Hypocalcemia is associated with severe COVID-19: A systematic review and meta-analysis

Background and aimsHypocalcemia is commonly in critically ill patients and studies have shown that hypocalcemia is prevalent in patients with COVID-19. This meta-analysis aimed to evaluate the prognostic performance of hypocalcemia in patients with coronavirus disease 2019 (COVID-19).MethodsWe performed a systematic literature search on PubMed, Scopus, and Embase with keywords “SARS-CoV-2″ OR″COVID-19″ OR ″2019-nCoV” AND “hypocalcemia” up until 10 December 2020. The key exposure was hypocalcemia, defined as serum calcium below study-defined cut-off points. The main outcome was poor outcome, which was a composite of mortality and severity. The effect estimate of the main outcome was reported as odds ratio (OR) and its 95% confidence interval (95% CI). We also generate sensitivity, specificity, positive and negative likelihood ratio (PLR & NLR), diagnostic odds ratio (DOR), and area under curve (AUC).ResultsThere are 2032 patients from 7 studies included in this systematic review and meta-analysis. The incidence of poor outcome in this study was 26%. Serum calcium was lower in patients with poor outcome (mean difference ?0.173 mmol/L [-0.259, ?0.087], p < 0.001; I²: 31.3%). Hypocalcemia was associated with poor outcome (OR 3.19 [2.02, 5.06], p < 0.001; I²: 32.86%); with sensitivity of 0.74 [0.53, 0.88], specificity of 0.54 [0.29, 0.77], PLR of 1.6 [1.1, 2.3], NLR of 0.49 [0.35, 0.66], DOR of 3 [2, 5], and AUC of 0.70 [0.66, 0.74]. In this pooled analysis, the post-test probability was 36% in patients with hypocalcemia and 15% in patients without hypocalcemia.ConclusionHypocalcemia was associated with poor outcome in COVID-19 patients.PROSPERO ID: CRD42020225506.     

Clinical symptoms,comorbidities and complications in severe and non-severe patients with COVID-19: A systematic review and meta-analysis without cases duplication

Background:The pandemic of COVID-19 poses a challenge to global healthcare. The mortality rates of severe cases range from 8.1% to 38%, and it is particularly important to identify risk factors that aggravate the disease.Methods:We performed a systematic review of the literature with meta-analysis, using 7 databases to identify studies reporting on clinical characteristics, comorbidities and complications in severe and non-severe patients with COVID-19. All the observational studies were included. We performed a random or fixed effects model meta-analysis to calculate the pooled proportion and 95% confidence interval (CI). Measure of heterogeneity was estimated by Cochran''s Q statistic, I² index and P value.Results:A total of 4881 cases from 25 studies related to COVID-19 were included. The most prevalent comorbidity was hypertension (severe: 33.4%, 95% CI: 25.4%–41.4%; non-severe 21.6%, 95% CI: 9.9%–33.3%), followed by diabetes (severe: 14.4%, 95% CI: 11.5%–17.3%; non-severe: 8.5%, 95% CI: 6.1%–11.0%). The prevalence of acute respiratory distress syndrome, acute kidney injury and shock were all higher in severe cases, with 41.1% (95% CI: 14.1%–68.2%), 16.4% (95% CI: 3.4%–29.5%) and 19.9% (95% CI: 5.5%–34.4%), rather than 3.0% (95% CI: 0.6%–5.5%), 2.2% (95% CI: 0.1%–4.2%) and 4.1% (95% CI: −4.8%–13.1%) in non-severe patients, respectively. The death rate was higher in severe cases (30.3%, 95% CI: 13.8%–46.8%) than non-severe cases (1.5%, 95% CI: 0.1%–2.8%).Conclusion:Hypertension, diabetes and cardiovascular diseases may be risk factors for severe COVID-19.     

Prevalence of post-COVID-19 symptoms in hospitalized and non-hospitalized COVID-19 survivors: A systematic review and meta-analysis

BackgroundSingle studies support the presence of several post-COVID-19 symptoms; however, no meta-analysis differentiating hospitalized and non-hospitalized patients has been published to date. This meta-analysis analyses the prevalence of post-COVID-19 symptoms in hospitalized and non-hospitalized patients recovered from COVID-19. MethodsMEDLINE, CINAHL, PubMed, EMBASE, and Web of Science databases, as well as medRxiv and bioRxiv preprint servers were searched up to March 15, 2021. Peer-reviewed studies or preprints reporting data on post-COVID-19 symptoms collected by personal, telephonic or electronic interview were included. Methodological quality of the studies was assessed using the Newcastle-Ottawa Scale. We used a random-effects models for meta-analytical pooled prevalence of each post-COVID-19 symptom, and I² statistics for heterogeneity. Data synthesis was categorized at 30, 60, and ≥90 days after. ResultsFrom 15,577 studies identified, 29 peer-reviewed studies and 4 preprints met inclusion criteria. The sample included 15,244 hospitalized and 9011 non-hospitalized patients. The methodological quality of most studies was fair. The results showed that 63.2, 71.9 and 45.9% of the sample exhibited ≥one post-COVID-19 symptom at 30, 60, or ≥90days after onset/hospitalization. Fatigue and dyspnea were the most prevalent symptoms with a pooled prevalence ranging from 35 to 60% depending on the follow-up. Other post-COVID-19 symptoms included cough (20–25%), anosmia (10–20%), ageusia (15–20%) or joint pain (15–20%). Time trend analysis revealed a decreased prevalence 30days after with an increase after 60days. ConclusionThis meta-analysis shows that post-COVID-19 symptoms are present in more than 60% of patients infected by SARS-CoV‑2. Fatigue and dyspnea were the most prevalent post-COVID-19 symptoms, particularly 60 and ≥90 days after.     

Comorbidities’ potential impacts on severe and non-severe patients with COVID-19: A systematic review and meta-analysis

Background:An ongoing outbreak of pneumonia associated with the severe acute respiratory coronavirus (SARS-CoV-2) emerged in December 2019 in Wuhan, China. Epidemiologic evidence suggests that patients with comorbidities and novel coronavirus disease 2019 (COVID-19) infection may have poor survival outcomes. However, the risk of these coexisting medical conditions in severe and non-severe cases has not been systematically reported.Purpose:The present study aimed to estimate the association of chronic comorbidities in severe and non-severe cases.Methods:A literature search was conducted using the databases PubMed, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang Database, Chinese Scientific Journals Full-text Database (CQVIP) from the inception dates to April 1, 2020, to identify cohort studies assessing comorbidity and risk of adverse outcome. Either a fixed- or random-effects model was used to calculate the overall combined risk estimates.Results:A total of 22 studies involving 3286 patients with laboratory-confirmed COVID-19 were included in the analysis. Overall, compared with the patients with non-severe cases, the pooled odds ratios (ORs) of hypertension, diabetes mellitus, and cardiovascular, cerebrovascular, and respiratory diseases in patients with severe cases were 2.79 (95% confidence intervals [95% CI]: 1.66–4.69), 1.64 (95% CI: 2.30–1.08), 1.79 (95% CI: 1.08–2.96), 3.92 (95% CI: 2.45–6.28), and 1.98 (95% CI: 1.26–3.12), respectively.Conclusions:This meta-analysis supports the finding that chronic comorbidities may contribute to severe outcome in patients with COVID-19. According to the findings of the present study, old age and 2 or more comorbidities are significantly impactful to COVID-19 outcomes in hospitalized patients in China.     

Clinical symptoms of COVID-19 pneumonia in children: A protocol for systematic review and meta-analysis

Background:This meta-analysis aimed to compare the clinical symptoms of COVID-19 pneumonia in children.Methods and analysis:Electronic databases including PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI) database, Wanfang Database, and Chinese Biomedical Literature Database (CBM) were searched from its inception to June 21, 2020. We only included studies that reported clinical symptoms of COVID pneumonia in children. Quality of the included studies was assessed by 2 authors. Pooled results were summarized by STATA 12.0 software.The heterogeneity was measured by I² tests (I² < 50 indicates little heterogeneity, I²≥50 indicates high heterogeneity). Publication bias was performed by funnel plot and statistically assessed by Begg test (P > .05 as no publication bias).Results:Results will be shown as figures or tables.Conclusion:Our study aims to systematically present the clinical symptoms of COVID-19 pneumonia patients in children, so as to further provide guidance for clinical management.     

The Effect of Metformin Consumption on Mortality in Hospitalized COVID-19 patients: a systematic review and meta-analysis

Background and aimsDiabetes is one of the most common comorbidities, and it is associated with poorer outcomes in patients with coronavirus disease 2019 (COVID-19). Preliminary findings showed that mortality was reduced in those who consume metformin compared to those who did not, and given its low cost and widespread availability; metformin is an attractive and potential agent to mitigate excessive risk in diabetic populations.MethodsSeveral medical databases (Pubmed, EuropePMC, EBSCOhost, Proquest, Cochrane library) and two health-science preprint servers (preprint.org and Medrxiv) were systematically searched for relevant literature.ResultsNine studies with 10,233 subjects were included in the qualitative and quantitative synthesis. Meta-analysis showed that metformin is associated with lower mortality in pooled non-adjusted model (OR 0.45 [0.25, 0.81], p = 0.008; I^2: 63.9%, p = 0.026) and pooled adjusted model (OR 0.64 [0.43, 0.97], p = 0.035; I²: 52.1%, p = 0.064).ConclusionThe analysis showed that metformin consumption was associated with lower mortality. Randomized controlled trials are needed to confirm this finding.     

Pathophysiological mechanisms underlying gastrointestinal symptoms in patients with COVID-19

Gastrointestinal (GI) symptoms, such as diarrhea, abdominal pain, vomiting, and anorexia, are frequently observed in patients with coronavirus disease 2019 (COVID-19). However, the pathophysiological mechanisms connecting these GI symptoms to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections remain elusive. Previous studies indicate that the entry of SARS-CoV-2 into intestinal cells leads to downregulation of angiotensin converting enzyme 2 (ACE2) receptors resulting in impaired barrier function. While intestinal ACE2 functions as a chaperone for the amino acid transporter B0AT1, the B0AT1/ACE2 complex within the intestinal epithelium acts as a regulator of gut microbiota composition and function. Alternations to the B0AT1/ACE2 complex lead to microbial dysbiosis through increased local and systemic immune responses. Previous studies have also suggested that altered serotonin metabolism may be the underlying cause of GI disorders involving diarrhea. The findings of elevated plasma serotonin levels and high fecal calprotectin in COVID-19 patients with diarrhea indicate that the viral infection evokes a systemic inflammatory response that specifically involves the GI. Interestingly, the elevated proinflammatory cytokines correlate with elevated serotonin and fecal calprotectin levels further supporting the evidence of GI inflammation, a hallmark of functional GI disorders. Moreover, the finding that rectal swabs of COVID-19 patients remain positive for SARS-CoV-2 even after the nasopharynx clears the virus, suggests that viral replication and shedding from the GI tract may be more robust than that of the respiratory tract, further indicating fecal-oral transmission as another important route of viral spread. This review summarized the evidence for pathophysiological mechanisms (impaired barrier function, gut inflammation, altered serotonin metabolism and gut microbiota dysbiosis) underlying the GI symptoms in patients with COVID-19.     

Prevalence and clinical outcomes of cardiac injury in patients with COVID-19: A systematic review and meta-analysis

Background and aimsEmerging data have linked the presence of cardiac injury with a worse prognosis in novel coronavirus disease 2019 (COVID-19) patients. However, available data cannot clearly characterize the correlation between cardiac injury and COVID-19. Thus, we conducted a meta-analysis of recent studies to 1) explore the prevalence of cardiac injury in different types of COVID-19 patients and 2) evaluate the association between cardiac injury and worse prognosis (severe disease, admission to ICU, and mortality) in patients with COVID-19.Methods and resultsLiterature search was conducted through PubMed, the Cochrane Library, Embase, and MedRxiv databases. A meta-analysis was performed with Stata 14.0. A fixed-effects model was used if the I² values ≤ 50%, otherwise the random-effects model was performed. The prevalence of cardiac injury was 19% (95% CI: 0.15–0.22, and p < 0.001) in total COVID-19 patients, 36% (95% CI: 0.25–0.47, and p < 0.001) in severe COVID-19 patients, and 48% (95% CI: 0.30–0.66, and p < 0.001) in non-survivors. Furthermore, cardiac injury was found to be associated with a significant increase in the risk of poor outcomes with a pooled effect size (ES) of 8.46 (95% CI: 3.76–19.06, and p = 0.062), severe disease with an ES of 3.54 (95% CI: 2.25–5.58, and p < 0.001), admission to ICU with an ES of 5.03 (95% CI: 2.69–9.39, and p < 0.001), and mortality with an ES of 4.99 (95% CI: 3.38–7.37, and p < 0.001).ConclusionsThe prevalence of cardiac injury was greatly increased in COVID-19 patients, particularly in patients with severe disease and non-survivors. COVID-19 patients with cardiac injury are more likely to be associated with poor outcomes, severity of disease, admission to ICU, and mortality.     

Prevalence and prognosis of increased pancreatic enzymes in patients with COVID-19: A systematic review and meta-analysis

IntroductionThe prevalence of increased pancreatic enzymes (elevated serum amylase and/or lipase) and its relationship to clinical outcomes in patients with coronavirus disease 2019 (COVID-19) infection is not known.MethodsA systematic review and meta-analysis of relevant studies reporting prevalence and impact of increased pancreatic enzymes (defined as an elevation in amylase and/or lipase levels above the upper limit of normal [ULN] value) in COVID-19 was undertaken.ResultsA total of 36,496 patients from 21 studies were included for this meta-analysis. The overall prevalence and mortality for increased pancreatic enzymes (>ULN) in COVID-19 were 25.4% (95% CI, 15.8%–36.2%) and 34.6% (95% CI, 25.5%–44.4%), respectively. The overall prevalence and mortality for increased pancreatic enzymes (>3 × ULN) were 6.1% (95% CI, 3.6%–9.2%) and 39.2% (95% CI, 18.7%–61.6%), respectively. Patients with increased pancreatic enzymes, including elevated serum lipase or amylase of either type, had worse clinical outcomes, including need for ICU admission, mechanical ventilation and mortality.DiscussionIncreased pancreatic enzymes is frequent and may exacerbate the consequences of COVID-19 infection.     

Antibody responses to COVID-19 vaccination in people with obesity: A systematic review and meta-analysis

COVID-19 vaccine is critical in preventing SARS-CoV-2 infection and transmission. However, obesity's effect on immune responses to COVID-19 vaccines is still unknown. We performed a meta-analysis of the literature and compared antibody responses with COVID-19 vaccines among persons with and without obesity. We used Pubmed, Embase, Web of Science, and Cochrane Library to identify all related studies up to April 2022. The Stata.14 software was used to analyze the selected data. Eleven studies were included in the present meta-analysis. Five of them provided absolute values of antibody titers in the obese group and non-obese group. Overall, we found that the obese population was significantly associated with lower antibody titers (standardized mean difference [SMD] = −0.228, 95% CI [−0.437, −0.019], P < 0.001) after COVID-19 vaccination. Significant heterogeneity was present in most pooled analyses but was reduced after subgroup analyses. No publication bias was observed in the present analysis. The Trim and Fill method did not change the results in the primary analysis. The present meta-analysis suggested that obesity was significantly associated with decreased antibody responses to SARS-CoV-2 vaccines. Future studies should be performed to unravel the mechanism of response to the COVID-19 vaccine in obese individuals.