Background: Around the globe, moderate cases account for the largest proportion of all coronavirus disease 2019 (COVID-19) patients, and deteriorated moderate patients contribute the most in mortality. However, published articles failed to address the deterioration details of moderate cases, especially on when and how they deteriorated.Methods: All moderate COVID-19 patients hospitalized in Guangdong Province from January 14 to March 16, 2020, were included in this multicenter retrospective cohort study and were divided into deteriorated and non-deteriorated groups according to clinical status. Symptoms and demographic, therapeutic, and laboratory test result characteristics were collected to explore the features of disease deterioration.Results: Of 1,168 moderate patients included, 148 (13%) deteriorated to severe (130 cases) or critical (18 cases) status. Over 20% of the older subgroup (>50 years old) showed deterioration. The median time for deterioration was 11 days after onset [interquartile range (IQR) 9–14 days]. In addition, 12.2% severe cases could further develop to critical status after 3 days (IQR 2–6.5 days) of having a severe condition. Respiratory dysfunction and hypoxia were the major manifestations as disease deterioration, while 76 cases (52.1%) showed respiratory rate >30 breaths/min, 119 cases (80.4%) showed SaO₂ <93%, 100 cases (67.5%) had 201 < PaO₂/FiO₂ < 300, and 27 cases (18.9%) had blood lactic acid >2.0 mmol/L. In view of multiple organ dysfunction, 87.8% of acute respiratory distress syndrome (ARDS), 20.2% of acute kidney injury (AKI), 6.8% of coagulopathy, 4% of acute heart failure (AHF), 3.4% of acute hepatic injury (AHI), and 5.4% of shock occurred in deteriorated patients, while organ injury occurred in the following sequence: ARDS, AKI, AHF, coagulopathy, AHI, and shock.Conclusions: The deteriorated pattern of moderate COVID-19 patients is characterized as the 11th day from onset (IQR 9–14 days) being an important time point of disease deterioration with further exacerbation to critical condition in 3 days (IQR 2–6.5 days), A RDS followed by AKI being the typical modes of sequential organ damage.

Scutellarin, an anti-inflammatory agent, effectively suppressed microglia activation in rats with middle cerebral artery occlusion (MCAO). Robust microglia activation, acute in onset, was followed by astrogliosis. This study was aimed to determine if scutellarin would also affect the reactive astrocytes that play an important role in tissue repair. Expression of GFAP and Notch-1 and its members: Notch receptor intracellular domain (NICD), and transcription factor hairy and enhancer of split-1 (HES-1), together with nestin and proinflammatory mediators was assessed by immunofluorescence staining in TNC1 astrocytes treated, respectively, with BV-2 conditioned medium (CM) and CM + lipopolysaccharide (LPS) (CM + L) serving as the controls, and conditioned medium derived from LPS-activated BV-2 cells pretreated with scutellarin (CM + SL). Study of the above biomarkers was then extended to reactive astrocytes in scutellarin injected MCAO rats. TNC1 astrocytes remained relatively unreactive in terms of expression of different biomarkers to direct scutellarin treatment when compared with the control cells. In comparison to cells in the control medium (CM, CM + L), they responded vigorously to CM + SL as evidenced by the enhanced protein expression of GFAP, Notch-1, NICD and HES-1 coupled with that of nestin, TNF-α, IL-1β, and iNOS by Western and immunofluorescence analysis. Electron microscopy showed marked hypertrophy and cell expansion of TNC1 astrocytes bearing many filamentous processes indicative of enhanced astrocyte reaction when treated with CM + SL. In MCAO rats, scutellarin also augmented the expression of the above markers in reactive astrocytes; moreover, astrocytes were evidently hypertrophic. The results suggest that scutellarin regulates astrogliosis; more importantly, it is microglia-mediated as demonstrated in vitro. Increased expression of Notch signaling in synchrony with nestin may be linked to proliferation and “de-differentiation” of reactive astrocytes; the significance of enhanced TNF-α, IL-1β and iNOS expression in reactive astrocytes by scutellarin may be neuroprotective but this remains speculative.

Background: The ongoing COVID-19 pandemic has brought significant challenges to health system and consumed a lot of health resources. However, evidence on the hospitalization costs and their associated factors in COVID-19 cases is scarce.Objectives: To describe the total and components of hospitalization costs of COVID-19 cases, and investigate the associated factors of costs.Methods: We included 876 confirmed COVID-19 cases admitted to 33 designated hospitals from January 15th to April 27th, 2020 in Guangdong, China, and collected their demographic and clinical information. A multiple linear regression model was performed to estimate the associations of hospitalization costs with potential associated factors.Results: The median of total hospitalization costs of COVID-19 cases was $2,869.4 (IQR: $3,916.8). We found higher total costs in male (% difference: 29.7, 95% CI: 15.5, 45.6) than in female cases, in older cases than in younger ones, in severe cases (% difference: 344.8, 95% CI: 222.5, 513.6) than in mild ones, in cases with clinical aggravation than those without, in cases with clinical symptoms (% difference: 47.7, 95% CI: 26.2, 72.9) than those without, and in cases with comorbidities (% difference: 21.1%, 21.1, 95% CI: 4.4, 40.6) than those without. We also found lower non-pharmacologic therapy costs in cases treated with traditional Chinese medicine (TCM) therapy (% difference: −47.4, 95% CI: −64.5 to −22.0) than cases without.Conclusion: The hospitalization costs of COVID-19 cases in Guangdong were comparable to the national level. Factors associated with higher hospitalization costs included sex, older age, clinical severity and aggravation, clinical symptoms and comorbidities at admission. TCM therapy was found to be associated with lower costs for some non-pharmacologic therapies.

Short-term recurrence of positive SARS-CoV-2 RNA PCR in discharged COVID-19 patients attracts the public’s concern. This study aimed to determine clinical and epidemiological results of such patients. This retrospective study was conducted on 32 designated hospitals for COVID-19 patients discharged from January 14 ^th to March 10 ^th, 2020. After 28-day followed-up, re-positive patients confirmed by SARS-CoV-2 RNA RT-PCR were re-admitted to hospital for further treatments. All the close contacts of re-positive patients were asked 14-day self-segregating. Data of epidemiology, symptoms, laboratory tests and treatments were analyzed in re-positive patients and their close contacts were investigated. Of 1,282 discharged patients, 189 (14.74%) were tested re-positive of SARS-CoV-2 RNA during 28-day follow-up. The median time from discharge to re-positivity was 8 days (IQR 5-13). Patients in re-positive group were younger (34yr vs 45yr, p&0.001) with higher proportion of moderate symptoms (95.77% vs 84.35%, p&0.001) in the first hospitalization than negative group. During the second hospitalization, all re-positive patients showed normal in peripheral white blood cell and lymphocyte, and no new symptoms of COVID-19; 78.31% further improved on chest CT scan compared with the first discharge, yet 25.93% accepted antiviral therapy. The median time of re-positive to negative was 8 days (IQR 4-15). None of close contacts developed COVID-19. Our data suggested that the short term recurrence of positive SARS-CoV-2 RNA in discharged patients is not a relapse of COVID-19, and the risk of onward transmission is very low. This provides important information for managing COVID-19 patients.