Extrapulmonary manifestations and complications of severe acute respiratory syndrome coronavirus 2 infection: a systematic review

Introduction: We aimed to describe the extrapulmonary manifestations of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, including their frequency, onset with respect to respiratory symptoms, pathogenesis and association with disease severity. Methods: We searched the MEDLINE and Embase databases for SARS-CoV-2-related studies. Meta-analysis, observational studies, case series and case reports published in English or Chinese between 1 January and 1 May 2020 were included. Reports with only paediatric or obstetric cases were excluded. Results: 169 articles were included. Early manifestations (preceding respiratory symptoms until Day 6 of onset) included olfactory and gustatory disturbance (self-reported in up to 68% and 85% of cases, respectively), gastrointestinal symptoms (up to 65.9%) and rash (up to 20.4%). From Day 7 onwards, hypercytokinaemia, paralleled multi-organ complications including acute cardiac injury (pooled incidence of 17.7% in 1,412 patients, mostly with severe disease and 17.4% mortality), kidney and liver injury (up to 17% and 33%, respectively) and thrombocytopenia (up to 30%). Hypercoagulability resulted in venous thromboembolic events in up to 31% of all patients. Uncommon disease presentation and complications comprised Guillain-Barré syndrome, rhabdomyolysis, otitis media, meningoencephalitis and spontaneous pneumomediastinum. Conclusion: Although the systemic manifestations of SARS-CoV-2 infection are variegated, they are deeply interwoven by shared mechanisms. Two phases of extrapulmonary disease were identified: (a) an early phase with possible gastrointestinal, ocular and cutaneous involvement and (b) a late phase characterised by multiorgan dysfunction and clinical deterioration. A clear, multidisciplinary consensus to define and approach thromboinflammation and cytokine release syndrome in SARS-CoV-2 is needed.

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Systematic review and patient-level meta-analysis of SARS-CoV-2 viral dynamics to model response to antiviral therapies

10.1101/2020.08.20.20178699 ◽

2020 ◽

Author(s):

Silke Gastine ◽

Juanita Pang ◽

Florencia A.T. Boshier ◽

Simon J Carter ◽

Dagan O. Lonsdale ◽

...

Keyword(s):

Systematic Review ◽

Viral Load ◽

Case Reports ◽

Meta Analysis ◽

Severe Disease ◽

Case Series ◽

Viral Clearance ◽

Viral Dynamics ◽

Viral Loads ◽

Patient Level

Background: SARS-CoV-2 viral loads change rapidly following symptom onset so to assess antivirals it is important to understand the natural history and patient factors influencing this. We undertook an individual patient-level meta-analysis of SARS-CoV-2 viral dynamics in humans to describe viral dynamics and estimate the effects of antivirals used to-date. Methods: This systematic review identified case reports, case series and clinical trial data from publications between 1/1/2020 and 31/5/2020 following PRISMA guidelines. A multivariable Cox proportional hazards regression model (Cox-PH) of time to viral clearance was fitted to respiratory and stool samples. A simplified four parameter nonlinear mixed-effects (NLME) model was fitted to viral load trajectories in all sampling sites and covariate modelling of respiratory viral dynamics was performed to quantify time dependent drug effects. Findings: Patient-level data from 645 individuals (age 1 month-100 years) with 6316 viral loads were extracted. Model-based simulations of viral load trajectories in samples from the upper and lower respiratory tract, stool, blood, urine, ocular secretions and breast milk were generated. Cox-PH modelling showed longer time to viral clearance in older patients, males and those with more severe disease. Remdesivir was associated with faster viral clearance (adjusted hazard ratio (AHR) = 9.19, p<0.001), as well as interferon, particularly when combined with ribavirin (AHR = 2.2, p=0.015; AHR = 6.04, p = 0.006). Interpretation: Combination therapy including interferons should be further investigated. A NLME model for designing and analysing viral pharmacodynamics in trials has been established.

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Gastrointestinal manifestations of COVID-19 in children: a systematic review and meta-analysis

Frontline Gastroenterology ◽

10.1136/flgastro-2020-101529 ◽

2020 ◽

pp. flgastro-2020-101529 ◽

Cited By ~ 1

Author(s):

Anthony K Akobeng ◽

Ciaran Grafton-Clarke ◽

Ibtihal Abdelgadir ◽

Erica Twum-Barimah ◽

Morris Gordon

Keyword(s):

Systematic Review ◽

English Language ◽

Case Reports ◽

Meta Analysis ◽

Gastrointestinal Symptoms ◽

Case Series ◽

Risk Of Bias ◽

Gastrointestinal Manifestations ◽

Published Evidence ◽

Pooled Prevalence

ObjectivesTo summarise the published evidence on the gastrointestinal manifestations of COVID-19 in children and to determine the prevalence of gastrointestinal symptoms.MethodsIn this systematic review and meta-analysis, we searched PubMed, Embase, CINAHL and the WHO’s database of publications on novel coronavirus. We included English language studies that had described original demographic and clinical characteristics of children diagnosed with COVID-19 and reported on the presence or absence of gastrointestinal symptoms. Meta-analysis was conducted using the random-effects model. The pooled prevalence of gastrointestinal symptoms was expressed as proportion and 95% CI.ResultsThe search identified 269 citations. Thirteen studies (nine case series and four case reports) comprising data for 284 patients were included. Overall, we rated four studies as having a low risk of bias, eight studies as moderate and one study as high risk of bias. In a meta-analysis of nine studies, comprising 280 patients, the pooled prevalence of all gastrointestinal symptoms was 22.8% (95% CI 13.1% to 35.2%; I2=54%). Diarrhoea was the most commonly reported gastrointestinal symptom followed by vomiting and abdominal pain.ConclusionsNearly a quarter of children with COVID-19 have gastrointestinal symptoms. It is important for clinicians to be aware of the gastrointestinal manifestation of COVID-19.PROSPERO registration numberCRD42020177569.

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Clinical Case Series of Gastrointestinal Symptoms in Patients With Novel Coronavirus 2019 Infection

Pharmaceutical and Biomedical Research ◽

10.18502/pbr.v7i2.7366 ◽

2021 ◽

Author(s):

Hamideh Abbaspour Kasgari ◽

Amir Mohammad Shabani ◽

Hafez Fakheri ◽

Parnian Mohammadzadeh

Keyword(s):

Respiratory Symptoms ◽

Acute Phase Proteins ◽

Severe Disease ◽

Gastrointestinal Symptoms ◽

Case Series ◽

Stable Condition ◽

Signs And Symptoms ◽

Case Series Study ◽

Gi Symptoms ◽

Loss Of Appetite

Background: Various digestive symptoms have been frequently reported in a significant portion of patients infected with the virus since the outbreak of Coronavirus Disease 2019 (COVID-19). Most patients with COVID-19 have a fever accompanied by respiratory signs and symptoms, such as cough and dyspnea. We present 36 cases with a chief complaint of Gastrointestinal (GI) symptoms along with respiratory symptoms. In this study, we aimed at investigating the prevalence and outcomes of COVID-19 patients with digestive symptoms. Methods: A variety of observed GI symptoms included nausea and vomiting (72.2%), diarrhea (25%), abdominal pain (19.4%), loss of appetite (14%), and anosmia (14%). The most nonGI symptoms were dyspnea (66.7%), fever (66.7%), dry cough (58.3%), myalgia (52.4%), and others. Six patients (16.6%) were critically ill, 7 (19.4%) were in stable condition, and 23 patients (64%) showed moderate symptoms. Among the patients, 7 (19.5%) needed critical care and were admitted to ICU. Leucopenia, lymphopenia, and elevated acute-phase proteins were other features observed in these patients. The most common antiviral regimen was hydroxychloroquine and oseltamivir. Finally, 32 patients (89%) were discharged, and 4 (11%) died. Conclusion: This case series study highlights that patients with COVID-19 are prone to GI symptoms along with fever and respiratory symptoms. Patients may even present with digestive symptoms and without any respiratory symptoms. Hence, clinicians should pay more attention to these patients and help diagnose COVID-19 earlier to start prompt treatment before the occurrence of severe disease.

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Urinary viral shedding of COVID-19 and its clinical associations: A Systematic Review and Meta-analysis of Observational Studies

10.1101/2020.05.15.20094920 ◽

2020 ◽

Cited By ~ 1

Author(s):

Amir H Kashi ◽

Jean de la Rosette ◽

Erfan Amini ◽

Hamidreza Abdi ◽

Morteza Fallah-karkan ◽

...

Keyword(s):

Systematic Review ◽

Sample Size ◽

Case Reports ◽

Meta Analysis ◽

Severe Disease ◽

Disease Onset ◽

Case Series ◽

Adult Patients ◽

Mild Disease ◽

Viral Shedding

Objectives: To review the current literature on the presence of COVID-19 virus in the urine of infected patients and to explore the clinical features that can predict the presence of COVID-19 in urine. Materials and Methods: A systematic review of published literature between 30th December 2019 and 21st June 2020 was conducted on Pubmed, Google Scholar, Ovid, Scopus, and ISI web of science. Studies investigating urinary viral shedding of COVID-19 in infected patients were included. Two reviewers selected relative studies and performed quality assessment of individual studies. Meta-analysis was performed on the pooled case reports and cohort with a sample size of >= 9. Results: Thirty-nine studies were finally included in the systematic review; 12 case reports, 26 case series, and one cohort study. Urinary samples from 533 patients were investigated. Fourteen studies reported the presence of COVID19 in the urinary samples from 24 patients. The crude overall rate of COVID-19 detection in urinary samples was 4.5%. Considering case series and cohorts with a sample size of >= 9, the estimated viral shedding frequency was 1.18 % (CI 95%: 0.14 - 2.87) in the metaanalysis. In adult patients, urinary shedding of COVID-19 was commonly detected in patients with moderate to severe disease (16 adult patients with moderate or severe disease versus two adult patients with mild disease). In children, urinary viral shedding of COVID-19 was reported in 4 children who all suffered from mild disease. Urinary viral shedding of COVID-19 was detected from day 1 to day 52 after disease onset. The pathogenicity of virus isolated from urine has been demonstrated in cell culture media in one study while another study failed to reveal replication of isolated viral RNA in cell cultures. Urinary symptoms were not attributed to urinary viral shedding. Conclusions: While COVID-19 is rarely detected in urine of infected individuals, infection transmission through urine still remains possible. In adult patients, infected urine is more likely in the presence of moderate or severe disease. Therefore, caution should be exerted when dealing with COVID-19 infected patients during medical interventions like endoscopy and urethral catheterization.

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The Natural History of Severe Acute Respiratory Syndrome Coronavirus 2–Related Multisystem Inflammatory Syndrome in Children: A Systematic Review

Journal of the Pediatric Infectious Diseases Society ◽

10.1093/jpids/piaa112 ◽

2020 ◽

Cited By ~ 3

Author(s):

Stephen C Aronoff ◽

Ashleigh Hall ◽

Michael T Del Vecchio

Keyword(s):

Systematic Review ◽

Natural History ◽

Severe Acute Respiratory Syndrome ◽

Myocardial Dysfunction ◽

Case Reports ◽

Clinical Manifestations ◽

Gastrointestinal Symptoms ◽

Case Series ◽

History Of ◽

Inflammatory Syndrome

Abstract Background The clinical manifestations and natural history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–related multisystem inflammatory syndrome in children (MIS-C) are poorly defined. Using a systematic review of individual cases and case series and collating elements of the clinical course, the objective of this study was to provide a detailed clinical description and natural history of MIS-C. Methods Case reports and series of MIS-C were recovered from repeated MEDLINE searches, a single EMBASE search, and table of contents reviews of major general medicine and pediatric journals performed between June 3 and July 23, 2020. Fever, evidence of inflammation, and evidence of organ dysfunction were required for inclusion. Results MEDLINE and EMBASE searches produced 129 articles, and 10 articles were identified from journal contents or article bibliographies; 16 reports describing 505 children with MIS-C comprise this review. Thirty-two children (14.7%) had negative results for SARS-CoV-2 by nucleic acid and/or antibody testing. The weighted median age was 9 years (6 months to 20 years). Clinical findings included fever (100%), gastrointestinal symptoms (88.0%), rash (59.2%), conjunctivitis (50.0%), cheilitis/ “strawberry tongue” (55.7%), or extremity edema/erythema (47.5%). Median serum C-reactive protein, ferritin, fibrinogen, and D-dimer concentrations were above the normal range. Intravenous gammaglobulin (78.1%) and methylprednisolone/prednisone (57.6%) were the most common therapeutic interventions; immunomodulation was used in 24.3% of cases. Myocardial dysfunction requiring ionotropic support (57.4%) plus extracorporeal membrane oxygenation (5.3%), respiratory distress requiring mechanical ventilation (26.1%), and acute kidney injury (11.9%) were the major complications; anticoagulation was used commonly (54.4%), but thrombotic events occurred rarely (3.5%). Seven (1.4%) children died. Conclusions MIS-C following SARS-CoV-2 infection frequently presents with gastrointestinal complaints and/or rash; conjunctivitis, cheilitis, and/or extremity changes also occur frequently. Serious complications occur frequently and respond to aggressive supportive therapy.

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COVID-19 and Tuberculosis Coinfection: An Overview of Case Reports/Case Series and Meta-Analysis

Frontiers in Medicine ◽

10.3389/fmed.2021.657006 ◽

2021 ◽

Vol 8 ◽

Author(s):

Wan-mei Song ◽

Jing-yu Zhao ◽

Qian-yun Zhang ◽

Si-qi Liu ◽

Xue-han Zhu ◽

...

Keyword(s):

Clinical Characteristics ◽

Case Reports ◽

Meta Analysis ◽

Severe Disease ◽

Case Series ◽

Level Of Evidence ◽

Significant Public Health ◽

Bilateral Lesions ◽

Worse Prognosis

Background: Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are two major infectious diseases posing significant public health threats, and their coinfection (aptly abbreviated COVID-TB) makes the situation worse. This study aimed to investigate the clinical features and prognosis of COVID-TB cases.Methods: The PubMed, Embase, Cochrane, CNKI, and Wanfang databases were searched for relevant studies published through December 18, 2020. An overview of COVID-TB case reports/case series was prepared that described their clinical characteristics and differences between survivors and deceased patients. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) for death or severe COVID-19 were calculated. The quality of outcomes was assessed using GRADEpro.Results: Thirty-six studies were included. Of 89 COVID-TB patients, 19 (23.46%) died, and 72 (80.90%) were male. The median age of non-survivors (53.95 ± 19.78 years) was greater than that of survivors (37.76 ± 15.54 years) (p < 0.001). Non-survivors were more likely to have hypertension (47.06 vs. 17.95%) or symptoms of dyspnea (72.73% vs. 30%) or bilateral lesions (73.68 vs. 47.14%), infiltrates (57.89 vs. 24.29%), tree in bud (10.53% vs. 0%), or a higher leucocyte count (12.9 [10.5–16.73] vs. 8.015 [4.8–8.97] × 109/L) than survivors (p < 0.05). In terms of treatment, 88.52% received anti-TB therapy, 50.82% received antibiotics, 22.95% received antiviral therapy, 26.23% received hydroxychloroquine, and 11.48% received corticosteroids. The pooled ORs of death or severe disease in the COVID-TB group and the non-TB group were 2.21 (95% CI: 1.80, 2.70) and 2.77 (95% CI: 1.33, 5.74) (P < 0.01), respectively.Conclusion: In summary, there appear to be some predictors of worse prognosis among COVID-TB cases. A moderate level of evidence suggests that COVID-TB patients are more likely to suffer severe disease or death than COVID-19 patients. Finally, routine screening for TB may be recommended among suspected or confirmed cases of COVID-19 in countries with high TB burden.

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Thrombosis in Cancer Patients Treated with Hematopoietic Growth Factors - A Meta-Analysis

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650276 ◽

1996 ◽

Vol 75 (02) ◽

pp. 368-371 ◽

Cited By ~ 51

Author(s):

T Barbul ◽

G Finazzi ◽

A Grassi ◽

R Marchioli

Keyword(s):

Cancer Patients ◽

Case Reports ◽

Meta Analysis ◽

Case Series ◽

Hematopoietic Growth Factors ◽

Patients With Cancer ◽

Cytotoxic Treatment ◽

Pertinent Data ◽

Thrombotic Complications ◽

Vascular Occlusions

SummaryHematopoietic colony-stimulating factors (CSFs) are largely used in patients with cancer undergoing cytotoxic treatment to accelerate neutrophil recovery and decrease the incidence of febrile neutropenia. Clinical practice guidelines for their use have been recently established (1), taking into account clinical benefit, but also cost and toxicity. Vascular occlusions have been recently reported among the severe reactions associated with the use of CSFs, in anedoctal case reports (2, 3), consecutive case series (4) and randomized clinical trial (5, 6). However, the role of CSFs in the pathogenesis of thrombotic complications is difficult to ascertain, because pertinent data are scanty and widely distributed over a number of heterogenous investigations. We report here a systematic review of relevant articles, with the aims to estimate the prevalence of thrombosis associated with the use of CSFs and to assess if this rate is significantly higher than that observed in cancer patients not receiving CSFs.

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Mechanical thrombectomy in pediatric stroke: systematic review, individual patient data meta-analysis, and case series

Journal of Neurosurgery Pediatrics ◽

10.3171/2019.5.peds19126 ◽

2019 ◽

Vol 24 (5) ◽

pp. 558-571 ◽

Cited By ~ 3

Author(s):

Kartik Bhatia ◽

Hans Kortman ◽

Christopher Blair ◽

Geoffrey Parker ◽

David Brunacci ◽

...

Keyword(s):

Systematic Review ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Mechanical Thrombectomy ◽

Case Reports ◽

Meta Analysis ◽

Case Series ◽

Neurological Outcomes

OBJECTIVEThe role of mechanical thrombectomy in pediatric acute ischemic stroke is uncertain, despite extensive evidence of benefit in adults. The existing literature consists of several recent small single-arm cohort studies, as well as multiple prior small case series and case reports. Published reports of pediatric cases have increased markedly since 2015, after the publication of the positive trials in adults. The recent AHA/ASA Scientific Statement on this issue was informed predominantly by pre-2015 case reports and identified several knowledge gaps, including how young a child may undergo thrombectomy. A repeat systematic review and meta-analysis is warranted to help guide therapeutic decisions and address gaps in knowledge.METHODSUsing PRISMA-IPD guidelines, the authors performed a systematic review of the literature from 1999 to April 2019 and individual patient data meta-analysis, with 2 independent reviewers. An additional series of 3 cases in adolescent males from one of the authors’ centers was also included. The primary outcomes were the rate of good long-term (mRS score 0–2 at final follow-up) and short-term (reduction in NIHSS score by ≥ 8 points or NIHSS score 0–1 at up to 24 hours post-thrombectomy) neurological outcomes following mechanical thrombectomy for acute ischemic stroke in patients < 18 years of age. The secondary outcome was the rate of successful angiographic recanalization (mTICI score 2b/3).RESULTSThe authors’ review yielded 113 cases of mechanical thrombectomy in 110 pediatric patients. Although complete follow-up data are not available for all patients, 87 of 96 (90.6%) had good long-term neurological outcomes (mRS score 0–2), 55 of 79 (69.6%) had good short-term neurological outcomes, and 86 of 98 (87.8%) had successful angiographic recanalization (mTICI score 2b/3). Death occurred in 2 patients and symptomatic intracranial hemorrhage in 1 patient. Sixteen published thrombectomy cases were identified in children < 5 years of age.CONCLUSIONSMechanical thrombectomy may be considered for acute ischemic stroke due to large vessel occlusion (ICA terminus, M1, basilar artery) in patients aged 1–18 years (Level C evidence; Class IIb recommendation). The existing evidence base is likely affected by selection and publication bias. A prospective multinational registry is recommended as the next investigative step.

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Neurological symptoms, manifestations, and complications associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 19 (COVID-19)

Journal of Neurology ◽

10.1007/s00415-021-10406-y ◽

2021 ◽

Author(s):

Biyan Nathanael Harapan ◽

Hyeon Joo Yoo

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Case Reports ◽

Case Series ◽

Altered Mental Status ◽

Neurological Complications ◽

Neurological Symptoms ◽

Neurological Manifestations ◽

Fisher Syndrome ◽

Novel Coronavirus ◽

The Impact

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, is responsible for the outbreak of coronavirus disease 19 (COVID-19) and was first identified in Wuhan, China in December 2019. It is evident that the COVID-19 pandemic has become a challenging world issue. Although most COVID-19 patients primarily develop respiratory symptoms, an increasing number of neurological symptoms and manifestations associated with COVID-19 have been observed. In this narrative review, we elaborate on proposed neurotropic mechanisms and various neurological symptoms, manifestations, and complications of COVID-19 reported in the present literature. For this purpose, a review of all current published literature (studies, case reports, case series, reviews, editorials, and other articles) was conducted and neurological sequelae of COVID-19 were summarized. Essential and common neurological symptoms including gustatory and olfactory dysfunctions, myalgia, headache, altered mental status, confusion, delirium, and dizziness are presented separately in sections. Moreover, neurological manifestations and complications that are of great concern such as stroke, cerebral (sinus) venous thrombosis, seizures, meningoencephalitis, Guillain–Barré syndrome, Miller Fisher syndrome, acute myelitis, and posterior reversible encephalopathy syndrome (PRES) are also addressed systematically. Future studies that examine the impact of neurological symptoms and manifestations on the course of the disease are needed to further clarify and assess the link between neurological complications and the clinical outcome of patients with COVID-19. To limit long-term consequences, it is crucial that healthcare professionals can early detect possible neurological symptoms and are well versed in the increasingly common neurological manifestations and complications of COVID-19.

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Risk of colectomy after conservative treatment of diverticulitis of the left hemicolon complicated by abdominal or pelvic abscess: protocol of a systematic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2020-042350 ◽

2020 ◽

Vol 10 (12) ◽

pp. e042350

Author(s):

Maximilian Sohn ◽

Ayman Agha ◽

Igors Iesalnieks ◽

Anna Tiefes ◽

Alfred Hochrein ◽

...

Keyword(s):

Systematic Review ◽

Emergency Surgery ◽

Case Reports ◽

Acute Diverticulitis ◽

Meta Analysis ◽

Case Series ◽

Pelvic Abscess ◽

Risk Of Bias ◽

Cochrane Central Register ◽

Review Manager

IntroductionAcute diverticulitis of the sigmoid colon is increasingly treated by a non-operative approach. The need for colectomy after recovery from a flare of acute diverticulitis of the left colon, complicated diverticular abscess is still controversial. The primary aim of this study is to assess the risk of interval emergency surgery by systematic review and meta-analysis.Methods and analysisThe systematic review and meta-analysis will be conducted in accordance to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols statement. PubMed/MEDLINE, Cochrane Central Register of Controlled Trials and EMBASE will be screened for the predefined searching term: (Diverticulitis OR Diverticulum) AND (Abscess OR pelvic abscess OR pericolic abscess OR intraabdominal abscess) AND (surgery OR operation OR sigmoidectomy OR drainage OR percutaneous drainage OR conservative therapy OR watchful waiting). All studies published in an English or German-speaking peer-reviewed journal will be suitable for this analysis. Case reports, case series of less than five patients, studies without follow-up information, systematic and non-systematic reviews and meta-analyses will be excluded. Primary endpoint is the rate of interval emergency surgery. Using the Review Manager Software (Review Manager/RevMan, V.5.3, Copenhagen, The Nordic Cochrane Centre, The Cochrane Collaboration, 2012) meta-analysis will be pooled using the Mantel-Haenszel method for random effects. The Risk of Bias in Non-randomized Studies of Interventions tool will be used to assess methodological quality of non-randomised studies. Risk of bias in randomised studies will be assessed using the Cochrane developed RoB 2-tool.Ethics and disseminationAs no new data are being collected, ethical approval is exempt for this study. This systematic review is to provide a new insight on the need for surgical treatment after a first attack of acute diverticulitis, complicated by intra-abdominal or pelvic abscesses. The results of this study will be presented at national and international meetings and published in a peer-reviewed journal.PROSPERO registration numberCRD42020164813.

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