Abstract

Importance: Infection with COVID-19 has been associated with long-term symptoms, but the frequency, variety, and severity of these complications are not well understood. Many published commentaries have proposed plans for pandemic control that are primarily based on mortality rates among older individuals without considering long-term morbidity among individuals of all ages. Reliable estimates of such morbidity are important for patient care, prognosis, and development of public health policy. Objective: To conduct a systematic review of studies examining the frequency and variety of persistent symptoms after COVID-19 infection. Evidence Review: A search of PubMed and Web of Science was conducted to identify studies published from January 1, 2020, to March 11, 2021, that examined persistent symptoms after COVID-19 infection. Persistent symptoms were defined as those persisting for at least 60 days after diagnosis, symptom onset, or hospitalization or at least 30 days after recovery from the acute illness or hospital discharge. Search terms included COVID-19, SARS-CoV-2, coronavirus, 2019-nCoV, long-term, after recovery, long-haul, persistent, outcome, symptom, follow-up, and longitudinal. All English-language articles that presented primary data from cohort studies that reported the prevalence of persistent symptoms among individuals with SARS-CoV-2 infection and that had clearly defined and sufficient follow-up were included. Case reports, case series, and studies that described symptoms only at the time of infection and/or hospitalization were excluded. A structured framework was applied to appraise study quality. Findings: A total of 1974 records were identified; of those, 1247 article titles and abstracts were screened. After removal of duplicates and exclusions, 92 full-text articles were assessed for eligibility; 47 studies were deemed eligible, and 45 studies reporting 84 clinical signs or symptoms were included in the systematic review. Of 9751 total participants, 5266 (54.0%) were male; 30 of 45 studies reported mean or median ages younger than 60 years. Among 16 studies, most of which comprised participants who were previously hospitalized, the median proportion of individuals experiencing at least 1 persistent symptom was 72.5% (interquartile range [IQR], 55.0%-80.0%). Individual symptoms occurring most frequently included shortness of breath or dyspnea (26 studies; median frequency, 36.0%; IQR, 27.6%-50.0%), fatigue or exhaustion (25 studies; median frequency, 40.0%; IQR, 31.0%-57.0%), and sleep disorders or insomnia (8 studies; median 29.4%, IQR, 24.4%-33.0%). There were wide variations in the design and quality of the studies, which had implications for interpretation and often limited direct comparability and combinability. Major design differences included patient populations, definitions of time zero (ie, the beginning of the follow-up interval), follow-up lengths, and outcome definitions, including definitions of illness severity. Conclusions and Relevance: This systematic review found that COVID-19 symptoms commonly persisted beyond the acute phase of infection, with implications for health-associated functioning and quality of life. Current studies of symptom persistence are highly heterogeneous, and future studies need longer follow-up, improved quality, and more standardized designs to reliably quantify risks.

Abstract

AIM: Persistent symptoms in adults after COVID-19 are emerging and the term long COVID is increasingly appearing in the literature. However, paediatric data are scarce. METHODS This paper contains a case report of five Swedish children and the long-term symptoms reported by their parents. It also includes a systematic literature review of the MEDLINE, EMBASE and Web of Science databases and the medRxiv/bioRxiv pre-print servers up to 2 November 2020. RESULTS The five children with potential long COVID had a median age of 12 years (range 9-15) and four were girls. They had symptoms for 6-8 months after their clinical diagnoses of COVID-19. None were hospitalised at diagnosis, but one was later admitted for peri-myocarditis. All five children had fatigue, dyspnoea, heart palpitations or chest pain, and four had headaches, difficulties concentrating, muscle weakness, dizziness and sore throats. Some had improved after 6-8 months, but they all suffered from fatigue and none had fully returned to school. The systematic review identified 179 publications and 19 of these were deemed relevant and read in detail. None contained any information on long COVID in children. CONCLUSION Children may experience similar long COVID symptoms to adults and females may be more affected.

Abstract

BACKGROUND Malnutrition is inevitable in patients with Coronavirus Disease 2019 (COVID-19) due to its effect on the gastrointestinal system, immune system, and high metabolic activity. However, the prevalence of malnutrition and its outcomes is uncertain. This study aimed to investigate the prevalence and outcome of malnutrition among patients with COVID-19. METHOD A comprehensive search was conducted in PubMed/Medline; Science direct and LILACS from December 29, 2019 to September, 2020 without language restriction. All observational studies reporting the prevalence of malnutrition were included while case reports and reviews were excluded. The data were extracted with two independent authors with a customized format and the disagreements were resolved by the other authors. The methodological quality of included studies was evaluated using a standardized critical appraisal tool. RESULTS A total of 511 articles were identified from different databases and 27 articles were selected for evaluation after the successive screening. Fourteen articles with 4187 participants were included. The pooled prevalence of malnutrition among hospitalized patients with COVID-19 was 49.11% (95% CI: 31.67 to 66.54). The odd of mortality among patients COVID-19 with malnutrition was 10 times more likely as compared to those who were well-nourished. CONCLUSION The prevalence of malnutrition and mortality associated with malnutrition among COVID-19 hospitalized patients was very high which entails a mitigating strategy by different stakeholders to prevent and manage malnutrition and its outcomes. REGISTRATION This systematic review was registered in Prospero's international prospective register of systematic reviews (CRD42020215396).

Abstract

BACKGROUND Micronutrients play roles in strengthening and maintaining immune function, but their supplementation and/or deficiency effects on respiratory tract infections are inconclusive. This review aims to systematically assess the associations between micronutrient supplementation or deficiency, with novel coronavirus incidence and disease severity. METHODS Systematic literature searches conducted in five electronic databases identified 751 unique studies, of which 33 studies (five supplementation studies, one supplementation and deficiency study, and 27 deficiency studies) were eventually included in this review. Proportions of incidence and severity outcomes in each group, and adjusted summary statistics with their relevant 95% confidence intervaIs (CI) were extracted. Data from 19 studies were pooled in meta-analysis using the generic inverse variance method. FINDINGS A total of 360,346 patients across 16 countries, with a mean age between 32 and 87.7 years, were involved across 33 studies. All studies were on COVID-19 infections. In individuals without micronutrient deficiency, there was a significant reduction on odds of COVID-19 incidence (pooled OR: 0.37, 95% CI: 0.18, 0.78), and ICU admissions or severe/critical disease onset when combined as a severity outcome (pooled OR: 0.26, 95% CI: 0.08, 0.89). Insignificant protective effects were observed on other outcome measures, namely mortality, ICU admission, progression to respiratory-related complications, severe/critical disease onset or requiring respiratory support and hospitalization rate. CONCLUSION The absence of micronutrient deficiency significantly reduced COVID-19 incidence and clinical deterioration in hospitalized patients. Usage of micronutrients as prophylaxis and complementary supplement in therapeutic management of COVID-19 patients may be a promising and cost-effective approach warranting in-depth investigation.

Abstract

OBJECTIVE In March 2020, several countries banned unnecessary outdoor activities during COVID-19, commonly called 'lockdowns. These lockdowns have the potential to impact associated levels of physical activity and sedentary behaviour. Given the numerous health outcomes associated with physical activity and sedentary behaviour, the aim of this review was to summarise literature that investigated differences in physical activity and sedentary behaviour before vs during the COVID-19 lockdown. DESIGN DATA SOURCES AND ELIGIBILITY CRITERIA Electronic databases were searched from November 2019 to October 2020 using terms and synonyms relating to physical activity, sedentary behaviour and COVID-19. The coprimary outcomes were changes in physical activity and/or sedentary behaviour captured via device-based measures or self-report tools. Risk of bias was measured using the Newcastle-Ottawa Scale. RESULTS Sixty six articles met the inclusion criteria and were included in the review (total n=86 981). Changes in physical activity were reported in 64 studies, with the majority of studies reporting decreases in physical activity and increases in sedentary behaviours during their respective lockdowns across several populations, including children and patients with a variety of medical conditions. CONCLUSION Given the numerous physical and mental benefits of increased physical activity and decreased sedentary behaviour, public health strategies should include the creation and implementation of interventions that promote safe physical activity and reduce sedentary behaviour should other lockdowns occur.

Abstract

BACKGROUND The coronavirus disease 2019 (COVID-19) pandemic has had a devastating impact worldwide, and timely detection and quarantine of infected patients are critical to prevent spread of disease. Serological antibody testing is an important diagnostic method used increasingly in clinics, although its clinical application is still under investigation. METHODS A meta-analysis was conducted to compare the diagnostic performance of severe acute respiratory syndrome coronavirus-2 antibody tests in patients with COVID-19. The test results analysed included: (1) IgM-positive but IgG-negative (IgM+IgG-); (2) IgG-positive but IgM-negative (IgG+IgM-); (3) both IgM-positive and IgG-positive (IgM+IgG+); (4) IgM-positive without IgG information (IgM+IgG+/-); (5) IgG-positive without IgM information (IgG+IgM+/-); (6) either IgM-positive or IgG-positive (IgM+ or IgG+); and (7) IgA-positive (IgA+). RESULTS Sixty-eight studies were included. Pooled sensitivities for IgM+IgG-, IgG+IgM-, IgM+IgG+, IgM+IgG+/-, IgG+IgM+/-, and IgM+ or IgG+ were 6%, 7%, 53%, 68%, 73% and 79% respectively. Pooled specificities ranged from 98% to 100%. IgA+ had a pooled sensitivity of 78% but a relatively low specificity of 88%. Tests conducted 2 weeks after symptom onset showed better diagnostic accuracy than tests conducted earlier. Chemiluminescence immunoassay and detection of S protein as the antigen could offer more accurate diagnostic results. DISCUSSION These findings support the supplemental role of serological antibody tests in the diagnosis of COVID-19. However, their capacity to diagnose COVID-19 early in the disease course could be limited.

Abstract

Eating behaviour is a complex construct that is liable to be modified by external factors. Due to the outbreak of coronavirus disease 2019 (COVID-19), many restrictive measures were carried out with the aim of reducing the impact of this disease. As a result, lifestyles were disrupted, which could affect eating behaviours. The aim of this systematic review of longitudinal studies was to assess changes in eating behaviour during the COVID-19 pandemic by establishing a comparison of eating behaviours before and after the outbreak of the pandemic. This study followed the PRISMA guidelines (PROSPERO CRD42020203246), whereas to assess the quality of the studies, the Newcastle-Ottawa Quality Assessment Scale (NOS) was applied. Out of a set of 826 studies, 23 were included in this systematic review. The main findings provided information about a shift towards modified eating behaviours, characterized by an increased snack frequency and a preference for sweets and ultra-processed food rather than fruits, vegetables, and fresh food. Additionally, an increased alcohol consumption was found among different countries. Consequently, adherence to healthy diets decreased. These findings are relevant to future policies and strategies to assess nutrition in cases of alarming situations such as the current COVID-19 pandemic.

Abstract

Fatigue is common not only in cancer patients but also after viral and other infections. Effective treatment options are still very rare. Therefore, the present knowledge on the pathophysiology of fatigue and the potential positive impact of treatment with vitamin C is illustrated. Additionally, the effectiveness of high-dose IV vitamin C in fatigue resulting from various diseases was assessed by a systematic literature review in order to assess the feasibility of vitamin C in post-viral, especially in long COVID, fatigue. Nine clinical studies with 720 participants were identified. Three of the four controlled trials observed a significant decrease in fatigue scores in the vitamin C group compared to the control group. Four of the five observational or before-and-after studies observed a significant reduction in pre-post levels of fatigue. Attendant symptoms of fatigue such as sleep disturbances, lack of concentration, depression, and pain were also frequently alleviated. Oxidative stress, inflammation, and circulatory disorders, which are important contributors to fatigue, are also discussed in long COVID fatigue. Thus, the antioxidant, anti-inflammatory, endothelial-restoring, and immunomodulatory effects of high-dose IV vitamin C might be a suitable treatment option.

Abstract

There are limited proven therapeutic options for the prevention and treatment of COVID-19. The role of vitamin and mineral supplementation or "immunonutrition" has previously been explored in a number of clinical trials in intensive care settings, and there are several hypotheses to support their routine use. The aim of this narrative review was to investigate whether vitamin supplementation is beneficial in COVID-19. A systematic search strategy with a narrative literature summary was designed, using the Medline, EMBASE, Cochrane Trials Register, WHO International Clinical Trial Registry, and Nexis media databases. The immune-mediating, antioxidant and antimicrobial roles of vitamins A to E were explored and their potential role in the fight against COVID-19 was evaluated. The major topics extracted for narrative synthesis were physiological and immunological roles of each vitamin, their role in respiratory infections, acute respiratory distress syndrome (ARDS), and COVID-19. Vitamins A to E highlighted potentially beneficial roles in the fight against COVID-19 via antioxidant effects, immunomodulation, enhancing natural barriers, and local paracrine signaling. Level 1 and 2 evidence supports the use of thiamine, vitamin C, and vitamin D in COVID-like respiratory diseases, ARDS, and sepsis. Although there are currently no published clinical trials due to the novelty of SARS-CoV-2 infection, there is pathophysiologic rationale for exploring the use of vitamins in this global pandemic, supported by early anecdotal reports from international groups. The final outcomes of ongoing trials of vitamin supplementation are awaited with interest.

Abstract

BACKGROUND More severe cases of COVID- 19 are more likely to be hospitalized and around one-fifth, needing ICU admission. Understanding the common laboratory features of COVID-19 in more severe cases versus non-severe patients could be quite useful for clinicians and might help to predict the model of disease progression. This systematic review and meta-analysis aimed to compare the laboratory test findings in severe vs. non-severe confirmed infected cases of COVID-19. METHODS Electronic databases were systematically searched in PubMed, EMBASE, Scopus, Web of Science, and Google Scholar from the beginning of 2019 to 3rd of March 2020. Heterogeneity across included studies was determined using Cochrane's Q test and the I2 statistic. We used the fixed or random-effect models to pool the weighted mean differences (WMDs) or standardized mean differences and 95% confidence intervals (CIs). FINDINGS Out of a total of 3009 citations, 17 articles (22 studies, 21 from China and one study from Singapore) with 3396 ranging from 12 to1099 patients were included. Our meta-analyses showed a significant decrease in lymphocyte, monocyte, and eosinophil, hemoglobin, platelet, albumin, serum sodium, lymphocyte to C-reactive protein ratio (LCR), leukocyte to C-reactive protein ratio (LeCR), leukocyte to IL-6 ratio (LeIR), and an increase in the neutrophil, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, blood urea nitrogen (BUN), creatinine (Cr), erythrocyte Sedimentation Rate (ESR), C-reactive protein (CRP), Procalcitonin (PCT), lactate dehydrogenase (LDH), fibrinogen, prothrombin time (PT), D-dimer, glucose level, and neutrophil to lymphocyte ratio (NLR) in the severe group compared with the non-severe group. No significant changes in white blood cells (WBC), Creatine Kinase (CK), troponin I, myoglobin, IL-6 and K between the two groups were observed. INTERPRETATION This meta-analysis provides evidence for the differentiation of severe cases of COVID-19 based on laboratory test results at the time of ICU admission. Future well-methodologically designed studies from other populations are strongly recommended.