Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

In its wake, the COVID-19 pandemic has ushered in a surge in the number of cases of mucormycosis. Most cases are temporally linked to COVID-19; hence, the entity is described as COVID-19-associated mucormycosis (CAM). The present systematic review was undertaken to provide an up-to-date summary of the hitherto available literature on CAM. PubMed, Scopus and Google Scholar databases were systematically searched using appropriate keywords till 14 May 2021, to identify case reports/case series pertaining to mucormycosis in patients with COVID-19. Relevant data extracted included demographic characteristics, comorbidity profile, clinical category of mucormycosis, glucocorticoid use, treatment offered and patient outcome. We identified 30 case reports/case series, pooling data retrieved from 99 patients with CAM. Most cases were reported from India (72%). The majority of the patients was male (78%) and had diabetes mellitus (85%). A prior history of COVID-19 was present in 37% patients with mucormycosis developing after an initial recovery. The median time interval between COVID-19 diagnosis and the first evidence of mucormycosis infection or CAM diagnosis was 15 days. Glucocorticoid use was reported in 85% of cases. Rhino-orbital mucormycosis was most common (42%), followed by rhino-orbito-cerebral mucormycosis (24%). Pulmonary mucormycosis was observed in 10 patients (10%). The mortality rate was 34%; the use of adjunct surgery, which was undertaken in 81% of patients, was associated with better clinical outcomes (p < .001). In conclusion, CAM is an emerging problem necessitating increased vigilance in COVID-19 patients, even those who have recovered. CAM portends a poor prognosis and warrants early diagnosis and treatment.

COVID-19-associated mucormycosis: An updated systematic review of literature.

COPD and the risk of poor outcomes in COVID-19: A systematic review and meta-analysis

This study applies an umbrella review approach to summarise the global evidence on the risk of severe COVID-19 outcomes in patients with pre-existing health conditions. Systematic reviews (SRs) were identified in PubMed, Embase/Medline and seven pre-print servers until December 11, 2020. Due to the absence of age-adjusted risk effects stratified by geographical regions, a re-analysis of the evidence was conducted. Primary studies were extracted from SRs and evaluated for inclusion in the re-analysis. Studies were included if they reported risk estimates (odds ratio (OR), hazard ratio (HR), relative risk (RR)) for hospitalisation, intensive care unit admission, intubation or death. Estimated associations were extracted from the primary studies for reported pre-existing conditions. Meta-analyses were performed stratified for each outcome by regions of the World Health Organization. The evidence certainty was assessed using GRADE. Registration number CRD42020215846. In total, 160 primary studies from 120 SRs contributed 464 estimates for 42 pre-existing conditions. Most studies were conducted in North America, European, and Western Pacific regions. Evidence from Africa, South/Latin America, and the Eastern Mediterranean region was scarce. No evidence was available from the South-East Asia region. Diabetes (HR range 1.2–2.0 (CI range 1.1–2.8)), obesity (OR range 1.5–1.75 (CI range 1.1–2.3)), heart failure (HR range 1.3–3.3 (CI range 0.9–8.2)), COPD (HR range 1.12–2.2 (CI range 1.1–3.2)) and dementia (HR range 1.4–7.7 (CI range 1.2–39.6)) were associated with fatal COVID-19 in different regions, although the estimates varied. Evidence from Europe and North America showed that liver cirrhosis (OR range 3.2–5.9 (CI range 0.9–27.7)) and active cancer (OR range 1.6–4.7 (CI range 0.5–14.9)) were also associated with increased risk of death. Association between HIV and undesirable COVID-19 outcomes showed regional heterogeneity, with an increased risk of death in Africa (HR 1.7 (CI 1.3–2.2)). GRADE certainty was moderate to high for most associations. Risk of undesirable COVID-19 health outcomes is consistently increased in certain patient subgroups across geographical regions, showing high variability in others. The results can be used to inform COVID-19 vaccine prioritisation or other intervention strategies.

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Pre-existing health conditions and severe COVID-19 outcomes: an umbrella review approach and meta-analysis of global evidence.

OBJECTIVE: Emerging data indicates an increased risk for cerebrovascular events with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and highlights the potential impact of coronavirus disease (COVID-19) on the management and outcomes of acute stroke We conducteda systematic review and meta-analysis to evaluate the aforementioned considerations METHODS: We performed a meta-analysis of observational cohort studies reporting on the occurrence and/or outcomes of patients with cerebrovascular events in association with their SARS-CoV-2 infection status We used a random-effects model Summary estimates were reported as odds ratios (ORs) and corresponding 95% confidence intervals (95%CI) RESULTS: We identified 18 cohort studies including 67,845 patients Among patients with SARS-CoV-2, 1 3% (95%CI:0 9-1 6%;I(2) =87%) were hospitalized for cerebrovascular events, 1 1% (95%CI:0 8-1 3%;I(2) =85%) for ischemic stroke, and 0 2% (95%CI:0 1-0 3%;I(2) =64%) for hemorrhagic stroke Compared to non-infected contemporary or historical controls, patients with SARS-CoV-2 infection had increased odds of ischemic stroke (OR=3 58,95%CI:1 43-8 92;I(2) =43%) and cryptogenic stroke (OR=3 98,95%CI:1 62-9 77;I(2) =0%) Diabetes mellitus was found to be more prevalent among SARS-CoV-2 stroke patients compared to non-infected contemporary or historical controls (OR=1 39, 95%CI:1 04-1 86;I(2) =0%) SARS-CoV-2 infection status was not associated with the likelihood of receiving intravenous thrombolysis (OR=1 42,95%CI:0 65-3 10;I(2) =0%) or endovascular thrombectomy (OR=0 78,95%CI:0 35-1 74;I(2) =0%) among hospitalized ischemic stroke patients during the COVID-19 pandemic Odds for in-hospital mortality were higher among SARS-CoV-2stroke patients compared to non-infected contemporary or historical stroke patients (OR=5 60,95%CI:3 19-9 80;I(2) =45%) INTERPRETATION: SARS-CoV-2 appears to be associated with an increased risk of ischemic stroke, and potentially cryptogenic stroke in particular It may also be related to an increased mortality risk This article is protected by copyright All rights reserved

The Impact of SARS-CoV-2 on Stroke Epidemiology and Care: A Meta-analysis

Background and aims To undertake a review and critical appraisal of published/preprint reports that offer methods of determining the effects of hypertension, diabetes, stroke, cancer, kidney issues, and high-cholesterol on COVID-19 disease severity Methods A search was conducted by two authors independently on the freely available COVID-19 Open Research Dataset (CORD-19) We developed an automated search engine to screen a total of 59,000 articles in a few seconds Filtering of the articles was then undertaken using keywords and questions, eg “Effects of diabetes on COVID/normal coronavirus/SARS-CoV-2/nCoV/COVID-19 disease severity, mortality?“ The search terms were repeated for all the comorbidities considered in this paper Additional articles were retrieved by searching via Google Scholar and PubMed Findings A total of 54 articles were considered for a full review It was observed that diabetes, hypertension, and cholesterol levels possess an apparent relation to COVID-19 severity Other comorbidities, such as cancer, kidney disease, and stroke, must be further evaluated to determine a strong relationship to the virus Conclusion Reports associating cancer, kidney disease, and stroke with COVID-19 should be carefully interpreted, not only because of the size of the samples, but also because patients could be old, have a history of smoking, or have any other clinical condition suggesting that these factors might be associated with the poor COVID-19 outcomes rather than the comorbidity itself Further research regarding this relationship and its clinical management is warranted

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Association of hypertension, diabetes, stroke, cancer, kidney disease, and high-cholesterol with COVID-19 disease severity and fatality: A systematic review.

The role of iron in the pathogenesis of COVID-19 and possible treatment with lactoferrin and other iron chelators.

Objective To undertake a review and critical appraisal of published/preprint reports that offer methods of determining the effects of hypertension, diabetes, stroke, cancer, kidney issues, and high-cholesterol on COVID-19 disease severity. Data sources Google Scholar, PubMed, COVID-19 Open Research Dataset: a resource of over 128,000 scholarly articles, including over 59,000 articles with full text related to COVID-19, SARS-CoV-2, and coronaviruses. Methods A search was conducted by two authors independently on the freely available COVID-19 Open Research Dataset (CORD-19). We developed an automated search engine to screen a total of 59,000 articles in a few seconds. The search engine was built using a retrieval function that ranks a set of documents based on the query terms appearing in each document regardless of their proximity within the document. Filtering of the articles was then undertaken using keywords and questions, e.g. “Effects of diabetes on COVID/normal coronavirus/SARS-CoV-2/nCoV/COVID-19 disease severity, mortality?”. The search terms were repeated for all the comorbidities considered in this paper. Additional articles were retrieved by searching via Google Scholar and PubMed. Findings A total of 54 articles were considered for a full review. It was observed that diabetes, hypertension, and cholesterol levels possess an apparent relation to COVID-19 severity. Other comorbidities, such as cancer, kidney disease, and stroke, must be further evaluated to determine a strong relationship to the virus. Reports associating cancer, kidney disease, and stroke with COVID-19 should be carefully interpreted, not only because of the size of the samples, but also because patients could be old, have a history of smoking, or have any other clinical condition suggesting that these factors might be associated with the poor COVID-19 outcomes rather than the comorbidity itself. Such reports could lead many oncologists and physicians to change their treatment strategies without solid evidence and recommendations. Further research regarding this relationship and its clinical management is warranted. Additionally, treatment options must be examined further to provide optimal treatment and ensure better outcomes for patients suffering from these comorbidities. It should be noted that, whether definitive measurements exist or not, the care of patients as well as the research involved should be largely prioritized to tackle this deadly pandemic.

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Association of hypertension, diabetes, stroke, cancer, kidney disease, and high-cholesterol with COVID-19 disease severity and fatality: a systematic review

Background: A novel form of coronavirus disease (SARS-CoV-2) has spread rapidly across the world. What risk factors influence the severity of the disease is of considerable importance.
Aim: This research offers a systematic review and meta-analysis of the correlation between common clinical conditions and comorbidities and the severity of COVID-19.
Methodology: Two independent researchers searched Europe PMC, Google Scholar, and PubMed databases for articles related to influence comorbidities have on the progress of the disease. A search engine was also created to screen a further 59,000 articles in COVID-19 Open Research Dataset (CORD-19). Random-effects modeling was used to pool 95% confidence intervals (CIs) and odds ratios (ORs). The significance of all comorbidities and clinical conditions to the severity of the disease was evaluated by employing machine-learning techniques. Publication bias was assessed by using funnel-plots and Egger9s test. Heterogeneity was tested using I2.
Results: The meta-analysis incorporated 12 studies spanning 4,101 confirmed COVID-19 patients who were admitted to Chinese hospitals. The prevalence of the most commonly associated co-morbidities and their corresponding odds ratio for disease severity were as follows: coronary heart disease (OR 2.97 [CI: 1.99-4.45], p < 0.0001), cancer (OR 2.65 [CI: 1.12-6.29], p < 0.03), cardiovascular disease (OR 2.89 [CI: 1.90-4.40], p < 0.0001), COPD (OR 3.24 [CI: 1.66-6.32], p = 0.0), and kidney disease (OR 2.2.4 [CI: 1.01-4.99], p = 0.05) with low or moderate level of heterogeneity. The most frequently exhibited clinical symptoms were fever (OR 1.37 [CI: 1.01-1.86], p = 0.04), myalgia/fatigue (OR 1.31 [CI: 1.11-1.55], p = 0.0018), and dyspnea (OR 3.61, [CI: 2.57-5.06], p = <0.0001). No significant associations between disease severity and liver disease, smoking habits, and other clinical conditions, such as a cough, respiratory/ARDS, diarrhea or chest tightness/pain were found. The meta-analysis also revealed that the incubation period was positively associated with disease severity. 
Conclusion: Existing comorbidities, including COPD, cardiovascular disease, and coronary heart disease, increase the severity of COVID-19. Some studies found a statistically significant association between comorbidities such as diabetes and hypertension and disease severity. However, these studies may be biased due to substantial heterogeneity.

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Sahar Ibrahim

Papers

Association of hypertension, diabetes, stroke, cancer, kidney disease, and high-cholesterol with COVID-19 disease severity and fatality: A systematic review.

The role of iron in the pathogenesis of COVID-19 and possible treatment with lactoferrin and other iron chelators.

Association of hypertension, diabetes, stroke, cancer, kidney disease, and high-cholesterol with COVID-19 disease severity and fatality: a systematic review

The influence of comorbidity on the severity of COVID-19 disease: A systematic review and analysis