Prevalence of post-acute COVID-19 syndrome symptoms at different follow-up periods: a systematic review and meta-analysis

BackgroundPost-acute coronavirus 2019 (COVID-19) syndrome is now recognized as a complex systemic disease that is associated with substantial morbidity.ObjectivesTo estimate the prevalence of persistent symptoms and signs at least 12 weeks after acute COVID-19 at different follow-up periods.Data sourcesSearches were conducted up to October 2021 in Ovid Embase, Ovid Medline, and PubMed.Study eligibility criteria, participants and interventionsArticles in English that reported the prevalence of persistent symptoms among individuals with confirmed severe acute respiratory syndrome coronavirus 2 infection and included at least 50 patients with a follow-up of at least 12 weeks after acute illness.MethodsRandom-effect meta-analysis was performed to produce a pooled prevalence for each symptom at four different follow-up time intervals. Between-study heterogeneity was evaluated using the I2 statistic and was explored via meta-regression, considering several a priori study-level variables. Risk of bias was assessed using the Joanna Briggs Institute tool and the Newcastle-Ottawa Scale for prevalence studies and comparative studies, respectively.ResultsAfter screening 3209 studies, a total of 63 studies were eligible, with a total COVID-19 population of 257 348. The most commonly reported symptoms were fatigue, dyspnea, sleep disorder, and difficulty concentrating (32%, 25%, 24%, and 22%, respectively, at 3- to <6-month follow-up); effort intolerance, fatigue, sleep disorder, and dyspnea (45%, 36%, 29%, and 25%, respectively, at 6- to <9-month follow-up); fatigue (37%) and dyspnea (21%) at 9 to <12 months; and fatigue, dyspnea, sleep disorder, and myalgia (41%, 31%, 30%, and 22%, respectively, at >12-month follow-up). There was substantial between-study heterogeneity for all reported symptom prevalences. Meta-regressions identified statistically significant effect modifiers: world region, male sex, diabetes mellitus, disease severity, and overall study quality score. Five of six studies including a comparator group consisting of COVID-19–negative cases observed significant adjusted associations between COVID-19 and several long-term symptoms.ConclusionsThis systematic review found that a large proportion of patients experience post-acute COVID-19 syndrome 3 to 12 months after recovery from the acute phase of COVID-19. However, available studies of post-acute COVID-19 syndrome are highly heterogeneous. Future studies need to have appropriate comparator groups, standardized symptom definitions and measurements, and longer follow-up.     

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.     

Prevalence of post-acute coronavirus disease 2019 symptoms twelve months after hospitalization in participants retained in follow-up: analyses stratified by gender from a large prospective cohort

ObjectivesPersistent post-acute coronavirus disease 2019 (COVID-19) symptoms (PACSs) have been reported up to 6 months after hospital discharge. Herein we assessed the symptoms that persisted 12 months (M12) after admission for COVID-19 in the longitudinal prospective national French coronavirus disease cohort.MethodsHospitalized patients with a confirmed virological diagnosis of COVID-19 were enrolled. Follow-up was planned until M12 after admission. Associations between persistence of ≥3 PACSs at M12 and clinical characteristics at admission were assessed through logistic regression according to gender.ResultsWe focused on participants enrolled between 24 January 2020 and 15 July 2020, to allow M12 follow-up. The M12 data were available for 737 participants. Median age was 61 years, 475 (64%) were men and 242/647 (37%) were admitted to intensive care units during the acute phase. At M12, 27% (194/710) of the participants had ≥3 persistent PACS, mostly fatigue, dyspnoea and joint pain. Among those who had a professional occupation before the acute phase, 91 out of 339 (27%) were still on sick leave at M12. Presence of ≥3 persistent PACS was associated with female gender, both anxiety and depression, impaired health-related quality of life and Medical Muscle Research Council Scale <57. Compared with men, women more often reported presence of ≥3 persistent PACSs (98/253, 39% vs. 96/457, 21%), depression and anxiety (18/152, 12% vs. 17/268, 6% and 33/156, 21% vs. 26/264, 10%, respectively), impaired physical health-related quality of life (76/141, 54% vs. 120/261, 46%). Women had less often returned to work than men (77/116, 66% vs. 171/223, 77%).ConclusionsOne fourth of the individuals admitted to hospital for COVID-19 still had ≥3 persistent PACSs at M12 post-discharge. Women reported more often ≥3 persistent PACSs, suffered more from anxiety and depression and had less often returned to work than men.     

Tocilizumab for coronavirus disease 2019 in pregnancy and lactation: a narrative review

BackgroundTocilizumab is a monoclonal antibody that interrupts interleukin-6 signalling, reducing downstream effects on inflammation and the innate immune response. It was shown to reduce mortality in patients with severe or critical coronavirus disease 2019 (COVID-19). Pregnant and breastfeeding people were largely excluded from clinical trials and hence, the extent to which results can be applied to these populations is not clear.ObjectivesTo synthesize published data on tocilizumab in pregnancy and lactation, highlight important knowledge gaps, and help inform clinical decision-making about tocilizumab's use in these populations with COVID-19.SourcesPubMed was searched for studies evaluating tocilizumab in pregnancy and lactation for COVID-19 and other indications. Literature on pharmacokinetics and reproductive/fetal safety of monoclonal antibodies in general was also sought. The US Food and Drug Administration and the European Medicines Agency guidance for the industry and regulatory approval documents were reviewed.ContentPublished data on tocilizumab in pregnancy include 610 cases (n = 20 with COVID-19) together with seven mother–infant breastfeeding pairs. Higher rates of spontaneous abortion and premature birth have been reported compared with the general population, but multiple confounding variables limit interpretation. There is little data on tocilizumab exposure in the second and third trimesters when transplacental transport is highest. The effects of tocilizumab on the developing immune system are unclear. Pregnant patients with COVID-19 who received tocilizumab were often critically ill and corticosteroid use was uncommon. Neonatal follow up was limited. Tocilizumab appears to be compatible with breastfeeding.ImplicationsAlthough the available data do not raise serious safety signals, they have significant limitations and are not sufficient to delineate the complete spectrum of potential adverse outcomes that may be associated with tocilizumab exposure during pregnancy and lactation. Diligent follow up and documentation of pregnancy outcomes will be important moving forward. A more effective regulatory framework to ensure equitable inclusion of pregnant people in research is clearly needed.     

Hepatic manifestations of coronavirus disease 2019 infection: Clinical and laboratory perspective

The novel coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2, has become a global challenge of unprecedented nature since December 2019. Although most patients with COVID-19 exhibit mild clinical manifestations and upper respiratory tract involvement, in approximately 5%-10% of patients, the disease is severe and involves multiple organs, leading to multi-organ dysfunction and failure. The liver and gastrointestinal tract are also frequently involved in COVID-19. In the context of liver involvement in patients with COVID-19, many key aspects need to be addressed in both native and transplanted organs. This review focuses on the clinical presentations and laboratory abnormalities of liver function tests in patients with COVID-19 with no prior liver disease, patients with pre-existing liver diseases and liver transplant recipients. A brief overview of the history of COVID-19 and etiopathogenesis of the liver injury will also be described as a prelude to better understanding the above aspects.     

多排螺旋CT联合多平面重建技术在新型冠状病毒肺炎诊断中的应用

目的探讨多排螺旋CT联合多平面重组技术(MPR)在新型冠状病毒肺炎(COVID-19)早期筛查诊断中的应用价值。方法回顾性分析2020年1~2月我院发热门诊32例疑似COVID-19患者的影像资料,对比原始CT轴位图像和重建后高分辨CT(HRCT)轴位图像结合MPR重组技术对COVID-19影像特征的检出能力,并用SPSS 17.0软件对病灶检出率进行χ2检验分析。结果重建后的HRCT轴位图像可以清楚显示肺小叶内部结构变化,尤其是结合MPR重组技术后在显示跨叶段病灶、支气管充气征、血管束增粗征等病变上优于原始CT轴位图像,差异具有统计学意义(P<0.05)。结论COVID-19疫情爆发期,尽早使用多排螺旋CT扫描,重建HRCT轴位图像并联合运用MPR技术,能够更加直观、立体地显示病灶,为COVID-19的快速鉴别诊断提供更丰富的影像依据,从而早隔离、早治疗,控制疫情发展。     

Tocilizumab for the treatment of severe coronavirus disease 2019

Tocilizumab, an interleukin-6 inhibitor, may ameliorate the inflammatory manifestations associated with severe coronavirus disease 2019 (COVID-19) and thus improve clinical outcomes. This was a retrospective review of patients with laboratory-confirmed severe COVID-19 who received tocilizumab and completed 14 days of follow up. Twenty-five patients were included, median age was 58 years (interquartile range, 50-63) and the majority were males (92%). Co-morbidities included diabetes mellitus (48%), chronic kidney disease (16%), and cardiovascular disease (12%). Fever (92%), cough (84%), and dyspnea (72%) were the commonest presenting symptoms. All patients received at least two concomitant investigational antiviral agents. Median oral temperature was on day 1, 3, and 7 was 38.0°C, 37.3°C (P = .043), and 37.0°C (P = .064), respectively. Corresponding median C-reactive protein was 193 and 7.9 mg/L (P < .0001) and <6 mg/L (P = .0001). Radiological improvement was noted in 44% of patients by day 7% and 68% by day 14. Nine patients (36%) were discharged alive from intensive care unit and three (12%) died. The proportion of patients on invasive ventilation declined from (84%) at the time of tocilizumab initiation to 60% on day 7 (P = .031) and 28% on day 14 (P = .001). The majority (92%) of patients experienced at least one adverse event. However, it is not possible to ascertain which adverse events were directly related to tocilizumab therapy. In patients with severe COVID-19, tocilizumab was associated with dramatic decline in inflammatory markers, radiological improvement and reduced ventilatory support requirements. Given the study's limitations, the results require assessment in adequately powered randomized controlled trials.     

A report of clinical diagnosis and treatment of nine cases of coronavirus disease 2019

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 has become an important public health issue in the world. More than 118 000 cases were confirmed around the world. The main clinical manifestations were respiratory symptoms and occasional gastrointestinal symptoms. However, there is no unified standard for the diagnosis and treatment of COVID-19. In the retrospective analysis, we report nine cases of COVID-19, describe the history of contact, clinical manifestations, the course of diagnosis and clinical treatment before, during and after treatment.     

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 sequelae of COVID-19 survivors in Wuhan,China: a single-centre longitudinal study

ObjectivesTo describe the prevalence, nature and risk factors for the main clinical sequelae in coronavirus disease 2019 (COVID-19) survivors who have been discharged from the hospital for more than 3 months.MethodsThis longitudinal study was based on a telephone follow-up survey of COVID-19 patients hospitalized and discharged from Renmin Hospital of Wuhan University, Wuhan, China before 1 March 2020. Demographic and clinical characteristics and self-reported clinical sequelae of the survivors were described and analysed. A cohort of volunteers who were free of COVID-19 and lived in the urban area of Wuhan during the outbreak were also selected as the comparison group.ResultsAmong 538 survivors (293, 54.5% female), the median (interquartile range) age was 52.0 (41.0–62.0) years, and the time from discharge from hospital to first follow-up was 97.0 (95.0–102.0) days. Clinical sequelae were common, including general symptoms (n = 267, 49.6%), respiratory symptoms (n = 210, 39%), cardiovascular-related symptoms (n = 70, 13%), psychosocial symptoms (n = 122, 22.7%) and alopecia (n = 154, 28.6%). We found that physical decline/fatigue (p < 0.01), postactivity polypnoea (p= 0.04) and alopecia (p < 0.01) were more common in female than in male subjects. Dyspnoea during hospitalization was associated with subsequent physical decline/fatigue, postactivity polypnoea and resting heart rate increases but not specifically with alopecia. A history of asthma during hospitalization was associated with subsequent postactivity polypnoea sequela. A history of pulse ≥90 bpm during hospitalization was associated with resting heart rate increase in convalescence. The duration of virus shedding after COVID-19 onset and hospital length of stay were longer in survivors with physical decline/fatigue or postactivity polypnoea than in those without.ConclusionsClinical sequelae during early COVID-19 convalescence were common; some of these sequelae might be related to gender, age and clinical characteristics during hospitalization.     

Controversial treatments: An updated understanding of the coronavirus disease 2019

An outbreak of severe acute respiratory syndrome-related coronavirus 2 infection has posed significant threats to international health and the economy. In the absence of specific treatment for this virus, there is an urgent need to learn from the experience and lessons in China. To reduce the case-fatality rate among coronavirus disease 2019 patients, we should not ignore the complications, such as RNAaemia, acute respiratory distress syndrome, and multiple organ dysfunction. To help understand the advantages and limitations of differential treatments, we provide a timely review and discuss the complications and corresponding major treatments, especially controversial ones such as antiviral therapy (remdesivir, ribavirin, and chloroquine), glucocorticoid therapy, extracorporeal support including an artificial liver system, and extracorporeal membrane oxygenation based on available evidence. As a result, we suggest that antiviral therapy and organ function support are vital to reduce mortality for mild patients and critical patients, respectively.     

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.     

Prolonged viral shedding in feces of pediatric patients with coronavirus disease 2019

ObjectiveTo determine the dynamic changes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in respiratory and fecal specimens in children with coronavirus disease 2019 (COVID-19).MethodsFrom January 17, 2020 to February 23, 2020, three paediatric cases of COVID-19 were reported in Qingdao, Shandong Province, China. Epidemiological, clinical, laboratory, and radiological characteristics and treatment data were collected. Patients were followed up to March 10, 2020, and dynamic profiles of nucleic acid testing results in throat swabs and fecal specimens were closely monitored.ResultsClearance of SARS-CoV-2 in respiratory tract occurred within two weeks after abatement of fever, whereas viral RNA remained detectable in stools of pediatric patients for longer than 4 weeks. Two children had fecal SARS-CoV-2 undetectable 20 days after throat swabs showing negative, while that of another child lagged behind for 8 days.ConclusionsSARS-CoV-2 may exist in children's gastrointestinal tract for a longer time than respiratory system. Persistent shedding of SARS-CoV-2 in stools of infected children raises the possibility that the virus might be transmitted through contaminated fomites. Massive efforts should be made at all levels to prevent spreading of the infection among children after reopening of kindergartens and schools.     

Three Taiwan's domestic family cluster infections of coronavirus disease 2019

Since the first case of coronavirus disease 2019 (COVID-19) was identified in Taiwan 2020.01.21. Several family cluster infections were found later. This study aimed to report family cluster infections and observe subsequent development. We collected domestic family cluster infections among COVID-19 confirmed cases from 21 January 2020 to 16 March 2020. There were three domestic family clusters infections in this period. The first cluster was cases 19 to 23. The infectious source was a Taiwanese passenger from Zhejiang. The second cluster was cases 24 to 26 and the third cluster was cases 27 to 32. The infectious sources of the latter clusters are currently uncertain. All contacts of three clusters have been isolated and no new confirmed cases have been identified to date. Some measures which have reduced the spread of these three clusters included: First, high suspicion of COVID-19 for unexplained pneumonia is very important for early detection. Second, immediate epidemic investigation is taken especially COVID-19 is infectious during the incubation period. Third, when the second and third clusters could not find infectious sources, CECC's press conference let the public know immediately the epidemic situation, so that people could raise their awareness and seek medical treatment or quarantine.     

Children with coronavirus disease 2019: A review of demographic,clinical, laboratory,and imaging features in pediatric patients

There is a current outbreak of coronavirus disease 2019 (COVID-19), with a global spread. With the rapid increase in the number of infections, an increase is observed in the number of children with COVID-19. Most research findings are regarding adult cases, which are not always transferrable to children. Evidence-based studies are still expected to formulate clinical decisions for pediatric patients. In this review, we included 2597 pediatric patients that reported recently and evaluated the demographic, clinical, laboratory, and imaging features of children with COVID-19. We found that even lymphopenia was the most common lab finding in adults; it infrequently occurred in children (9.8%). Moreover, elevated creatine kinase MB isoenzyme was much more commonly observed in children (27.0%) than that in adults, suggesting that heart injury would be more likely to occur in pediatric patients. Our analysis may contribute to determine the spectrum of disease in children and to develop strategies to control the disease transmission.     

Diagnostic accuracy of antibody-based rapid diagnostic tests in detecting coronavirus disease 2019: systematic review

IntroductionThe rapid transmission of coronavirus disease 2019 (COVID-19) requires a fast, accurate, and affordable detection method. Despite doubts of their diagnostic accuracy, rapid diagnostic tests (RDTs) are used worldwide due to their practicality. This systematic review aims to determine the diagnostic accuracy of antibody-based RDTs in detecting COVID-19.Material and methodsA literature search was carried out on five journal databases using the PRISMA-P 2015 method. We included all studies published up to February 2021. The risk of bias was evaluated using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Diagnostic Test Accuracy Studies. Data regarding peer-review status, study design, test kit information, immunoglobulin class, target antigen, and the number of samples were extracted and tabulated. We estimated the pooled sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) with a 95% confidence interval.ResultsThirty-three studies met the eligibility criteria. The pooled data results showed that the combined detection method of IgM or IgG had the highest sensitivity and NPV, which were 73.41% (95% CI: 72.22–74.57) and 75.34% (95% CI: 74.51–76.16), respectively. The single IgG detection method had the highest specificity and PPV of 96.68% (95% CI: 96.25–97.07) and 95.97% (95% CI: 95.47–96.42%), respectively.ConclusionsAntibody-based RDTs are not satisfactory as primary diagnostic tests but have utility as a screening tool.     

Early risk factors of the exacerbation of coronavirus disease 2019 pneumonia

The purpose of this study was to investigate the early risk factors for the exacerbation of coronavirus disease 2019 (COVID-19) pneumonia. Restrospective analysis of clinical data of 85 patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including gender, age, comorbidities, symptoms, blood routine, clotting profile, biochemical examination, albumin, myocardial enzyme profile, inflammatory markers, and chest computed tomography (CT). All laboratory examinations were measured within first 24 hours after admission, and chest CT was performed before admission. A total of 56 (65.9%) patients had a history of exposure to the Huanan seafood market in Wuhan. Fever and dry cough accounted for the highest percentage of all symptoms. Male COVID-2019 patients were more likely to develop severe pneumonia. Patients with severe and critical conditions are older and have higher rates of hypertension (P = .003) and coronary heart disease (P = .017). All severe and critical patients infected with SARS-CoV-2 showed bilateral lung involvement and have more multiple lobes involvement than common patients (P < .001). Severe and critical patients showed higher white blood cell count (P = .006), neutrophil (NEU) count (P = .001), NEU% (P = .002), procalcitonin (P = .011), C-reactive protein (P = .003), prothrombin time (P = .035), D-dimer (P = .025), aspartate aminotransferase (P = .006), and lower lymphocyte (LYM) count (P = .019), LYM% (P = .001), albumin (P < .001). Logistic regression analysis showed that NEU count is an independent risk factor for deterioration, with the threshold of 6.5 × 10⁹·L⁻¹. We concluded that the laboratory independent risk factor for the progression of COVID-19 pneumonia is NEU count. In addition, COVID-19 patients with bilateral lung involvement or multiple lobes involvement should be taken seriously and actively treated to prevent deterioration of the disease.