September 7, 2023

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Clinical Reports

Temporal changes in fecal microbiota of patients infected with COVID-19: a longitudinal cohort
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a multifaceted disease potentially responsible for various clinical manifestations including gastro-intestinal symptoms. Several evidences suggest that the intestine is a critical site of immune cell development, gut microbiota could therefore play a key role in lung immune response. Researchers designed a monocentric longitudinal observational study to describe the gut microbiota profile in COVID-19 patients and compare it to a pre-existing cohort of ventilated non-COVID-19 patients. From March to December 2020, researchers included patients admitted for COVID-19 in medicine (43 not ventilated) or intensive care unit (ICU) (14 ventilated) with a positive SARS-CoV-2 RT-PCR assay in a respiratory tract sample. 16S metagenomics was performed on rectal swabs from these 57 COVID-19 patients, 35 with one and 22 with multiple stool collections. Nineteen non-COVID-19 ICU controls were also enrolled, among which 14 developed ventilator-associated pneumonia (pneumonia group) and five remained without infection (control group). SARS-CoV-2 viral loads in fecal samples were measured by qPCR. Although similar at inclusion, Shannon alpha diversity appeared significantly lower in COVID-19 and pneumonia groups than in the control group at day 7. Furthermore, the microbiota composition became distinct between COVID-19 and non-COVID-19 groups. The fecal microbiota of COVID-19 patients was characterized by increased Bacteroides and the pneumonia group by Prevotella. In a distance-based redundancy analysis, only COVID-19 presented significant effects on the microbiota composition. Moreover, patients in ICU harbored increased Campylobacter and decreased butyrate-producing bacteria, such as Lachnospiraceae, Roseburia and Faecalibacterium as compared to patients in medicine. Both the stay in ICU and patient were significant factors affecting the microbiota composition. SARS-CoV-2 viral loads were higher in ICU than in non-ICU patients. Overall, researchers identified distinct characteristics of the gut microbiota in COVID-19 patients compared to control groups. COVID-19 patients were primarily characterized by increased Bacteroides and decreased Prevotella. Moreover, disease severity showed a negative correlation with butyrate-producing bacteria. These features could offer valuable insights into potential targets for modulating the host response through the microbiota and contribute to a better understanding of the disease's pathophysiology.

Antiviral Therapeutics and Vaccines

Comparison of bivalent and monovalent mRNA vaccine boosters
In this cohort study conducted in Hong Kong where both bivalent and monovalent formulations of BNT162b2 were available, there was no significant differences in the mortality or hospitalization between those who received bivalent and monovalent mRNA as second boosters. Bivalent and monovalent mRNA boosters appear equally protective against clinical outcomes.

Diagnostics

Acute blood biomarker profiles predict cognitive deficits 6 and 12 months after COVID-19 hospitalization
Post-COVID cognitive deficits, including ‘brain fog’, are clinically complex, with both objective and subjective components. They are common and debilitating, and can affect the ability to work, yet their biological underpinnings remain unknown. In this prospective cohort study of 1,837 adults hospitalized with COVID-19, researchers identified two distinct biomarker profiles measured during the acute admission, which predict cognitive outcomes 6 and 12 months after COVID-19. A first profile links elevated fibrinogen relative to C-reactive protein with both objective and subjective cognitive deficits. A second profile links elevated D-dimer relative to C-reactive protein with subjective cognitive deficits and occupational impact. This second profile was mediated by fatigue and shortness of breath. Neither profile was significantly mediated by depression or anxiety. Results were robust across secondary analyses. They were replicated, and their specificity to COVID-19 tested, in a large-scale electronic health records dataset. These findings provide insights into the heterogeneous biology of post-COVID cognitive deficits.

Epidemiology

Mpox: China’s health authorities fight surge in cases of unknown origin
Chinese health authorities are facing an escalating outbreak of mpox where most cases are of unknown origin. A World Health Organization mpox situation report published on 14 August singled out “sustained community transmission in China” as driving the rise in cases in the region, which has bucked a broad global decline. Confirmed cases of the viral infection, which primarily spreads through contact with infectious lesions, increased nearly fivefold to 491 on the Chinese mainland in July, according to China’s Center for Disease Control and Prevention (China CDC). That was up from 106 cases in June. No deaths were recorded. Four in five of the cases had no known origin, according to a post on the China CDC website on 9 August.
Prevalence and associated outcomes of co-infection between SARS-CoV-2 and influenza: a systematic review and meta-analysis
Researchers systematically searched Web of Science, PubMed, Scopus, Embase, The Cochrane Library, and CNKI for studies published between January 1, 2020 and May 31, 2023. Meta-analysis was performed to estimate the pooled prevalence of co-infection and the impact on clinical outcomes. A total of 95 studies involving 62,107 COVID-19 patients were included. The pooled prevalence of co-infection with influenza virus was 2.45% (95% CI: 1.67%-3.58%), with a high proportion of influenza A. Compared with mono-infected patients (COVID-19 only), the odds ratio (OR) for severe outcomes (including Intensive Care Unit admission (OR = 2.20, 95% CI: 1.68-2.87, P < 0.001), mechanical ventilation support (OR = 2.73, 95% CI: 1.46-5.10, P = 0.002), and mortality (OR = 2.92, 95% CI: 1.16-7.30, P = 0.022)) was significantly higher among patients co-infected influenza A. Although the prevalence of co-infection is low, co-infected patients are at higher risk of severe outcomes. Enhanced identification of both viruses, as well as individualized treatment protocols for co-infection, are recommended to reduce the occurrence of serious disease outcomes in the future.
Analysis of seasonal variation of antibiotic prescribing for respiratory tract diagnoses in primary care practices
Office visits for the entire cohort were categorized based on ICD-10 codes by the likelihood that an antibiotic was indicated (tier 1: always indicated; tier 2: sometimes indicated; tier 3: rarely indicated). Medical records were reviewed for 1,200 randomly selected office visits to determine appropriateness. Based on this reference standard, metrics and prescriber characteristics associated with inappropriate antibiotic prescribing were determined. Characteristics of antibiotic prescribing were compared between winter and summer months. A significantly greater proportion of RTD visits had an antibiotic prescribed in winter [20,558/51,090 (40.2%)] compared to summer months [11,728/38,537 (30.4%)][standardized difference (SD) = 0.21]. A significantly greater proportion of winter compared to summer visits was associated with tier 2 RTDs (29.4% vs 23.4%, SD = 0.14), but less tier 3 RTDs (68.4% vs 74.4%, SD = 0.13). A greater proportion of visits in winter compared to summer months had an antibiotic prescribed for tier 2 RTDs (80.2% vs 74.2%, SD = 0.14) and tier 3 RTDs (22.9% vs 16.2%, SD = 0.17). The proportion of inappropriate antibiotic prescribing was higher in winter compared to summer months (72.4% vs 62.0%, P < .01). Increases in antibiotic prescribing for RTD visits from summer to winter were likely driven by shifts in diagnoses as well as increases in prescribing for certain diagnoses. At least some of this increased prescribing was inappropriate.
Optimal Duration of Systemic Corticosteroids in Coronavirus Disease 2019 Treatment: A Systematic Review and Meta-analysis
Corticosteroids confer a survival benefit in individuals hospitalized with coronavirus disease 2019 (COVID-19) who require oxygen. This meta-analysis seeks to determine the duration of corticosteroids needed to optimize this mortality benefit. Electronic databases were searched to 9 March 2022, for studies reporting corticosteroid versus no corticosteroid treatment in hospitalized COVID-19 patients. We estimated the effect of corticosteroids on mortality by random-effects meta-analyses. Subgroup analyses and meta-analyses were conducted to assess the optimal duration of corticosteroid treatment while adjusting for the severity of disease, age, duration of symptoms, and proportion of control group given steroids. Researchers identified 27 eligible studies consisting of 13 404 hospitalized COVID-19 patients. Seven randomized controlled trials and 20 observational studies were included in the meta-analysis of mortality, which suggested a protective association with corticosteroid therapy (risk ratio [RR], 0.71 [95% confidence interval {CI}, .58–.87]). Pooled analysis of 18 studies showed the greatest survival benefit for a treatment duration up to 6 days (RR, 0.54 [95% CI, .39–.74]). Survival benefit was 0.65 (95% CI, .51–.83) up to 7 days, and no additional survival benefit was observed beyond 7 days of treatment (RR, 0.64 [95% CI, .44–.93]). The survival benefit was not confounded by severity of disease, age, duration of symptoms, or proportion of control group given steroids. In this meta-analysis, optimal duration of corticosteroid treatment for hospitalized COVID-19 patients was up to 6 days, with no additional survival benefit with >7 days of treatment.
Long-term survival after intensive care for COVID-19: a nationwide cohort study of more than 8000 patients
Was it worth it—what is the outcome after the extended ICU (intensive care unit) length of stay for COVID-19 patients? Surprisingly, data on long-term mortality in large cohorts are lacking. Researchers investigate long-term mortality including differences between men and women, as previous studies show that men generally suffer a more severe course of COVID-19 in terms of severity of illness and short-term mortality. Nationwide cohort including all adult COVID-19 patients admitted to Swedish ICUs until August 12, 2022. Primary outcome was 360-day mortality after ICU admission. Logistic regression was used to estimate associations between demographics, comorbidities, clinical characteristics and mortality. In total, 8392 patients were included. Median (IQR) age was 63 (52–72) years and the majority (70.1%) were men. Among the 7390 patients with complete 360-day mortality data, 1775 (24.4%) patients died within 30 days, 2125 (28.8%) within 90 days and 2206 (29.8%) within 360 days from ICU admission. 360-day mortality was 27.1% in women and 31.0% in men. Multivariable logistic regression analysis showed increased risk of 360-day mortality in men compared to women (OR: 1.33, 95% CI: 1.17–1.52). Other variables associated with poor 360-day mortality were age, cardiac disease, COPD/asthma, diabetes, immune deficiency, chronic kidney disease, neuromuscular disease, and malignancy. This study confirms the increased severity of disease in critically ill men with COVID-19, even in a long-term perspective. However, mortality beyond 90 days was strikingly low, indicating high probability of survival after the acute phase of illness.