Multisystem Inflammatory Syndrome in Children after SARS-CoV-2 Vaccination.

Multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory state that occurs after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We present 2 cases of MIS-C after SARS-CoV-2 vaccination; 1 patient had evidence of recent SARS-CoV-2 infection. Our findings suggest that vaccination modulates the pathogenesis of MIS-C.

The frequency of pregnancy and exposure to cytomegalovirus infections among women with a young child in day care.

OBJECTIVE: The purpose of this study was to determine the frequency of pregnancy and exposure to cytomegalovirus (CMV) among mothers contemplating a possible additional pregnancy and with a child less than 2 years of age in group day care. STUDY DESIGN: We performed a prospective observational study that included a demographic questionnaire and serologic and virologic monitoring of mothers and their children in day care. RESULTS: Of 60 women, 62% were seronegative and 20% had a child shedding CMV. Of the 60 women, 23 women or 38% (95% CI, 0.27-0.51) became pregnant on average 10 months after enrollment. During pregnancy, 8 or 35% (95% CI, 0.19-0.55) of these pregnant women had a child in day care who shed CMV. CONCLUSION: These results illustrate the potential magnitude of the public problem associated with exposure to a silent viral infection during pregnancy. Our data, when extrapolated to the US population, estimate that every 2 years between 31,000 and 168,000 susceptible pregnant women will be exposed to CMV by an infected child.

Antivirals for cytomegalovirus infection in neonates and infants: focus on pharmacokinetics, formulations, dosing, and adverse events.

Cytomegalovirus (CMV) infection is very common throughout the world, and has become more of a pediatric clinical concern given the high incidence of congenital CMV infections as well as the increasing numbers of immunocompromised patients. Because of this, the need for antiviral therapies in infants and neonates is growing. Currently, there are four antivirals available that are active against CMV: ganciclovir, valganciclovir, foscarnet, and cidofovir. At this time, none have approved indications for use in children. Although there are limited data regarding the dose, pharmacokinetics (PK), safety, and adverse events for some of these antivirals, ganciclovir, and its oral prodrug valganciclovir, have been the best studied in the infant and neonate populations. In general, pharmaceutical PK studies in young children are limited by the constraints of sampling difficulties and blood volume requirements; fewer sampling times and studies may be available for drug evaluation. Given this caveat, ganciclovir and valganciclovir PK in children thus far appears to follow a monocompartmental model, contrary to what has been described in adults. However, when normalized for weight, the volume of distribution, clearance, and half-life of ganciclovir are similar to those found in adults. Given the findings that ganciclovir (and thus valganciclovir) clearance is directly proportionate to renal function, care must be taken when administering the drug to patients with impaired renal function. Recent studies evaluating valganciclovir PK in infants (at a dose of 16 mg/kg every 12 hours) have shown similar areas under the plasma concentration-time curve (AUCs) to intravenous ganciclovir (at a dose of 6 mg/kg every 12 hours), and that these AUCs remain quite stable over a number of weeks. As seen in adults, oral ganciclovir has a low bioavailability (4.8% in a pediatric analysis) and is therefore a poor alternative for treating serious CMV infections. Neutropenia is the most frequent toxicity associated with ganciclovir and valganciclovir therapy, whereas significant (and possibly irreversible) renal toxicity can be seen with cidofovir. Foscarnet administration can also result in renal toxicity as well as significant electrolyte imbalances. Several of these drugs have potential toxicities that are of concern, including carcinogenesis, teratogenesis, and azospermia (ganciclovir, valganciclovir, and cidofovir) and deposition into bone or dentition (foscarnet) that may have significant implications when treating an infant. Given these potential ill effects, careful consideration of the indications for the clinical use of these antivirals is necessary before using them for CMV infection in neonates and infants.

Avidity maturation following immunization with two human cytomegalovirus (CMV) vaccines: a live attenuated vaccine (Towne) and a recombinant glycoprotein vaccine (gB/MF59).

Two human cytomegalovirus (CMV) vaccines have been previously evaluated for their immunogenicity: a recombinant gB/MF59 vaccine and an attenuated strain of CMV (Towne). In healthy adults, we measured the antibody avidity maturation indices that occurred after vaccination with each. For Towne, administered as a single dose, the rise in IgG antibody avidity to CMV glycoprotein gB occurred slowly and continued for 24 months post-immunization. For gB/MF59, administered as two priming doses and a booster dose given at 6 months, the booster rapidly induced IgG antibodies to gB whose avidity was maximal at 7 months after the initial priming dose. Both vaccines induced antibody levels and avidity maturation indices that equaled those induced by wild-type virus suggesting that both vaccines may be effective in controlling CMV infections.

Avidity of antibodies to cytomegalovirus in HIV-seropositive patients with and without CMV retinitis.

Antibodies of high avidity may protect the fetus from CMV infection, but the association of avidity with other CMV infections is unknown. To determine if anti-CMV antibody avidity is altered in HIV-seropositive patients, either untreated or treated with HAART, and to determine if alterations in avidity are associated with CMV retinitis, we obtained sera from 164 CMV-seropositive adults: 68 were HIV-seronegative healthy adults and 96 were HIV seropositive. Of the HIV-positive, 57 had no current or prior evidence of CMV retinitis (29 were being treated with HAART, and 28 were receiving no therapy when sampled), and 39 had either active CMV retinitis or were immunorestored by HAART with quiescent CMV retinitis. IgG antibody avidity was determined for each serum run in duplicate using an EIA assay and 5M urea as a dissociating agent. After correction for the significantly higher levels of IgG antibodies to CMV in the HIV-seropositive sera as compared to the normal healthy individuals, both HIV-infected and HIV-uninfected individuals had nearly identical average avidity indices (avidity index = 76). There was also no significant difference in average avidity index between HAART-treated and untreated patients, or between patients with active and immunorestored, quiescent CMV retinitis). These results indicate antibody avidity is unaltered in HIV disease and does not play an important role in the pathogenesis of AIDS-related CMV disease.

Lack of autoantibody production associated with cytomegalovirus infection.

To confirm an association between cytomegalovirus (CMV) infection and the presence of antibodies to Smith (Sm), to ribonucleoprotein (RNP), and to a component of the U1 ribonucleoproteins (U1-70 kD), we measured antibodies to these protein antigens using an enzyme immunoassay and an immunoblot. The antibodies were measured in the sera of 80 healthy subjects, one-half of whom were naturally CMV seropositive and one-half were CMV seronegative, and in eight subjects immunized with a live attenuated strain of CMV. None of the vaccinees developed antibodies to Sm, to RNP, or to U1-70 kD at either 4 or 12 months after immunization. Additionally, there was no statistically significant association between levels of antibodies to Sm or to RNP and between sera obtained from vaccinees, natural CMV seropositive individuals, and CMV seronegative individuals. One CMV seropositive serum and one CMV seronegative serum tested positive for antibodies to U1-70 kD. These data indicate that neither wild-type infection nor the live-attenuated Towne vaccine frequently induce autoantibody production.