Low serum level of apolipoprotein A1 may predict the severity of COVID‐19: A retrospective study

BackgroundDyslipidemia has been observed in patients with coronavirus disease 2019 (COVID‐19). This study aimed to investigate blood lipid profiles in patients with COVID‐19 and to explore their predictive values for COVID‐19 severity.MethodsA total of 142 consecutive patients with COVID‐19 were included in this single‐center retrospective study. Blood lipid profile characteristics were investigated in patients with COVID‐19 in comparison with 77 age‐ and gender‐matched healthy subjects, their predictive values for COVID‐19 severity were analyzed by using multivariable logistic regression analysis, and their prediction efficiencies were evaluated by using receiver operator characteristic (ROC) curves.ResultsThere were 125 and 17 cases in the non‐severe and severe groups, respectively. Total cholesterol (TC), high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C), and apolipoprotein A1 (ApoA1) gradually decreased across the groups in the following order: healthy controls, non‐severe group, and severe group. ApoA1 was identified as an independent risk factor for COVID‐19 severity (adjusted odds ratio [OR]: 0.865, 95% confidence interval [CI]: 0.800–0.935, p < 0.001), along with interleukin‐6 (IL‐6) (adjusted OR: 1.097, 95% CI: 1.034–1.165, p = 0.002). ApoA1 exhibited the highest area under the ROC curve (AUC) among all single markers (AUC: 0.896, 95% CI: 0.834–0.941); moreover, the risk model established using ApoA1 and IL‐6 enhanced prediction efficiency (AUC: 0.977, 95% CI: 0.932–0.995).ConclusionBlood lipid profiles in patients with COVID‐19 are quite abnormal compared with those in healthy subjects, especially in severe cases. Serum ApoA1 may represent a good indicator for predicting the severity of COVID‐19.     

The effect of smoking on COVID‐19–linked biomarkers in hospitalized patients with COVID‐19

BackgroundThe coronavirus pandemic, an infection (coronavirus disease 2019—COVID‐19), caused by severe acute respiratory disease coronavirus 2 (SARS‐CoV‐2), continues to have a strong influence worldwide. Although smoking is a major known risk factor for respiratory infectious disease, the effects of smoking on COVID‐19 are unclear. In this study, we aimed to evaluate the relationship between smoking and important hematologic (lymphocyte count, neutrophil count, platelet count, neutrophil‐lymphocyte ratio [NLR], platelet‐lymphocyte ratio [PLR]), inflammatory, and biochemical biomarkers in the prognosis of hospitalized patients with COVID‐19.MethodsIn a COVID‐19 pandemic hospital between June and August 2020, 200 adult patients aged over 18 years were hospitalized with COVID‐19 inflammatory and hematologic biomarkers at their first admission and smoking data were selected for this study.ResultsThe rate of smokers was much higher among men (91.5%) than in women (8.5%) (p = 0.001). Neutrophil counts were evaluated and was significantly higher in current smokers (p < 0.001) and ex‐smokers (p = 0.001), and NLR (p = 0.008) and ferritin (p = 0.004) levels were higher than in never smokers. The saturation of patients had a negative significant linear correlation of NLR, PLR, and pack years of smoking. Compared with never smokers, current smokers had higher neutrophil counts (OR = 0.828 [0.750–0.915]; p = 0.041), NLR values (OR = 0.948 [0.910–0.987]; p = 0.009), and CRP levels (OR = 0.994 [0.990–0.999]; p = 0.019).ConclusionSerum neutrophil, NLR, and ferritin levels, which are widely used in determining the prognosis of COVID‐19, were found higher in current smokers/ex‐smokers. These results support the view that a poor prognosis of COVID‐19 is associated with smoking.     

Kynurenine pathway in Coronavirus disease (COVID‐19): Potential role in prognosis

BackgroundIt is known that inflammatory responses play an important role in the pathophysiology of COVID‐19.AimsIn this study, we aimed to examine the role of kynurenine (KYN) metabolism on the severity of COVID‐19 disease AQ5.Materials & MethodsSeventy COVID‐19 patients of varying severity and 30 controls were included in the study. In addition to the classical laboratory parameters, KYN, tryptophan (TRP), kynurenic acid (KYNA), 3 hydroxykynurenine (3OHKYN), quinolinic acid (QA), and picolinic acid (PA) were measured with mass spectrometry.ResultsTRP, KYN, KYN:TRP ratio, KYNA, 3OHKYN, PA, and QA results were found to be significantly different in COVID‐19 patients (p < 0.001 for all). The KYN:TRP ratio and PA of severe COVID‐19 patients was statistically higher than that of mild‐moderate COVID‐19 patients (p < 0.001 for all). When results were examined, statistically significant correlations with KYN:TRP ratio, IL‐6, ferritin, and procalcitonin were only found in COVID‐19 patients. ROC analysis indicated that highest AUC values were obtained by KYN:TRP ratio and PA (0.751 vs 0.742). In determining the severity of COVID‐19 disease, the odd ratios (and confidence intervals) of KYN:TRP ratio and PA levels that were adjusted according to age, gender, and comorbidity were determined to be 1.44 (1.1–1.87, p = 0.008) and 1.06 (1.02–1.11, p = 0.006), respectively.Discussion & ConclusionAccording to the results of this study, KYN metabolites play a role in the pathophysiology of COVID‐19, especially KYN:TRP ratio and PA could be markers for identification of severe COVID‐19 cases.     

COVID‐19 in HIV‐positive patients: A systematic review of case reports and case series

IntroductionCoronavirus disease 2019 (COVID‐19) and acquired immune deficiency syndrome (AIDS) are two viral diseases for which there are currently no definitive treatments. Nowadays, because of the health system''s focus on the COVID‐19 epidemic, the control of human immunodeficiency virus (HIV) has received less attention. In this review, we will discuss the characteristics of COVID‐19 in HIV‐positive patients.Material and MethodsUsing the PRISMA guideline, the databases of Scopus, PubMed, and Web of Science were searched systematically from January 1, 2019 to February 24, 2021. The following keywords were used: “Human Immunodeficiency Virus,” “acquired immune deficiency syndrome,” “HIV,” “AIDS,” “COVID‐19,” “severe acute respiratory syndrome coronavirus 2,” “novel coronavirus,” “SARS‐CoV‐2,” “nCoV disease,” “SARS2,” and “2019‐nCoV disease.”ResultsTwenty‐one percent of studies were conducted in the USA (n = 13), 16% in China (n = 10), and 13% in Italy (n = 8), respectively. The majority of the patients were men (74.3%). Tenofovir disoproxil fumarate was used in 47.4% of patients, emtricitabine in 58.4%, and lamivudine in 34.8% to treat HIV. Symptoms of HIV patients with COVID‐19 included coughing (81.3%), fever (62.8%), and dyspnea (60%). Hydroxychloroquine (39.34%) and azithromycin (36.58%) were the common treatment options for COVID‐19. The total death rate in HIV‐positive patients with COVID‐19 was about 9%.ConclusionIn the current systematic review, we demonstrated that HIV‐positive patients co‐infected with COVID‐19 have high comorbidity of hypertension and diabetes mellitus. HIV/COVID‐19 co‐infection might have negatively influenced the HIV treatment and diagnosis, which indicates the need to regularly screen HIV patients in the COVID‐19 pandemic.     

Association between serum inflammatory parameters and the disease severity in COVID‐19 patients

ObjectiveMost patients infected with the novel coronavirus (SARS‐CoV‐2), as the causative agent of COVID‐19 disease, show mild symptoms, but some of them develop severe illness. The purpose of this study was to analyze the blood markers of COVID‐19 patients and to investigate the correlation between serum inflammatory cytokines and the disease severity.MethodsIn this prospective cross‐sectional study, 50 patients with COVID‐19 and 20 patients without COVID‐19 were enrolled. According to ICU admission criteria, patients were divided into two groups of non‐severe and severe. Differences in the serum levels of C‐reactive protein (CRP), IL‐6, and TNF‐α, as well as erythrocyte sedimentation rate (ESR), lymphocytes (LYM) count, and neutrophils (NEU) count between the two groups were determined and analyzed.ResultsOut of the 50 patients with COVID‐19, 14 were diagnosed as severe cases. There was no significant difference between the two groups of COVID‐19 patients in terms of gender and age. Blood tests of COVID‐19 patients showed a significant decrease and increase in NEU and LYM counts, respectively. There were significant differences in the serum levels of IL‐6, TNF‐α, and CRP between the severe and non‐severe groups, which were higher in the severe group.Also, there was a significant correlation between the disease severity and CRP with ESR (r = 0.79), CRP with IL‐6 (r = 0.74), LYM with NEU (r = −0.97), and ESR with TNF‐α (r = 0.7).ConclusionThe findings of this study, as the first study in Iran, suggest that the levels of IL‐6, TNF‐α, ESR, and CRP could be used to predict the severity of COVID‐19 disease.     

Gamma‐Glutamyl Transpeptidase‐to‐Platelet ratio predicts liver fibrosis in patients with concomitant chronic hepatitis B and nonalcoholic fatty liver disease

ObjectivesThe aim of this study was to compare the correlation of gamma‐glutamyl transpeptidase‐to‐platelet ratio (GPR), aspartate aminotransferase‐to‐platelet ratio index (APRI), fibrosis index‐4 (FIB‐4), and liver stiffness measurement (LSM) in the diagnosis of liver fibrosis, and perform a diagnostic value of GPR for predicting fibrosis in CHB patients with NAFLD.MethodsA retrospective study was conducted on CHB patients concurrent with NAFLD between September 2019 and December 2020. They were divided into control group (LSM ≤ 9.7 kpa) and fibrosis group (LSM ≥ 9.8 kpa). Demographic data were collected; ALT, AST, and PLT were also detected. LSM was measured by transient elastography (TE). The GPR, APRI, and FIB‐4 were calculated. The correlation between GPR, APRI, FIB‐4, and LSM was compared. The accuracy of predicting liver fibrosis using GPR, APRI, and FIB‐4 was assessed.ResultsEighty‐five CHB patients with NAFLD were enrolled. Multivariate analysis showed that age (p = 0.005), GGT (p = 0.001), and PLT (p = 0.013) were the independent risk factors for LSM. The GPR (p = 0.008), APRI (p = 0.001), and FIB‐4 (p = 0.001) values in fibrosis group were higher than control group. Pearson linear correlation was used to analyze the correlations between LSM and GPR, APRI, and FIB‐4. LSM was correlated with GPR, APRI, and FIB‐4. The AUCs of GPR, APRI, and FIB4 were 0.805, 0.766, and 0.826 in assessing liver fibrosis, respectively. No significant differences in the areas of GPR were comparable to that of APRI and FIB‐4.ConclusionGPR has a good correlation with LSM in assessing liver fibrosis and can be used as a noninvasive index for the assessment of liver fibrosis in patients with concomitant CHB and NAFLD.     

The prognostic value of general laboratory testing in patients with COVID‐19

BackgroundLymphocyte count (LYM) of peripheral blood and some indices of general biochemical analysis had diagnostic and prognostic value for coronavirus disease 2019 (COVID‐19), and the value of other remaining indices is rare.MethodsA total of 94 patients with COVID‐19 were enrolled at Renmin Hospital of Wuhan University. According to the severity of COVID‐19, the patients were divided into three groups (moderate 49, severe 35, and critical 10), and 40 healthy cases were enrolled in the same period as healthy controls. The diagnostic and prognostic value of indices in peripheral blood cell count and general biochemical analysis was analyzed.ResultsCompared with healthy cases, the value differences in peripheral blood analysis in patients with COVID‐19 were statistically significant (p < 0.01), the differences in LYM, neutrophil count (Neu), platelet count (PLT), and white blood cell count (WBC) were statistically significant among different severity of COVID‐19 (p < 0.05). Compared with healthy cases, the differences in general biochemical results in patients with COVID‐19 were statistically significant (p < 0.01), the value differences in direct bilirubin (DBIL), low‐density lipoprotein cholesterol (LDL‐Ch), and nitrogen (urea) were statistically significant among different severity of COVID‐19 (p < 0.05). Neutrophil/lymphocyte ratio (NLR) had higher sensitivity and specificity for COVID‐19 diagnosis.ConclusionsSome indices of peripheral blood cell count and general biochemical analysis were valuable in discriminating COVID‐19 and predicting severity and adverse outcome of patients with COVID‐19. For clinician, it is better to use more economical and easy‐to‐get indices to diagnose and predict the prognosis of COVID‐19.     

Worldwide prevalence of microbial agents’ coinfection among COVID‐19 patients: A comprehensive updated systematic review and meta‐analysis

BackgroundTo provide information about pathogens’ coinfection prevalence with SARS‐CoV‐2 could be a real help to save patients’ lives. This study aims to evaluate the pathogens’ coinfection prevalence among COVID‐19 patients.MethodIn order to find all of the relevant articles, we used systematic search approach. Research‐based databases including PubMed, Web of Science, Embase, and Scopus, without language restrictions, were searched to identify the relevant bacterial, fungal, and viral coinfections among COVID‐19 cases from December 1, 2019, to August 23, 2021. In order to dig deeper, other scientific repositories such as Medrxiv were probed.ResultsA total of 13,023 studies were found through systematic search. After thorough analysis, only 64 studies with 61,547 patients were included in the study. The most common causative agents of coinfection among COVID‐19 patients were bacteria (pooled prevalence: 20.97%; 95% CI: 15.95–26.46; I ²: 99.9%) and less frequent were virus coinfections (pooled prevalence: 12.58%; 95% CI: 7.31–18.96; I ²: 98.7%). The pooled prevalence of fungal coinfections was also 12.60% (95% CI: 7.84–17.36; I ²: 98.3%). Meta‐regression analysis showed that the age sample size and WHO geographic region did not influenced heterogeneity.ConclusionWe identified a high prevalence of pathogenic microorganism coinfection among COVID‐19 patients. Because of this rate of coinfection empirical use of antibacterial, antifungal, and antiviral treatment are advisable specifically at the early stage of COVID‐19 infection. We also suggest running simultaneously diagnostic tests to identify other microbiological agents’ coinfection with SARS‐CoV‐2.     

Assessment of antiphospholipid antibodies and calprotectin as biomarkers for discriminating mild from severe COVID‐19

BackgroundTo explore the association of thrombo‐inflammatory biomarkers with severity in coronavirus disease (COVID‐19), we measured antiphospholipid antibodies (aPL) and calprotectin in sera of COVID‐19 patients.MethodsAnticardiolipin antibodies (aCL) and anti‐β2‐glycoprotein I antibodies were measured using enzyme‐linked immunosorbent assay (ELISA) and multiplex flow immunoassay (MFIA) in hospitalized COVID‐19 patients (N = 105) and healthy controls (N = 38). Anti‐phosphatidylserine/prothrombin antibodies, calprotectin, and C‐reactive protein (CRP) levels were also measured. We assessed the potential correlation between calprotectin levels and various laboratory parameters that were measured during the hospitalization period. After stratifying COVID‐19 patients into two groups by their oxygenation status or acute respiratory distress syndrome presentation, the discriminatory performance of each biomarker was evaluated.ResultsA high proportion of COVID‐19 patients (29.5%, 31/105) had low aCL IgM titers that were detectable by ELISA but mostly below the detection limit of MFIA. Calprotectin levels in severe groups of COVID‐19 were significantly higher than those in non‐severe groups, while CRP levels revealed no significant differences. Serum calprotectin levels showed strong to moderate degree of correlation with other routinely used parameters including peak levels of CRP, ferritin, procalcitonin, BUN, and neutrophil‐to‐lymphocyte ratio, but a negative correlation with minimal lymphocyte count and CD4⁺ T cells. The discriminatory performance was highest for calprotectin in discriminating severe groups of COVID‐19.ConclusionsSerum calprotectin levels were significantly elevated in severe COVID‐19 cases. The prevalence of clinically significant aPL did not differ. The link between calprotectin and inflammatory pathway in COVID‐19 may help improve the management and outcomes of COVID‐19 patients.     

Evaluation of hematological parameters as an indicator of disease severity in Covid‐19 patients: Pakistan's experience

BackgroundThe severity of COVID‐19 could be evaluated by examining several blood parameters mainly white blood cell (WBC) count, granulocytes, platelet, and novel hemocytometric markers neutrophils to lymphocyte ratio (NLR), platelet‐to‐lymphocyte (PLR), and lymphocyte to monocyte ratio (LMR). The current study was conducted to investigate alteration in blood parameters and their association with the severity and mortality of COVID‐19 patients.MethodologyAn observational cross‐sectional study was conducted retrospectively, a total of 101 COVID‐19 positive patients were examined: 52 were mild, 24 were moderate, 09 were severe, and 16 were critically diseased patients. We also recorded 16 deaths associated with the critical group. The overall mean age observed in our study was 48.94 years, where the mean age for critical individuals was 62.12 ± 14.35 years.ResultsA significant association between the disease severity and elevation in blood parameters were observed. The WBC''s and granulocyte count were significantly increased (p value <0.001) while the mean platelet count (165.0 × 10⁹/L) and red blood cell volume distribution width (RDW) were decreased in the critical group (57.86%) compared to mild group''s patients (177.3%) (p = 0.83). The lymphocytes count was decreased in critical patients (1.40 × 10⁹/L) compared to mild patients (1.92 × 10⁹/L) (p = 0.28). A significant association was observed in platelet‐lymphocyte ratio (p < 0.001), Neutrophil‐Lymphocyte ratio (p = <0.001), and Lymphocyte‐Monocyte ratio (0.011).ConclusionThese blood parameters could be used as a suitable biomarker for the prognosis and severity of COVID‐19. Evaluating novel hemograms NLR, PLR, and LMR can aid clinicians to identify potentially severe cases at early stages, initiate effective management in time, and conduct early triage which may reduce the overall mortality of COVID‐19 patients.     

Serum calprotectin can indicate current and future severity of COVID‐19

BackgroundPredictive and prognostic biomarkers to guide 2019 novel coronavirus disease (COVID‐19) are critically evolving. Dysregulated immune responses are the pivotal cause of severity mainly mediated by neutrophil activation. Thus, we evaluated the association of calprotectin, neutrophil secretory protein, and other mediators of inflammation with the severity and outcomes of COVID‐19.MethodsThis two‐center prospective study focused on PCR‐proven COVID‐19 patients (n = 76) with different clinical presentations and SARS‐CoV‐2 negative control subjects (n = 24). Serum calprotectin (SC) was compared with IL‐6 and other laboratory parameters.ResultsMedian levels of SC were significantly higher in COVID‐19 patients in comparison to the control group (3760 vs. 2100 ng/ml, p < 0.0001). Elevated SC was significantly respective of disease severity (3760 ng/ml in mild up to 5700 ng/ml in severe cases, p < 0.0001). Moreover, the significant positive and negative correlations of SC with disease severity and oxygenation status indicated disease progression and respiratory worsening, respectively. It was found that SC was high in severe patients during hospitalization and significantly declined to normal after recovery. The logistic analysis identified the independent predictive power of SC for respiratory status or clinical severity. Indeed, SC behaved as a better discriminator for both outcomes, as it exhibited the largest area under the curve (receiver operating curve analysis), with the highest specificity and sensitivity when the predictive value of inflammatory biomarkers was compared.ConclusionCalprotectin can be used as a reliable prognostic tool to predict the poor clinical outcomes of COVID‐19 patients.     

Cautions on the laboratory indicators of COVID‐19 patients on and during admission

BackgroundDifferent disease severities of COVID‐19 patients could be reflected on clinical laboratory findings.MethodsIn this single‐centered retrospective study, demographic, clinical, and laboratory indicators on and during admission were compared among 74 participants with mild, moderate, critical severe, or severe classification. Risk factors associated with disease severity were analyzed by multivariate analyses. The AUC and 95% CI of the ROC curve were calculated.ResultsThe most common manifestations of these patients were fever and cough. Critical severe or severe group owned the longest length of stay (23 (19,31), p < 0.001). After multivariate logistic regression, independent influence factors on admission for severity of disease were CK‐MB (OR 0.674; 95% CI 0.489–0.928; p = 0.016), LDH (OR 1.111 or 1.107; 95% CI 1.026–1.204 or 1.022–1.199; p = 0.009 or 0.013), normal T‐BIL (OR 4.58 × 10⁻⁸; 95% CI 3.05 × 10⁻⁹–6.88 × 10⁻⁷; p < 0.001), LYM% (OR 0.008; 95% CI 0–0.602; p = 0.029), and normal ESR (OR 0.016; 95% CI 0–0.498; p = 0.019). Factors during hospitalization were normal T‐BIL (OR 8.56 × 10⁻⁹; 95% CI 8.30 × 10⁻¹⁰–8.83 × 10⁻⁸; p < 0.001), LYM (OR 0.068; 95% CI 0.005–0.934; p = 0.044), albumin (OR 0.565; 95% CI 0.327–0.977; p = 0.041), and normal NEU% (OR 0.013; 95% CI 0.000–0.967; p = 0.048). Combined indicators of AUC were 0.860 (LYM, LDH, and normal ESR on admission, p < 0.001) and 0.750 (CK‐MB, LDH, and normal T‐BIL during hospitalization, p = 0.020) when predicting for severe or critical severe patients.ConclusionTo pay close attention to the progression of COVID‐19 and take measures promptly, we should be cautious of the laboratory indicators when patients on admission especially CK‐MB, LDH, LYM%, T‐BIL as well as ESR; and T‐BIL, LYM, albumin, NEU% with the process of disease.     

A risk score based on procalcitonin for predicting acute kidney injury in COVID‐19 patients

BackgroundAcute kidney injury (AKI) has been reported developing commonly in coronavirus disease 2019 (COVID‐19) patients and could increase the risk of poor outcomes in these patients. We design this study to explore the value of serum procalcitonin (PCT) on predicting AKI and construct risk score for predicting AKI in COVID‐19 patients.MethodsPatients diagnosed with COVID‐19 and hospitalized in Renmin Hospital of Wuhan University between January 30 and February 24, 2020, were included. The least absolute shrinkage and selection operator (LASSO) regression was performed to identify the strongest predictors of AKI. Multivariate logistic regression analysis was conducted to find independent risk factors for AKI and construct risk score using odds ratio (OR) value of those risk factors. Receiver operating characteristics (ROC) curves were plotted, and area under the ROC curve (AUC) value was calculated to evaluate the predictive value of single PCT level and the constructed risk score.ResultsAmong 389 included COVID‐19 patients, 28 (7.2%) patients developed AKI. LASSO regression showed hypertension, saturation of arterial oxygen (SaO₂), PCT, and blood urea nitrogen (BUN) were the strongest predictors for AKI. After multivariate logistic regression analysis, only SaO₂ (<0.001), PCT (p = 0.004), and BUN (p = 0.005) were independently associated with development of AKI in COVID‐19 patients. The AUC of single PCT and constructed risk score was 0. 881 and 0.928, respectively.ConclusionPCT level is correlated with AKI in COVID‐19 patients. The efficient risk score consisted of SaO₂, PCT, and BUN is readily accessible for physicians to evaluate the possibility of AKI in COVID‐19 patients.     

Clinical and biochemical indexes of 11 COVID‐19 patients and the genome sequence analysis of the tested SARS‐CoV‐2

BackgroundAt present, SARS‐CoV‐2 epidemic in the world rapidly spread. It is a serious global public health emergency.MethodsIn this study, we described the clinical characteristics of 11 COVID‐19 patients hospitalized in the Meizhou People''s Hospital, and viral genome sequences of SARS‐CoV‐2 from these patients were analyzed.ResultsOf the 11 patients, six cases developed fever, 9 cases developed a cough, and two cases developed headache and chills. Four patients (36.4%) had underlying diseases. Pneumonia is the most common complication. The laboratory test results showed that there were no adult patients with increased lymphocyte/lymphocyte percentage (LYM/LYM%). Most patients had normal total protein (TP) and albumin (ALB), but only two patients had decreased. Most patients had increased or normal levels of erythrocyte sedimentation rate (ESR), C reactive protein (CRP), activated partial thromboplastin time (APTT), fibrinogen (FIB), creatine kinase isoenzymes (CK‐MB), and lactate dehydrogenase (LDH). Neutrophil (NEU) (r = 0.664, p = 0.026), CK‐MB (r = 0.655, p = 0.029) and blood urea nitrogen (BUN) (r = 0.682, p = 0.021) were significantly associated with SARS‐CoV‐2 virus cycle threshold (Ct) value. Multiple sequence alignment (MSA) shows that two different SNPs were identified at positions 8781 and 28144, and have a complete linkage genetic form of 8781C‐28144T and 8781T‐28144C.ConclusionsThe reports of the 11 COVID‐19 patients in our hospital will provide useful information for the diagnosis, treatment, and drug development of SARS‐CoV‐2.     

Clinical manifestations,treatment options,and comorbidities in COVID‐19 relapse patients: A systematic review

IntroductionInterest revolving around coronavirus disease 2019 (COVID‐19) reinfection is escalating rapidly. By definition, reinfection denotes severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), PCR redetection, and COVID‐19 recurrence within three months of the initial symptoms. The main aim of the current systematic review was to evaluate the features of COVID‐19 relapse patients.Materials and methodsFor this study, we used a string of terms developed by a skilled librarian and through a systematical search in PubMed, Web of Science, and Embase for eligible studies. Clinical surveys of any type were included from January 2019 to March 2021. Eligible studies consisted of two positive assessments separated by a negative result via RT‐PCR.ResultsFifty‐four studies included 207 cases of COVID‐19 reinfection. Children were less likely to have COVID‐19 relapse. However, the most patients were in the age group of 20–40 years. Asthenia (66.6%), headache (66.6%), and cough (54.7%) were prevalent symptoms in the first SARS‐CoV‐2 infection. Asthenia (62.9%), myalgia (62.9%), and headache (61.1%) were most frequent in the second one. The most common treatment options used in first COVID‐19 infection were lopinavir/ritonavir (80%), oxygen support (69.2%), and oseltamivir (66.6). However, for the treatment of second infection, mostly antibiotics (100%), dexamethasone (100%), and remdesivir (80%) were used. In addition, obesity (32.5%), kidney failure (30.7%), and hypertension (30.1%) were the most common comorbidities. Unfortunately, approximately 4.5% of patients died.ConclusionWe found the potency of COVID‐19 recurrence as an outstanding issue. This feature should be regarded in the COVID‐19 management. Furthermore, the first and second COVID‐19 are similar in clinical features. For clinically practical comparison of the symptoms severity between two epochs of infection, uniform data of both are required. We suggest that future studies undertake a homogenous approach to establish the clinical patterns of the reinfection phenomena.     

Colchicine,COVID‐19 and hematological parameters: A meta‐analysis

IntroductionColchicine has the potential in reducing patient morbidity and mortality in COVID‐19 infection owing to its anti‐inflammatory properties. This study aims to determine the efficacy of colchicine in optimizing inflammatory hematological biomarker levels among COVID‐19 patients.MethodsIn accordance to Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) 2020 statement guidelines, a systematic search was conducted using the following keywords: Colchicine, covid*, SARS‐CoV‐2, anti‐inflammatory, trials, clinical, hematological, laboratory. Databases were searched from December 2019 until August 26, 2021: MEDLINE/PubMed, Web of Science, Cochrane, Scopus, and EMBASE. Other sources were located through ClinicalTrials.Gov, manually searching SAGE, Science Direct, Elsevier, and Google Scholar. The meta‐analysis was conducted using Review Manager 5.4.ResultsIn total, six studies were included, of which four reported c‐reactive protein (CRP) standardized mean reductions in the colchicine group (N = 165) as opposed to the control (N = 252; SMD = −0.49, p < 0.001). On noting lactate dehydrogenase (LDH) values post treatment, the colchicine group (N = 204) showed significant reductions at the end of treatment compared to control (N = 290; SMD = −0.85, p < 0.001). Finally, the D‐dimer values in colchicine groups (N = 129) compared to control (N = 216) also documented a negative effect size (SMD = −0.9, p < 0.001).ConclusionColchicine has efficacy in reducing inflammatory biomarkers observed in moderate‐to‐severe COVID‐19 patients. It may be worthwhile to consider monitoring the clinical and laboratory parameters of patients in further trials to consider colchicine as a strong candidate for an adjunct to COVID‐19 treatment.     

Dynamic changes of IgM and IgG antibodies in asymptomatic patients as an effective way to detect SARS‐CoV‐2 infection

BackgroundCOVID‐19 has become a global pandemic, and close contacts and asymptomatic patients are worthy of attention.MethodsA total of 1844 people in close contacts with 76 COVID‐19 patients were investigated, and nasopharyngeal swabs and venous blood were collected for centralized medical quarantine observation. Real‐time fluorescence was used to detect SARS‐CoV‐2 nucleic acid in nasopharyngeal swabs of all close contacts, and the colloidal gold method was used to detect serum‐specific antibodies. Levels of IgM‐ and IgG‐specific antibodies were detected quantitatively through chemiluminescence from the first nucleic acid turned negative date (0 week) and on weekly intervals of ≤1 week, 1–2 weeks, 2–3 weeks, 3–4 weeks, 4–5 weeks, 5–6 weeks, and 6–7 weeks.ResultsThe total positive rate of the colloidal gold method (88.5%, 23/26) was significantly higher (χ² = 59.182, p < 0.001) than that of the healthy control group (2.0%, 1/50). There was significant difference in IgG concentration at different time points (0–7 weeks) after negative nucleic acid conversion (χ² = 14.034, p = 0.029). Serum IgG levels were significantly higher at weekly time points of 4–5 weeks (Z = −2.399, p = 0.016), 5–6 weeks (Z = −2.049, p = 0.040), and 6–7 weeks (Z = −2.197, p = 0.028) compared with 1–2 weeks after negative nucleic acid conversion. However, there was no significant difference (χ² = 4.936, p = 0.552) in IgM concentration between time points tested (0–7 weeks) after negative nucleic acid conversion. The positive rates of IgM and IgG in asymptomatic patients (χ² = 84.660, p < 0.001) were significantly higher than those in the healthy control group (χ² = 9.201, p = 0.002) within 7 weeks of negative nucleic acid conversion.ConclusionsThe IgG concentration in asymptomatic cases remained at a high level after nucleic acid turned negative. Nucleic acid detection combined with IgM and IgG antibody detection is an effective way to screen asymptomatic infections.     

Anakinra treatment efficacy in reduction of inflammatory biomarkers in COVID‐19 patients: A meta‐analysis

IntroductionAnakinra is being empirically considered for the treatment of COVID‐19 patients. The aim is to assess the efficacy of anakinra treatment on inflammatory marker reduction, including c‐reactive protein (CRP) concentrations, serum ferritin, and serum d‐dimer levels.MethodsAdhering to PRISMA 2020 statement guidelines, a systematic search was conducted across the following databases from December 2019 until January 10, 2022: PubMed/MEDLINE, Cochrane Central, Web of Science, Scopus, and EMBASE. The following keywords were employed: Anakinra, COVID*, SARS‐CoV‐2, inflammatory, CRP, D‐dimer, Ferritin, hematological, laboratory, clinical, trials. The findings were collated and presented in a tabulated manner, and statistically analyzed using Review Manger 5.4 (Cochrane).ResultsIn total, 2032 patients were included (881 in the anakinra and 1151 in the control/standard care group); 69.1% of them were males. Overall, the mean difference from admission until last follow‐up in CRP values was −9.66, where notable reductions were seen in the anakinra group (SMD = −0.46, p < 0.00001, N = 655). Serum ferritin mean values were reduced by 1467.16 in the anakinra group (SMD = −0.31, p = 0.004, N = 537). D‐dimer mean values were largely reduced by 4.04 in the anakinra group (SMD = −0.38, p = 0.0004, N = 375).ConclusionThis study finds that anakinra is potentially a strong candidate as an anti‐inflammatory agent to reduce mortality in COVID‐19 patients, specifically in patients with elevated inflammatory biomarkers.     

Neurological manifestations in patients with COVID‐19: A systematic review and meta‐analysis

IntroductionThe intensification of coronavirus disease 2019 (COVID‐19) complications, severe symptoms, and high mortality rate has led researchers to focus on this significant issue. While respiratory and cardiac complications have been described as high‐risk manifestations in patients with COVID‐19, neurological complications can also enhance mortality. This study aimed to evaluate the prevalence of neurological complications arises from SARS‐CoV‐2 and assess the mortality rate from neurological complications.Material and MethodsLiterature review was conducted by searching in PubMed/Medline, Web of Sciences, and Embase. After performing search strategies with relevant terms, a number of articles were excluded, including review articles, systematic review or meta‐analysis, duplicate publication of same researchers, congress abstracts, animal studies, case reports, case series, and articles reporting a history of neurological features prior to COVID‐19 infection. After retrieving the data, statistical analysis was performed using the STATA Version 14 software.ResultsFrom 4455 retrieved publications, 20 articles were selected for further analysis. Among 18,258 included patients, 2791 showed neurological symptoms, which were classified into different groups. Headache, confusion, and fatigue were reported as the most non‐specific neurological features in confirmed COVID‐19 patients. Psychiatric symptoms, CNS disorders, cerebrovascular disorders, CNS inflammatory disorders, PNS disorders, neuromuscular disorders, etc., were defined as specific neurological manifestations. The pooled prevalence of neurological manifestations and mortality rate of COVID‐19 patients with neurological features were estimated to be 23.0% (95% CI: 17.8–29.2) and 29.1% (95% CI: 20.3–39.8), respectively.ConclusionNeurological manifestations may commonly happen in patients with COVID‐19. This study reported a high prevalence of neurological complications and mortality rates in COVID‐19 patients. Therefore, patients with COVID‐19 who indicated neurological symptoms should be taken seriously and should receive early treatment to prevent undesirable events.     

Distribution and reference interval establishment of neutral‐to‐lymphocyte ratio (NLR), lymphocyte‐to‐monocyte ratio (LMR), and platelet‐to‐lymphocyte ratio (PLR) in Chinese healthy adults

BackgroundNeutral‐to‐lymphocyte ratio (NLR), lymphocyte‐to‐monocyte ratio (LMR), and platelet‐to‐lymphocyte ratio (PLR) are associated with coronavirus disease 2019 (COVID‐19) and many diseases, but there are few data about the reference interval (RI) of NLR, LMR, and PLR.MethodsThe neutrophil count, lymphocyte count, monocyte count, and platelet count of 404,272 Chinese healthy adults (>18 years old) were measured by Sysmex XE‐2100 automatic hematology analyzer, and NLR, LMR, and PLR were calculated. According to CLSI C28‐A3, the nonparametric 95% percentile interval is defined as the reference interval.ResultsThe results of Mann‐Whitney U test showed that NLR (p < .001) in male was significantly higher than that in female; LMR (p < .001) and PLR (p < .001) in male were significantly lower than that in female. Kruskal‐Wallis H test showed that there were significant differences in NLR, LMR, and PLR among different genders and age groups (p < .001). The linear graph showed that the reference upper limit of NLR and PLR increased with age and the reference upper limit of LMR decreases with age in male population. In female population, the reference upper limit of NLR in 50–59 group, LMR in >80 group, and PLR in 70–79 group appeared a trough; the reference upper limit of NLR in >80 group, LMR in 50–59 group, and PLR in 40–49 group appeared peak.ConclusionThe establishment of RI for NLR, LMR, and PLR in Chinese healthy adults according to gender and age will promote the standardization of clinical application.