A review of COVID-19 therapeutics in pregnancy and lactation

Pregnant people have an elevated risk of severe COVID-19-related complications compared to their non-pregnant counterparts, underscoring the need for safe and effective therapies. In this review, we summarize published data on COVID-19 therapeutics in pregnancy and lactation to help inform clinical decision-making about their use in this population. Although no serious safety signals have been raised for many agents, data clearly have serious limitations and there are many important knowledge gaps about the safety and efficacy of key therapeutics used for COVID-19. Moving forward, diligent follow-up and documentation of outcomes in pregnant people treated with these agents will be essential to advance our understanding. Greater regulatory push and incentives are needed to ensure studies to obtain pregnancy data are expedited.

Occupation and COVID-19 diagnosis, hospitalisation and ICU admission among foreign-born and Swedish-born employees: a register-based study

BackgroundResearch on occupation and risk of COVID-19 among foreign-born workers is lacking. We investigated whether working in essential occupations was associated with COVID-19 diagnosis, hospitalisation and intensive care unit (ICU) admission and whether foreign-born workers in similar occupations as Swedish-born individuals had a higher risk of the studied outcomes.MethodsOccupational data (2018–2019) of 326 052 employees (20–65 years) who were resident in Sweden as of 1 January 2020 were linked to COVID-19 data registered from 1 January 2020 to 28 February 2021. We analysed the risk of COVID-19 outcomes in different occupational groups and in four immigrant/occupation intersectional groups using Cox proportional hazards regression with adjustments for sociodemographic and socioeconomic characteristics and pre-existing comorbidities.ResultsWe identified 29797, 1069 and 152 cases of COVID-19 diagnosis, hospitalisations and ICU admissions, respectively, in our cohort. Workers in essential occupations had an elevated risk of COVID-19 diagnosis, hospitalisation, and ICU admissions. Healthcare workers had a higher risk of all the outcomes compared with other essential workers. Relative to Swedish-born workers in non-essential occupations, foreign-born workers in essential occupations had 1.85 (95% CI 1.78 to 1.93), 3.80 (95% CI 3.17 to 4.55) and 3.79 (95% CI 2.33 to 6.14) times higher risk of COVID-19 diagnosis, hospitalisation and ICU admission, respectively. The corresponding risks among Swedish-born workers in essential occupations were 1.44 (95% CI 1.40 to 1.49), 1.30 (95% CI 1.08 to 1.56) and 1.46 (95% CI 0.90 to 2.38).ConclusionOccupation was associated with COVID-19 outcomes and contributed to the burden of COVID-19 among foreign-born individuals in this study.

Not all biodiversity rich spots are climate refugia

Anthropogenic climate change is increasingly threatening biodiversity on a global scale. Rich spots of biodiversity, regions with exceptionally high endemism and/or number of species, are a top priority for nature conservation. Terrestrial studies have hypothesized that rich spots occur in places where long-term climate change was dampened relative to other regions. Here we tested whether biodiversity rich spots are likely to provide refugia for organisms during anthropogenic climate change. We assessed the spatial distribution of both historic (absolute temperature change and climate change velocities) and projected climate change in terrestrial, freshwater, and marine rich spots. Our analyses confirm the general consensus that global warming will impact almost all rich spots of all three realms and suggest that their characteristic biota is expected to witness similar forcing to other areas, including range shifts and elevated risk of extinction. Marine rich spots seem to be particularly sensitive to global warming: they have warmed more, have higher climate velocities, and are projected to experience higher future warming than non-rich-spot areas. However, our results also suggest that terrestrial and freshwater rich spots will be somewhat less affected than other areas. These findings emphasize the urgency of protecting a comprehensive and representative network of biodiversity-rich areas that accommodate species range shifts under climate change.

Autoimmune Encephalitis and Autism Spectrum Disorder

The concept of “acquired autism” refers to the hypothesis that amongst the massive heterogeneity that encompasses autism spectrum disorder (ASD) there may be several phenotypes that are neither syndromic nor innate. Strong and consistent evidence has linked exposure to various pharmacological and infective agents with an elevated risk of a diagnosis of ASD including maternal valproate use, rubella and herpes encephalitis. Autoimmune encephalitis (AE) describes a group of conditions characterised by the body's immune system mounting an attack on healthy brain cells causing brain inflammation. The resultant cognitive, psychiatric and neurological symptoms that follow AE have also included ASD or autism-like traits and states. We review the current literature on AE and ASD. Drawing also on associated literature on autoimmune psychosis (AP) and preliminary evidence of a psychosis-linked subtype of ASD, we conclude that AE may either act as a potentially causative agent for ASD, and/or produce symptoms that could easily be mistaken for or misdiagnosed as autism. Further studies are required to discern the connection between AE and autism. Where autism is accompanied by regression and atypical onset patterns, it may be prudent to investigate whether a differential diagnosis of AE would be more appropriate.

Differential Risk of SARS-CoV-2 Infection by Occupation: Evidence from the Virus Watch prospective cohort study in England and Wales

Background: Workers differ in their risk of SARS-CoV-2 infection according to their occupation, but the direct contribution of occupation to this relationship is unclear. This study aimed to investigate how infection risk differed across occupational groups in England and Wales up to October 2021, after adjustment for potential confounding and stratification by pandemic phase. Methods: Data from 12,182 employed/self-employed participants in the Virus Watch prospective cohort study were used to generate risk ratios for virologically- or serologically-confirmed SARS-CoV-2 infection using robust Poisson regression, adjusting for socio-demographic and health-related factors and non-work public activities. We calculated attributable fractions (AF) amongst the exposed for each occupational group based on adjusted risk ratios (aRR). Findings: Increased risk was seen in nurses (aRR=1.90 [1.40-2.40], AF=47%); doctors (1.74 [1.26-2.40], 42%); carers (2.18 [1.63-2.92], 54%); teachers (primary = 1.94 [1.44- 2.61], 48%; secondary =1.64, [1.23-2.17], 39%), and warehouse and process/plant workers (1.58 [1.20-2.09], 37%) compared to both office-based professional occupations (reported above) and all other occupations. Differential risk was apparent in the earlier phases (Feb 2020 - May 2021) and attenuated later (June - October 2021) for most groups, although teachers demonstrated persistently elevated risk. Interpretation: Occupational differentials in SARS-CoV-2 infection risk are robust to adjustment for socio-demographic, health-related, and activity-related potential confounders. Patterns of differential infection risk varied over time, and ongoing excess risk was observed in education professionals. Direct investigation into workplace factors underlying elevated risk and how these change over time is needed to inform occupational health interventions.

Transmission Jeopardy of Adenomatosis Polyposis Coli and Methylenetetrahydrofolate Reductase in Colorectal Cancer

Colorectal cancer (CRC) is one of the globally prevalent and virulent types of cancer with a distinct alteration in chromosomes. Often, any alterations in the adenomatosis polyposis coli (APC), a tumor suppressor gene, and methylenetetrahydrofolate reductase (MTHFR) gene are related to surmise colorectal cancer significantly. In this study, we have investigated chromosomal and gene variants to discern a new-fangled gene and its expression in the southern populations of India by primarily spotting the screened APC and MTHFR variants in CRC patients. An equal number of CRC patients and healthy control subjects ( n = 65 ) were evaluated to observe a chromosomal alteration in the concerted and singular manner for APC and MTHFR genotypes using standard protocols. The increasing prognosis was observed in persons with higher alcoholism and smoking ( P < 0.05 ) with frequent alterations in chromosomes 1, 5, 12, 13, 15, 17, 18, 21, and 22. The APC Asp 1822Val and MTHFR C677T genotypes provided significant results, while the variant alleles of this polymorphism were linked with an elevated risk of CRC. Chromosomal alterations can be the major cause in inducing carcinogenic outcomes in CRCs and can drive to extreme pathological states.

Prognostic Risk Assessment and Prediction of Radiotherapy Benefit for Women with Ductal Carcinoma In Situ (DCIS) of the Breast, in a Randomized Clinical Trial (SweDCIS)

Prediction of radiotherapy (RT) benefit after breast-conserving surgery (BCS) for DCIS is crucial. The aim was to validate a biosignature, DCISionRT®, in the SweDCIS randomized trial. Women were randomly assigned to RT or not after BCS, between 1987 and 2000. Tumor blocks were collected, and slides were sent to PreludeDxTM for testing. In 504 women with complete data and negative margins, DCISionRT divided 52% women into Elevated (DS > 3) and 48% in Low (DS ≤ 3) Risk groups. In the Elevated Risk group, RT significantly decreased relative 10-year ipsilateral total recurrence (TotBE) and 10-year ipsilateral invasive recurrence (InvBE) rates, HR 0.32 and HR 0.24, with absolute decreases of 15.5% and 9.3%. In the Low Risk group, there were no significant risk differences observed with radiotherapy. Using a cutoff of DS > 3.0, the test was not predictive for RT benefit (p = 0.093); however, above DS > 2.8 RT benefit was greater for InvBE (interaction p = 0.038). Recurrences at 10 years without radiotherapy increased significantly per 5 DS units (TotBE HR:1.5 and InvBE HR:1.5). Continuous DS was prognostic for TotBE risk although categorical DS did not reach significance. Absolute 10-year TotBE and InvBE risks appear sufficiently different to indicate that DCISionRT can aid physicians in selecting individualized adjuvant DCIS treatment strategies. Further analyses are planned in combined cohorts to increase statistical power.

Hypertensive disorders in pregnancy and child development at 36 months in the All Our Families prospective cohort study

Hypertensive disorders in pregnancy (HDP) are associated with increased risk of offspring neurodevelopmental disorders, suggesting long-term adverse impacts on fetal brain development. However, the relationship between HDP and deficits in general child development is unclear. Our objective was to assess the association between HDP and motor and cognitive developmental delay in children at 36 months of age. We analyzed data from the All Our Families community-based cohort study (n = 1554). Diagnosis of HDP–gestational or chronic hypertension, preeclampsia, or eclampsia–was measured through medical records. Child development was measured by maternal-report on five domains of the Ages and Stages Questionnaire (ASQ-3). Standardized cut-off scores were used to operationalize binary variables for any delay, motor delay, and cognitive delay. We calculated adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) using logistic regression, sequentially controlling for potential confounders followed by factors suspected to lie on the causal pathway. Overall, 8.0% of women had HDP and hypertension-exposed children had higher prevalence of delay than unexposed children. Hypertension-exposed children had elevated risk for developmental delay, but CIs crossed the null. The aRRs quantifying the fully adjusted effect of HDP on child development were 1.19 (95% CI 0.92, 1.53) for any delay, 1.18 (95% CI 0.86, 1.61) for motor delay, and 1.24 (95% CI 0.83, 1.85) for cognitive delay. We did not find a statistically significant association between HDP and developmental delay. Confidence intervals suggest that children exposed to HDP in utero have either similar or slightly elevated risk of any, motor, and cognitive delay at 36 months after controlling for maternal and obstetric characteristics. The observed direction of association aligns with evidence of biological mechanisms whereby hypertensive pathology can disrupt fetal neurodevelopment; however, more evidence is needed. Findings may have implications for early developmental monitoring and intervention following prenatal hypertension exposure.