Safety and efficacy of convalescent plasma for severe COVID-19: a randomized, single blinded, parallel, controlled clinical study.

BACKGROUND: Convalescent plasma (CP) has been widely used to treat COVID-19 and is under study. However, the variability in the current clinical trials has averted its wide use in the current pandemic. We aimed to evaluate the safety and efficacy of CP in severe coronavirus disease 2019 (COVID-19) in the early stages of the disease. METHODS: A randomized controlled clinical study was conducted on 101 patients admitted to the hospital with confirmed severe COVID-19. Most participants had less than 14 days from symptoms onset and less than seven days from hospitalization. Fifty patients were assigned to receive CP plus standard therapy (ST), and 51 were assigned to receive ST alone. Participants in the CP arm received two doses of 250 mL each, transfused 24 h apart. All transfused plasma was obtained from "super donors" that fulfilled the following criteria: titers of anti-SARS-CoV-2 S1 IgG ≥ 1:3200 and IgA ≥ 1:800 antibodies. The effect of transfused anti-IFN antibodies and the SARS-CoV-2 variants at the entry of the study on the overall CP efficacy was evaluated. The primary outcomes were the reduction in viral load and the increase in IgG and IgA antibodies at 28 days of follow-up. The per-protocol analysis included 91 patients. RESULTS: An early but transient increase in IgG anti-S1-SARS-CoV-2 antibody levels at day 4 post-transfusion was observed (Estimated difference [ED], - 1.36; 95% CI, - 2.33 to - 0.39; P = 0.04). However, CP was not associated with viral load reduction in any of the points evaluated. Analysis of secondary outcomes revealed that those patients in the CP arm disclosed a shorter time to discharge (ED adjusted for mortality, 3.1 days; 95% CI, 0.20 to 5.94; P = 0.0361) or a reduction of 2 points on the WHO scale when compared with the ST group (HR adjusted for mortality, 1.6; 95% CI, 1.03 to 2.5; P = 0.0376). There were no benefits from CP on the rates of intensive care unit admission (HR, 0.82; 95% CI, 0.35 to 1.9; P = 0.6399), mechanical ventilation (HR, 0.66; 95% CI, 0.25 to 1.7; P = 0.4039), or mortality (HR, 3.2; 95% CI, 0.64 to 16; P = 0.1584). Anti-IFN antibodies and SARS-CoV-2 variants did not influence these results. CONCLUSION: CP was not associated with viral load reduction, despite the early increase in IgG anti-SARS-CoV-2 antibodies. However, CP is safe and could be a therapeutic option to reduce the hospital length of stay. Trial registration NCT04332835.

Autochthonous Chagas Disease - Missouri, 2018.

On December 13, 2017, the Missouri Department of Health and Senior Services (MDHSS) was notified of a suspected case of Chagas disease in a Missouri woman. The patient had donated blood, and laboratory screening revealed antibodies to Trypanosoma cruzi, the parasite that causes Chagas disease. Evaluation by physicians found no clinical symptoms consistent with Chagas disease. The patient had no travel history that would have suggested a significant risk for Chagas disease risk and had no occupational exposure to the disease agent. She had never received a blood transfusion or organ transplant. Confirmatory testing of the patient's serum at CDC for T. cruzi antibody was consistent with infection. These findings raise the possibility that the exposure to T. cruzi occurred locally (autochthonously) in Missouri. Although the insect vector for the parasite T. cruzi, triatomines (commonly known as "kissing bugs"), has been identified previously in Missouri, no locally acquired human cases of Chagas disease have been identified in the state. Health care providers and public health professionals should be aware of the possibility of locally acquired Chagas disease in the southern United States.

Imported Infections in Rural Mid-West United States - A Report from a Tertiary Care Center.

BACKGROUND: There is lack of specific data on imported infections in the mid-west United States (U.S.). METHODS: Retrospective data on demographic and geographic data of imported infections seen by the infectious diseases clinics and consultation service from 2001-2018 was collected. RESULTS: Of the 64 infections, tuberculosis(TB) was most common [20(31.3%); pulmonary(11,55%), lymphadenopathy(8,40%), gastrointestinal(4,20%), disseminated(2,10%), and 1(5%) each of genitourinary and vertebral spine infection, 4 Human immune-deficiency virus infection and 1 echinococcosis)] followed by malaria(11,17.2%). Other infections: Cysticercosis [7,10.9%], giardiasis (4,6.3%), 3 each (4.7%) Human T-lymphotrophic Virus infection and schistosomiasis, 2 each (3.1%) leprosy, strongyloidiasis, and typhoid fever, one each (1.6%) of ascariasis, brucellosis, Chagas disease, Chikungunya virus, hepatitis A virus, echinococcosis, Japanese encephalitis virus, loiasis, paratyphoid fever, Q fever, and unspecified parasitosis. Geographic origins: Africa(26,40.6%), Asia(16,25%), Central America(11,17.2%), Europe(2,3.1%), Oceania(2,3.1%), South America(2,3.1%), and Unknown(5). More cases were seen after 2015. CONCLUSIONS: With increasing tourism, it is important to educate rural mid-west healthcare professionals on travel medicine. The current COVID-19 pandemic illustrates the importance of this type of education and data accumulation now and in the future.

Laboratory Tests for COVID-19: A Review of Peer-Reviewed Publications and Implications for Clinical Use.

Diagnostic tests for the coronavirus infection 2019 (COVID-19) are critical for prompt diagnosis, treatment and isolation to break the cycle of transmission. A positive real-time reverse-transcriptase polymerase chain reaction (RT-PCR), in conjunction with clinical and epidemiologic data, is the current standard for diagnosis, but several challenges still exist. Serological assays help to understand epidemiology better and to evaluate vaccine responses but they are unreliable for diagnosis in the acute phase of illness or assuming protective immunity. Serology is gaining attention, mainly because of convalescent plasma gaining importance as treatment for clinically worsening COVID-19 patients. We provide a narrative review of peer-reviewed research studies on RT-PCR, serology and antigen immune-assays for COVID-19, briefly describe their lab methods and discuss their limitations for clinical practice.

Approach to Positive Blood Cultures in the Hospitalized Patient: A Review.

The use of blood cultures as a diagnostic tool has increased over the years along with improvements in techniques and results. The diagnostic dilemma arises when blood cultures are positive and there is possibility of contamination. Hence obtaining blood cultures in the appropriate setting and the interpretation of blood cultures by the hospitalist is imperative to the management of the hospitalized patient.

Early diagnosis of Ehrlichia ewingii infection in a lung transplant recipient by peripheral blood smear.

Ehrlichiosis in lung transplant (LT) recipients is associated with severe outcomes. Ehrlichia ewingii is a less frequent cause of symptomatic ehrlichiosis, characterized by cytoplasmic inclusions (morulae) within circulating neutrophils. We report a case of E. ewingii infection in an LT recipient diagnosed promptly by blood smear exam and confirmed with molecular studies.

VITRECTOMY-ASSISTED BIOPSY FOR MOLECULAR PROGNOSTICATION OF CHOROIDAL MELANOMA 2 MM OR LESS IN THICKNESS WITH A 27-GAUGE CUTTER.

PURPOSE: Fine-needle aspiration biopsy of small choroidal melanomas 2 mm or less in thickness may be associated with a low biopsy yield. This report describes our center's experience using the 27-gauge vitreous cutter to perform tumor sampling in these small melanomas. METHODS: This was a retrospective analysis of all patients who underwent a 27-gauge vitreous cutter biopsy for molecular prognostication at the time of iodine-125 plaque placement for local treatment of choroidal melanoma ≤2.0 mm in height. RESULTS: Seventeen consecutive patients with a mean baseline tumor height of 1.67 mm (range, 1.31-2.03 mm) and median follow-up time of 7.0 months (range, 3.3-19.5 months) were included. The 27-gauge cutter biopsy yielded sufficient material for multiplex-ligation probe amplification (MLPA) or gene expression profiling (GEP) in 17/17 (100%) patients. Complications were limited to focal vitreous hemorrhage in 13/17 patients and diffuse vitreous hemorrhage in 1/17 patients, with no instance of retinal detachment or nonclearing vitreous hemorrhage. CONCLUSION: Tumor sampling of small choroidal melanoma with a 27-gauge vitreous cutter is safe and offers excellent biopsy yield for molecular prognostication when cancer prognosis is desired by patients.

Meeting the Consultation Surge: A Nationwide Survey of Consult Volume and Mitigation Strategies in Infectious Diseases Fellowship Programs.

High patient volume in fellowship programs can affect learning, wellness, and patient outcomes. Training programs must find ways to mitigate high consultation volume to protect the learning environment. This survey describes average new consults and average censuses for infectious diseases training programs and strategies implemented to mitigate high volume.

Pulmonary tuberculosis and Cryptococcal native knee septic arthritis with osteomyelitis in an immunocompetent patient: Mycobacterial effect on CD4 function and cellular immunity.

Clinically significant cryptococcal disease is typically seen in patients with human immunodeficiency virus (HIV). However, Cryptococcosis has also been observed among non-HIV immunocompromised hosts. Cryptococcosis and tuberculosis (TB) infections both occur due to impaired cell mediated immunity but co-infection is rare among immunocompromised patients. Co-infection of these pathogens is even less reported in immunocompetent hosts. We present a case of Cryptococcal left native knee septic arthritis with tibial osteomyelitis in an HIV negative patient with recently active tuberculosis.

Acute retinal necrosis secondary to Varicella Zoster Virus.

A 54 year old female presented to the ophthalmology clinic with pain and decreased vision in her left eye. No past medical history other than primary varicella zoster infection, in her childhood. The eye exam revealed a macular region with scattered areas of retinal opacity along with patches of necrosis on the periphery. She was started on valganciclovir and referred to the infectious disease clinic. Cell Count, blood chemistry and HIV were negative. Serum was sent for polymerase chain reaction (PCR) for Varicella Zoster Virus (VZV), Herpes Simplex Virus (HSV) and Cytomegalovirus (CMV). The VZV PCR was positive. She had decreased vision on the right eye two days later, and exam revealed peripheral retinal whitening. She was admitted and started on intravenous acyclovir. VZV is one of the most common causes of ARN and has been described in both immunocompetent and immunocompromised persons. Visual changes are usually noted weeks to months after the antecedent herpes zoster. Retinal involvement is bilateral in over half of cases, suggesting that VZV reaches the central nervous system hematogenously. The retinal exam reveals multifocal necrotizing lesions, often initially involving the peripheral retina. Therapy includes intravenous acyclovir with consideration of intravitreal foscarnet and other antivirals for progressing disease.

Comparison of Gene Expression Profiling and Chromosome 3 Analysis by Fluorescent in situ Hybridization and Multiplex Ligation Probe Amplification in Fine-Needle Aspiration Biopsy Specimens of Uveal Melanoma.

PURPOSE: The aim of this paper was to assess the concordance between results of DecisionDx-UM specific gene expression profiling (GEP) and fluorescence in situ hybridization (FISH) for chromosome 3 analysis, and between DecisionDx-UM GEP and multiplex ligation probe amplification (MLPA) in uveal melanoma undergoing intraoperative fine-needle aspiration biopsy (FNAB) for metastatic prognostication during brachytherapy. METHODS: We retrospectively reviewed consecutive patients diagnosed with posterior uveal melanoma who underwent intraoperative FNAB prior to placement of an iodine-125 radioactive plaque between 2012 and 2014. Two cohorts of patients were identified: Cohort 1 - tumors in which both GEP and FISH results were obtained, and Cohort 2 - tumors in which both GEP and MLPA results were obtained. RESULTS: Forty-four patients were identified for Cohort 1. FISH and GEP results were discordant in 7 tumors (15.9%). Forty-three patients were identified for Cohort 2. MLPA and GEP were discordant in 7 tumors (16.3%). CONCLUSIONS: Discordance between GEP and chromosome 3 status by FISH and MLPA occurred in our series at a rate of 15.9 and 16.3%, respectively. Caution must be advised when counseling a patient with a good-prognosis GEP "Class 1" result that the uveal tumor may actually harbor monosomy 3, which is associated with a poor prognosis for metastasis in nearly 20% of the patients.

Disseminated histoplasmosis in a patient with common variable immunodeficiency: A coincidence or the result of T cell defects?

BACKGROUND: In endemic regions, histoplasmosis is often seen in hosts with defective cell mediated immunity. We report a case of disseminated histoplasmosis in a patient with common variable immunodeficiency (CVID), a disorder mainly characterized by B cell defects. CASE: A 35 year old male with CVID developed fever, headache, dyspnea and pancytopenia within few weeks of swimming in the Tennessee River. After a non-revealing initial evaluation he was transferred to a tertiary facility for fever of unknown origin, where massive splenomegaly was noted. Clinical course was complicated by hypoxia from extensive bilateral lung infiltrates requiring non-invasive ventilation. Urine and serum Histoplasma antigens were positive. He was treated with liposomal amphotericin B followed by itraconazole after clinical improvement within 48 h and discharged home by day 6. Fungal blood cultures sent on day 1 grew Histoplasma capsulatum on day 19. After 5 months splenomegaly completely resolved and he successfully completed one year of treatment with itraconazole. CONCLUSIONS: Our case highlights the significance of T cell defects in CVID. More research focusing on T cell defects in CVID is required to understand the extent of vulnerability to such intracellular pathogens in CVID.

Primary cytomegalovirus infection in immunocompetent adults in the United States - A case series.

Primary Cytomegalovirus (CMV) infection is often not suspected as a cause of fever of unknown origin (FUO) in immune-competent adults. We present a case-series of symptomatic primary CMV infection in immunocompetent adults presenting as fever of unknown origin (FUO). All patients with CMV serology tested between November 2008 and June 2016 underwent chart review. Cases were defined as those between 18 and 65 years of age with documented fever and elevated serum anti-CMV IgM. Exclusion criteria were organ specific CMV disease, positive serum anti-EBV IgM, or presence of any immunocompromising condition. Sixteen patients (69% male, mean age 42.2 ± 11.7 years) met criteria. Mean duration of illness was 4.6 ± 3.3 weeks. Common symptoms other than fever included fatigue (94%), night sweats (81%), malaise (75%), myalgias (63%), and headache (56%). Eleven patients (68.8%) had contact with young children; six (35.3%) patients had children in daycare. Twelve (75%) patients had extensive testing and multiple visits or hospitalizations prior to consulting with an infectious disease specialist. Peripheral smear was done in twelve (75%) patients and all had atypical lymphocytes. Five patients (31.3%) had a leukocytosis. Peak serum transaminases were: AST 115.25 ± 50.5 IU/L and ALT 168.38 ± 92.0 IU/L. One patient had splenic infarcts. In addition, two cases of hydrops fetalis were attributed to primary CMV infection. In summary, primary CMV infection can present as FUO in immunocompetent adults. Contact with young children in daycare may be a risk factor. Heightened clinical suspicion will promote earlier diagnosis and avoid unnecessary testing.

A Case of Fatal Serotonin Syndrome-Like Human Rabies Caused by Tricolored Bat-Associated Rabies Virus.

Human rabies is a fatal disease, transmitted by saliva of infected animals, and the diagnosis requires a high index of suspicion. Very few cases are reported annually in the United States. We present a case of human rabies without a clear exposure history that masqueraded as serotonin syndrome.

Catheter-Related Bloodstream Infections in Patients on Emergent Hemodialysis.

OBJECTIVE: This study had 2 objectives: (1) to describe the epidemiology of catheter-related bloodstream infections (CRBSI) in patients with end-stage renal disease (ESRD) who have no access to scheduled dialysis and (2) to evaluate whether a positive culture of the heparin-lock solution is associated with subsequent development of bacteremia. DESIGN: Retrospective observational cohort design for objective 1; and prospective cohort design for objective 2. SETTING AND PARTICIPANTS: The study was conducted in a 770-bed public academic tertiary hospital in Dallas, Texas. The participants were patients with ESRD undergoing scheduled or emergent hemodialysis. METHODS: We reviewed the records of 147 patients who received hemodialysis between January 2011 and May 2011 and evaluated the rate of CRBSI in the previous 5 years. For the prospective study, we cultured the catheter heparin-lock solution in 62 consecutive patients between June 2012 and August 2012 and evaluated the incidence of CRBSI at 6 months. RESULTS: Of the 147 patients on emergent hemodialysis, 125 had a tunneled catheter, with a CRBSI rate of 2.61 per 1,000 catheter days. The predominant organisms were Gram-negative rods (GNR). In the prospective study, we found that the dialysis catheter was colonized more frequently in patients on emergent hemodialysis than in those on scheduled hemodialysis. Colonization with GNR or Staphylococcus aureus was associated with subsequent CRBSI at 6 months follow-up. CONCLUSIONS: Patients undergoing emergent hemodialysis via tunneled catheter are predisposed to Gram-negative CRBSI. Culturing the heparin-lock solution may predict subsequent episodes of CRBSI if it shows colonization with GNR or Staphylococcus aureus. Prevention approaches in this population need to be studied further.

Variable Results for Uveal Melanoma-Specific Gene Expression Profile Prognostic Test in Choroidal Metastasis.

IMPORTANCE: We report our experience with uveal melanoma-specific gene expression profile (GEP) testing on a series of choroidal metastatic tumors confirmed by cytopathology so that clinicians may be aware that receiving a class 1 or class 2 test result in nonmelanoma is possible. OBSERVATIONS: Retrospective review of all cytopathology and DecisionDx-UM GEP reports between January 2012 to December 2014 from intraoperative fine-needle aspiration biopsy of choroidal tumors undergoing brachytherapy. Four patients were identified to have cytopathology consistent with a nonmelanoma primary. All 4 patients presented with a unilateral, single choroidal tumor, which was treated with iodine-125 brachytherapy and underwent intraoperative fine-needle aspiration biopsy for cytopathology and uveal melanoma-specific GEP testing for molecular prognostication. Gene expression profile testing of the choroidal tumor in each patient revealed class 1A in 3 patients and class 2 in 1 patient. CONCLUSIONS AND RELEVANCE: DecisionDx-UM GEP may be a helpful test for molecular prognostication in patients with uveal melanoma; however, class 1 and class 2 test results are indeed possible in the setting of a nonmelanoma malignancy. We recommend that cytopathology and/or other melanoma-specific testing be performed in all cases of suspected choroidal melanoma because GEP with this assay is unable to rule out the diagnosis of a choroidal melanoma.