Risk factors for impaired pulmonary diffusion function in convalescent COVID-19 patients: A systematic review and meta-analysis.

Background: The long-term prognosis of COVID-19 survivors remains poorly understood. It is evidenced that the lung is the main damaged organ in COVID-19 survivors, most notably in impairment of pulmonary diffusion function. Hence, we conducted a meta-analysis of the potential risk factors for impaired diffusing capacity for carbon monoxide (DLCO) in convalescent COVID-19 patients. Methods: We performed a systematic search of PubMed, Web of Science, Embase, and Ovid databases for relevant studies from inception until January 7, 2022, limited to papers involving human subjects. Studies were reviewed for methodological quality. Fix-effects and random-effects models were used to pool results. Heterogeneity was assessed using I2. The publication bias was assessed using the Egger's test. PROSPERO registration: CRD42021265377. Findings: A total of eighteen qualified articles were identified and included in the systematic review, and twelve studies were included in the meta-analysis. Our results showed that female (OR: 4.011; 95% CI: 2.928-5.495), altered chest computerized tomography (CT) (OR: 3.002; 95% CI: 1.319-6.835), age (OR: 1.018; 95% CI: 1.007-1.030), higher D-dimer levels (OR: 1.012; 95% CI: 1.001-1.023) and urea nitrogen (OR: 1.004;95% CI: 1.002-1.007) were identified as risk factors for impaired DLCO. Interpretation: Pulmonary diffusion capacity was the most common impaired lung function in recovered patients with COVID-19. Several risk factors, such as female, altered chest CT, older age, higher D-dimer levels and urea nitrogen are associated with impairment of DLCO. Raising awareness and implementing interventions for possible modifiable risk factors may be valuable for pulmonary rehabilitation. Funding: This work was financially supported by Emergency Key Program of Guangzhou Laboratory (EKPG21-29, EKPG21-31), Incubation Program of National Science Foundation for Distinguished Young Scholars by Guangzhou Medical University (GMU2020-207).

Dynamic changes of pulmonary diffusion capacity in survivors of non-critical COVID-19 during the first six months.

BACKGROUND: The dynamic trends of pulmonary function in coronavirus disease 2019 (COVID-19) survivors since discharge have been rarely described. We aimed to describe the changes of lung function and identify risk factors for impaired diffusion capacity. METHODS: Non-critical COVID-19 patients admitted to the Guangzhou Eighth People's Hospital, China, were enrolled from March to June 2020. Subjects were prospectively followed up with pulmonary function tests at discharge, three and six months after discharge. FINDINGS: Eighty-six patients completed diffusion capacity tests at three timepoints. The mean diffusion capacity for carbon monoxide (DLCO)% pred was 79.8% at discharge and significantly improved to 84.9% at Month-3. The transfer coefficient of the lung for carbon monoxide (KCO)% pred significantly increased from 91.7% at discharge to 95.7% at Month-3. Both of them showed no further improvement at Month-6. The change rates of DLCO% pred and KCO% pred were significantly higher in 0-3 months than in 3-6 months. The alveolar ventilation (VA) improved continuously during the follow-ups. At Month-6, impaired DLCO% pred was associated with being female (OR 5.2 [1.7-15.8]; p = 0.004) and peak total lesion score (TLS) of chest CT > 8.5 (OR 6.6 [1.7-26.5]; p = 0.007). DLCO% pred and KCO% pred were worse in females at discharge. And in patients with impaired diffusion capacity, females' DLCO% pred recovered slower than males. INTERPRETATION: The first three months is the critical recovery period for diffusion capacity. The impaired diffusion capacity was more severe and recovered slower in females than in males. Early pulmonary rehabilitation and individualized interventions for recovery are worthy of further investigations.

Artificial intelligence for stepwise diagnosis and monitoring of COVID-19.

BACKGROUND: Main challenges for COVID-19 include the lack of a rapid diagnostic test, a suitable tool to monitor and predict a patient's clinical course and an efficient way for data sharing among multicenters. We thus developed a novel artificial intelligence system based on deep learning (DL) and federated learning (FL) for the diagnosis, monitoring, and prediction of a patient's clinical course. METHODS: CT imaging derived from 6 different multicenter cohorts were used for stepwise diagnostic algorithm to diagnose COVID-19, with or without clinical data. Patients with more than 3 consecutive CT images were trained for the monitoring algorithm. FL has been applied for decentralized refinement of independently built DL models. RESULTS: A total of 1,552,988 CT slices from 4804 patients were used. The model can diagnose COVID-19 based on CT alone with the AUC being 0.98 (95% CI 0.97-0.99), and outperforms the radiologist's assessment. We have also successfully tested the incorporation of the DL diagnostic model with the FL framework. Its auto-segmentation analyses co-related well with those by radiologists and achieved a high Dice's coefficient of 0.77. It can produce a predictive curve of a patient's clinical course if serial CT assessments are available. INTERPRETATION: The system has high consistency in diagnosing COVID-19 based on CT, with or without clinical data. Alternatively, it can be implemented on a FL platform, which would potentially encourage the data sharing in the future. It also can produce an objective predictive curve of a patient's clinical course for visualization. KEY POINTS: • CoviDet could diagnose COVID-19 based on chest CT with high consistency; this outperformed the radiologist's assessment. Its auto-segmentation analyses co-related well with those by radiologists and could potentially monitor and predict a patient's clinical course if serial CT assessments are available. It can be integrated into the federated learning framework. • CoviDet can be used as an adjunct to aid clinicians with the CT diagnosis of COVID-19 and can potentially be used for disease monitoring; federated learning can potentially open opportunities for global collaboration.

Current status of diagnosis and treatment of advanced non-small cell lung cancer in China during the COVID-19 pandemic.

BACKGROUND: The purpose of this study was to investigate the current status of diagnosis and treatment of Chinese patients with advanced non-small cell lung cancer (NSCLC) and the expert recommendation of the therapeutic regimens during the coronavirus disease 2019 (COVID-19) pandemic, and to analyze and summarize relevant rules. METHODS: Under the planning and coordination of the Lung Cancer Group of the Chinese Thoracic Society, we performed an online questionnaire survey among experts in lung cancer and patients with NSCLC. Convenience sampling was adopted for questionnaire survey of experts, and random sampling was adopted for questionnaire survey of patients. After collecting and sorting out the questionnaire, a descriptive analysis of the data was performed. RESULTS: Within 24 h from the distribution of questionnaires to the deadline, a total of 808 and 321 valid questionnaires from patients and experts were collected across China, respectively. There were 83.81% of the experts performed moderately and strongly anti-tumor therapy for patients with NSCLC during the COVID-19 pandemic. 76.6% of patients mainly receive online public welfare treatment, and the patient satisfaction rate reached up to 64.97%. For driver gene-positive patients with advanced NSCLC and non-COVID-19, 82.87% of the experts recommended first-line simple targeted therapy, and 12.77% of the experts recommended targeted therapy with oral anti-angiogenic drugs. For patients who were unable to return to the hospital for treatment and showed resistance to the tyrosine kinase inhibitor (TKI) therapy, 92.21% of the experts recommended oral anti-angiogenic drugs as the third-line home-based therapy and above. For patients with advanced NSCLC combined with COVID-19, 98.76% and 95.95% of the experts recommended discontinuation of chemotherapy and immunotherapy, respectively. CONCLUSIONS: During COVID-19, most Chinese patients with NSCLC were still able to receive timely diagnosis and treatment either by online public welfare consultation or at nearby hospitals.

Associations between screen time, physical activity, and depressive symptoms during the 2019 coronavirus disease (COVID-19) outbreak among Chinese college students.

BACKGROUND: The 2019 novel coronavirus disease (COVID-19) emerges in China, which spreads rapidly and becomes a public health emergency of international concern. Chinese government has promptly taken quarantine measures to block the transmission of the COVID-19, which may cause deleterious consequences on everyone's behaviors and psychological health. Few studies have examined the associations between behavioral and mental health in different endemic areas. This study aimed to describe screen time (ST), physical activity (PA), and depressive symptoms, as well as their associations among Chinese college students according to different epidemic areas. METHODS: The study design is cross-sectional using online survey, from 4 to 12 February 2020, 14,789 college students accomplished this online study, participants who did not complete the questionnaire were excluded, and finally this study included 11,787 college students from China. RESULTS: The average age of participants was 20.51 ± 1.88 years. 57.1% of the college students were male. In total, 25.9% of college students reported depression symptoms. ST > 4 h/day was positively correlated with depressive symptoms (ß = 0.48, 95%CI 0.37-0.59). COVID-19ST > 1 h/day was positively correlated with depressive symptoms (ß = 0.54, 95%CI 0.43-0.65), compared with COVID-19ST ≤ 0.5 h/day. Compared with PA ≥ 3 day/week, PA < 3 day/week was positively associated with depression symptoms (ß = 0.01, 95%CI 0.008-0.012). Compared with low ST and high PA, there was an interaction association between high ST and low PA on depression (ß = 0.31, 95%CI 0.26-0.36). Compared with low COVID-19ST and high PA, there was an interaction association between high COVID-19ST and low PA on depression (ß = 0.37, 95%CI 0.32-0.43). There were also current residence areas differences. CONCLUSIONS: Our findings identified that high ST or low PA was positively associated with depressive symptoms independently, and there was also an interactive effect between ST and PA on depressive symptoms.

Rigorous Assessment of Guidelines on COVID-19-Related Thrombotic or Thromboembolic Disease: Implications for Clinical Practice of Prevention, Diagnosis, and Treatment.

PURPOSE: Severe COVID-19 patients were prone to develop venous thromboembolism. Unfortunately, to date, there is no evidence of any effective medications for thromboembolism in COVID-19. The management of the disease relies on symptomatic and supportive treatments, giving rise to a variety of guidelines. However, the quality of methodology and clinical recommendations remains unknown. MATERIALS AND METHODS: We searched Medline, Cochrane Library, Web of Science, websites of international organizations and medical societies, and gray literature databases. Four well-trained appraisers independently evaluated the quality of eligible guidelines and extracted recommendations using well-recognized guideline appraisal tools. Furthermore, recommendations were extracted and reclassified according to a composite grading system. RESULTS: The search identified 23 guidelines that offered 108 recommendations. Guidelines scored average on AGREE II criteria, with Scope and Purpose and Clarity of Presentation highest. Only five (22%) guidelines provided high-quality recommendations. The existed clinical recommendations were inconsistent in terms of prophylaxis, diagnosis, and treatment of thromboembolic disease to some extent. CONCLUSION: Current guidelines for COVID-19 thromboembolism are generally of low quality, and clinical recommendations on thromboembolism are principally supported by insufficient evidence. There is still an urgent need for more well-designed clinical trials as evidence to prevent adverse events and improve prognosis during COVID-19 treatment.

Clinical Characteristics of Coronavirus Disease 2019 in China.

BACKGROUND: Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. METHODS: We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. RESULTS: The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. CONCLUSIONS: During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.).

Transmission, viral kinetics and clinical characteristics of the emergent SARS-CoV-2 Delta VOC in Guangzhou, China.

BACKGROUND: A novel variant of SARS-CoV-2, the Delta variant of concern (VOC, also known as lineage B.1.617.2), is fast becoming the dominant strain globally. We reported the epidemiological, viral, and clinical characteristics of hospitalized patients infected with the Delta VOC during the local outbreak in Guangzhou, China. METHODS: We extracted the epidemiological and clinical information pertaining to the 159 cases infected with the Delta VOC across seven transmission generations between May 21 and June 18, 2021. The whole chain of the Delta VOC transmission was described. Kinetics of viral load and clinical characteristics were compared with a cohort of wild-type infection in 2020 admitted to the Guangzhou Eighth People's Hospital. FINDINGS: There were four transmission generations within the first ten days. The Delta VOC yielded a significantly shorter incubation period (4.0 vs. 6.0 days), higher viral load (20.6 vs. 34.0, cycle threshold of the ORF1a/b gene), and a longer duration of viral shedding in pharyngeal swab samples (14.0 vs. 8.0 days) compared with the wild-type strain. In cases with critical illness, the proportion of patients over the age of 60 was higher in the Delta VOC group than in the wild-type strain (100.0% vs. 69.2%, p = 0.03). The Delta VOC had a higher risk than wild-type infection in deterioration to critical status (hazards ratio 2.98 [95%CI 1.29-6.86]; p = 0.01). INTERPRETATION: Infection with the Delta VOC is characterized by markedly increased transmissibility, viral loads and risk of disease progression compared with the wild-type strain, calling for more intensive prevention and control measures to contain future outbreaks. FUNDING: National Grand Program, National Natural Science Foundation of China, Guangdong Provincial Department of Science and Technology, Guangzhou Laboratory.

Critical Review of the Scientific Evidence and Recommendations in COVID-19 Management Guidelines.

BACKGROUND: Little is known about the quality and potential impacts of the guidelines for coronavirus disease 2019 (COVID-19) management. METHODS: We systematically searched PubMed, Web of Science, Cochrane Library, guideline databases, and specialty society websites to evaluate the quality of the retrieved guidelines using the Appraisal of Guidelines for Research and Evaluation II. RESULTS: A total of 66 guidelines were identified. Only 24% were categorized as "recommended" for clinical practice. The 211 identified recommendations for COVID-19 management were classified into 4 topics: respiratory support (27), acute respiratory distress syndrome management (31), antiviral or immunomodulatory therapy (95), or other medicines (58). Only 63% and 56% of recommendations were supported by, respectively, assessment of the strength of the recommendations or level of evidence. There were notable discrepancies between the different guidelines regarding the recommendations on COVID-19 management. CONCLUSIONS: The quality of the guidelines for COVID-19 management is heterogeneous, and the recommendations are rarely supported by evidence.

Secondary infection in severe and critical COVID-19 patients in China: a multicenter retrospective study.

BACKGROUND: Since 2020 COVID-19 pandemic became an emergent public sanitary incident. The epidemiology data and the impact on prognosis of secondary infection in severe and critical COVID-19 patients in China remained largely unclear. METHODS: We retrospectively reviewed medical records of all adult patients with laboratory-confirmed COVID-19 who were admitted to ICUs from January 18th 2020 to April 26th 2020 at two hospitals in Wuhan, China and one hospital in Guangzhou, China. We measured the frequency of bacteria and fungi cultured from respiratory tract, blood and other body fluid specimens. The risk factors for and impact of secondary infection on clinical outcomes were also assessed. RESULTS: Secondary infections were very common (86.6%) when patients were admitted to ICU for >72 hours. The majority of infections were respiratory, with the most common organisms being Klebsiella pneumoniae (24.5%), Acinetobacter baumannii (21.8%), Stenotrophomonas maltophilia (9.9%), Candida albicans (6.8%), and Pseudomonas spp. (4.8%). Furthermore, the proportions of multidrug resistant (MDR) bacteria and carbapenem resistant Enterobacteriaceae (CRE) were high. We also found that age ≥60 years and mechanical ventilation ≥13 days independently increased the likelihood of secondary infection. Finally, patients with positive cultures had reduced ventilator free days in 28 days and patients with CRE and/or MDR bacteria positivity showed lower 28-day survival rate. CONCLUSIONS: In a retrospective cohort of severe and critical COVID-19 patients admitted to ICUs in China, the prevalence of secondary infection was high, especially with CRE and MDR bacteria, resulting in poor clinical outcomes.

Earlier diagnosis improves COVID-19 prognosis: a nationwide retrospective cohort analysis.

BACKGROUND: Risk of adverse outcomes in COVID-19 patients by stratifying by the time from symptom onset to confirmed diagnosis status is still uncertain. METHODS: We included 1,590 hospitalized COVID-19 patients confirmed by real-time RT-PCR assay or high-throughput sequencing of pharyngeal and nasal swab specimens from 575 hospitals across China between 11 December 2019 and 31 January 2020. Times from symptom onset to confirmed diagnosis, from symptom onset to first medical visit and from first medical visit to confirmed diagnosis were described and turned into binary variables by the maximally selected rank statistics method. Then, survival analysis, including a log-rank test, Cox regression, and conditional inference tree (CTREE) was conducted, regarding whether patients progressed to a severe disease level during the observational period (assessed as severe pneumonia according to the Chinese Expert Consensus on Clinical Practice for Emergency Severe Pneumonia, admission to an intensive care unit, administration of invasive ventilation, or death) as the prognosis outcome, the dependent variable. Independent factors included whether the time from symptom onset to confirmed diagnosis was longer than 5 days (the exposure) and other demographic and clinical factors as multivariate adjustments. The clinical characteristics of the patients with different times from symptom onset to confirmed diagnosis were also compared. RESULTS: The medians of the times from symptom onset to confirmed diagnosis, from symptom onset to first medical visit, and from first medical visit to confirmed diagnosis were 6, 3, and 2 days. After adjusting for age, sex, smoking status, and comorbidity status, age [hazard ratio (HR): 1.03; 95% CI: 1.01-1.04], comorbidity (HR: 1.84; 95% CI: 1.23-2.73), and a duration from symptom onset to confirmed diagnosis of >5 days (HR: 1.69; 95% CI: 1.10-2.60) were independent predictors of COVID-19 prognosis, which echoed the CTREE models, with significant nodes such as time from symptom onset to confirmed diagnosis, age, and comorbidities. Males, older patients with symptoms such as dry cough/productive cough/shortness of breath, and prior COPD were observed more often in the patients who procrastinated before initiating the first medical consultation. CONCLUSIONS: A longer time from symptom onset to confirmed diagnosis yielded a worse COVID-19 prognosis.

Circadian rhythm abnormalities during the COVID-19 outbreak related to mental health in China: a nationwide university-based survey.

OBJECTIVE/BACKGROUND: School closure and home quarantine has been implemented worldwide during the coronavirus disease 2019 (COVID-19) outbreak. The study aims to assess the associations of circadian rhythm abnormalities (CRA) during the COVID-19 outbreak with mental health in Chinese undergraduates. METHODS: A nationwide cross-sectional university-based survey was conducted from 4th February to 12th, 2020. Based on different geographical locations and purposive sampling approach, 19 universities from 16 provinces or municipalities in the mainland of China were selected. A total of 14,789 participants were recruited by using multistage stratified random sampling. The data of CRA were collected by self-reported questionnaires consist of four items involved rest-activity cycle, diet rhythm, wake up rhythm and sleep rhythm. The Patient Health Questionnaire and the Generalized Anxiety Disorder were applied to evaluate the symptoms of depression and anxiety. Chi-square test and ordinal logistic regression models were used to describe the distributions and associations of CRA and mental health. RESULTS: A total of 11,787 students [female: 6731(57.1%)] aged 15-26 years old (M = 20.45, SD = 1.76) were analyzed (response rate: 79.7%). The results showed the percentage of CRA were 17.5-28.7%. The prevalence of depression and anxiety were significantly higher in students with single CRA. Students who reported the coexistence of four CRA were more likely to be with the symptoms of depression (OR: 4.43, 95% CI: 3.91-5.03) and anxiety (OR: 3.11, 95% CI: 2.70-3.60). Dose-response relationships were found between multiple CRA and mental problems. CONCLUSION: Circadian rhythm abnormalities are positively associated with mental health among university studies. Mental health care is needed for college students during the COVID-19 epidemic period.

Predictors of fatal outcomes among hospitalized COVID-19 patients with pre-existing hypertension in China.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging, rapidly evolving pandemic, hypertension is one of the most common co-existing chronic conditions and a risk factor for mortality. Nearly one-third of the adult population is hypertensive worldwide, it is urgent to identify the factors that determine the clinical course and outcomes of COVID-19 patients with hypertension. METHODS AND RESULTS: 148 COVID-19 patients with pre-existing hypertension with clarified outcomes (discharge or deceased) from a national cohort in China were included in this study, of whom 103 were discharged and 45 died in hospital. Multivariate regression showed higher odds of in-hospital death associated with high-sensitivity cardiac troponin (hs-cTn) > 28 pg/ml (hazard ratio [HR]: 3.27, 95% confidence interval [CI]: 1.55-6.91) and interleukin-6 (IL-6) > 7 pg/ml (HR: 3.63, 95% CI:1.54-8.55) at admission. Patients with uncontrolled blood pressure (BP) (n = 52) which were defined as systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg for more than once (≥2 times) during hospitalization, were more likely to have ICU admission (p = 0.037), invasive mechanical ventilation (p = 0.028), and renal injury (p = 0.005). A stricter BP control with the threshold of 130/80 mm Hg was associated with lower mortality. Treatment with renin-angiotensin-aldosterone system (RAAS) suppressors, including angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARB), and spironolactone, was associated with a lower rate of ICU admission compared to other types of anti-hypertensive medications (8 (22.9%) vs. 25 (43.1%), p = 0.048). CONCLUSION: Among COVID-19 patients with pre-existing hypertension, elevated hs-cTn and IL-6 could help clinicians to identify patients with fatal outcomes at an early stage, blood pressure control is associated with better clinical outcomes, and RAAS suppressors do not increase mortality and may decrease the need for ICU admission.

Epidemiological and clinical characteristics of suspected COVID-19 patients in the isolation ward in Guangzhou, China: a cohort study.

BACKGROUND: Since there are reports of cases of 2019-coronavirus disease (COVID-19) asymptomatic carriers in China recently and fever is one of the main symptoms, we aimed to distinguish COVID-19 cases from other febrile patients with clinical examinations in this study. METHODS: A total of 134 suspected COVID-19 patients in the isolation ward of the First Affiliated Hospital of Guangzhou Medical University were recruited from January 23 to May 23, 2020. We analyze the pathogenic form and clinical characteristics. RESULTS: Among them, pathogens were identified in only 84 patients (62.7%), including 23 (17.1%) with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), 30 (22.3%) with other viruses, 31 (25.0%) with other pathogens and 3 (3.5%) with mixed infections. The commonly observed symptoms of COVID-19 patients were cough, fever, fatigue, and muscle aches, which were significantly different than the symptoms of nonviral infections (P<0.05) but from those of other viral infections (P>0.05). Furthermore, lactate dehydrogenase and the neutrophil/lymphocyte were found significantly high in COVID-19 patients compared to non-COVID-19 patients (P<0.05). The most common manifestations of COVID-19 patients were ground-glass opacities (100%) with or without lung consolidation, however, they also often showed involvement of several lobes of both lungs (P<0.05). Due to the clear differential diagnosis, the overall antibiotic use rate was 35.8% (31/87). CONCLUSIONS: When diagnosing COVID-19, infections with other pathogens should not be ignored. Successful pathogen identification will support accurate treatment.

Longitudinal virological changes and underlying pathogenesis in hospitalized COVID-19 patients in Guangzhou, China.

Prolonged viral RNA shedding and recurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in coronavirus disease 2019 (COVID-19) patients have been reported. However, the clinical outcome and pathogenesis remain unclear. In this study, we recruited 43 laboratory-confirmed COVID-19 patients. We found that prolonged viral RNA shedding or recurrence mainly occurred in severe/critical patients (P<0.05). The average viral shedding time in severe/critical patients was more than 50 days, and up to 100 days in some patients, after symptom onset. However, chest computed tomography gradually improved and complete absorption occurred when SARS-CoV-2 RT-PCR was still positive, but specific antibodies appeared. Furthermore, the viral shedding time significantly decreased when the A1,430G or C12,473T mutation occurred (P<0.01 and FDR<0.01) and increased when G227A occurred (P<0.05 and FDR<0.05). High IL1R1, IL1R2, and TNFRSF21 expression in the host positively correlated with viral shedding time (P<0.05 and false discovery rate <0.05). Prolonged viral RNA shedding often occurs but may not increase disease damage. Prolonged viral RNA shedding is associated with viral mutations and host factors.

Changes of quantitative CT-based airway wall dimensions in patients with COVID-19 during early recovery.

BACKGROUND: As the coronavirus disease 19 (COVID-19) pandemic evolves, the need for recognizing the structural pulmonary changes of the disease during early convalescence has emerged. Most studies focus on parenchymal destruction of the disease; but little is known about whether the disease affects the airway. This study was conducted to investigate the changes in airway dimensions and explore the associated factors during early convalescence in patients with COVID-19. METHODS: We retrospectively analyzed quantitative computed tomography (CT)-based airway measures of 69 patients with COVID-19 from 5 February to 17 March 2020, and 32 non-COVID-19 participants from 1 January 2018 to 31 December 2019 from Guangzhou, China. The well-established measures of wall area fraction and the square root of the wall area of a hypothetical bronchus with an inner perimeter of 10 mm, were used to describe airway wall dimensions. We described the characteristics of the dimensions and inner area of airways in 66 patients with COVID-19 at the initial and convalescent stages of the disease, and compared them with the non-COVID-19 group. Linear regression models were constructed to investigate the association of airway dimensions with duration of hospitalization or disease severity after recovery. Partial correlation coefficients were calculated to investigate whether inflammatory markers were related to airway dimensions. RESULTS: Among 66 patients with COVID-19, airway dimensions were greater during disease initiation than early convalescence, which was significantly greater than in non-COVID-19 participants. No significant difference was found between the patients with COVID-19 at the initial stage and the non-COVID-19 controls regarding the first to eighth generations of the inner area. In adjusted regression models, duration of hospitalization was negatively associated with wall area fraction of the first to the sixth generation of airways. No significant associations exist between airway dimensions and disease severity, or airway dimensions with inflammatory markers. CONCLUSIONS: Airway dimensions in patients with COVID-19 during disease initiation are greater than those in non-COVID-19 participants. Such structural airway changes continue to remain significantly greater during early convalescence. No evidence shows that disease severity or inflammatory markers are associated with airway dimensions, implying that the primary lesion attacked by COVID-19 might not be the airways.

The use of non-invasive ventilation in COVID-19: A systematic review.

OBJECTIVE: Guidelines from different regions on the use of non-invasive ventilation in COVID-19 have generally been inconsistent. The aim of this systematic review was to appraise the quality and availability of guidelines, and whether non-invasive ventilation in the early stages of the pandemic is of importance. DESIGN AND METHOD: Databases, including PubMed, Web of Science, and Cochrane Library, as well as websites of international organizations and gray literature, were searched up to June 23, 2020. The reference lists of eligible papers were also hand-searched. RESULTS: A total of 26 guidelines met the inclusion criteria. According to the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument, the guidelines' methodological quality was low. Among six domains, Rigour of Development and Editorial Independence were of the lowest quality. Given the lack of evidence from randomized clinical trials and the great variation between different regions, recommendations for non-invasive ventilation have generated considerable debate regarding the early stages of COVID-19. CONCLUSIONS: Improving the methodological quality of the guidelines should be a goal with regard to future pandemics. Additionally, better-designed randomized clinical trials are needed to resolve contradictions regarding the impact of non-invasive ventilation. PROSPERO REGISTRATION NUMBER: CRD42020198410.