Pulmonary Fibrosis and Its Related Factors in Discharged Patients with New Coronavirus Pneumonia: A Cohort Study of 90-150 Days Follow-Up after Onset (preprint)

Background: The Coronavirus Disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic, posing a serious threat to public health worldwide. Whether survivors of COVID-19 pneumonia may be at risk of pulmonary fibrosis is still unknown.Methods: This study involves 462 laboratory confirmed patients with COVID-19 who were admitted to Shenzhen Third People’s Hospital. A total of 457 patients underwent thin-section chest CT scans during the hospitalization or after discharge to identify the pulmonary lesion. A total of 287 patients were followed up from 90 days to 150 days after the onset of the disease.Finding: 397 (86.87%), 311 (74.40%), 222 (79.56%), 141 (68.12%) and 49 (62.03%) patients developed with pulmonary fibrosis during the 0-30, 31-60, 61-90, 91-120 and >120 days after onset, respectively. Reversal of pulmonary fibrosis were found in 18 (4.53%), 61 (19.61%), 40 (18.02%), 54 (38.30%) and 24 (48.98%) COVID-19 patients during the 0-30, 31-60, 61-90, 91-120 and >120 days after onset, respectively. It was observed that Age, BMI, Fever, and Highest PCT were predictive factors for sustaining fibrosis even after 90 days from onset. Only a fraction of COVID-19 patients suffered with abnormal lung function after 90 days from onset.Interpretation: Long-term pulmonary fibrosis was more likely to develop in patients with older age, high BMI, severe/critical condition, fever, long time to turn the viral RNA negative, pre-existing disease and delay to admission. Fibrosis developed in COVID-19 patients could be reversed in about a half of the patients after 120 days from onset. The pulmonary function of most of COVID-19 patients with pulmonary fibrosis could turn to normal condition after three months from onset.Funding Statement: Shenzhen Science and Technology Research and Development Project (202002073000001 and 202002073000002), Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties (SZGSP011).Declaration of Interests: The authors declare no competing interests.Ethics Approval Statement: This study was conducted at Shenzhen Third People's Hospital and approved by the Ethics Committees, each patient gave written informed consent.

Pulmonary fibrosis and its related factors in discharged patients with new coronavirus pneumonia: A cohort study (preprint)

Background: Thousands of the Coronavirus Disease 2019 (COVID-19) patients have been discharged from hospitals, persistent follow-up studies are required to evaluate the prevalence of post-COVID-19 fibrosis.Methods: This study involves 462 laboratory confirmed patients with COVID-19 who were admitted to Shenzhen Third People’s Hospital from January 11, 2020 to April 26, 2020. A total of 457 patients underwent thin-section chest CT scans during the hospitalization or after discharge to identify the pulmonary lesion. A total of 287 patients were followed up from 90 days to 150 days after the onset of the disease, and lung function tests were conducted in about three months after the onset. The risk factors affecting the persistence of pulmonary fibrosis were identified through regression analysis and the prediction model of the persistence of pulmonary fibrosis was established.Results:  Parenchymal bands, irregular interfaces, reticulation and traction bronchiectasis were the most common CT features in all COVID-19 patients. During the 0-30, 31-60, 61-90, 91-120 and >120 days after onset, 86.87%, 74.40%, 79.56%, 68.12% and 62.03% patients developed with pulmonary fibrosis and 4.53%, 19.61%, 18.02%, 38.30% and 48.98% patients reversed pulmonary fibrosis, respectively. It was observed that Age, BMI, Fever, and Highest PCT were predictive factors for sustaining fibrosis even after 90 days from onset. A predictive model of the persistence with pulmonary fibrosis was developed based-on the Logistic Regression method with an accuracy, PPV, NPV, Sensitivity and Specificity of the model of 76%, 71%, 79%, 67%, and 82%, respectively. More than half of COVID-19 patients revealed abnormal condition in lung function after 90 days from onset, and the ratio of abnormal lung function did not differ on a statistically significant level between the fibrotic and non-fibrotic groups.Conclusions: Persistent pulmonary fibrosis was more likely to develop in patients with older age, high BMI, severe/critical condition, fever, long time to turn the viral RNA negative, pre-existing disease and delay to admission. Fibrosis developed in COVID-19 patients could be reversed in about a third of the patients after 120 days from onset. The pulmonary function of less than half of COVID-19 patients could turn to normal condition after three months from onset. An effective prediction model with an average Area Under the Curve (AUC) of 0.84 was established to predict the persistence of pulmonary fibrosis in COVID-19 patients for early diagnosis.

Viral shedding and immunological features of children COVID-19 patients (preprint)

Abstract Background SARS-CoV-2 could infect people at all ages, and the viral shedding and immunological features of children COVID-19 patients were analyzed. Methods Epidemiological information and clinical data were collected from 35 children patients. Viral RNAs in respiratory and fecal samples were detected. Plasma of 11 patients were collected and measured for 48 cytokines. Results 40% (14/35) of the children COVID-19 patients showed asymptomatic infections, while pneumonia shown by CT scan occurred in most of the cases (32/35, 91.43%). Elevated LDH, AST, CRP, neutropenia, leukopenia, lymphopenia and thrombocytopenia occurred in some cases, and CD4 and CD8 counts were normal. A total of 22 cytokines were significantly higher than the healthy control, and IP-10, IFN-2 of them in children were significantly lower than the adult patients. Meanwhile, MCP-3, HGF, MIP-1, and IL-1ra were similar or lower than healthy control, while significantly lower than adult patients. Viral RNAs were detected as early as the first day after illness onset (d.a.o) in both the respiratory and fecal samples. Viral RNAs decreased as the disease progression and mostly became negative in respiratory samples within 18 d.a.o, while maintained relatively stable during the disease progression and still detectable in some cases during 36~42 d.a.o. Conclusion COVID-19 in children was mild, and asymptomatic infection was common. Immune responses were relatively normal in children COVID-19 patients. Cytokine storm also occurred in children patients, while much weaker than adult patients. Positive rate of viral RNAs in fecal samples was high, and profile of viral shedding were different between respiratory and gastrointestinal tract.

Viral shedding and immunological features of children COVID-19 patients (preprint)

Background SARS-CoV-2 could infect people at all ages, and the viral shedding and immunological features of children COVID-19 patients were analyzed.Methods Epidemiological information and clinical data were collected from 35 children patients. Viral RNAs in respiratory and fecal samples were detected. Plasma of 11 patients were collected and measured for 48 cytokines.Results 40% (14/35) of the children COVID-19 patients showed asymptomatic infections, while pneumonia shown by CT scan occurred in most of the cases (32/35, 91.43%). Elevated LDH, AST, CRP, neutropenia, leukopenia, lymphopenia and thrombocytopenia occurred in some cases, and CD4 and CD8 counts were normal. A total of 22 cytokines were significantly higher than the healthy control, and IP-10, IFN-α2 of them in children were significantly lower than the adult patients. Meanwhile, MCP-3, HGF, MIP-1α, and IL-1ra were similar or lower than healthy control, while significantly lower than adult patients. Viral RNAs were detected as early as the first day after illness onset (d.a.o) in both the respiratory and fecal samples. Viral RNAs decreased as the disease progression and mostly became negative in respiratory samples within 18 d.a.o, while maintained relatively stable during the disease progression and still detectable in some cases during 36~42 d.a.o. Conclusion COVID-19 in children was mild, and asymptomatic infection was common. Immune responses were relatively normal in children COVID-19 patients. Cytokine storm also occurred in children patients, while much weaker than adult patients. Positive rate of viral RNAs in fecal samples was high, and profile of viral shedding were different between respiratory and gastrointestinal tract.

Exuberant elevation of IP-10, MCP-3 and IL-1ra during SARS-CoV-2 infection is associated with disease severity and fatal outcome (preprint)

The outbreak of Coronavirus Disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, December 2019, and continuously poses a serious threat to public health. Our previous study has shown that cytokine storm occurred during SARS-CoV-2 infection, while the detailed role of cytokines in the disease severity and progression remained unclear due to the limited case number. In this study, we examined 48 cytokines in the plasma samples from 53 COVID-19 cases, among whom 34 were severe cases, and the others moderate. Results showed that 14 cytokines were significantly elevated upon admission in COVID-19 cases. Moreover, IP-10, MCP-3, and IL-1ra were significantly higher in severe cases, and highly associated with the PaO2/FaO2 and Murray score. Furthermore, the three cytokines were independent predictors for the progression of COVID-19, and the combination of IP-10, MCP-3 and IL-1ra showed the biggest area under the curve (AUC) of the receiver-operating characteristics (ROC) calculations. Serial detection of IP-10, MCP-3 and IL-1ra in 14 severe cases showed that the continuous high levels of these cytokines were associated with disease deterioration and fatal outcome. In conclusion, we report three cytokines that closely associated with disease severity and outcome of COVID-19. These findings add to our understanding of the immunopathologic mechanisms of SARS-CoV-2 infection, which suggested novel therapeutic targets and strategy.