Simplified Lung Ultrasound Examination and Telehealth Feasibility in Early SARS-CoV-2 Infection.

BACKGROUND: In COVID-19, inpatient studies have demonstrated that lung ultrasound B-lines relate to disease severity and mortality and can occur in apical regions that can be imaged by patients themselves. However, as illness begins in an ambulatory setting, the aim of this study was to determine the prevalence of apical B-lines in early outpatient infection and then test the accuracy of their detection using telehealth and automated methods. METHODS: Consecutive adult patients (N = 201) with positive results for SARS-CoV-2, at least one clinical risk factor, and mild to moderate disease were prospectively enrolled at a monoclonal antibody infusion clinic. Physician imaging of the lung apices for three B-lines (ultrasound lung comet [ULC]) using 3-MHz ultrasound was performed on all patients for prevalence data and served as the standard for a nested subset (n = 50) to test the accuracy of telehealth methods, including patient self-imaging and automated B-line detection. Patient characteristics, vaccination data, and hospitalizations were analyzed for associations with the presence of ULC. RESULTS: Patients' mean age was 54 ± 15 years, and all lacked hypoxemia or fever. ULC was present in 55 of 201 patients (27%) at a median of 7 symptomatic days (interquartile range, 5-8 days) and in four of five patients who were later hospitalized (P = .03). Presence of ULC was associated with unvaccinated status (odds ratio [OR], 4.11; 95% CI, 1.85-9.33; P = .001), diabetes (OR, 2.56; 95% CI, 1.08-6.05; P = .03), male sex (OR, 2.14; 95% CI, 1.07-4.37; P = .03), and hypertension or cardiovascular disease (OR, 2.06; 95% CI, 1.02-4.23; P = .04), while adjusting for body mass index > 25 kg/m2. Telehealth and automated B-line detection had 84% and 82% accuracy, respectively. CONCLUSIONS: In high-risk outpatients, B-lines in the upper lungs were common in early SARS-CoV-2 infection, were related to subsequent hospitalization, and could be detected by telehealth and automated methods.

Immune Thrombocytopenic Purpura: A Sequelae of Mycoplasma pneumoniae Infection.

Our patient presented with a mild upper respiratory infection, which quickly developed into atypical pneumonia. Although atypical pneumonia is a common clinical presentation, our case is unique due to the rare hematologic complications associated with the underlying etiology of this atypical pneumonia case. Most cases of atypical pneumonia are simple, but ours developed immune thrombocytopenic purpura (ITP), which is a rare complication associated with an acute Mycoplasma pneumoniae infection (evidenced by positive IgM titers). Although our patient did not develop significant bleeding, our review of the literature demonstrated that ITP associated with M. pneumoniae infection can be fatal. Platelet count should be closely monitored and promptly treated.

Review of Associations Between Type 2 Diabetes and Cancer.

Debate is ongoing regarding the relationship between type 2 diabetes and cancer, and the pathways linking the two are incompletely understood. Some posit that the relationship hinges on a common predisposing factor such as obesity, insulin resistance, or chronic inflammation that increases the risk of cancer independently. Others speculate that diabetes acts as an independent risk factor for cancer because of other molecular pathways and interactions. Additionally, antidiabetic medications have been associated with changes in cancer risk. This review presents a summary of the latest studies and data concerning the relationships among type 2 diabetes, antidiabetic medications, cancer risk, and cancer prognosis.

Seropositive anti-MOG antibody-associated acute disseminated encephalomyelitis (ADEM): a sequelae of Mycoplasma pneumoniae infection.

Acute disseminated encephalomyelitis (ADEM) is a demyelinating, autoimmune disease of the central nervous system (CNS). It causes motor and sensory deficits, altered mental status and other neurological symptoms. Though rarely fatal, it has been associated with residual motor and neurocognitive deficits. Our case consisted of a 4-year-old girl who presented with fatigue and unsteady gait after a respiratory illness. During her hospital course, she became progressively weaker and experienced seizures. Imaging showed sections of demyelination in the CNS, and appropriate treatment was started. Additional labs resulted in positive Mycoplasma pneumoniae serum serology. Antimyelin oligodendrocyte glycoprotein (anti-MOG) antibodies were also found, which is a risk factor for relapsing, multiphasic ADEM. To our knowledge, this is the first case of anti-MOG antibody-associated ADEM due to M. pneumoniae infection. Our patient has made a complete recovery. The parents only report slightly increased fatigue and irritability.

Mapping of Ebolavirus Neutralization by Monoclonal Antibodies in the ZMapp Cocktail Using Cryo-Electron Tomography and Studies of Cellular Entry.

UNLABELLED: ZMapp, a cocktail of three monoclonal antibodies (MAbs; c2G4, c4G7, and c13C6) against the ebolavirus (EBOV) glycoprotein (GP), shows promise for combatting outbreaks of EBOV, as occurred in West Africa in 2014. Prior studies showed that Fabs from these MAbs bind a soluble EBOV GP ectodomain and that MAbs c2G4 and c4G7, but not c13C6, neutralize infections in cell cultures. Using cryo-electron tomography, we extended these findings by characterizing the structures of c2G4, c4G7, and c13C6 IgGs bound to native, full-length GP from the West African 2014 isolate embedded in filamentous viruslike particles (VLPs). As with the isolated ectodomain, c13C6 bound to the glycan cap, whereas c2G4 and c4G7 bound to the base region of membrane-bound GP. The tomographic data suggest that all three MAbs bind with high occupancy and that the base-binding antibodies can potentially bridge neighboring GP spikes. Functional studies indicated that c2G4 and c4G7, but not c13C6, competitively inhibit entry of VLPs bearing EBOV GP into the host cell cytoplasm, without blocking trafficking of VLPs to NPC1(+) endolysosomes, where EBOV fuses. Moreover, c2G4 and c4G7 bind to and can block entry mediated by the primed (19-kDa) form of GP without impeding binding of the C-loop of NPC1, the endolysosomal receptor for EBOV. The most likely mode of action of c2G4 and c4G7 is therefore by inhibiting conformational changes in primed, NPC1-bound GP that initiate fusion between the viral and target membranes, similar to the action of certain broadly neutralizing antibodies against influenza hemagglutinin and HIV Env. IMPORTANCE: The recent West African outbreak of ebolavirus caused the deaths of more than 11,000 individuals. Hence, there is an urgent need to be prepared with vaccines and therapeutics for similar future disasters. ZMapp, a cocktail of three MAbs directed against the ebolavirus glycoprotein, is a promising anti-ebolavirus therapeutic. Using cryo-electron tomography, we provide structural information on how each of the MAbs in this cocktail binds to the ebolavirus glycoprotein as it is displayed-embedded in the membrane and present at high density-on filamentous viruslike particles that recapitulate the surface structure and entry functions of ebolavirus. Moreover, after confirming that two of the MAbs bind to the same region in the base of the glycoprotein, we show that they competitively block the entry function of the glycoprotein and that they can do so after the glycoprotein is proteolytically primed and bound to its intracellular receptor, Niemann-Pick C1. These findings should inform future developments of ebolavirus therapeutics.