Anaemia of acute inflammation: a higher acute systemic inflammatory response is associated with a larger decrease in blood haemoglobin levels in patients with COVID-19 infection.

AIMS: The study tests the hypothesis that a higher acute systemic inflammatory response was associated with a larger decrease in blood hemoglobin levels in patients with Coronavirus 2019 (COVID-19) infection. METHODS: All patients with either suspected or confirmed COVID-19 infection admitted to a busy UK hospital from February 2020 to December 2021 provided data for analysis. The exposure of interest was maximal serum C-reactive protein (CRP) level after COVID-19 during the same admission. RESULTS: A maximal serum CRP >175mg/L was associated with a decrease in blood haemoglobin (-5.0 g/L, 95% confidence interval: -5.9 to -4.2) after adjustment for covariates, including the number of times blood was drawn for analysis.Clinically, for a 55-year-old male patient with a maximum haemoglobin of 150 g/L who was admitted for a 28-day admission, a peak CRP >175 mg/L would be associated with an 11 g/L decrease in blood haemoglobin, compared with only 6 g/L if the maximal CRP was <4 mg/L. CONCLUSIONS: A higher acute systemic inflammatory response is associated with larger decreases in blood haemoglobin levels in patients with COVID-19. This represents an example of anaemia of acute inflammation, and a potential mechanism by which severe disease can increase morbidity and mortality.

Is Vaccination Against COVID-19 Associated With Inflammatory Bowel Disease Flare? Self-Controlled Case Series Analysis Using the UK CPRD.

INTRODUCTION: To investigate the association between vaccination against coronavirus disease 2019 (COVID-19) and inflammatory bowel disease (IBD) flare. METHODS: Patients with IBD vaccinated against COVID-19 who consulted for disease flare between December 1, 2020, and December 31, 2021, were ascertained from the Clinical Practice Research Datalink. IBD flares were identified using consultation and corticosteroid prescription records. Vaccinations were identified using product codes and vaccination dates. The study period was partitioned into vaccine-exposed (vaccination date and 21 days immediately after), prevaccination (7 days immediately before vaccination), and the remaining vaccine-unexposed periods. Participants contributed data with multiple vaccinations and IBD flares. Season-adjusted incidence rate ratios (aIRR) and 95% confidence intervals (CI) were calculated using self-controlled case series analysis. RESULTS: Data for 1911 cases with IBD were included; 52% of them were female, and their mean age was 49 years. Approximately 63% of participants had ulcerative colitis (UC). COVID-19 vaccination was not associated with increased IBD flares in the vaccine-exposed period when all vaccinations were considered (aIRR [95% CI] 0.89 [0.77-1.02], 0.79 [0.66-0.95], and 1.00 [0.79-1.27] in IBD overall, UC, and Crohn's disease, respectively). Analyses stratified to include only first, second, or third COVID-19 vaccinations found no significant association between vaccination and IBD flares in the vaccine-exposed period (aIRR [95% CI] 0.87 [0.71-1.06], 0.93 [0.75-1.15], and 0.86 [0.63-1.17], respectively). Similarly, stratification by COVID-19 before vaccination and by vaccination with vectored DNA or messenger RNA vaccine did not reveal an increased risk of flare in any of these subgroups. DISCUSSION: Vaccination against COVID-19 was not associated with IBD flares regardless of prior COVID-19 infection and whether messenger RNA or DNA vaccines were used.

Differential pulse oximetry readings between ethnic groups & delayed transfer to intensive care units.

BACKGROUND: Pulse oximeters are widely used to monitor blood oxygen saturations, although concerns exist that they are less accurate in individuals with pigmented skin. AIMS: This study aimed to determine if patients with pigmented skin were more severely unwell at the period of transfer to intensive care units than individuals with White skin. METHODS: Using data from a large teaching hospital, measures of clinical severity at the time of transfer of patients with Covid-19 infection to intensive care units were assessed, and how this varied by ethnic group. RESULTS: Data were available on 748 adults. Median pulse oximetry demonstrated similar oxygen saturations at the time of transfer to intensive care units (Kruskal Wallis test, p = 0.51), although median oxygen saturation measurements from arterial blood gases at this time demonstrated lower oxygen saturations in patients classified as Indian/Pakistani ethnicity (91.6%) and Black/Mixed ethnicity (93.0%), compared to those classified as a White ethnicity (94.4%, Kruskal Wallis test, p = 0.005). There were significant differences in mean respiratory rates in these patients (p < 0.0001), ranging from 26 breaths/minute in individuals with White ethnicity to 30 breaths/minute for those classified as Indian/Pakistani ethnicity and 31 for those who were classified as Black/Mixed ethnicity. CONCLUSIONS: These data are consistent with the hypothesis that differential measurement error for pulse oximeter readings negatively impact on the escalation of clinical care in individuals from other than White ethnic groups. This has implications for healthcare in Africa and South-East Asia, and may contribute to differences in health outcomes across ethnic groups globally.

Predicting Need for Escalation of Care or Death From Repeated Daily Clinical Observations and Laboratory Results in Patients With Severe Acute Respiratory Syndrome Coronavirus 2.

We compared the performance of prognostic tools for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using parameters fitted either at the time of hospital admission or across all time points of an admission. This cohort study used clinical data to model the dynamic change in prognosis of SARS-CoV-2 at a single hospital center in the United Kingdom, including all patients admitted from February 1, 2020, to December 31, 2020, and then followed up for 60 days for intensive care unit (ICU) admission, death, or discharge from the hospital. We incorporated clinical observations and blood tests into 2 time-varying Cox proportional hazards models predicting daily 24- to 48-hour risk of admission to the ICU for those eligible for escalation of care or death for those ineligible for escalation. In developing the model, 491 patients were eligible for ICU escalation and 769 were ineligible for escalation. Our model had good discrimination of daily risk of ICU admission in the validation cohort (n = 1,141; C statistic: C = 0.91, 95% confidence interval: 0.89, 0.94) and our score performed better than other scores (National Early Warning Score 2, International Severe Acute Respiratory and Emerging Infection Comprehensive Clinical Characterisation Collaboration score) calculated using only parameters measured on admission, but it overestimated the risk of escalation (calibration slope = 0.7). A bespoke daily SARS-CoV-2 escalation risk prediction score can predict the need for clinical escalation better than a generic early warning score or a single estimation of risk calculated at admission.

Age modifies both the maximal temperature and inflammatory response in patients with SARS-CoV-2 infection.

OBJECTIVE: To determine the maximal response of the temperature and inflammatory response to SARS-CoV-2 infection and how these are modified by age. METHODS: Participants were patients admitted to hospital with SARS-CoV-2 infection. For each participant, the maximal temperature and serum C-reactive protein (CRP) were identified and stratified by age. In a secondary analysis, these were compared in patients treated before and after dexamethasone. RESULTS: Mean maximal temperature varied by age (p<0.001; ANOVA) with the highest mean maximal temperature of 37.3°C observed in patients aged 30-49 years and decreasing maximal mean temperatures in the older age groups, with the lowest measure of 36.8°C observed in individuals aged 90-99 years. The mean maximal serum CRP also varied across age groups (p<0.001; ANOVA) and increased with age across all age categories from 34.5 mg/dL (95% confidence interval (CI) 22.0-47.0) for individuals aged 20-29 years to 77.6 mg/dL (95% CI 72.0-83.2) in those aged 80-89 years. After dexamethasone became standard treatment for COVID-19 pneumonia, mean maximal CRP decreased by 17 mg/dL (95% CI -22 to -11). CONCLUSION: Age modifies both maximal temperature and systemic inflammatory response in patients with SARS-CoV-2 infection.

Silent hypoxia is not an identifiable characteristic in patients with COVID-19 infection.

BACKGROUND: We aimed to assess whether asymptomatic ("happy") hypoxia was an identifiable physiological phenotype of COVID-19 acute respiratory distress syndrome (ARDS), and associated with need for ICU admission. METHODS: We performed an observational cohort study of all adult patients admitted with hypoxaemic respiratory failure to a large acute hospital Trust serving the East Midlands, UK. Patients with confirmed COVID-19 were compared to those without. Physiological response to hypoxaemia was modelled using a linear mixed effects model. RESULTS: Of 1,586 patients included, 75% tested positive for SARS-CoV-2. The ROX index was 2.08 min-1 lower (1.56-2.61, p < 0.001) in the COVID-19 cohort when adjusted for age and ethnicity, suggesting an enhanced respiratory response to hypoxia compared to the non-Covid-19 patients. There was substantial residual inter- and intra-patient variability in the respiratory response to hypoxaemia. 33% of the infected cohort required ICU, and of these 31% died within 60 days. ICU admission and mortality were both associated with an enhanced respiratory response for all degrees of hypoxaemia. CONCLUSIONS: Patients with COVID-19 display a more symptomatic phenotype in response to hypoxaemia than those with other causes of hypoxaemic respiratory failure, however individual patients exhibit a wide range of responses. As such although asymptomatic hypoxaemia may be a phenomenon in any individual patient with hypoxaemic respiratory failure, it is no more frequently observed in those with SARS-CoV-2 infection than without.

Chest Radiograph Scoring Alone or Combined with Other Risk Scores for Predicting Outcomes in COVID-19.

Background Radiographic severity may help predict patient deterioration and outcomes from COVID-19 pneumonia. Purpose To assess the reliability and reproducibility of three chest radiograph reporting systems (radiographic assessment of lung edema [RALE], Brixia, and percentage opacification) in patients with proven SARS-CoV-2 infection and examine the ability of these scores to predict adverse outcomes both alone and in conjunction with two clinical scoring systems, National Early Warning Score 2 (NEWS2) and International Severe Acute Respiratory and Emerging Infection Consortium: Coronavirus Clinical Characterization Consortium (ISARIC-4C) mortality. Materials and Methods This retrospective cohort study used routinely collected clinical data of patients with polymerase chain reaction-positive SARS-CoV-2 infection admitted to a single center from February 2020 through July 2020. Initial chest radiographs were scored for RALE, Brixia, and percentage opacification by one of three radiologists. Intra- and interreader agreement were assessed with intraclass correlation coefficients. The rate of admission to the intensive care unit (ICU) or death up to 60 days after scored chest radiograph was estimated. NEWS2 and ISARIC-4C mortality at hospital admission were calculated. Daily risk for admission to ICU or death was modeled with Cox proportional hazards models that incorporated the chest radiograph scores adjusted for NEWS2 or ISARIC-4C mortality. Results Admission chest radiographs of 50 patients (mean age, 74 years ± 16 [standard deviation]; 28 men) were scored by all three radiologists, with good interreader reliability for all scores, as follows: intraclass correlation coefficients were 0.87 for RALE (95% CI: 0.80, 0.92), 0.86 for Brixia (95% CI: 0.76, 0.92), and 0.72 for percentage opacification (95% CI: 0.48, 0.85). Of 751 patients with a chest radiograph, those with greater than 75% opacification had a median time to ICU admission or death of just 1-2 days. Among 628 patients for whom data were available (median age, 76 years [interquartile range, 61-84 years]; 344 men), opacification of 51%-75% increased risk for ICU admission or death by twofold (hazard ratio, 2.2; 95% CI: 1.6, 2.8), and opacification greater than 75% increased ICU risk by fourfold (hazard ratio, 4.0; 95% CI: 3.4, 4.7) compared with opacification of 0%-25%, when adjusted for NEWS2 score. Conclusion Brixia, radiographic assessment of lung edema, and percentage opacification scores all reliably helped predict adverse outcomes in SARS-CoV-2 infection. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Little in this issue.