Clinical Characteristics and Abnormal Parameters Evolution in Patients With Novel Coronavirus Infection: A Case Series of 272 Cases in Guangzhou.

OBJECTIVE: The aim of this study was to present the clinical characteristics and dynamic changes in laboratory parameters of the coronavirus disease 2019 (COVID-19) in Guangzhou, and explore the probable early warning indicators of disease progression. METHOD: We enrolled all the patients diagnosed with COVID-19 in the Guangzhou No. 8 People's Hospital. The patients' demographic and epidemiologic data were collected, including chief complaints, lab results, and imaging examination findings. RESULTS: The characteristics of the patients in Guangzhou are different from those in Wuhan. The patients were younger in age, predominately female, and their condition was not commonly combined with other diseases. A total of 75% of patients suffered fever on admission, followed by cough occurring in 62% patients. Comparing the mild/normal and severe/critical patients, being male, of older age, combined with hypertension, abnormal blood routine test results, raised creatine kinase, glutamic oxaloacetic transaminase, lactate dehydrogenase, C-reactive protein, procalcitonin, D-dimer, fibrinogen, activated partial thromboplastin time, and positive proteinuria were early warning indicators of severe disease. CONCLUSION: The patients outside epidemic areas showed different characteristics from those in Wuhan. The abnormal laboratory parameters were markedly changed 4 weeks after admission, and also were different between the mild and severe patients. More evidence is needed to confirm highly specific and sensitive potential early warning indicators of severe disease.

Correction: Incidence, clinical course and risk factor for recurrent PCR positivity in discharged COVID-19 patients in Guangzhou, China: A prospective cohort study.

[This corrects the article DOI: 10.1371/journal.pntd.0008648.].

Cardiac involvement in patients recovering from Delta Variant of COVID-19: a prospective multi-parametric MRI study.

AIMS: The cardiac injury and sequelae of Delta Variant of coronavirus disease 2019 (COVID-19) remain unknown. This study aimed to evaluate the presence of cardiac involvement in patients recovering from Delta Variant of COVID-19 based on multi-parametric cardiac magnetic resonance imaging (MRI). METHODS AND RESULTS: We prospectively assessed patients recovering from Delta Variant of COVID-19 using multi-parametric cardiac magnetic resonance imaging (MRI) between June 2021 and July 2021. Comparison was made with 25 healthy controls. Forty-four patients (median age 51 years, 28 women) recovering from Delta Variant were recruited and had a median time of 35 days between diagnosis and cardiac MRI. There were no patients with chest pain (0/44, 0%) and high sensitivity cardiac troponin T troponin elevation (median levels 2.20 pg/mL, IQR levels 0.85-4.40 pg/mL). Regarding the cardiac imaging findings, a total of 14 (32%) patients presented cardiac tissue feature abnormalities, and a total of 9 (20%) patients had a myocarditis-like injury based on cardiac MRI 2018 Lake Louise criteria. When we further assessed the T1 and T2 mapping values for of patients' individual, abnormal raised global native T1, T2, and extracellular volume were seen in 6 (14%), 6 (14%), and 4 (9%) patients, respectively. Comparing with controls, the patients had lower LV global longitudinal strain and (-22.2 ± 2.8% vs. -24.6 ± 2.0%, P < 0.001) and global circumferential strain (-20.7 ± 6.8% vs. -24.3 ± 2.9%, P = 0.014), but higher global native T1 (1318.8 ± 55.5 ms vs. 1282.9 ± 38.1 ms, P = 0.006). Four (9%) patients presented myocardial late gadolinium enhancement with subepicardial pattern mostly common seen, and two (5%) patients presented pericardial enhancement. CONCLUSIONS: The cardiac MRI could detect subclinical functional and myocardial tissue characteristic abnormalities in individuals who were recovering from Delta Variant without cardiac-related clinical findings. The native T1 mapping and strain imaging may be a sensitive tool for the noninvasive detection of a subset of patients who are at risk for cardiac sequelae and more prone to myocardial damage in survivors with Delta Variant.

COVID-19 induces new-onset insulin resistance and lipid metabolic dysregulation via regulation of secreted metabolic factors.

Abnormal glucose and lipid metabolism in COVID-19 patients were recently reported with unclear mechanism. In this study, we retrospectively investigated a cohort of COVID-19 patients without pre-existing metabolic-related diseases, and found new-onset insulin resistance, hyperglycemia, and decreased HDL-C in these patients. Mechanistically, SARS-CoV-2 infection increased the expression of RE1-silencing transcription factor (REST), which modulated the expression of secreted metabolic factors including myeloperoxidase, apelin, and myostatin at the transcriptional level, resulting in the perturbation of glucose and lipid metabolism. Furthermore, several lipids, including (±)5-HETE, (±)12-HETE, propionic acid, and isobutyric acid were identified as the potential biomarkers of COVID-19-induced metabolic dysregulation, especially in insulin resistance. Taken together, our study revealed insulin resistance as the direct cause of hyperglycemia upon COVID-19, and further illustrated the underlying mechanisms, providing potential therapeutic targets for COVID-19-induced metabolic complications.

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.).

Protective humoral and cellular immune responses to SARS-CoV-2 persist up to 1 year after recovery.

SARS-CoV-2 vaccination has been launched worldwide to build effective population-level immunity to curb the spread of this virus. The effectiveness and duration of protective immunity is a critical factor for public health. Here, we report the kinetics of the SARS-CoV-2 specific immune response in 204 individuals up to 1-year after recovery from COVID-19. RBD-IgG and full-length spike-IgG concentrations and serum neutralizing capacity decreases during the first 6-months, but is maintained stably up to 1-year after hospital discharge. Even individuals who had generated high IgG levels during early convalescent stages had IgG levels that had decreased to a similar level one year later. Notably, the RBD-IgG level positively correlates with serum neutralizing capacity, suggesting the representative role of RBD-IgG in predicting serum protection. Moreover, viral-specific cellular immune protection, including spike and nucleoprotein specific, persisted between 6 months and 12 months. Altogether, our study supports the persistence of viral-specific protective immunity over 1 year.

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.

Longitudinal Peripheral Blood Transcriptional Analysis Reveals Molecular Signatures of Disease Progression in COVID-19 Patients.

Coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with some patients developing severe illness or even death. Disease severity has been associated with increased levels of proinflammatory cytokines and lymphopenia. To elucidate the atlas of peripheral immune response and pathways that might lead to immunopathology during COVID-19 disease course, we performed a peripheral blood RNA sequencing analysis of the same patient's samples collected from symptom onset to full recovery. We found that PBMCs at different disease stages exhibited unique transcriptome characteristics. We observed that SARS-CoV-2 infection caused excessive release of inflammatory cytokines and lipid mediators as well as an aberrant increase of low-density neutrophils. Further analysis revealed an increased expression of RNA sensors and robust IFN-stimulated genes expression but a repressed type I IFN production. SARS-CoV-2 infection activated T and B cell responses during the early onset but resulted in transient adaptive immunosuppression during severe disease state. Activation of apoptotic pathways and functional exhaustion may contribute to the reduction of lymphocytes and dysfunction of adaptive immunity, whereas increase in IL2, IL7, and IL15 may facilitate the recovery of the number and function of lymphocytes. Our study provides comprehensive transcriptional signatures of peripheral blood response in patients with moderate COVID-19.

[Cardiac presentations in severe and critical coronavirus disease 2019].

OBJECTIVE: To investigate the cardiac presentations and the possible influencing factors of severe and critical coronavirus disease 2019 (COVID-19). METHODS: A retrospective study was conducted. Patients with severe and critical COVID-19 admitted to the Eighth People's Hospital of Guangzhou from January 21st to February 24th 2020 were enrolled. According to the clinical classification, the patients were divided into severe group and critical group. The myocardial injury markers, such as lactate dehydrogenase (LDH), aspartate aminotransferase (AST), creatine kinase (CK), cardiac troponin I (cTnI), myoglobin (MYO), MB isoenzyme of creatine kinase (CK-MB), B-type natriuretic peptide (BNP) and electrocardiogram (ECG) changes were compared between the two groups. RESULTS: A total of 55 COVID-19 patients were selected, including 15 critical cases and 40 severe cases. The patients with severe and critical COVID-19 were male-dominated (61.8%), the average age was (61.2±13.0) years old, 83.6% (46 cases) of them had contact history of Hubei, 38.2% (21 cases) of them were complicated with hypertension. There was no significant difference in baseline data between the critical group and the severe group. Myocardial injury markers of critical and severe COVID-19 patients were increased in different proportion, LDH increased in most patients (20 severe cases and 7 critical cases), followed by AST (16 severe cases and 5 critical cases). There was significant difference in the number of patients with elevated CK between severe group and critical group (cases: 1 vs. 4, P = 0.027). Abnormal ECG was found in 39 of 42 patients with ECG examination. Nonspecific change of T wave was the most common. Before and after treatment, 9 of 15 patients with changes of ECG and myocardial injury markers had oxygenation index less than 100 mmHg (1 mmHg = 0.133 kPa), and the prominent changes of ECG were heart rate increasing and ST-T change. CONCLUSIONS: The increase of myocardial injury markers and abnormal ECG were not specific to the myocardial injury of severe and critical COVID-19 patients. At the same time, the dynamic changes of myocardial injury markers and ECG could reflect the situation of myocardial damage.

Clinical Characteristics of Patients Infected With the Novel 2019 Coronavirus (SARS-Cov-2) in Guangzhou, China.

BACKGROUND: The clinical manifestations and factors associated with the severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections outside of Wuhan are not clearly understood. METHODS: All laboratory-confirmed cases with SARS-Cov-2 infection who were hospitalized and monitored in Guangzhou Eighth People's Hospital were recruited from January 20 to February 10. RESULTS: A total of 275 patients were included in this study. The median patient age was 49 years, and 63.6% had exposure to Wuhan. The median virus incubation period was 6 days. Fever (70.5%) and dry cough (56.0%) were the most common symptoms. A decreased albumin level was found in 51.3% of patients, lymphopenia in 33.5%, and pneumonia based on chest computed tomography in 86%. Approximately 16% of patients (n = 45) had severe disease, and there were no deaths. Compared with patients with nonsevere disease, those with severe disease were older, had a higher frequency of coexisting conditions and pneumonia, and had a shorter incubation period (all P < .05). There were no differences between patients who likely contacted the virus in Wuhan and those who had no exposure to Wuhan. Multivariate logistic regression analysis indicated that older age, male sex, and decreased albumin level were independently associated with disease severity. CONCLUSIONS: Most of the patients infected with SARS-CoV-2 in Guangzhou, China are not severe cases and patients with older age, male, and decreased albumin level were more likely to develop into severe ones.

Longitudinal clinical and radiographic evaluation reveals interleukin-6 as an indicator of persistent pulmonary injury in COVID-19.

Rationale: Previous studies of coronavirus disease 2019 (COVID-19) were mainly focused on cross-sectional analysis. In this study, we sought to evaluate the dynamic changes of immunological and radiographic features, and the association with the outcome of pulmonary lesions in COVID-19 patients. Methods: Peripheral blood samples and radiographic data were collected longitudinally for up to 8 weeks from 158 laboratory-confirmed COVID-19 patients. The chest computed tomography (CT) scans were scored based on a semi-quantification assessment according to the extent of pulmonary abnormalities; the temporal change of the immunological and radiographic features was analyzed. Results: Compared with mild and moderate patients, severe patients had significantly decreased counts of lymphocytes, CD4+ T cells, CD8+ T cells, and CD19+ B cells but dramatically elevated counts of neutrophils and levels of interleukin (IL)-6. Sequential monitoring showed a sustained increase in lymphocytes counts and significantly decreased levels of IL-6 in severe patients during the disease course. Notably, patients with persistent pulmonary lesions (CT score ≥ 5 in week 8) showed high levels of IL-6 during the follow-up period, compared with those with recovery lesions (CT score < 5 in week 8). More importantly, the peak expression of IL-6 prior to the aggravated lung injury was mainly found in patients with persistent lesions, and multivariate analysis showed that IL-6 level upon admission was an independent factor associated with the persistent pulmonary injury. Conclusion: Prolonged elevation of IL-6 is associated with persistent pulmonary lesions in COVID-19 patients. Sequential monitoring and timely intervention of IL-6 may favor the clinical management of COVID-19.

Risk Factors of Fatal Outcome in Hospitalized Subjects With Coronavirus Disease 2019 From a Nationwide Analysis in China.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) has become a global health emergency. The cumulative number of new confirmed cases and deaths are still increasing out of China. Independent predicted factors associated with fatal outcomes remain uncertain. RESEARCH QUESTION: The goal of the current study was to investigate the potential risk factors associated with fatal outcomes from COVID-19 through a multivariate Cox regression analysis and a nomogram model. STUDY DESIGN AND METHODS: A retrospective cohort of 1,590 hospitalized patients with COVID-19 throughout China was established. The prognostic effects of variables, including clinical features and laboratory findings, were analyzed by using Kaplan-Meier methods and a Cox proportional hazards model. A prognostic nomogram was formulated to predict the survival of patients with COVID-19. RESULTS: In this nationwide cohort, nonsurvivors included a higher incidence of elderly people and subjects with coexisting chronic illness, dyspnea, and laboratory abnormalities on admission compared with survivors. Multivariate Cox regression analysis showed that age ≥ 75 years (hazard ratio [HR], 7.86; 95% CI, 2.44-25.35), age between 65 and 74 years (HR, 3.43; 95% CI, 1.24-9.5), coronary heart disease (HR, 4.28; 95% CI, 1.14-16.13), cerebrovascular disease (HR, 3.1; 95% CI, 1.07-8.94), dyspnea (HR, 3.96; 95% CI, 1.42-11), procalcitonin level > 0.5 ng/mL (HR, 8.72; 95% CI, 3.42-22.28), and aspartate aminotransferase level > 40 U/L (HR, 2.2; 95% CI, 1.1-6.73) were independent risk factors associated with fatal outcome. A nomogram was established based on the results of multivariate analysis. The internal bootstrap resampling approach suggested the nomogram has sufficient discriminatory power with a C-index of 0.91 (95% CI, 0.85-0.97). The calibration plots also showed good consistency between the prediction and the observation. INTERPRETATION: The proposed nomogram accurately predicted clinical outcomes of patients with COVID-19 based on individual characteristics. Earlier identification, more intensive surveillance, and appropriate therapy should be considered in patients at high risk.

Prognostic Factors for COVID-19 Pneumonia Progression to Severe Symptoms Based on Earlier Clinical Features: A Retrospective Analysis.

Approximately 15-20% of COVID-19 patients will develop severe pneumonia, and about 10% of these will die if not properly managed. Earlier discrimination of potentially severe patients basing on routine clinical and laboratory changes and commencement of prophylactical management will not only save lives but also mitigate the otherwise overwhelming healthcare burden. In this retrospective investigation, the clinical and laboratory features were collected from 125 COVID-19 patients who were classified into mild (93 cases) or severe (32 cases) groups according to their clinical outcomes after 3-7 days post-admission. The subsequent analysis with single-factor and multivariate logistic regression methods indicated that 17 factors on admission differed significantly between mild and severe groups but that only comorbidity with underlying diseases, increased respiratory rate (>24/min), elevated C-reactive protein (CRP >10 mg/L), and lactate dehydrogenase (LDH >250 U/L) were independently associated with the later disease development. Finally, we evaluated their prognostic values with receiver operating characteristic curve (ROC) analysis and found that the above four factors could not confidently predict the occurrence of severe pneumonia individually, though a combination of fast respiratory rate and elevated LDH significantly increased the predictive confidence (AUC = 0.944, sensitivity = 0.941, and specificity = 0.902). A combination consisting of three or four factors could further increase the prognostic value. Additionally, measurable serum viral RNA post-admission independently predicted the severe illness occurrence. In conclusion, a combination of general clinical characteristics and laboratory tests could provide a highly confident prognostic value for identifying potentially severe COVID-19 pneumonia patients.

Application of high-flow nasal cannula oxygen therapy in patients with severe COVID-19

Objective: To investigate the clinical value of high-flow nasal cannula oxygen therapy(HFNC) in patients with severe coronavirus disease 2019 (COVID-19).

Factors associated with clinical outcomes in patients with Coronavirus Disease 2019 in Guangzhou, China.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) is threatening billions of people. We described the clinical characteristics and explore virological and immunological factors associated with clinical outcomes. METHODS: 297 COVID-19 patients hospitalized in Guangzhou Eighth People's Hospital between January 20 and February 20, 2020 were included. Epidemiological, clinical and laboratory data were collected and analyzed. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) RNA in respiratory tract, blood samples and digestive tract was detected and lymphocyte subsets were tested periodically. RESULT: Among the 297 patients (median age of 48 years), 154 (51.9 %) were female, 245 (82.5 %) mild/moderate cases, and 52 (17.5 %) severe/critical cases. 270 patients were detected for SARS-CoV-2 RNA in anal swabs and/or blood samples, and the overall positive rate was 23.0 % (62/270), higher in severe/critical cases than in mild/moderate cases (52.0 % vs. 16.4 %, P < 0.001). The CD4/CD8 ratio on admission was significantly higher in severe/critical cases than in mild/moderate cases (1.84 vs. 1.50, P = 0.022). During a median follow-up period of 17 days, 36 (12.1 %) patients were admitted to intensive care unit (ICU), 16 (5.4 %) patients developed respiratory failure and underwent mechanical ventilation, four (1.3 %) patients needed extracorporeal membrane oxygenation (ECMO), only one (0.34 %) patients died of multiple organ failure. Detectable SARS-CoV-2 RNA in anal swabs and/or blood samples, as well as higher CD4/CD8 ratio were independent risk factors of respiratory failure and ICU admission. CONCLUSIONS: Most of COVID-19 patients in Guangzhou are mild/moderate, and presence of extrapulmonary virus and higher CD4/CD8 ratio are associated with higher risk of worse outcomes.

A compromised specific humoral immune response against the SARS-CoV-2 receptor-binding domain is related to viral persistence and periodic shedding in the gastrointestinal tract.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been redetected after discharge in some coronavirus disease 2019 (COVID-19) patients. The reason for the recurrent positivity of the test and the potential public health concern due to this occurrence are still unknown. Here, we analyzed the viral data and clinical manifestations of 289 domestic Chinese COVID-19 patients and found that 21 individuals (7.3%) were readmitted for hospitalization after detection of SARS-CoV-2 after discharge. First, we experimentally confirmed that the virus was involved in the initial infection and was not a secondary infection. In positive retests, the virus was usually found in anal samples (15 of 21, 71.4%). Through analysis of the intracellular viral subgenomic messenger RNA (sgmRNA), we verified that positive retest patients had active viral replication in their gastrointestinal tracts (3 of 16 patients, 18.7%) but not in their respiratory tracts. Then, we found that viral persistence was not associated with high viral titers, delayed viral clearance, old age, or more severe clinical symptoms during the first hospitalization. In contrast, viral rebound was associated with significantly lower levels of and slower generation of viral receptor-binding domain (RBD)-specific IgA and IgG antibodies. Our study demonstrated that the positive retest patients failed to create a robust protective humoral immune response, which might result in SARS-CoV-2 persistence in the gastrointestinal tract and possibly in active viral shedding. Further exploration of the mechanism underlying the rebound in SARS-CoV-2 in this population will be crucial for preventing virus spread and developing effective vaccines.

Effect of Recombinant Human Granulocyte Colony-Stimulating Factor for Patients With Coronavirus Disease 2019 (COVID-19) and Lymphopenia: A Randomized Clinical Trial.

Importance: Lymphopenia is common and correlates with poor clinical outcomes in patients with coronavirus disease 2019 (COVID-19). Objective: To determine whether a therapy that increases peripheral blood leukocyte and lymphocyte cell counts leads to clinical improvement in patients with COVID-19. Design, Setting and Participants: Between February 18 and April 10, 2020, we conducted an open-label, multicenter, randomized clinical trial at 3 participating centers in China. The main eligibility criteria were pneumonia, a blood lymphocyte cell count of 800 per µL (to convert to ×109/L, multiply by 0.001) or lower, and no comorbidities. Severe acute respiratory syndrome coronavirus 2 infection was confirmed with reverse-transcription polymerase chain reaction testing. Exposures: Usual care alone, or usual care plus 3 doses of recombinant human granulocyte colony-stimulating factor (rhG-CSF, 5 µg/kg, subcutaneously at days 0-2). Main Outcomes and Measures: The primary end point was the time from randomization to improvement of at least 1 point on a 7-category disease severity score. Results: Of 200 participants, 112 (56%) were men and the median (interquartile range [IQR]) age was 45 (40-55) years. There was random assignment of 100 patients (50%) to the rhG-CSF group and 100 (50%) to the usual care group. Time to clinical improvement was similar between groups (rhG-CSF group median of 12 days (IQR, 10-16 days) vs usual care group median of 13 days (IQR, 11-17 days); hazard ratio, 1.28; 95% CI, 0.95-1.71; P = .06). For secondary end points, the proportion of patients progressing to acute respiratory distress syndrome, sepsis, or septic shock was lower in the rhG-CSF group (rhG-CSF group, 2% vs usual care group, 15%; difference, -13%; 95%CI, -21.4% to -5.4%). At 21 days, 2 patients (2%) had died in the rhG-CSF group compared with 10 patients (10%) in the usual care group (hazard ratio, 0.19; 95%CI, 0.04-0.88). At day 5, the lymphocyte cell count was higher in the rhG-CSF group (rhG-CSF group median of 1050/µL vs usual care group median of 620/µL; Hodges-Lehmann estimate of the difference in medians, 440; 95% CI, 380-490). Serious adverse events, such as sepsis or septic shock, respiratory failure, and acute respiratory distress syndrome, occurred in 29 patients (14.5%) in the rhG-CSF group and 42 patients (21%) in the usual care group. Conclusion and Relevance: In preliminary findings from a randomized clinical trial, rhG-CSF treatment for patients with COVID-19 with lymphopenia but no comorbidities did not accelerate clinical improvement, but the number of patients developing critical illness or dying may have been reduced. Larger studies that include a broader range of patients with COVID-19 should be conducted. Trial Registration: Chinese Clinical Trial Registry: ChiCTR2000030007.

Incidence, clinical course and risk factor for recurrent PCR positivity in discharged COVID-19 patients in Guangzhou, China: A prospective cohort study.

The phenomenon of COVID-19 patients tested positive for SARS-CoV-2 after discharge (redetectable as positive, RP) emerged globally. The data of incidence rate and risk factors for RP event and the clinical features of RP patients may provide recommendations for virus containment and cases management for COVID-19. We prospectively collected and analyzed the epidemiological, clinical and virological data from 285 adult patients with COVID-19 and acquired their definite clinical outcome (getting PCR positive or not during post-discharge surveillance). By March 10, 27 (9.5%) discharged patients had tested positive for SARS-CoV-2 in their nasopharyngeal swab after a median duration of 7·0 days (IQR 5·0-8·0). Compared to first admission, RP patients generally had milder clinical symptoms, lower viral load, shorter length of stay and improved pulmonary conditions at readmission (p<0.05). Elder RP patients (≥ 60 years old) were more likely to be symptomatic compared to younger patients (7/8, 87.5% vs. 3/19, 18.8%, p = 0.001) at readmission. Age, sex, epidemiological history, clinical symptoms and underlying diseases were similar between RP and non-RP patients (p>0.05). A prolonged duration of viral shedding (>10 days) during the first hospitalization [adjusted odds ratio [aOR]: 5.82, 95% confidence interval [CI]: 2.50-13.57 for N gene; aOR: 9.64, 95% CI: 3.91-23.73 for ORF gene] and higher Ct value (ORF) in the third week of the first hospitalization (aOR: 0.69; 95% CI: 0.50-0.95) were associated with RP events. In conclusion, RP events occurred in nearly 10% of COVID-19 patients shortly after the negative tests, were not associated with worsening symptoms and unlikely reflect reinfection. Patients' lack of efficiency in virus clearance was a risk factor for RP result. It is noteworthy that elder RP patients (≥ 60 years old) were more susceptible to clinical symptoms at readmission.