Meta-analysis of 16S rRNA microbial data identified alterations of the gut microbiota in COVID-19 patients during the acute and recovery phases.

BACKGROUND: Dozens of studies have demonstrated gut dysbiosis in COVID-19 patients during the acute and recovery phases. However, a consensus on the specific COVID-19 associated bacteria is missing. In this study, we performed a meta-analysis to explore whether robust and reproducible alterations in the gut microbiota of COVID-19 patients exist across different populations. METHODS: A systematic review was conducted for studies published prior to May 2022 in electronic databases. After review, we included 16 studies that comparing the gut microbiota in COVID-19 patients to those of controls. The 16S rRNA sequence data of these studies were then re-analyzed using a standardized workflow and synthesized by meta-analysis. RESULTS: We found that gut bacterial diversity of COVID-19 patients in both the acute and recovery phases was consistently lower than non-COVID-19 individuals. Microbial differential abundance analysis showed depletion of anti-inflammatory butyrate-producing bacteria and enrichment of taxa with pro-inflammatory properties in COVID-19 patients during the acute phase compared to non-COVID-19 individuals. Analysis of microbial communities showed that the gut microbiota of COVID-19 recovered patients were still in unhealthy ecostates. CONCLUSIONS: Our results provided a comprehensive synthesis to better understand gut microbial perturbations associated with COVID-19 and identified underlying biomarkers for microbiome-based diagnostics and therapeutics.

COVID-19 and resilience of healthcare systems in ten countries.

Declines in health service use during the Coronavirus Disease 2019 (COVID-19) pandemic could have important effects on population health. In this study, we used an interrupted time series design to assess the immediate effect of the pandemic on 31 health services in two low-income (Ethiopia and Haiti), six middle-income (Ghana, Lao People's Democratic Republic, Mexico, Nepal, South Africa and Thailand) and high-income (Chile and South Korea) countries. Despite efforts to maintain health services, disruptions of varying magnitude and duration were found in every country, with no clear patterns by country income group or pandemic intensity. Disruptions in health services often preceded COVID-19 waves. Cancer screenings, TB screening and detection and HIV testing were most affected (26-96% declines). Total outpatient visits declined by 9-40% at national levels and remained lower than predicted by the end of 2020. Maternal health services were disrupted in approximately half of the countries, with declines ranging from 5% to 33%. Child vaccinations were disrupted for shorter periods, but we estimate that catch-up campaigns might not have reached all children missed. By contrast, provision of antiretrovirals for HIV was not affected. By the end of 2020, substantial disruptions remained in half of the countries. Preliminary data for 2021 indicate that disruptions likely persisted. Although a portion of the declines observed might result from decreased needs during lockdowns (from fewer infectious illnesses or injuries), a larger share likely reflects a shortfall of health system resilience. Countries must plan to compensate for missed healthcare during the current pandemic and invest in strategies for better health system resilience for future emergencies.

Safety and Optimal Timing of BCG Vaccination in Infants Born to Mothers Receiving Anti-TNF Therapy for Inflammatory Bowel Disease.

BACKGROUNDS AND AIMS: We aimed to evaluate the safety of Bacille Calmette-Guérin [BCG] vaccination in infants born to mothers receiving anti-tumour necrosis factor [anti-TNF] therapy for inflammatory bowel disease. METHODS: Adverse events of BCG vaccination were evaluated in 90 infants who were last exposed to anti-TNF agents at a median of gestational week 30. RESULTS: After receiving BCG vaccination at a median age of 6 months [range, 0.25-11 months], three infants [3.3%] showed injection site swelling, two of whom also showed axillar lymphadenopathy. The rates of adverse events were similar between infants who were last exposed to anti-TNF agents before the third trimester [n = 35] and those who were last exposed in the third trimester [n = 55] [2.9% vs 3.6%; p = 1.00]. All adverse events were spontaneously resolved and there were no serious adverse events such as active tuberculosis infection or death. CONCLUSIONS: BCG vaccination after 6 months of age is of low risk in infants exposed to anti-TNF agents in utero.

Impact of Insurance Benefits and Education on Point-of-Care Ultrasound Use in a Single Emergency Department: An Interrupted Time Series Analysis.

Background and Objectives: Point-of-care ultrasound (POCUS) is a useful tool that helps clinicians properly treat patients in emergency department (ED). This study aimed to evaluate the impact of specific interventions on the use of POCUS in the ED. Materials and Methods: This retrospective study used an interrupted time series analysis to assess how interventions changed the use of POCUS in the emergency department of a tertiary medical institute in South Korea from October 2016 to February 2021. We chose two main interventions-expansion of benefit coverage of the National Health Insurance (NHI) for emergency ultrasound (EUS) and annual ultrasound educational workshops. The primary variable was the EUS rate, defined as the number of EUS scans per 1000 eligible patients per month. We compared the level and slope of EUS rates before and after interventions. Results: A total of 5188 scanned records were included. Before interventions, the EUS rate had increased gradually. After interventions, except for the first workshop, the EUS rate immediately increased significantly (p < 0.05). The difference in the EUS rate according to the expansion of the NHI was estimated to be the largest (p < 0.001). However, the change in slope significantly decreased after the third workshop during the coronavirus disease 2019 pandemic (p = 0.004). The EUS rate increased significantly in the presence of physicians participating in intensive POCUS training (p < 0.001). Conclusion: This study found that expansion of insurance coverage for EUS and ultrasound education led to a significant and immediate increase in the use of POCUS, suggesting that POCUS use can be increased by improving education and insurance benefits.

Mobility restrictions were associated with reductions in COVID-19 incidence early in the pandemic: evidence from a real-time evaluation in 34 countries.

Most countries have implemented restrictions on mobility to prevent the spread of Coronavirus disease-19 (COVID-19), entailing considerable societal costs but, at least initially, based on limited evidence of effectiveness. We asked whether mobility restrictions were associated with changes in the occurrence of COVID-19 in 34 OECD countries plus Singapore and Taiwan. Our data sources were the Google Global Mobility Data Source, which reports different types of mobility, and COVID-19 cases retrieved from the dataset curated by Our World in Data. Beginning at each country's 100th case, and incorporating a 14-day lag to account for the delay between exposure and illness, we examined the association between changes in mobility (with January 3 to February 6, 2020 as baseline) and the ratio of the number of newly confirmed cases on a given day to the total number of cases over the past 14 days from the index day (the potentially infective 'pool' in that population), per million population, using LOESS regression and logit regression. In two-thirds of examined countries, reductions of up to 40% in commuting mobility (to workplaces, transit stations, retailers, and recreation) were associated with decreased cases, especially early in the pandemic. Once both mobility and incidence had been brought down, further restrictions provided little additional benefit. These findings point to the importance of acting early and decisively in a pandemic.

Reversion of Gut Microbiota during the Recovery Phase in Patients with Asymptomatic or Mild COVID-19: Longitudinal Study.

Patients with COVID-19 have been reported to experience gastrointestinal symptoms as well as respiratory symptoms, but the effects of COVID-19 on the gut microbiota are poorly understood. We explored gut microbiome profiles associated with the respiratory infection of SARS-CoV-2 during the recovery phase in patients with asymptomatic or mild COVID-19. A longitudinal analysis was performed using the same patients to determine whether the gut microbiota changed after recovery from COVID-19. We applied 16S rRNA amplicon sequencing to analyze two paired fecal samples from 12 patients with asymptomatic or mild COVID-19. Fecal samples were selected at two time points: during SARS-CoV-2 infection (infected state) and after negative conversion of the viral RNA (recovered state). We also compared the microbiome data with those from 36 healthy controls. Microbial evenness of the recovered state was significantly increased compared with the infected state. SARS-CoV-2 infection induced the depletion of Bacteroidetes, while an abundance was observed with a tendency to rapidly reverse in the recovered state. The Firmicutes/Bacteroidetes ratio in the infected state was markedly higher than that in the recovered state. Gut dysbiosis was observed after infection even in patients with asymptomatic or mild COVID-19, while the composition of the gut microbiota was recovered after negative conversion of SARS-CoV-2 RNA. Modifying intestinal microbes in response to COVID-19 might be a useful therapeutic alternative.

Detection of SARS-CoV-2 in Fecal Samples From Patients With Asymptomatic and Mild COVID-19 in Korea.

BACKGROUND & AIMS: Although coronavirus disease 2019 (COVID-19) is characterized by fever and respiratory symptoms, some patients have no or mild symptoms. Severe acute respiratory syndrome-coronavirus (SARS-CoV-2) has been detected in feces of patients. We investigated gastrointestinal symptoms and shedding of virus into feces of patients with asymptomatic or mild COVID-19. METHODS: We collected data from 46 patients (median age, 26 y; 46% men) with asymptomatic or mild COVID-19 (without fever and pneumonia) and prolonged respiratory shedding of SARS-CoV-2, quarantined from April 4, 2020, through April 24, 2020, in Korea. Respiratory specimens included upper respiratory specimens (nasopharyngeal and oropharyngeal swabs) and lower respiratory specimens (sputum), and were collected twice per week. The median interval between COVID-19 diagnosis to the start of fecal sample collection was 37 days (range, 29-41 d); 213 stool specimens were collected from 46 patients. We used real-time reverse-transcription polymerase chain reaction to detect SARS-CoV-2 in the respiratory and fecal specimens. RESULTS: Gastrointestinal manifestations were observed in 16 of the 46 patients (35%); diarrhea was the most common (15%), followed by abdominal pain (11%), dyspepsia (11%), and nausea (2%). Virus RNA was detected in feces from 2 patients without gastrointestinal symptoms (4%). Mean cycle threshold values from the time of quarantine to the time of fecal collection tended to be lower in patients with virus detected in fecal samples than in patients without virus in fecal samples (29.91 vs 33.67 in the first week, 29.47 vs 35.71 in the fifth week, respectively). Shedding of virus into feces persisted until day 50 after diagnosis; fecal samples began to test negative before or at approximately the time that respiratory specimens also began to test negative. CONCLUSIONS: In an analysis of fecal and respiratory specimens from patients with COVID-19 in quarantine in Korea, we found that the gastrointestinal tract could be a route of transmission of SARS-CoV-2 even in patients with asymptomatic or mild disease, with no gastrointestinal symptoms. The viral load of the respiratory specimens appears be related to shedding of the virus into feces in this group of patients.