Gastrointestinal Manifestations and Outcomes of COVID-19: A Comprehensive Systematic Review and Meta-analysis.

Introduction Pulmonary symptoms are the most prominent manifestations of Coronavirus disease 2019 (COVID-19). However, gastrointestinal (GI) symptoms have been reported widely as well. Literature describing the relation of these symptoms with outcomes of COVID-19 patients is limited in terms of sample size, geographic diversity, and the spectrum of GI symptoms included. We aim to evaluate the association of GI symptoms with outcomes of hospitalized COVID-19 patients. Methods A systematic review and meta-analysis of observational studies assessing GI symptoms and outcomes in COVID-19 patients were undertaken using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria and the Meta-analysis of Observational Studies in Epidemiology (MOOSE) checklist. Details on outcomes included ICU vs. non-ICU admission, severe vs. non-severe disease, invasive mechanical ventilation (IMV) vs. no-IMV use, oxygen saturation <90% vs. >90%, in-hospital mortality vs. discharged alive and survivors. We obtained the odds ratio (OR), 95% confidence interval (95%CI), and forest plots. Sensitivity analysis was used to analyze publication bias and heterogeneity. Results In 35 studies with 7931 confirmed COVID-19 patients, we found that anorexia (pooled OR:2.05; 95%CI: 1.36-3.09, p=0.0006) and abdominal pain (OR 2.80; 95%CI: 1.41-5.54, p=0.003) were associated with a higher risk of poor outcomes and no such association was found for diarrhea (OR 1.04; 95%CI: 0.85-1.26, p=0.71), nausea (OR 0.73; 95%CI: 0.38-1.39, p=0.34) and vomiting (OR 1.24; 95%CI 0.86-1.79, p=0.25). Conclusion The meta-analysis concludes that anorexia and abdominal pain are associated with poor outcomes in hospitalized COVID-19 patients, while diarrhea, nausea, and vomiting have no association. Future research should focus on whether detecting GI invasion in conjunction with fecal polymerase chain reaction (PCR) testing can aid in the early triage of high-risk individuals and improve outcomes.

In TB, an 8-wk, 5-drug regimen was noninferior to a standard 24-wk, 4-drug regimen for clinical outcomes at 96 wk.

SOURCE CITATION: Paton NI, Cousins C, Suresh C, et al; TRUNCATE-TB Trial Team. Treatment strategy for rifampin-susceptible tuberculosis. N Engl J Med. 2023;388:873-887. 36808186.

In adults, risk for infective endocarditis varied for invasive dental procedures and by antibiotic prophylaxis.

SOURCE CITATION: Thornhill MH, Gibson TB, Yoon F, et al. Antibiotic prophylaxis against infective endocarditis before invasive dental procedures. J Am Coll Cardiol. 2022;80:1029-41. 35987887.

In nonhospitalized, unvaccinated adults with COVID-19, molnupiravir reduced hospitalization or death at 29 d.

SOURCE CITATION: Jayk Bernal A, Gomes da Silva MM, Musungaie DB, et al. Molnupiravir for oral treatment of Covid-19 in nonhospitalized patients. N Engl J Med. 2022;386:509-20. 34914868.

"When to Nuss? patient age as a risk factor for complications of minimally invasive repair of pectus excavatum: a systematic review and meta-analysis".

PURPOSE: The optimal age for minimally invasive repair of pectus excavatum (MIRPE) is unclear; this study investigates the differences in complication rates among different age groups undergoing repair. METHODS: PubMed and Embase databases were searched from inception to October 2020. To assess age as a risk factor for complications, odds ratios from relevant studies were analyzed using the Mantel-Haenszel method with a random-effects model for younger vs older patients. Specific complication rates were compared between the two cohorts using a chi-squared test. RESULTS: Of the 4448 studies retrieved, 25 studies stratified complication data by age groups. From these studies, ten studies compared groups at ages < 18 and ≥ 18 and four studies compared ages < 20 and ≥ 20, and one study compared ages < 19 and ≥ 19. These fifteen studies reported on 5978 patients, with 1188 complications, for a complication rate of 19.87%. Older patients were more likely to have complications in a pooled analysis of studies comparing older vs younger patients (OR = 1.66, 95% CI = 1.28-2.14, heterogeneity I2 = 49%). Specifically, older patients were significantly more likely to experience pneumothorax, pleural effusion, wound infection, bar displacement, and reoperations. CONCLUSION: Increased age is a risk factor for complications of MIRPE. This supports repair of pectus excavatum prior to late adolescence.

Autoimmune conditions in the World Trade Center general responder cohort: A nested case-control and standardized incidence ratio analysis.

BACKGROUND: The World Trade Center (WTC) general responder cohort (GRC) was exposed to environmental toxins possibly associated with increased risk of developing autoimmune conditions. OBJECTIVES: Two study designs were used to assess incidence and risks of autoimmune conditions in the GRC. METHODS: Three clinically trained professionals established the status of possible GRC cases of autoimmune disorders adhering to diagnostic criteria, supplemented, as needed, by specialists' review of consenting responders' medical records. Nested case-control analyses using conditional logistic regression estimated the risk associated with high WTC exposure (being in the 9/11/2001 dust cloud or ≥median days' response worked) compared with low WTC exposure (all other GRC members'). Four controls were matched to each case on age at case diagnosis (±2 years), sex, race/ethnicity, and year of program enrollment. Sex-specific and sensitivity analyses were performed. GRC age- and sex-adjusted standardized incidence ratios (SIRs) were compared with the Rochester Epidemiology Project (REP). Complete REP inpatient and outpatient medical records were reviewed by specialists. Conditions meeting standardized criteria on ≥2 visits were classified as REP confirmed cases. RESULTS: Six hundred and twenty-eight responders were diagnosed with autoimmune conditions between 2002 and 2017. In the nested case-control analyses, high WTC exposure was not associated with autoimmune domains and conditions (rheumatologic domain odds ratio [OR] = 1.03, 95% confidence interval [CI] = 0.77, 1.37; rheumatoid arthritis OR = 1.12, 95% CI = 0.70, 1.77). GRC members had lower SIR than REP. Women's risks were generally greater than men's. CONCLUSIONS: The study found no statistically significant increased risk of autoimmune conditions with WTC exposures.

The Novavax vaccine had 90% efficacy against COVID-19 ≥7 d after the second dose.

SOURCE CITATION: Heath PT, Galiza EP, Baxter DN, et al. Safety and efficacy of NVX-CoV2373 Covid-19 vaccine. N Engl J Med. 2021;385:1172-83. 34192426.

The single-dose J&J vaccine had 67% efficacy against moderate to severe-critical COVID-19 at ≥14 d.

SOURCE CITATION: Sadoff J, Gray G, Vandebosch A, et al. Safety and efficacy of single-dose Ad26.COV2.S vaccine against Covid-19. N Engl J Med. 2021. [Epub ahead of print.] 33882225.

Biomarkers and outcomes of COVID-19 hospitalisations: systematic review and meta-analysis.

OBJECTIVE: To evaluate association between biomarkers and outcomes in COVID-19 hospitalised patients. COVID-19 pandemic has been a challenge. Biomarkers have always played an important role in clinical decision making in various infectious diseases. It is crucial to assess the role of biomarkers in evaluating severity of disease and appropriate allocation of resources. DESIGN AND SETTING: Systematic review and meta-analysis. English full text observational studies describing the laboratory findings and outcomes of COVID-19 hospitalised patients were identified searching PubMed, Web of Science, Scopus, medRxiv using Medical Subject Headings (MeSH) terms COVID-19 OR coronavirus OR SARS-CoV-2 OR 2019-nCoV from 1 December 2019 to 15 August 2020 following Meta-analyses Of Observational Studies in Epidemiology (MOOSE) guidelines. PARTICIPANTS: Studies having biomarkers, including lymphocyte, platelets, D-dimer, lactate dehydrogenase (LDH), C reactive protein (CRP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, procalcitonin (PCT) and creatine kinase (CK), and describing outcomes were selected with the consensus of three independent reviewers. MAIN OUTCOME MEASURES: Composite poor outcomes include intensive care unit admission, oxygen saturation <90%, invasive mechanical ventilation utilisation, severe disease, in-hospital admission and mortality. The OR and 95% CI were obtained and forest plots were created using random-effects models. Publication bias and heterogeneity were assessed by sensitivity analysis. RESULTS: 32 studies with 10 491 confirmed COVID-19 patients were included. We found that lymphopenia (pooled-OR: 3.33 (95% CI: 2.51-4.41); p<0.00001), thrombocytopenia (2.36 (1.64-3.40); p<0.00001), elevated D-dimer (3.39 (2.66-4.33); p<0.00001), elevated CRP (4.37 (3.37-5.68); p<0.00001), elevated PCT (6.33 (4.24-9.45); p<0.00001), elevated CK (2.42 (1.35-4.32); p=0.003), elevated AST (2.75 (2.30-3.29); p<0.00001), elevated ALT (1.71 (1.32-2.20); p<0.00001), elevated creatinine (2.84 (1.80-4.46); p<0.00001) and LDH (5.48 (3.89-7.71); p<0.00001) were independently associated with higher risk of poor outcomes. CONCLUSION: Our study found a significant association between lymphopenia, thrombocytopenia and elevated levels of CRP, PCT, LDH, D-dimer and COVID-19 severity. The results have the potential to be used as an early biomarker to improve the management of COVID-19 patients, by identification of high-risk patients and appropriate allocation of healthcare resources in the pandemic.

Accuracy of point-of-care diagnostic tests for SARS-CoV-2 antibodies (IgM/IgG) is heterogeneous.

SOURCE CITATION: Riccò M, Ferraro P, Gualerzi G, et al. Point-of-care diagnostic tests for detecting SARS-CoV-2 antibodies: a systematic review and meta-analysis of real-world data. J Clin Med. 2020;9:1515. 32443459.

Early epidemiological indicators, outcomes, and interventions of COVID-19 pandemic: A systematic review.

BACKGROUND: Coronavirus disease-2019 (COVID-19), a pandemic that brought the whole world to a standstill, has led to financial and health care burden. We aimed to evaluate epidemiological characteristics, needs of resources, outcomes, and global burden of the disease. METHODS: Systematic review was performed searching PubMed from December 1, 2019, to March 25, 2020, for full-text observational studies that described epidemiological characteristics, following MOOSE protocol. Global data were collected from the JHU-Corona Virus Resource Center, WHO-COVID-2019 situation reports, KFF.org, and Worldometers.info until March 31, 2020. The prevalence percentages were calculated. The global data were plotted in excel to calculate case fatality rate (CFR), predicted CFR, COVID-19 specific mortality rate, and doubling time for cases and deaths. CFR was predicted using Pearson correlation, regression models, and coefficient of determination. RESULTS: From 21 studies of 2747 patients, 8.4% of patients died, 20.4% recovered, 15.4% were admitted to ICU and 14.9% required ventilation. COVID-19 was more prevalent in patients with hypertension (19.3%), smoking (11.3%), diabetes mellitus (10%), and cardiovascular diseases (7.4%). Common complications were pneumonia (82%), cardiac complications (26.4%), acute respiratory distress syndrome (15.7%), secondary infection (11.2%), and septic shock (4.3%). Though CFR and COVID-19 specific death rates are dynamic, they were consistently high for Italy, Spain, and Iran. Polynomial growth models were best fit for all countries for predicting CFR. Though many interventions have been implemented, stern measures like nationwide lockdown and school closure occurred after very high infection rates (>10cases per 100 000population) prevailed. Given the trend of government measures and decline of new cases in China and South Korea, most countries will reach the peak between April 1-20, if interventions are followed. CONCLUSIONS: A collective approach undertaken by a responsible government, wise strategy implementation and a receptive population may help contain the spread of COVID-19 outbreak. Close monitoring of predictive models of such indicators in the highly affected countries would help to evaluate the potential fatality if the second wave of pandemic occurs. The future studies should be focused on identifying accurate indicators to mitigate the effect of underestimation or overestimation of COVID-19 burden.

Age-Adjusted Risk Factors Associated with Mortality and Mechanical Ventilation Utilization Amongst COVID-19 Hospitalizations-a Systematic Review and Meta-Analysis.

The increasing COVID-19 cases in the USA have led to overburdening of healthcare in regard to invasive mechanical ventilation (IMV) utilization as well as mortality. We aim to identify risk factors associated with poor outcomes (IMV and mortality) of COVID-19 hospitalized patients. A meta-analysis of observational studies with epidemiological characteristics of COVID-19 in PubMed, Web of Science, Scopus, and medRxiv from December 1, 2019 to May 31, 2020 following MOOSE guidelines was conducted. Twenty-nine full-text studies detailing epidemiological characteristics, symptoms, comorbidities, complications, and outcomes were included. Meta-regression was performed to evaluate effects of comorbidities, and complications on outcomes using a random-effects model. The pooled correlation coefficient (r), 95% CI, and OR were calculated. Of 29 studies (12,258 confirmed cases), 17 reported IMV and 21 reported deaths. The pooled prevalence of IMV was 23.3% (95% CI: 17.1-30.9%), and mortality was 13% (9.3-18%). The age-adjusted meta-regression models showed significant association of mortality with male (r: 0.14; OR: 1.15; 95% CI: 1.07-1.23; I 2: 95.2%), comorbidities including pre-existing cerebrovascular disease (r: 0.35; 1.42 (1.14-1.77); I 2: 96.1%), and chronic liver disease (r: 0.08; 1.08 (1.01-1.17); I 2: 96.23%), complications like septic shock (r: 0.099; 1.10 (1.02-1.2); I 2: 78.12%) and ARDS (r: 0.04; 1.04 (1.02-1.06); I 2: 90.3%), ICU admissions (r: 0.03; 1.03 (1.03-1.05); I 2: 95.21%), and IMV utilization (r: 0.05; 1.05 (1.03-1.07); I 2: 89.80%). Similarly, male (r: 0.08; 1.08 (1.02-1.15); I 2: 95%), comorbidities like pre-existing cerebrovascular disease (r: 0.29; 1.34 (1.09-1.63); I 2:93.4%), and cardiovascular disease (r: 0.28; 1.32 (1.1-1.58); I 2: 89.7%) had higher odds of IMV utilization. COVID-19 patients with comorbidities including cardiovascular disease, cerebrovascular disease, and chronic liver disease had poor outcomes. Diabetes and hypertension had higher prevalence but no association with mortality and IMV. Our study results will be helpful in right allocation of resources towards patients who need them the most.

Cancer in General Responders Participating in World Trade Center Health Programs, 2003-2013.

BACKGROUND: Following the September 11, 2001, attacks on the World Trade Center (WTC), thousands of workers were exposed to an array of toxins known to cause adverse health effects, including cancer. This study evaluates cancer incidence in the WTC Health Program General Responder Cohort occurring within 12 years post exposure. METHODS: The study population consisted of 28 729 members of the General Responder Cohort enrolled from cohort inception, July 2002 to December 31, 2013. Standardized incidence ratios (SIRs) were calculated with cancer case inclusion and follow-up starting post September 11, 2001 (unrestricted) and, alternatively, to account for selection bias, with case inclusion and follow-up starting 6 months after enrollment in the WTC Health Program (restricted). Case ascertainment was based on linkage with six state cancer registries. Under the restricted criterion, hazard ratios were estimated using multivariable Cox proportional hazards models for all cancer sites combined and for prostate cancer. RESULTS: Restricted analyses identified 1072 cancers in 999 responders, with elevations in cancer incidence for all cancer sites combined (SIR = 1.09, 95% confidence interval [CI] = 1.02 to 1.16), prostate cancer (SIR = 1.25, 95% CI = 1.11 to 1.40), thyroid cancer (SIR = 2.19, 95% CI = 1.71 to 2.75), and leukemia (SIR = 1.41, 95% CI = 1.01 to 1.92). Cancer incidence was not associated with any WTC exposure index (composite or individual) for all cancer sites combined or for prostate cancer. CONCLUSION: Our analyses show statistically significant elevations in cancer incidence for all cancer sites combined and for prostate and thyroid cancers and leukemia. Multivariable analyses show no association with magnitude or type of exposure.

The Effect of Female Sex on Hepatitis C Incidence Among People Who Inject Drugs: Results From the International Multicohort InC3 Collaborative.

Background: The objective of this study was to assess differences in hepatitis C virus (HCV) incidence by sex in people who inject drugs (PWID), using a large international multicohort set of pooled biological and behavioral data from prospective observational studies of incident human immunodeficiency virus (HIV) and HCV infections in high-risk cohorts (the InC3 Collaborative). Methods: HCV infection date was estimated based on a hierarchy of successive serological (anti-HCV), virological (HCV RNA), and clinical (symptoms and/or liver function tests) data. We used a Cox proportional hazards model to calculate the crude and adjusted female to male (F:M) hazard ratio (HR) for HCV incidence using biological sex as the main exposure. Results: A total of 1868 PWID were observed over 3994 person-years of observation (PYO). Unadjusted F:M HR was 1.38 (95% confidence interval [CI], 1.15-1.65) and remained significant after adjusting for behavioral and demographic risk factors (1.39 [95% CI, 1.12-1.72]). Although syringe and equipment sharing were associated with the highest HCV incidence rate in women (41.62 and 36.83 PYO, respectively), we found no sex differences attributed to these risk factors. Conclusions: Our findings indicate that women who inject drugs may be at greater risk of HCV acquisition than men, independent of demographic characteristics and risk behaviors. Multiple factors, including biological (hormonal), social network, and differential access to prevention services, may contribute to increased HCV susceptibility in women who inject drugs.