disease course. Once hospitalized, discerning which patients may progress to critical disease would be valuable for resource planning. Medical records were reviewed for consecutive hospitalized patients with COVID-19 in a large healthcare system in Texas. The main outcome was progression to critical disease within 10 days from admission. Albumin trends from admission to 7 days were analyzed using mixed-effects models, and progression to critical disease was modeled by multivariable logistic regression of laboratory results. Risk models were evaluated in an independent group. Of 153 non-critical patients, 28 (18%) progressed to critical disease. The rate of decrease in mean baseline-corrected (Δ) albumin was -0.08 g/dL/day (95% CI -0.11 to -0.04; p<0.001) or four times faster, in those who progressed compared with those who did not progress. A model of Δ albumin combined with lymphocyte percentage predicting progression to critical disease was validated in 60 separate patients (sensitivity, 0.70; specificity, 0.74). ALLY (delta albumin and lymphocyte percentage) is a simple tool to identify patients with COVID-19 at higher risk of disease progression when: (1) a 0.9 g/dL or greater albumin drop from baseline within 5 days of admission or (2) baseline lymphocyte of ≤10% is observed. The ALLY tool identified >70% of hospitalized cases that progressed to critical COVID-19 disease. We recommend prospectively tracking albumin. This is a globally applicable tool for all healthcare systems.

Gottlieb, R.L. and Spak, C.W. (2021). “The Olympiad of SARS-CoV-2 vaccinology: Fundamentals to Complement Technical Frontiers.” Clin Infect Dis Jan 30;ciab088. [Epub ahead of print].

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SARS-CoV-2 is a consequential and devastating virus, yet it is unlikely to be a particularly “fit,” having limited genomic size and a constrained sequence space to sample for escape mutations. If spike mutations happen to decrease efficacy of spike-specific vaccine strategies, the world may require comparative efficacy data from multiple workarounds. Chimeric derivatives of mRNA or vectored vaccines encoding various different spike variant cassettes may suffice, but inactivated vaccines offer a back-up of alternative epitopes just in case. Like saline for cholera, or like a goal in sports, vaccinology does not need to be fancy… it just needs to work. The world eagerly awaits the next steps – objective data from phase 3 trials of this, and similar, inactivated SARS-CoV-2 vaccines. [No abstract; excerpt from article].