SARS-CoV-2 variant of concern fitness and adaptation in primary human airway epithelia.

The severe acute respiratory syndrome coronavirus 2 pandemic is characterized by the emergence of novel variants of concern (VOCs) that replace ancestral strains. Here, we dissect the complex selective pressures by evaluating variant fitness and adaptation in human respiratory tissues. We evaluate viral properties and host responses to reconstruct forces behind D614G through Omicron (BA.1) emergence. We observe differential replication in airway epithelia, differences in cellular tropism, and virus-induced cytotoxicity. D614G accumulates the most mutations after infection, supporting zoonosis and adaptation to the human airway. We perform head-to-head competitions and observe the highest fitness for Gamma and Delta. Under these conditions, RNA recombination favors variants encoding the B.1.617.1 lineage 3' end. Based on viral growth kinetics, Alpha, Gamma, and Delta exhibit increased fitness compared to D614G. In contrast, the global success of Omicron likely derives from increased transmission and antigenic variation. Our data provide molecular evidence to support epidemiological observations of VOC emergence.

Magnitude and Durability of the Antibody Response to mRNA-Based Vaccination Among SARS-CoV-2 Seronegative and Seropositive Health Care Personnel.

Few studies have described changes in SARS-CoV-2 antibody levels in response to infection and vaccination at frequent intervals and over extended follow-up periods. The purpose of this study was to assess changes in SARS-CoV-2-specific antibody responses among a prospective cohort of health care personnel over 18 months with up to 22 samples per person. Antibody levels and live virus neutralization were measured before and after mRNA-based vaccination with results stratified by (1) SARS-CoV-2 infection status prior to initial vaccination and (2) SARS-CoV-2 infection at any point during follow-up. We found that the antibody response to the first dose was almost 2-fold higher in individuals who were seropositive prior to vaccination, although neutralization titers were more variable. The antibody response induced by vaccination appeared to wane over time but generally persisted for 8 to 9 months, and those who were infected at any point during the study had slightly higher antibody levels over time vs those who remained uninfected. These findings underscore the need to account for SARS-CoV-2 natural infection as a modifier of vaccine responses, and they highlight the importance of frequent testing of longitudinal antibody titers over time. Together, our results provide a clearer understanding of the trajectories of antibody response among vaccinated individuals with and without prior SARS-CoV-2 infection.

Dengue virus 4/2 envelope domain chimeric virus panel maps type-specific responses against dengue serotype 2.

IMPORTANCE: The four dengue virus (DENV) serotypes infect several hundred million people each year. Although primary infection is generally mild, subsequent infection by differing serotypes increases the risk for symptomatic disease ranging from fever to life-threatening shock. Despite the availability of licensed vaccines, a comprehensive understanding of antibodies that target the viral envelope protein and protect from infection remains incomplete. In this manuscript, we develop a panel of recombinant viruses that graft each envelope domain of DENV2 onto the DENV4 envelope glycoprotein, revealing protein interactions important for virus viability. Furthermore, we map neutralizing antibody responses after primary DENV2 natural infection and a human challenge model to distinct domains on the viral envelope protein. The panel of recombinant viruses provides a new tool for dissecting the E domain-specific targeting of protective antibody responses, informing future DENV vaccine design.

SARS-CoV-2 seropositivity after infection and antibody response to mRNA-based vaccination.

The effect of SARS-CoV-2 infection on response to mRNA-based SARS-CoV-2 vaccines is not well-described. We assessed longitudinal SARS-CoV-2-specific antibody responses pre- and post-vaccination among individuals with and without prior infection. The antibody response to the first vaccine dose was almost two-fold higher in individuals who were seropositive before vaccination compared to those who were seronegative, suggesting that prior infection primes the immune response to the first dose of mRNA-based vaccine.

Patterns of peritraumatic threat perceptions in patients evaluated for suspected acute coronary syndrome according to prior and current posttraumatic stress symptoms.

OBJECTIVE: Prior posttraumatic stress disorder (PTSD) and elevated threat perceptions predict posttraumatic psychopathology after evaluation for acute coronary syndrome (ACS), but most research has measured threat retrospectively. We investigated how threat perceptions during ACS evaluation in the emergency department (ED) and upon recall were associated with posttraumatic psychopathology burden due to prior trauma and the suspected ACS. METHODS: Perceived threat was assessed in the ED, and ED threat recall was assessed upon inpatient transfer/discharge, along with acute stress disorder (ASD) symptoms due to suspected ACS and PTSD symptoms due to prior trauma. The sample comprised 894 participants (mean age = 60.7 ±â€¯13.1 years; 46.8% female; 56.3% Hispanic; 20.5% Black). One-way ANOVAs examined how those with consistent posttraumatic psychopathology (prior PTSD/ASD; 14.8%), prior posttraumatic psychopathology (prior PTSD/no ASD; 6.8%), new-onset posttraumatic psychopathology (no PTSD/ASD; 15.7%), or no posttraumatic psychopathology (no PTSD/no ASD; 62.8%) differed in threat perception, threat recall, and their discrepancy. RESULTS: Threat perception scores ranged from 6 to 24. Participants with consistent posttraumatic psychopathology had higher threat perceptions (M = 14.01) than those with prior posttraumatic psychopathology (M = 12.02) and new-onset posttraumatic psychopathology (M = 12.21) (ps ≤ 0.001); the latter two did not differ significantly but had higher threat perceptions than those with no posttraumatic psychopathology (M = 9.84) (p < .001). Similar results were observed for threat recall (p < .001). The new-onset posttraumatic psychopathology group also had a greater increase in perceived threat versus the no posttraumatic psychopathology group (p = .06). Results were similar adjusting for potential confounders. CONCLUSIONS: Assessing threat perceptions during ACS evaluation and hospitalization may help identify those at risk for emotional difficulties post-ACS.

Outcomes of cleft lip repair for internationally adopted children.

BACKGROUND: Large numbers of international children with cleft lip-cleft palate are adopted in the United States; many underwent their first operation before arrival. METHODS: The authors reviewed records of internationally adopted children with cleft lip-cleft palate treated by one surgeon over 25 years. This study focused on anatomical types, frequency/methods of repair, correction of unrepaired deformities, and secondary procedures in this country. RESULTS: Of 105 internationally adopted children with cleft lip-cleft palate, 91 percent were Asian; 75 percent had labial or labiopalatal closure in their native country. Of repaired unilateral cleft lips, 43 percent required complete revision, 49 percent required minor revisions, and 8 percent required no revision. All repaired bilateral cleft lips were revised; 90 percent were complete and 10 percent were minor. "Delayed" primary nasal correction was always necessary in both unilateral and bilateral forms. Labial closure was scheduled first in young infants with an unrepaired unilateral defect, whereas palatal closure took precedence in older children. Premaxillary setback and palatoplasty were scheduled first in older children with unrepaired bilateral cleft lip-cleft palate. Of children arriving with repaired palate, 43 percent required a pharyngeal flap. CONCLUSIONS: Whenever cleft lip-cleft palate is repaired in another country, revision rates are high for both unilateral and bilateral types. Nevertheless, primary closure in the native country may increase the likelihood for adoption. Traditional surgical protocols often are altered for an adoptee with an unrepaired cleft lip-cleft palate, particularly the sequence of labial and palatal closure, depending on the child's age and type of defect.