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Although measles was eliminated in the United States in 2000, a severe outbreak occurred between October 2018 and September 2019. New York was especially hard hit. Serology played an integral role in determining immune status (IgG) and identifying, along with molecular analyses, acute measles infections (IgM). Although an indirect immunofluorescence assay (IFA) was historically used by the New York State Department of Health for measles IgM detection, a higher throughput assay was needed to address the increased specimen numbers. Four commercial enzyme-linked immunosorbent assays (ELISAs) were evaluated for sensitivity and specificity in detecting measles IgM. Two ELISA formats were compared, indirect ELISA and IgM antibody capture. Both formats had comparable specificity as determined by cross-reactivity to non-measles specimens. Overall, the sensitivity of the capture ELISAs was greater than the indirect ELISAs and comparable to the indirect immunofluorescence assay with benefits regarding capacity, cost, and turnaround time.

We describe a premature infant with congenital measles. Laboratory testing confirmed measles in the mother (polymerase chain reaction- and IgM-positive) and congenital measles in the infant (polymerase chain reaction-positive, culture-positive and IgM-positive). The infant never developed a rash, pneumonia, or neurologic complications. This case supports using compatible laboratory findings to diagnose congenital measles in infants without clinical manifestations of measles.

COVID-19 is associated with a wide spectrum of disease presentation, ranging from asymptomatic infection to acute respiratory distress syndrome (ARDS). Paradoxically, a direct relationship has been suggested between COVID-19 disease severity and the levels of circulating SARS-CoV-2-specific antibodies, including virus neutralizing titers. A serological analysis of 536 convalescent healthcare workers reveal that SARS-CoV-2-specific and virus-neutralizing antibody levels are elevated in individuals that experience severe disease. The severity-associated increase in SARS-CoV-2-specific antibody is dominated by IgG, with an IgG subclass ratio skewed towards elevated receptor binding domain (RBD)- and S1-specific IgG3. In addition, individuals that experience severe disease show elevated SARS-CoV-2 specific antibody binding to the inflammatory receptor FcɣRIIIa. Based on these correlational studies, we propose that Spike-specific IgG subclass utilization may contribute to COVID-19 disease severity through potent Fc-mediated effector functions. These results may have significant implications for SARS-CoV-2 vaccine design and convalescent plasma therapy., Graphical Abstract, In a serological analysis of convalescent healthcare workers, Yates et al. explore antibody profiles associated with COVID-19 severity. Their analysis reveals an IgG subclass ratio skewed toward IgG3 that correlates with COVID-19 disease severity. The authors hypothesize a link between IgG3, Fc effector functions, and inflammation characteristic of severe COVID-19.

SummaryCOVID-19 is associated with a wide spectrum of disease severity, ranging from asymptomatic to acute respiratory distress syndrome (ARDS). Paradoxically, a direct relationship has been suggested between COVID-19 disease severity, and the levels of circulating SARS-CoV-2-specific antibodies, including virus neutralizing titers. Through a serological analysis of serum samples from 536 convalescent healthcare workers, we found that SARS-CoV-2-specific and virus-neutralizing antibody levels were indeed elevated in individuals that experienced severe disease. The severity-associated increase in SARS-CoV-2-specific antibody was dominated by IgG, with an IgG subclass ratio skewed towards elevated receptor binding domain (RBD)- and S1-specific IgG3. However, RBD- and S1-specific IgG1, rather than IgG3 were best correlated with virus-neutralizing titers.We propose that Spike-specific IgG3 subclass utilization contributes to COVID-19 disease severity through potent Fc-mediated effector functions. These results have significant implications for SARS-CoV-2 vaccine design, and convalescent plasma therapy.

Background: Measles can cause miscarriages and preterm birth in nonimmune pregnant women. During the 2018–2019 measles outbreak in New York, a woman with measles delivered an extremely low birth weight preterm infant at our Women and Children’s Hospital. We describe our measles preparedness strategies and infection prevention and control (IPC) management relevant to congenital measles. Methods: Because of the measles outbreak, in Q4 2018, IPC verified measles immunity in all obstetric and pediatric staff, per state regulations, and recommended determining the measles immune status of all pregnant women. To prevent measles exposure, visitor restrictions for the neonatal intensive care unit (NICU) were implemented (May 2019); only 3 visitors were permitted for each infant, including parents. All visitors had to provide written documentation of immunity to measles, regardless of epidemiologic risk factors or receive an MMR vaccine prior to visiting. New York state and New York City health departments performed measles diagnostic testing for maternal and infant specimens. Results: Our hospital was informed of the imminent transfer of a woman in preterm labor with suspected measles. To avoid any exposure, the mother was masked in the ambulance bay and taken by commandeered elevator to the obstetrical operating room suite, which was cleared of other patients. She delivered by C-section and was transferred to an airborne infection isolation (AII) room. The 25-week-gestation infant was transported by isolette to the NICU and was placed on AII. Testing confirmed measles in the mother (measles PCR- and IgM-positive) and congenital measles in the infant (Table 1). The mother was allowed to visit the NICU when her respiratory symptoms and rash resolved, as confirmed by her provider, ~10 days after discharge. The infant never developed a rash, pneumonia, or neurologic findings. AII was discontinued on day of life 61 in consultation with the health departments. The infant was discharged at ~36 weeks gestation. No secondary cases of measles occurred among patients, visitors, or staff. Conclusions: We safely cared for an extremely preterm infant with congenital measles. Laboratory testing suggested prolonged presence of measles virus, but it is unknown how long an infant in the NICU should remain on AII. The current Council of State and Territorial Epidemiologists case definition for measles requires the presence of rash. This case provides support to revise this case definition if laboratory findings are consistent with congenital measles.Funding: NoneDisclosures: None

The recent outbreak of Zika virus (ZIKV) in the Americas has challenged diagnostic laboratory testing strategies. At the Wadsworth Center, ZIKV serological testing was performed for over 10,000 specimens, using a combination of an enzyme-linked immunosorbent assay (ELISA) for IgM antibodies (Abs) to ZIKV, a polyvalent microsphere immunoassay (MIA) to detect Abs broadly reactive with flaviviruses, and a plaque reduction neutralization test (PRNT) for further testing. Overall, 42% of patients showed serological evidence of flavivirus infection (primarily past dengue virus [DENV] infection), while 7% possessed IgM Abs to ZIKV and/or DENV. ZIKV IgM Abs typically arose within 3 to 4 days, with only one instance of duration beyond 100 days after reported symptoms. PRNT analysis of 826 IgM-positive specimens showed 7% positive neutralization to ZIKV alone, 9% to DENV alone, and 85% to both ZIKV and DENV. Thus, the extensive Ab cross-reactivity among flaviviruses significantly reduced the value of performing PRNT analysis, especially when a traditional paired serum algorithm with viral neutralization titering was used. Nevertheless, the finding of a negative ZIKV result by PRNT was invaluable for reassuring both physicians and patients. The MIA detected both IgM and IgG, which enabled us to identify patients who presented without IgM anti-ZIKV Abs but still had ZIKV-specific neutralizing Abs. On the basis of these results, a new algorithm, which included an IgM Ab capture (MAC)-ELISA to detect recent infection, a flavivirus MIA to identify patients no longer producing IgM, and a single-dilution PRNT for ZIKV exclusion and occasional discrimination of ZIKV and DENV, was implemented.

Disease caused by Powassan virus (POWV), a tick-borne flavivirus, ranges from asymptomatic to severe neurologic compromise and death. Two cases of POWV meningoencephalitis in New York, USA, highlight diagnostic techniques, neurologic outcomes, and the effect of POWV on communities to which it is endemic.

The Centers for Disease Control and Prevention currently recommends a 2-tier serologic approach to Lyme disease laboratory diagnosis, comprised of an initial serum enzyme immunoassay (EIA) for antibody to Borrelia burgdorferi followed by supplementary IgG and IgM Western blotting of EIA-positive or -equivocal samples. Western blot accuracy is limited by subjective interpretation of weakly positive bands, false-positive IgM immunoblots, and low sensitivity for detection of early disease. We developed an objective alternative second-tier immunoassay using a multiplex microsphere system that measures VlsE1-IgG and pepC10-IgM antibodies simultaneously in the same sample. Our study population comprised 79 patients with early acute Lyme disease, 82 patients with early-convalescent-phase disease, 47 patients with stage II and III disease, 34 patients post-antibiotic treatment, and 794 controls. A bioinformatic technique called partial receiver-operator characteristic (ROC) regression was used to combine individual antibody levels into a single diagnostic score with a single cutoff; this technique enhances test performance when a high specificity is required (e.g., >95%). Compared to Western blotting, the multiplex assay was equally specific (95.6%) but 20.7% more sensitive for early-convalescent-phase disease (89.0% versus 68.3%, respectively; 95% confidence interval [95% CI] for difference, 12.1% to 30.9%) and 12.5% more sensitive overall (75.0% versus 62.5%, respectively; 95% CI for difference, 8.1% to 17.1%). As a second-tier test, a multiplex assay for VlsE1-IgG and pepC10-IgM antibodies performed as well as or better than Western blotting for Lyme disease diagnosis. Prospective validation studies appear to be warranted. Lyme disease (LD) is the most common vector-borne disease in the United States, with a reported incidence of nearly 35,000 new cases annually (10, 21). There are three disease stages: stage I is the early acute phase, characterized by a rash (erythema migrans [EM]) that occurs in at least 70% of patients; stage II represents early disseminated infection, including lymphocytic meningitis, cranial neuropathy, radiculopathy, and Lyme carditis; and stage III represents late disseminated