COVID-19 Vaccine Effectiveness Among Pregnant People

Background. COVID-19 presents a serious health risk to pregnant people and pregnancy outcomes. However, pregnant people were not included in pivotal phase III COVID-19 vaccine efficacy trials. Methods. We used Cox regression models in a cohort study to determine hazard ratios (HR) of a PCR positive test ("infection") comparing vaccinated with unvaccinated pregnant persons in Kaiser Permanente Northern California. HRs were adjusted for age, race/ethnicity, type of insurance coverage, geographical area, BMI, preexisting diabetes, hypertension, parity, time since pregnancy onset and smoking status. Vaccine effectiveness (VE), calculated as 1 minus adjusted HR, was estimated for fully vaccinated < 150 and >= 150 days prior to infection. VE was estimated for before and during Delta, and Omicron. We also calculated incidence rates of COVID-pneumonia associated hospitalization by vaccination status. Results. Among 68836 pregnancies between 12/15/2020 and 3/31/2022, 21834 (31.7%) were fully vaccinated and 5980 (8.7%) were boosted by the end of pregnancy. Compared with unvaccinated persons, the HRs of infection for fully vaccinated < 150 days prior were 0.13 (95% CI: 0.07 - 0.23;VE=87% [77% - 93%]) before Delta;0.25 (CI: 0.20 - 0.30;VE=75% [70% - 80%]) during Delta and 0.76 (CI: 0.61 - 0.94;VE= 24% [16% - 39%]) during Omicron. The HRs for >= 150 days prior were 0.38 (CI: 0.31 - 0.46;VE=62 % [54% - 69%]) during Delta and 1.04 (CI: 0.89 - 1.22;VE= -0.04% [-0.22% - 0.11%]) during Omicron. The HRs for boosted persons were 0.10 (CI: 0.04 - 0.25;VE= 90% [75% - 96%]) during Delta and 0.42 (CI: 0.34 - 0.52;VE=58% [48% - 66%]) during Omicron periods. Incidence rates (IR) per 1000 person-years for hospitalization before delta were 0.75 among unvaccinated and zero among vaccinated. During Delta, the IR was 6.64 for unvaccinated and zero for fully vaccinated and boosted. During Omicron, the IR was 10.27 for unvaccinated, zero for fully vaccinated < 150 days prior, 2.48 for fully vaccinated >= 150 days prior and zero for those boosted. Conclusion. COVID-19 vaccines protect against infection and hospitalization among pregnant people. However, vaccine effectiveness against infection wanes over time and was lower during Omicron. Booster doses are necessary for continuous protection.

Primary results of the cTRAK TN trial: A clinical trial utilising ctDNA mutation tracking to detect minimal residual disease and trigger intervention in patients with moderate and high risk early stage triple negative breast cancer

Background Detection of circulating tumour DNA (ctDNA) in patients (pts) who have completed treatment for early-stage triple negative breast cancer (TNBC) is associated with a very high risk of future relapse. Identifiying those at high risk of subsequent relapse may allow tailoring of further therapy to delay or prevent recurrence. The c-TRAK TN trial assessed the utility of prospective ctDNA surveillance in pts treated for TNBC and the activity of pembrolizumab (P) in pts with ctDNA detected. Methods c-TRAK TN, a multi-centre phase II trial with integrated prospective screening component, enrolled pts with early-stage TNBC and either residual disease following neoadjuvant chemotherapy, or tumour size >20mm and/or axillary lymph node involvement if adjuvant chemotherapy was given. Tumour tissue was sequenced to identify somatic mutations suitable for tracking using personalised digital PCR ctDNA assays (BioRad QX200). Pts had "active" ctDNA surveillance via blood sample testing every 3 months to 12 months (potential up to 18 months if S samples missed due to COVID) during which time if ctDNA was detected (ctDNA+) pts could be randomised 2:1 to P (200mg i.v. q 3 weeks for 1 year) or observation (Obs). Pts and clinicians were blinded to ctDNA+ results unless they were allocated P, when staging scans were done and those free of clinical recurrence started treatment. Following advice from the Independent Data Monitoring Committee, the Obs arm closed on 16/06/2020 with all subsequent ctDNA+ pts allocated P. Following the completion of active ctDNA surveillance, 3-monthly visits continued to 24 months to be analysed retrospectively. The aim was to recruit 150 pts to ctDNA surveillance, assuming 30% would be ctDNA+ within 12 months, allowing ctDNA+ rate to be estimated with a 2-sided 95%CI of +/-7.3%. Co-primary endpoints are i) rates of ctDNA detection by 12 and 24 months from start of ctDNA surveillance;ii) rates of sustained ctDNA clearance on P defined as absence of detectable ctDNA, or disease recurrence 6 months after starting P. Results 208 pts were registered between 30/01/18 and 06/12/19, 185 had tumour sequenced, 171 (92.4%) had trackable mutations, and 161 entered ctDNA surveillance. The rate of ctDNA detection by 12 months after start of surveillance was 27.3% (44/161, 95% CI 20.6-34.9). ctDNA+ rates from baseline, 3, 6, 9 and 12 month ctDNA samples were 23/161 (14.3%), 6/115 (5.2%), 6/99 (5.1%), 7/84 (8.3%), and 2/84 (2.4%) respectively. An additional 2 pts were ctDNA+ on COVID extended active surveillance at 15 (1/51, 2%) or 18 months (1/11, 9%). 7 pts relapsed without prior ctDNA detection. 45 pts entered the therapeutic component of the trial (initially 31 to P and 14 to Obs). 1 Obs pt was re-allocated to P. Of pts allocated to P, 72% (23/32) had metastatic disease at time of ctDNA detection on staging scans (75% (12/16) who were ctDNA+ at baseline and 69% (11/16) at other timepoints). 4 pts declined to start P, largely due to COVID concerns. Of the 5 pts who commenced P, at the time of analysis none achieved sustained ctDNA clearance and 4 had recurred. In pts allocated to Obs, median time to recurrence was 4.1 months (95% CI: 3.2-not-defined). Conclusion The c-TRAK TN trial is to our knowledge the first study to assess the proof-of-principle of whether ctDNA assays have clinical utility in guiding further therapy in TNBC. Relatively few pts commenced P treatment precluding assessment of potential activity. At enrollment, patients had a relatively high of rate of undiagnosed metastatic disease when imaged. Our findings have implications for future trial design, emphasizing the importance of early start of ctDNA testing, and more sensitive and/or more frequent ctDNA testing regimes.

COVID-19 vaccination coverage among insured persons aged ≤16 years, by race/ethnicity and other selected characteristics ⇔ eight integrated health care organizations, United States, December 14, 2020–May 15, 2021

COVID-19 vaccination is critical to ending the COVID-19 pandemic. Members of minority racial and ethnic groups have experienced disproportionate COVID-19–associated morbidity and mortality (1);however, COVID-19 vaccination coverage is lower in these groups (2). CDC used data from CDC’s Vaccine Safety Datalink (VSD)* to assess disparities in vaccination coverage among persons aged ≥16 years by race and ethnicity during December 14, 2020–May 15, 2021. Measures of coverage included receipt of ≥1 COVID-19 vaccine dose (i.e., receipt of the first dose of the Pfizer-BioNTech or Moderna COVID-19 vaccines or 1 dose of the Janssen COVID-19 vaccine [Johnson And Johnson]) and full vaccination (receipt of 2 doses of the Pfizer-BioNTech or Moderna COVID-19 vaccines or 1 dose of Janssen COVID-19 vaccine). Among 9.6 million persons aged ≥16 years enrolled in VSD during December 14, 2020–May 15, 2021, ≥1-dose coverage was 48.3%, and 38.3% were fully vaccinated. As of May 15, 2021, coverage with ≥1 dose was lower among non-Hispanic Black (Black) and Hispanic persons (40.7% and 41.1%, respectively) than it was among non-Hispanic White (White) persons (54.6%). Coverage was highest among non-Hispanic Asian (Asian) persons (57.4%). Coverage with ≥1 dose was higher among persons with certain medical conditions that place them at higher risk for severe COVID-19 (high-risk conditions) (63.8%) than it was among persons without such conditions (41.5%) and was higher among persons who had not had COVID-19 (48.8%) than it was among those who had (42.4%). Persons aged 18–24 years had the lowest ≥1-dose coverage (28.7%) among all age groups. Continued monitoring of vaccination coverage and efforts to improve equity in coverage are critical, especially among populations disproportionately affected by COVID-19. VSD is a collaboration between CDC’s Immunization Safety Office and eight integrated health care organizations in six U.S. states.† VSD captures information on COVID-19 vaccine doses administered, regardless of where they are received, based on an automated search within the organizations’ facilities (outpatient and inpatient records) and external systems (e.g., health insurance claims and state or local immunization What is already known about this topic? Non-Hispanic Black and Hispanic persons experience higher COVID-19–associated morbidity and mortality, yet COVID-19 vaccination coverage is lower in these groups. What is added by this report? As of May 15, 2021, 48.3% of persons identified in CDC’s Vaccine Safety Datalink aged ≥16 years had received ≥1 COVID-19 vaccine dose and 38.3% were fully vaccinated. Coverage with ≥1 dose was lower among non-Hispanic Black (40.7%) and Hispanic persons (41.1%) than among non-Hispanic White persons (54.6%);coverage was highest (57.4%) among non-Hispanic Asian persons. What are the implications for public health practice? Continued monitoring of vaccination coverage and efforts to improve equity in vaccination coverage are critical, especially among populations disproportionately affected by COVID-19. © 2021 Department of Health and Human Services. All rights reserved.

Post-covid organizing pneumonia

A myriad of acute clinicopathological effects of novel SARS Coronavirus 2 (SARS-Cov-2) infection are being described. Here, we present a case report which illustrates a biopsy proven distinct chronic complication of Covid-19 disease which afflicts some survivors: Post Covid-19 Organizing Pneumonia (PCOP). A 30 year old African-American female with known Human Immunodeficiency Virus (HIV) infection on anti-retroviral therapy (ART) and recently diagnosed nodular marginal zone lymphoma, on chemotherapy, became infected with SARS-Cov-2 in early August, 2020. She presented with fever, increased cough, and shortness of breath worsening over two weeks. In the emergency room, she had temperature 102o F, heart rate of 110 with oxygen saturation 88% on room air. Lab work was significant for Leukocytosis of 17.62 k/uL and recent absolute CD4 of 590/mm3. SARSCoV-2 Polymerase Chain Reaction (PCR) test was positive. Admission Chest Roentgenogram (X-ray) revealed bilateral basal opacities consistent with Covid-19 Pneumonia. Our patient was admitted and received Dexamethasone and a course of empiric antibiotics for community acquired pneumonia. She was discharged on brief oral prednisone taper with home oxygen 2L/min;However, she would be readmitted to hospital twice more over the next eight weeks with similar complaints of cough, recurrent fever, and dyspnea with new focal opacities on serial chest imaging (Figure 1). Her symptoms persisted despite broadened empiric antibiotics including antifungal therapy. Extensive lab work-up for secondary infection and autoimmune disease was unrevealing. Bronchoscopy was finally done with Transbronchial Cryobiopsy (TBC) revealing acute and chronic inflammation with interstitial fibrosis. Bronchoalveolar lavage (BAL) cultures were negative. As evidenced by serial imaging (Figure 1), our patient consistently improved with empiric steroids for organizing pneumonia. Her clinical findings recurred with attempts to taper steroids even at five months post initial positive SARS-CoV-2 PCR. This case illustrates Post Covid-19 Organizing Pneumonia (PCOP). It is a Clinicopathologic syndrome characterized by rapid resolution with corticosteroids, but frequent relapses when treatment is tapered or stopped.1 It also illustrates several salient issues in caring for patients who survive acute SARS-CoV-2 infection: i) Delayed viral clearance related to chronic immunosuppression,2 ii) Delayed Bronchoscopy in an effort to mitigate infection risk to care providers, iii) The impact of ongoing therapy on consequent delayed pathology findings,3 iv) Increased morbidity associated with both late disease recognition and our attempts to taper chronic steroid therapy in the setting of an Organizing Pneumonia4 and v) The possibility that earlier biopsy, diagnosis and uninterrupted therapy may prevent pulmonary fibrosis.