COVID diagnostics by molecular methods: A systematic review of nucleic acid based testing systems

BackgroundThe selection of appropriate kit and PCR equipment for the detection of SARS CoV-2 is critically important in view of many options available in the diagnostic market. Since last year many molecular products are available for COVID-19 diagnostics., some of these diagnostics have become commercially available for healthcare workers and clinical laboratories. However, the diagnostic technologies have specific limitations and reported several false-positive and false-negative cases, especially during the early stages of kit development and use.The current article addresses these and other relevant questions important to the medical microbiologists running or aspiring to run COVID diagnostic services using PCR and related technologies.MethodsIn this Systematic Review we follow Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies (PRISMA-DTA). A total of 258 citations retrieved, among those 77 peer reviewed articles was assessed for eligibility, and 181 studies were excluded. Based on inclusion criteria final data extraction was done.ResultsThe question of diagnostic dilemma has also been addressed in view of discordant results between assays, inter-test variability, repeat testing requirements in specific settings and inconclusive or indeterminate results. Kit efficiency was satisfactory for all assays and the estimates varied within sample types and technology. Using clinical samples, we observed some variations in detection rate between kits. Importantly, none of the assays showed cross-reactivity with other respiratory (corona) viruses, except as expected for the SARS-CoV-1 E-gene.ConclusionsWe conclude SARS CoV-2 related molecular assays differed considerably in performance. Hence we need to understand importance of molecular diagnostics test interpretation in light of the latest pandemic virus.     

Clinical features,therapeutic outcomes,and recovery period of long COVID

To characterize the clinical features of long COVID, 286 patients who received care in our outpatient clinic for long COVID from May to December 2021 were surveyed. The recovery periods of each symptom and the key factors contributing to early recovery were statistically analysed. The median age of the patients was 35.8 years, with 137 men and 149 women. The median number of symptoms was 2.8. The most frequent symptoms were respiratory manifestations (52.1%), followed by fatigue (51.4%). Respiratory symptoms, fatigue, and headache/arthralgia were major complaints in the initial phase, whereas hair loss was a major complaint in the late phase, suggesting that the chief complaint of patients with long COVID may vary temporally. The best treatment outcome was observed for pulmonary symptoms, and hair loss had the worst outcome. COVID-19 severity, the number of manifestations, and the delay in starting treatment exerted a negative effect on the recovery period of long COVID. In addition, the smoking habit was an independent risk factor for slowing the recovery period from long COVID. This study provides insights into the clinical course of each manifestation and therapeutic options with a more certain future of long COVID to meet the unmet medical needs.     

Long COVID: An inevitable sequela of SARS-CoV-2 infection

At present, there are more than 560 million confirmed cases of the coronavirus disease 2019 (COVID-19) worldwide. Although more than 98% of patients with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection can survive acute COVID, a significant portion of survivors can develop residual health problems, which is termed as long COVID. Although severe COVID-19 is generally associated with a high risk of long COVID, patients with asymptomatic or mild disease can also show long COVID. The definition of long COVID is inconsistent and its clinical manifestations are protean. In addition to general symptoms, such as fatigue, long COVID can affect many organ systems, including the respiratory, neurological, psychosocial, cardiovascular, gastrointestinal, and metabolic systems. Moreover, patients with long COVID may experience exercise intolerance and impaired daily function and quality of life. Long COVID may be caused by SARS-CoV-2 direct injury or its associated immune/inflammatory response. Assessment of patients with long COVID requires comprehensive evaluation, including history taking, physical examination, laboratory tests, radiography, and functional tests. However, there is no known effective treatment for long COVID. Based on the limited evidence, vaccines may help to prevent the development of long COVID. As long COVID is a new clinical entity that is constantly evolving, there are still many unknowns, and further investigation is warranted to enhance our understanding of this disease.     

Clinical efficacy of antiviral agents against coronavirus disease 2019: A systematic review of randomized controlled trials

Despite aggressive efforts on containment measures for the coronavirus disease 2019 (COVID-19) pandemic around the world, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously spreading. Therefore, there is an urgent need for an effective antiviral agent. To date, considerable research has been conducted to develop different approaches to COVID-19 therapy. In addition to early observational studies, which could be limited by study design, small sample size, non-randomized design, or different timings of treatment, an increasing number of randomized controlled trials (RCTs) investigating the clinical efficacy and safety of antiviral agents are being carried out. This study reviews the updated findings of RCTs regarding the clinical efficacy of eight antiviral agents against COVID-19, including remdesivir, lopinavir/ritonavir, favipiravir, sofosbuvir/daclatasvir, sofosbuvir/ledipasvir, baloxavir, umifenovir, darunavir/cobicistat, and their combinations. Treatment with remdesivir could accelerate clinical improvement; however, it lacked additional survival benefits. Moreover, 5-day regimen of remdesivir might show adequate effectiveness in patients with mild to moderate COVID-19. Favipiravir was only marginally effective regarding clinical improvement and virological assessment based on the results of small RCTs. The present evidence suggests that sofosbuvir/daclatasvir may improve survival and clinical outcomes in patients with COVID-19. However, the sample sizes for analysis were relatively small, and all studies were exclusively conducted in Iran. Further larger RCTs in other countries are warranted to support these findings. In contrast, the present findings of limited RCTs did not indicate the use of lopinavir/ritonavir, sofosbuvir/ledipasvir, baloxavir, umifenovir, and darunavir/cobicistat in the treatment of patients hospitalized for COVID-19.     

Quercetin for the treatment of COVID-19 patients: A systematic review and meta-analysis

Currently approved therapies for COVID-19 are mostly limited by their low availability, high costs or the requirement of parenteral administration by trained medical personnel in an in-hospital setting. Quercetin is a cheap and easily accessible therapeutic option for COVID-19 patients. However, it has not been evaluated in a systematic review until now. We aimed to conduct a meta-analysis to assess the effect of quercetin on clinical outcomes in COVID-19 patients. Various databases including PubMed, the Cochrane Library and Embase were searched from inception until 5 October 2022 and results from six randomized controlled trials (RCTs) were pooled using a random-effects model. All analyses were conducted using RevMan 5.4 with odds ratio (OR) as the effect measure. Quercetin decreased the risk of intensive care unit admission (OR = 0.31; 95% confidence interval (CI) 0.10–0.99) and the incidence of hospitalisation (OR = 0.25; 95% CI 0.10–0.62) but did not decrease the risk of all-cause mortality and the rate of no recovery. Quercetin may be of benefit in COVID-19 patients, especially if administered in its phytosome formulation which greatly enhances its bioavailability but large-scale RCTs are needed to confirm these findings.     

Clinical features of neonates born to mothers with coronavirus disease-2019: A systematic review of 105 neonates

BackgroundDespite the increasingly recognized impact of novel coronavirus disease (COVID-19), caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), on many aspects of health in adults and children, its effects on neonates born to infected mothers remain unclear. We conducted this study to investigate the outcomes of neonates born to mothers with COVID-19.MethodsWe searched the medical databases from inception to March 31, 2020 to perform a systematic review of outcomes in neonates born to mothers with COVID-19. Data were pooled using a random effects regression model. Primary and secondary outcomes were neonatal clinical outcomes and infectious status, respectively.ResultsFourteen studies involving 105 neonates fulfilling the study criteria were identified. The rates of preterm neonates and those small for gestational age (SGA) were 25 (23.8%) and 10 (11.2%), respectively. Among 91 neonates who were tested, 8 (8.8%) were positive for nucleic acids or antibodies for SARS-CoV-2. Additionally, 28 (26.7%) of the neonates were symptomatic and two test-negative neonates died, including one stillbirth. Between test-positive and test-negative groups, the rates of SGA, preterm delivery, duration between maternal symptom onset and delivery, and perinatal complication were not significantly different; but the rate of symptomatic after birth reached significant difference (62.5% vs 20.5%, p = 0.008).ConclusionsMost neonates born to infected mothers had favorable outcomes. Although direct evidences of intrauterine infection were scarce, the risk of intrauterine infection should be considered based on a positive test in 8.8% of the neonates. Symptomatic neonates born to infected mothers should receive tests for SARS-CoV-2 to initiate appropriate treatment and quarantine. Further studies are warranted to assess the outcomes of COVID-19 in neonates.     

Clinical patterns of somatic symptoms in patients suffering from post-acute long COVID: a systematic review

European Journal of Clinical Microbiology & Infectious Diseases - Long COVID-19 may affect patients after hospital discharge. This study aims to describe the burden of the long-term persistence...     

Cardiac sequelae after coronavirus disease 2019 recovery: a systematic review

BackgroundCoronavirus disease 2019 (COVID-19) has been implicated in a wide spectrum of cardiac manifestations following the acute phase of the disease.ObjectivesTo assess the range of cardiac sequelae after COVID-19 recovery.Data sourcesPubMed, Embase, Scopus (inception through 17 February 2021) and Google scholar (2019 through 17 February 2021).Study eligibility criteriaProspective and retrospective studies, case reports and case series.ParticipantsAdult patients assessed for cardiac manifestations after COVID-19 recovery.ExposureSevere acute respiratory syndrome coronavirus 2 infection diagnosed by PCR.MethodsSystematic review.ResultsThirty-five studies (fifteen prospective cohort, seven case reports, five cross-sectional, four case series, three retrospective cohort and one ambidirectional cohort) evaluating cardiac sequelae in 52 609 patients were included. Twenty-nine studies used objective cardiac assessments, mostly cardiac magnetic resonance imaging (CMR) in 16 studies, echocardiography in 15, electrocardiography (ECG) in 16 and cardiac biomarkers in 18. Most studies had a fair risk of bias. The median time from diagnosis/recovery to cardiac assessment was 48 days (1–180 days). Common short-term cardiac abnormalities (<3 months) included increased T1 (proportion: 30%), T2 (16%), pericardial effusion (15%) and late gadolinium enhancement (11%) on CMR, with symptoms such as chest pain (25%) and dyspnoea (36%). In the medium term (3–6 months), common changes included reduced left ventricular global longitudinal strain (30%) and late gadolinium enhancement (10%) on CMR, diastolic dysfunction (40%) on echocardiography and elevated N-terminal proB-type natriuretic peptide (18%). In addition, COVID-19 survivors had higher risk (risk ratio 3; 95% CI 2.7–3.2) of developing heart failure, arrythmias and myocardial infarction.ConclusionsCOVID-19 appears to be associated with persistent/de novo cardiac injury after recovery, particularly subclinical myocardial injury in the earlier phase and diastolic dysfunction later. Larger well-designed and controlled studies with baseline assessments are needed to better measure the extent of cardiac injury and its clinical impact.     

Effectiveness of treatments for people living with severe dementia: A systematic review and meta-analysis of randomised controlled clinical trials

BackgroundDementia is a progressive neurodegenerative syndrome that has no cure. Although a significant proportion of people with dementia progress into the severe stages of the disease, evidence on the clinical effectiveness of treatments for people with severe dementia remains limited.AimsTo systematically review the effectiveness of pharmacological and non-pharmacological treatments for people living with severe dementia and assess the quality of the evidence.MethodWe searched MEDLINE, EMBASE, PsycINFO, CINAHL and online clinical trial registers up to January 2022, for Randomised Controlled Trials (RCT) in people living with severe dementia. Quality and risk of bias were assessed independently by two authors.ResultsA total of 30 trials met our inclusion criteria of which 14 evaluated the effectiveness of pharmacological treatments, and 16 evaluated a non-pharmacological intervention. Pharmacological treatments: Meta-analyses indicated that pharmacological treatments (donepezil: 10 mg, 5 mg; galantamine: 24 mg; memantine: 10 mg) are associated with better outcomes compared to placebo for: severity of symptoms (standardized mean difference (SMD) 0.37, 95% CI 0.26–0.48; 4 studies; moderate-certainty evidence), activities of daily living (SMD 0.15, 95% CI 0.04–0.26; 5 studies; moderate-certainty evidence), and clinical impression of change (Relative Risk (RR) 1.34, 95% CI 1.14–1.57; 4 studies; low-certainty evidence). Pharmacological treatments were also more likely to reduce mortality compared to placebo (RR 0.60, 95% CI 0.40–0.89; 6 studies; low-certainty evidence). Non-pharmacological treatments: Five trials were included in the meta-analyses of non-pharmacological interventions (multi-sensory stimulation, needs assessment, and activities-based interventions); results showed that non-pharmacological interventions may reduce neuropsychiatric symptoms of dementia compared to usual care (SMD −0.33, 95% CI −0.59 to −0.06; low certainty evidence).ConclusionsThere is moderate-certainty evidence that pharmacological treatments may decrease disease severity and improve function for people with severe dementia. Non-pharmacological treatments are probably effective in reducing neuropsychiatric symptoms but the quality of evidence remains low. There is an urgent need for high-quality evidence for other outcomes and for developing service-user informed interventions for this under-served group.     

Effect of COVID-19 vaccination on semen parameters: A systematic review and meta-analysis

The aim of this study was to investigate the effect of coronavirus disease 2019 (COVID-19) vaccination on semen parameters through systematic review and meta-analysis. PubMed, EMBASE, Web of Science, and Cochrane Library were comprehensively searched by June 2022. Studies were considered eligible if they compared semen parameters before and after COVID-19 vaccination or between vaccinated and unvaccinated men, with no restrictions on vaccine types or doses. The effect size was calculated as mean difference (MD) with 95% confidence interval (CI) using a random-effects model. Subgroup and sensitivity analyses were conducted to assess the sources of heterogeneity measured by the I² statistic, with publication bias evaluated by Egger's test. Twelve cohort studies involving 914 participants fulfilled the inclusion criteria. In a comparison of vaccinated versus unvaccinated group, the pooled data revealed no significant differences in semen volume (MD = 0.18 ml, 95% CI −0.02 to 0.38), sperm concentration (MD = 1.16 million/ml, 95% CI −1.34 to 3.66), total sperm motility (MD = −0.14%, 95% CI −2.84 to 2.56), progressive sperm motility (MD = −1.06%, 95% CI −2.88 to 0.77), total sperm count (MD = 5.92 million, 95% CI −10.22 to 22.05), total motile sperm count (MD = 2.18 million, 95% CI −1.28 to 5.63), total progressively motile sperm count (MD = −3.87 million, 95% CI −13.16 to 5.43), and sperm morphology (MD = 0.07%, 95% CI −0.84 to 0.97). The results also remained similar across messenger ribonucleic acid, viral-vector, and inactivated COVID-19 vaccines. Sensitivity analysis identified two individual studies that contributed to heterogeneity, while the effect size was not materially altered. No obvious publication bias was detected among included studies. Our finding suggested that COVID-19 vaccination had no detrimental impact on semen quality, which could be potentially helpful to reduce male vaccine hesitancy and increase vaccination coverage.     

The clinical characteristics of pediatric inpatients with SARS‐CoV‐2 infection: A meta‐analysis and systematic review

Millions of people were infected with the coronavirus disease 2019 (COVID‐19) all over the world. Data on clinical symptoms of pediatric inpatients with COVID‐19 infection were unclear. The aim of study was to investigate the clinical features of pediatric inpatients with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. PubMed, EMBASE, and the Cochrane Library were searched to seek for studies providing details on pediatric inpatients with SARS‐CoV‐2 infection which were published from 1st January to 21st April 2020. Studies with more than five pediatric inpatients were included in our meta‐analysis.This study was registered in the PROSPERO database (CRD42020183550). As the results shown, fever (46%) and cough (42%) were the main clinical characters of pediatric inpatients with SARS‐CoV‐2 infection and the other clinical characters, such as diarrhea, vomiting, nasal congestion, and fatigue account for 10% in pediatric inpatients. The proportion of asymptomatic cases was 0.42 (95% confidence interval [CI]: 0.27‐0.59) and severe cases was 0.03 (95% CI: 0.01‐0.06). For the laboratory result, leukopenia (21%) and lymphocytosis (22%) were the mainly indicators for pediatric inpatients, followed by high aspartate aminotransferase (19%), lymphopenia (16%), high alanine aminotransferase (15%), high C‐reactive protein (17%), leukocytosis (13%), high D‐dimer (12%) and high creatine kinase‐MB (5%). Regard to chest imaging features, unilateral and bilateral accounts for 22% in pediatric inpatients, respectively. In conclusion, compared with adult inpatients with SARS‐CoV‐2 infection, the pediatric inpatients had mild clinical characters, lab test indicators, and chest imaging features. More clinical studies focus on the pediatric patients with SARS‐CoV‐2 infection in other countries should be conducted.     

Bioethical perspective of convalescent plasma therapy for COVID-19: A systematic review

Convalescent plasma therapy (CP) has long been used to prevent and treat various infectious diseases before COVID-19 such as SARS, MERS, and H1N1. Because the viral and clinical characteristics of COVID-19 share the similarities between SARS and MERS, CP treatment could be a promising treatment option to save COVID-19. With only low quality medical evidence, but massive media support and a very significant public demand for the use of convalescent plasma for COVID-19, we are now faced with an ethical dilemma. Therefore, this paper uses a structured analysis that focuses on the preferred reporting items for a systematic review of ethical issues regarding the use of Convalescent Plasma Therapy for COVID-19. The use of convalescent plasma must meet the ethical principles of autonomy; such as voluntary, informed consent, and confidentiality. Consideration of the risk-benefit ratio for potential donor recipients also needs to be considered in order to meet the beneficence and non-maleficence principles. The principle of justice also needs to be applied both to donors, donor recipients and health workers, such as determining the priority of donor recipients, due to the increasing demand for convalescent plasma amid the limited circumstances of patients who have recovered from Covid-19 who voluntarily donate.     

Impact of COVID-19 on liver disease: From the experimental to the clinic perspective

Coronavirus disease 2019 (COVID-19) has caused a global pandemic unprecedented in over a century. Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a predominantly respiratory infection, various degrees of liver function abnormalities have been reported. Pre-existing liver disease in patients with SARS-CoV-2 infection has not been comprehensively evaluated in most studies, but it can critically compromise survival and trigger hepatic decompensation. The collapse of the healthcare services has negatively impacted the diagnosis, monitoring, and treatment of liver diseases in non-COVID-19 patients. In this review, we aim to discuss the impact of COVID-19 on liver disease from the experimental to the clinic perspective.