Faculty Bibliography

The COVID-19 pandemic and associated increase in family care responsibilities resulted in unsustainable personal and professional workloads for Infectious Diseases (ID) faculty on the front lines. This was especially true for early-stage faculty (ESF), many of whom had caregiving responsibilities. In addition, women faculty, underrepresented in medicine and science faculty, and particularly ESF experienced marked declines in research productivity, which significantly impacts career trajectories. When combined with staffing shortages due to an aging workforce and suboptimal recruitment and retention in ID, these work-life imbalances have brought the field to an inflection point. We propose actionable recommendations and call on ID leaders to act to close the gender, racial, and ethnic gaps to improve the recruitment, retention, and advancement of ESF in ID. By investing in systemic change to make the ID workforce more equitable, we can embody the shared ideals of diversity and inclusion and prepare for the next pandemic.

While detection of SARS-CoV-2 by diagnostic RT-PCR is highly sensitive for viral RNA, the nucleic acid amplification of subgenomic RNAs (sgRNA) that are the product of viral replication may more accurately identify replication. We characterized the diagnostic RT-PCR and sgRNA detection from nasal swabs collected daily by participants in post exposure prophylaxis or treatment studies for SARS-CoV-2. Among 1932 RT-PCR-positive swabs with sgRNA tests, 40% (767) had detectable sgRNA. Above a diagnostic PCR viral load threshold of 5.1 log10 copies/mL, 96% of samples had detectable sgRNA with viral loads that followed a linear trend. The trajectories of diagnostic and sgRNA viral loads differed, with 80% peaking on the same day but duration of sgRNA detection being shorter (8 versus 14 days). With a large sample of daily swabs we provide comparative sgRNA kinetics and a diagnostic PCR threshold that correlates with replicating virus independent of symptoms or duration of illness.

COVID-19 symptom definitions rarely include symptom severity. We collected daily nasal swabs and symptom diaries from contacts of SARS-CoV-2 cases. Requiring ≥1 moderate or severe symptom reduced sensitivity to predict SARS-CoV-2 shedding from 60.0% (CI: 52.9-66.7%) to 31.5% (CI: 25.7-38.0%), but increased specificity from 77.5% (CI:75.3-79.5%) to 93.8% (CI: 92.7-94.8%).

The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits reduced susceptibility to vaccine-induced neutralizing antibodies, requiring a boost to generate protective immunity. We assess the magnitude and short-term durability of neutralizing antibodies after homologous and heterologous boosting with mRNA and Ad26.COV2.S vaccines. All prime-boost combinations substantially increase the neutralization titers to Omicron, although the boosted titers decline rapidly within 2 months from the peak response compared with boosted titers against the prototypic D614G variant. Boosted Omicron neutralization titers are substantially higher for homologous mRNA vaccine boosting, and for heterologous mRNA and Ad26.COV2.S vaccine boosting, compared with homologous Ad26.COV2.S boosting. Homologous mRNA vaccine boosting generates nearly equivalent neutralizing activity against Omicron sublineages BA.1, BA.2, and BA.3 but modestly reduced neutralizing activity against BA.2.12.1 and BA.4/BA.5 compared with BA.1. These results have implications for boosting requirements to protect against Omicron and future variants of SARS-CoV-2. This trial was conducted under ClincalTrials.gov: NCT04889209.

BACKGROUND:Although the three vaccines against coronavirus disease 2019 (Covid-19) that have received emergency use authorization in the United States are highly effective, breakthrough infections are occurring. Data are needed on the serial use of homologous boosters (same as the primary vaccine) and heterologous boosters (different from the primary vaccine) in fully vaccinated recipients. METHODS:virus particles, or BNT162b2 (Pfizer-BioNTech) at a dose of 30 μg. The primary end points were safety, reactogenicity, and humoral immunogenicity on trial days 15 and 29. RESULTS:Of the 458 participants who were enrolled in the trial, 154 received mRNA-1273, 150 received Ad26.COV2.S, and 153 received BNT162b2 as booster vaccines; 1 participant did not receive the assigned vaccine. Reactogenicity was similar to that reported for the primary series. More than half the recipients reported having injection-site pain, malaise, headache, or myalgia. For all combinations, antibody neutralizing titers against a SARS-CoV-2 D614G pseudovirus increased by a factor of 4 to 73, and binding titers increased by a factor of 5 to 55. Homologous boosters increased neutralizing antibody titers by a factor of 4 to 20, whereas heterologous boosters increased titers by a factor of 6 to 73. Spike-specific T-cell responses increased in all but the homologous Ad26.COV2.S-boosted subgroup. CD8+ T-cell levels were more durable in the Ad26.COV2.S-primed recipients, and heterologous boosting with the Ad26.COV2.S vaccine substantially increased spike-specific CD8+ T cells in the mRNA vaccine recipients. CONCLUSIONS:Homologous and heterologous booster vaccines had an acceptable safety profile and were immunogenic in adults who had completed a primary Covid-19 vaccine regimen at least 12 weeks earlier. (Funded by the National Institute of Allergy and Infectious Diseases; DMID 21-0012 ClinicalTrials.gov number, NCT04889209.).

Importance:The SARS-CoV-2 viral trajectory has not been well characterized in incident infections. These data are needed to inform natural history, prevention practices, and therapeutic development. Objective:To characterize early SARS-CoV-2 viral RNA load (hereafter referred to as viral load) in individuals with incident infections in association with COVID-19 symptom onset and severity. Design, Setting, and Participants:This prospective cohort study was a secondary data analysis of a remotely conducted study that enrolled 829 asymptomatic community-based participants recently exposed (<96 hours) to persons with SARS-CoV-2 from 41 US states from March 31 to August 21, 2020. Two cohorts were studied: (1) participants who were SARS-CoV-2 negative at baseline and tested positive during study follow-up, and (2) participants who had 2 or more positive swabs during follow-up, regardless of the initial (baseline) swab result. Participants collected daily midturbinate swab samples for SARS-CoV-2 RNA detection and maintained symptom diaries for 14 days. Exposure:Laboratory-confirmed SARS-CoV-2 infection. Main Outcomes and Measures:The observed SARS-CoV-2 viral load among incident infections was summarized, and piecewise linear mixed-effects models were used to estimate the characteristics of viral trajectories in association with COVID-19 symptom onset and severity. Results:A total of 97 participants (55 women [57%]; median age, 37 years [IQR, 27-52 years]) developed incident infections during follow-up. Forty-two participants (43%) had viral shedding for 1 day (median peak viral load cycle threshold [Ct] value, 38.5 [95% CI, 38.3-39.0]), 18 (19%) for 2 to 6 days (median Ct value, 36.7 [95% CI, 30.2-38.1]), and 31 (32%) for 7 days or more (median Ct value, 18.3 [95% CI, 17.4-22.0]). The cycle threshold value has an inverse association with viral load. Six participants (6%) had 1 to 6 days of viral shedding with censored duration. The peak mean (SD) viral load was observed on day 3 of shedding (Ct value, 33.8 [95% CI, 31.9-35.6]). Based on the statistical models fitted to 129 participants (60 men [47%]; median age, 38 years [IQR, 25-54 years]) with 2 or more SARS-CoV-2-positive swab samples, persons reporting moderate or severe symptoms tended to have a higher peak mean viral load than those who were asymptomatic (Ct value, 23.3 [95% CI, 22.6-24.0] vs 30.7 [95% CI, 29.8-31.4]). Mild symptoms generally started within 1 day of peak viral load, and moderate or severe symptoms 2 days after peak viral load. All 535 sequenced samples detected the G614 variant (Wuhan strain). Conclusions and Relevance:This cohort study suggests that having incident SARS-CoV-2 G614 infection was associated with a rapid viral load peak followed by slower decay. COVID-19 symptom onset generally coincided with peak viral load, which correlated positively with symptom severity. This longitudinal evaluation of the SARS-CoV-2 G614 with frequent molecular testing serves as a reference for comparing emergent viral lineages to inform clinical trial designs and public health strategies to contain the spread of the virus.

The COVID-19 pandemic has disproportionately impacted LGBTQ+ communities. Many disparities mirror those of the HIV/AIDS epidemic. These health inequities have repeated throughout history due to the structural oppression of LGBTQ+ people. We aim to demonstrate that the familiar patterns of LGBTQ+ health disparities reflect a perpetuating, deeply rooted cycle of injustice imposed on LGBTQ+ people. Here, we contextualize COVID-19 inequities through the history of the HIV/AIDS crisis, describe manifestations of LGBTQ+ structural oppression exacerbated by the pandemic, and provide recommendations for medical professionals and institutions seeking to reduce health inequities.

Background/UNASSIGNED:While Coronavirus disease 2019 (Covid-19) vaccines are highly effective, breakthrough infections are occurring. Booster vaccinations have recently received emergency use authorization (EUA) for certain populations but are restricted to homologous mRNA vaccines. We evaluated homologous and heterologous booster vaccination in persons who had received an EUA Covid-19 vaccine regimen. Methods/UNASSIGNED:virus particles, or Pfizer-BioNTech BNT162b2 30-μg; nine combinations). The primary outcomes were safety, reactogenicity, and humoral immunogenicity on study days 15 and 29. Results/UNASSIGNED:458 individuals were enrolled: 154 received mRNA-1273, 150 received Ad26.CoV2.S, and 153 received BNT162b2 booster vaccines. Reactogenicity was similar to that reported for the primary series. Injection site pain, malaise, headache, and myalgia occurred in more than half the participants. Booster vaccines increased the neutralizing activity against a D614G pseudovirus (4.2-76-fold) and binding antibody titers (4.6-56-fold) for all combinations; homologous boost increased neutralizing antibody titers 4.2-20-fold whereas heterologous boost increased titers 6.2-76-fold. Day 15 neutralizing and binding antibody titers varied by 28.7-fold and 20.9-fold, respectively, across the nine prime-boost combinations. Conclusion/UNASSIGNED:Homologous and heterologous booster vaccinations were well-tolerated and immunogenic in adults who completed a primary Covid-19 vaccine regimen at least 12 weeks earlier. (Funded by National Institute of Allergy and Infectious Diseases; Clinical Trials.gov number, NCT04889209 ).

Disseminated strongyloidiasis and hyperinfection syndrome can cause significant morbidity and mortality after transplantation. Screening and treatment prior to transplantation can reduce or prevent this disease. Targeted screening of transplant candidates, based on assessed risk, fails to identify all who would benefit. We implemented universal serology-based screening for Strongyloides at our transplant center, located in a non-endemic area. Of 200 transplant candidates who were evaluated for cardiothoracic transplant from January 2018 to June 2019, 169 were screened serologically and 21 (12.4%) were seropositive. Among seropositive patients, 57% reported travel to an endemic region, 38% were born outside the USA, 38% had eosinophilia, 5% had history of gram-negative bacteremia. We estimate that universal screening for strongyloidiasis could identify an average of 17 additional candidates for preventive treatment for every 200 transplant candidates.