Infectious Disease

Carey, S.A., Afzal, A., Jamil, A., Williams, S. and Gottlieb, R.L. (2020). “Outpatient COVID-19 surveillance testing in orthotopic heart transplant recipients.” Clin Transplant Sep 25;e14105. [Epub ahead of print.]. e14105.

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COVID-19 case fatality rate in the United States is currently reported at 4.8% based on the confirmed cases of COVID-19. However, there are conflicting reports of estimated deaths in the post-cardiac transplantation patient population associated with COVID-19. METHODS: Observational, retrospective analysis of a large cohort of post Orthotopic Heart Transplantation (OHT) patients in a high volume heart transplantation program in Dallas, Texas underwent outpatient COVID-19 screening and testing for both SARS-CoV-2 nasopharyngeal RT-PCR and anti-SARS-CoV2 IgG serology as a result of a clinic protocol to facilitate re-opening of face-to-face outpatient clinical visits. RESULTS: The full outpatient cohort tested at time of their clinic visit tested negative for COVID-19 by nasopharyngeal RT-PCR. Only 2 patients tested seropositive for anti-SARS-COV2 IgG. Five positive inpatient cases were also identified and all, but one recovered. CONCLUSION: A COVID-19 surveillance protocol can be easily instituted in this high-risk population and facilitate safe transplant clinic operation. As the cases and prevalence increase across the United States, further strategies will need to be developed to determine the best course of action to help manage this select population while minimizing their exposure to the ongoing pandemic.

Spinner, C.D., Gottlieb, R.L., Criner, G.J., Arribas López, J.R., Cattelan, A.M., Soriano Viladomiu, A., Ogbuagu, O., Malhotra, P., Mullane, K.M., Castagna, A., Chai, L.Y.A., Roestenberg, M., Tsang, O.T.Y., Bernasconi, E., Le Turnier, P., Chang, S.C., SenGupta, D., Hyland, R.H., Osinusi, A.O., Cao, H., Blair, C., Wang, H., Gaggar, A., Brainard, D.M., McPhail, M.J., Bhagani, S., Ahn, M.Y., Sanyal, A.J., Huhn, G. and Marty, F.M. (2020). “Effect of Remdesivir vs Standard Care on Clinical Status at 11 Days in Patients With Moderate COVID-19: A Randomized Clinical Trial.” Jama 324(11): 1048-1057.

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IMPORTANCE: Remdesivir demonstrated clinical benefit in a placebo-controlled trial in patients with severe coronavirus disease 2019 (COVID-19), but its effect in patients with moderate disease is unknown. OBJECTIVE: To determine the efficacy of 5 or 10 days of remdesivir treatment compared with standard care on clinical status on day 11 after initiation of treatment. DESIGN, SETTING, AND PARTICIPANTS: Randomized, open-label trial of hospitalized patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and moderate COVID-19 pneumonia (pulmonary infiltrates and room-air oxygen saturation >94%) enrolled from March 15 through April 18, 2020, at 105 hospitals in the United States, Europe, and Asia. The date of final follow-up was May 20, 2020. INTERVENTIONS: Patients were randomized in a 1:1:1 ratio to receive a 10-day course of remdesivir (n = 197), a 5-day course of remdesivir (n = 199), or standard care (n = 200). Remdesivir was dosed intravenously at 200 mg on day 1 followed by 100 mg/d. MAIN OUTCOMES AND MEASURES: The primary end point was clinical status on day 11 on a 7-point ordinal scale ranging from death (category 1) to discharged (category 7). Differences between remdesivir treatment groups and standard care were calculated using proportional odds models and expressed as odds ratios. An odds ratio greater than 1 indicates difference in clinical status distribution toward category 7 for the remdesivir group vs the standard care group. RESULTS: Among 596 patients who were randomized, 584 began the study and received remdesivir or continued standard care (median age, 57 [interquartile range, 46-66] years; 227 [39%] women; 56% had cardiovascular disease, 42% hypertension, and 40% diabetes), and 533 (91%) completed the trial. Median length of treatment was 5 days for patients in the 5-day remdesivir group and 6 days for patients in the 10-day remdesivir group. On day 11, patients in the 5-day remdesivir group had statistically significantly higher odds of a better clinical status distribution than those receiving standard care (odds ratio, 1.65; 95% CI, 1.09-2.48; P = .02). The clinical status distribution on day 11 between the 10-day remdesivir and standard care groups was not significantly different (P = .18 by Wilcoxon rank sum test). By day 28, 9 patients had died: 2 (1%) in the 5-day remdesivir group, 3 (2%) in the 10-day remdesivir group, and 4 (2%) in the standard care group. Nausea (10% vs 3%), hypokalemia (6% vs 2%), and headache (5% vs 3%) were more frequent among remdesivir-treated patients compared with standard care. CONCLUSIONS AND RELEVANCE: Among patients with moderate COVID-19, those randomized to a 10-day course of remdesivir did not have a statistically significant difference in clinical status compared with standard care at 11 days after initiation of treatment. Patients randomized to a 5-day course of remdesivir had a statistically significant difference in clinical status compared with standard care, but the difference was of uncertain clinical importance. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04292730.

Balasubramani, G.K., Choi, W.S., Nowalk, M.P., Zimmerman, R.K., Monto, A.S., Martin, E.T., Belongia, E.A., McLean, H.Q., Gaglani, M., Murthy, K., Jackson, M.L., Jackson, L.A., Chung, J.R., Spencer, S., Fry, A.M., Patel, M. and Flannery, B. (2020). “Relative effectiveness of high dose versus standard dose influenza vaccines in older adult outpatients over four seasons, 2015-16 to 2018-19.” Vaccine Aug 12;S0264-410X(20)31032-X. [Epub ahead of print.].

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BACKGROUND: New influenza vaccine formulations are designed to improve vaccine effectiveness and protect those most vulnerable to infection. High dose trivalent inactivated influenza vaccine (HD-IIV3), licensed for ages ≥65 years, produces greater antibody responses and efficacy in clinical trials, but post-licensure vaccine effectiveness (VE) compared to standard dose (SD-IIV3/4) vaccine remains an open question. METHODS: Using a test-negative, case control design and propensity analyses to adjust for confounding, US Influenza VE Network data from the 2015-2016 through 2018-2019 seasons were analyzed to determine relative VE (rVE) between HD-IIV3 and SD-IIV3/4 among outpatients ≥65 years old presenting with acute respiratory illness. Influenza vaccination status was derived from electronic medical records and immunization registries. RESULTS: Among 3861 enrollees, 2993 (78%) were vaccinated; 1573 (53%) received HD-IIV3 and 1420 (47%) received SD-IIV3/4. HD-IIV3 recipients differed from SD-IIV3/4 recipients by race, previous vaccination, number of outpatient visits in the previous year and timing of vaccination, and were balanced in the propensity model except the timing of vaccination. Compared with no vaccination, significant protection against any influenza A was observed from both HD-IIV3 (VE = 29%; 95%CI = 10%, 44%) and SD-IIV3/4 (VE = 24%; 95%CI = 5%, 39%); rVE = 18% (95%CI = 0%, 33%, SD as referent). When stratified by virus type, against A/H1N1, HD-IIV3 VE was 30% (95%CI = -7%, 54%), SD-IIV3/4 VE was 40% (95%CI = 10%, 61%), and rVE = -32%; (95%CI = -94%, 11%); Against A/H3N2, HD-IIV3 VE was 31% (95%CI = 9%, 47%), SD-IIV3/4 VE was 19% (95%CI = -5%, 37%), and rVE = 27%; (95% CI = 9%, 42%). CONCLUSIONS: Among adults ≥65 years of age, recipients of standard and high dose influenza vaccines differed significantly in their characteristics. After adjusting for these differences, high dose vaccine offered more protection against A/H3N2 and borderline significant protection against all influenza A requiring outpatient care during the 2015-2018 influenza seasons.

Flannery, B., J. K. Meece, J. V. Williams, E. T. Martin, M. Gaglani, M. L. Jackson and H. K. Talbot (2020). “Systematic testing for influenza and COVID-19 among patients with respiratory illness.” Clin Infect Dis 2020 Jul 20;ciaa1023. [Epub ahead of print.].

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A recent report by Rosenberg and colleagues highlights the importance of multiple sources of information for monitoring trends in the COVID-19 pandemic [1]. The authors use influenzalike illness (ILI) surveillance data and laboratory-confirmed influenza and COVID-19 cases to estimate population-based rates of illness during the beginnings of the pandemic in New York state. Because SARS-CoV-2 testing was rapidly increasing during this period in many areas of the U.S., numbers of COVID-19 cases were likely underestimated. This raises the question of whether COVID-19 contributed to ILI trends prior to widespread testing. [No abstract; excerpt from article].

Dixon, M. K., C. L. Dayton and G. M. Anstead (2020). “Parinaud’s Oculoglandular Syndrome: A Case in an Adult with Flea-Borne Typhus and a Review.” Trop Med Infect Dis 5(3).

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Parinaud’s oculoglandular syndrome (POGS) is defined as unilateral granulomatous conjunctivitis and facial lymphadenopathy. The aims of the current study are to describe a case of POGS with uveitis due to flea-borne typhus (FBT) and to present a diagnostic and therapeutic approach to POGS. The patient, a 38-year old man, presented with persistent unilateral eye pain, fever, rash, preauricular and submandibular lymphadenopathy, and laboratory findings of FBT: hyponatremia, elevated transaminase and lactate dehydrogenase levels, thrombocytopenia, and hypoalbuminemia. His condition rapidly improved after starting doxycycline. Soon after hospitalization, he was diagnosed with uveitis, which responded to topical prednisolone. To derive a diagnostic and empiric therapeutic approach to POGS, we reviewed the cases of POGS from its various causes since 1976 to discern epidemiologic clues and determine successful diagnostic techniques and therapies; we found multiple cases due to cat scratch disease (CSD; due to Bartonella henselae) (twelve), tularemia (ten), sporotrichosis (three), Rickettsia conorii (three), R. typhi/felis (two), and herpes simplex virus (two) and single cases due to tuberculosis, paracoccidioidomycosis, Yersinia enterocolitica, Pasteurella multocida, Chlamydia trachomatis, Epstein-Barr virus, and Nocardia brasiliensis. Preauricular lymphadenopathy is a common clinical clue for POGS and is unusual in viral and bacterial conjunctivitis. For POGS, the major etiological consideration is B. henselae, which is usually diagnosed by the indirect immunofluorescence serologic technique. Although CSD POGS is usually self-limited, oral azithromycin may hasten resolution. However, other possible etiologies of POGS may also arise from cat or cat flea contact: sporotrichosis, tularemia, Pasteurella multocida, or FBT. If there is no cat contact, other epidemiologic and clinical findings should be sought, because several of these conditions, such as tularemia, paracoccidioidomycosis, and tuberculosis, may have grave systemic complications. Although there are usually no long-term ocular sequelae if POGS is properly diagnosed, it still may cause prolonged ocular discomfort and require multiple physician contacts.