Economic uncertainty before and during the COVID-19 pandemic.

We consider several economic uncertainty indicators for the US and UK before and during the COVID-19 pandemic: implied stock market volatility, newspaper-based policy uncertainty, Twitter chatter about economic uncertainty, subjective uncertainty about business growth, forecaster disagreement about future GDP growth, and a model-based measure of macro uncertainty. Four results emerge. First, all indicators show huge uncertainty jumps in reaction to the pandemic and its economic fallout. Indeed, most indicators reach their highest values on record. Second, peak amplitudes differ greatly - from a 35% rise for the model-based measure of US economic uncertainty (relative to January 2020) to a 20-fold rise in forecaster disagreement about UK growth. Third, time paths also differ: Implied volatility rose rapidly from late February, peaked in mid-March, and fell back by late March as stock prices began to recover. In contrast, broader measures of uncertainty peaked later and then plateaued, as job losses mounted, highlighting differences between Wall Street and Main Street uncertainty measures. Fourth, in Cholesky-identified VAR models fit to monthly U.S. data, a COVID-size uncertainty shock foreshadows peak drops in industrial production of 12-19%.

Rapid early innate control of hepatitis C virus during IFN-α treatment compromises adaptive CD4+ T-cell immunity.

The ability to control HCV with IFN-α-based treatments provides an opportunity in humans to study how the rate of viral clearance in vivo impinges on the development of antiviral responses. Ex vivo (IFN-γ-producing) and cultured antiviral CD4(+) T cells, serum cytokines, and viral loads were measured repeatedly in a cohort of chronically HCV-infected subjects (n = 33) receiving IFN-α. Rapid control of virus indicated by an increased calculated rate of virus clearance, occurred in those subjects demonstrating absent/minimal T-cell responses (p < 0.0006). Surprisingly, in subjects who demonstrated the most robust T-cell responses (and reduced serum IL-10), there was actually a reduced rate of early virus clearance. A subsequent analysis of NK-cell function in available subjects (n = 8) revealed an inverse correlation between pretreatment NK-cell expression of NKp46 and the potential to upregulate cytotoxic function on exposure to IFN-α (p < 0.004), as well as the subsequent measured rate of viral clearance (p = 0.045). Thus, the CD4(+) T-cell response during IFN-α treatment appears to be shaped by the rate of innate virus suppression. These data suggest that individuals who respond most effectively to immune intervention may be most in need of subsequent vaccination to prevent reinfection.

Suppression of tumour-specific CD4⁺ T cells by regulatory T cells is associated with progression of human colorectal cancer.

BACKGROUND: There is indirect evidence that T cell responses can control the metastatic spread of colorectal cancer (CRC). However, an enrichment of CD4(+)Foxp3(+) regulatory T cells (Tregs) has also been documented. OBJECTIVE: To evaluate whether CRC promotes Treg activity and how this influences anti-tumour immune responses and disease progression. METHODS: A longitudinal study of Treg activity on a cohort of patients was performed before and after tumour resection. Specific CD4(+) T cell responses were also measured to the tumour associated antigens carcinoembryonic antigen (CEA) and 5T4. RESULTS: Tregs from 62 preoperative CRC patients expressed a highly significant increase in levels of Foxp3 compared to healthy age-matched controls (p=0.007), which returned to normal after surgery (p=0.0075). CD4(+) T cell responses to one or both of the tumour associated antigens, CEA and 5T4, were observed in approximately two-thirds of patients and one third of these responses were suppressed by Tregs. Strikingly, in all patients with tumour recurrence at 12 months, significant preoperative suppression was observed of tumour-specific (p=0.003) but not control CD4(+) T cell responses. CONCLUSION: These findings demonstrate that the presence of CRC drives the activity of Tregs and accompanying suppression of CD4(+) T cell responses to tumour-associated antigens. Suppression is associated with recurrence of tumour at 12 months, implying that Tregs contribute to disease progression. These findings offer a rationale for the manipulation of Tregs for therapeutic intervention.

Lockdown Britain: Evidence for reduced incidence and severity of some non-COVID acute medical illnesses.

Large reductions in emergency department attendances and hospitalisations with non-COVID acute medical illness early during the pandemic were attributed to reluctance to seek medical help and higher referral thresholds. Here, we compare acute medical admissions with a comparison cohort from 2017. Deaths in the same geographic area were examined, and Wales-wide deaths during these 4 weeks in 2020 were compared with a seasonally matched period in 2019. There were 528 patients admitted with non-COVID illness in 2020, versus 924 in 2017 (a reduction of 43%). Deaths from non-COVID causes increased by 10.9% compared with 2017, over half this rise being from neurological causes including stroke and dementia. While far fewer patients required hospitalisation as medical emergencies, rises in local non-COVID deaths proved small. Wales-wide non-COVID deaths rose by just 1% compared with 2019. The findings suggest that changes in population behaviour and lifestyle during lockdown brought about unforeseen health benefits.

Acute kidney injury risk assessment at the hospital front door: what is the best measure of risk?

BACKGROUND: We examined the prevalence of acute kidney injury (AKI) risk factors in the emergency medical unit, generated a modified risk assessment tool and tested its ability to predict AKI. METHODS: A total of 1196 patients admitted to medical admission units were assessed for patient-associated AKI risk factors. Subsequently, 898 patients were assessed for a limited number of fixed risk factors with the addition of hypotension and sepsis. This was correlated to AKI episodes. RESULTS: In the first cohort, the prevalence of AKI risk factors was 2.1 ± 2.0 per patient, with a positive relationship between age and the number of risk factors and a higher number of risk factors in patients ≥65 years. In the second cohort, 12.3% presented with or developed AKI. Patients with AKI were older and had a higher number of AKI risk factors. In the AKI cohort, 72% of the patients had two or more AKI risk factors compared with 43% of the cohort with no AKI. When age ≥65 years was added as an independent risk factor, 84% of those with AKI had two or more AKI risk factors compared with 55% of those with no AKI. Receiver operating characteristic analysis suggests that the use of common patient-associated known AKI risk factors performs no better than age alone as a predictor of AKI. CONCLUSIONS: Detailed assessment of well-established patient-associated AKI risk factors may not facilitate clinicians to apportion risk. This suggests that additional work is required to develop a more sensitive validated AKI-predictive tool that would be useful in this clinical setting.