Longitudinal analysis of antibody dynamics in COVID-19 convalescents reveals neutralizing responses up to 16 months after infection.

Elucidating the dynamics of the neutralizing antibody (nAb) response in coronavirus disease 2019 (COVID-19) convalescents is crucial in controlling the pandemic and informing vaccination strategies. Here we measured nAb titres across 411 sequential plasma samples collected during 1-480 d after illness onset or laboratory confirmation (d.a.o.) from 214 COVID-19 convalescents, covering the clinical spectrum of disease and without additional exposure history after recovery or vaccination against SARS-CoV-2, using authentic SARS-CoV-2 microneutralization (MN) assays. Forty-eight samples were also tested for neutralizing activities against the circulating variants using pseudotyped neutralization assay. Results showed that anti-RBD IgG and MN titres peaked at ~120 d.a.o. and subsequently declined, with significantly reduced nAb responses found in 91.67% of COVID-19 convalescents (≥50% decrease in current MN titres compared with the paired peak MN titres). Despite this decline, majority of the COVID-19 convalescents maintained detectable anti-RBD IgG and MN titres at 400-480 d.a.o., with undetectable neutralizing activity found in 14.41% (16/111) of the mild and 50% (5/10) of the asymptomatic infections at 330-480 d.a.o. Persistent antibody-dependent immunity could provide protection against circulating variants after one year, despite significantly decreased neutralizing activities against Beta, Delta and Mu variants. In conclusion, these data show that despite a marked decline in neutralizing activity over time, nAb responses persist for up to 480 d in most convalescents of symptomatic COVID-19, whereas a high rate of undetectable nAb responses was found in convalescents from asymptomatic infections.

A Wearable Tele-Health System towards Monitoring COVID-19 and Chronic Diseases.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic since early 2020. The coronavirus disease 2019 (COVID-19) has already caused more than three million deaths worldwide and affected people's physical and mental health. COVID-19 patients with mild symptoms are generally required to self-isolate and monitor for symptoms at least for 14 days in the case the disease turns towards severe complications. In this work, we overviewed the impact of COVID-19 on the patients' general health with a focus on their cardiovascular, respiratory and mental health, and investigated several existing patient monitoring systems. We addressed the limitations of these systems and proposed a wearable telehealth solution for monitoring a set of physiological parameters that are critical for COVID-19 patients such as body temperature, heart rate, heart rate variability, blood oxygen saturation, respiratory rate, blood pressure, and cough. This physiological information can be further combined to potentially estimate the lung function using artificial intelligence (AI) and sensor fusion techniques. The prototype, which includes the hardware and a smartphone app, showed promising results with performance comparable to or better than similar commercial devices, thus potentially making the proposed system an ideal wearable solution for long-term monitoring of COVID-19 patients and other chronic diseases.

A comparative analysis of eleven neural networks architectures for small datasets of lung images of COVID-19 patients toward improved clinical decisions.

The 2019 novel severe acute respiratory syndrome coronavirus 2-SARS-CoV2, commonly known as COVID-19, is a highly infectious disease that has endangered the health of many people around the world. COVID-19, which infects the lungs, is often diagnosed and managed using X-ray or computed tomography (CT) images. For such images, rapid and accurate classification and diagnosis can be performed using deep learning methods that are trained using existing neural network models. However, at present, there is no standardized method or uniform evaluation metric for image classification, which makes it difficult to compare the strengths and weaknesses of different neural network models. This paper used eleven well-known convolutional neural networks, including VGG-16, ResNet-18, ResNet-50, DenseNet-121, DenseNet-169, Inception-v3, Inception-v4, SqueezeNet, MobileNet, ShuffeNet, and EfficientNet-b0, to classify and distinguish COVID-19 and non-COVID-19 lung images. These eleven models were applied to different batch sizes and epoch cases, and their overall performance was compared and discussed. The results of this study can provide decision support in guiding research on processing and analyzing small medical datasets to understand which model choices can yield better outcomes in lung image classification, diagnosis, disease management and patient care.

Protective Effect of Remdesivir Against Pulmonary Fibrosis in Mice.

Pulmonary fibrosis is a known sequela of severe or persistent lung damage. Existing clinical, imaging and autopsy studies have shown that the lungs exhibit a pathological pulmonary fibrosis phenotype after infection with coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pulmonary fibrosis may be one of the most serious sequelae associated with coronavirus disease 2019 (COVID-19). In this study, we aimed to examine the preventative effects of the antiviral drug remdesivir on pulmonary fibrosis. We used a mouse model of bleomycin-induced pulmonary fibrosis to evaluate the effects of remdesivir on pulmonary fibrosis in vivo and further explored the potential pharmacological mechanisms of remdesivir in lung fibroblasts and alveolar epithelial cells in vitro. The preventive remdesivir treatment was started on the day of bleomycin installation, and the results showed that remdesivir significantly alleviated bleomycin-induced collagen deposition and improved pulmonary function. In vitro experiments showed that remdesivir dose-dependently suppressed TGF-ß1-induced lung fibroblast activation and improved TGF-ß1-induced alveolar epithelial to mesenchymal transition. Our results indicate that remdesivir can preventatively alleviate the severity of pulmonary fibrosis and provide some reference for the prevention of pulmonary fibrosis in patients with COVID-19.

Effect of dihydromyricetin on SARS-CoV-2 viral replication and pulmonary inflammation and fibrosis.

BACKGROUND: COVID-19 (Coronavirus Disease-2019) has spread widely around the world and impacted human health for millions. The lack of effective targeted drugs and vaccines forces scientific world to search for new effective antiviral therapeutic drugs. It has reported that flavonoids have potential inhibitory activity on SARS-CoV-2 Mpro and anti-inflammatory properties. Dihydromyricetin, as a flavonol, also has antiviral and anti-inflammatory potential. However, the inhibition of dihydromyricetin on SARS-CoV-2 Mpro and the protective effect of dihydromyricetin on pulmonary inflammation and fibrosis have not been proved and explained. PURPOSE: The coronavirus main protease (Mpro) is essential for SARS-CoV-2 replication and to be recognized as an attractive drug target, we expect to find the inhibitor of Mpro. Novel coronavirus infection can cause severe inflammation and even sequelae of pulmonary fibrosis in critically ill patients. We hope to find a drug that can not only inhibit virus replication but also alleviate inflammation and pulmonary fibrosis in patients. METHODS: FRET-based enzymatic assay was used to evaluate the inhibit activity of dihydromyricetin on SARS-CoV-2 Mpro. Molecular docking was used to identify the binding pose of dihydromyricetin with SARS-CoV-2 Mpro. The protective effects of dihydromyricetin against BLM-induced pulmonary inflammation and fibrosis were investigated in C57BL6 mice. BALF and lung tissue were collected for inflammation cells count, ELISA, masson and HE staining, western blotting and immunohistochemistry to analyze the effects of dihydromyricetin on pulmonary inflammation and fibrosis. MTT, western blotting, reverse transcription-polymerase chain reaction (RT-PCR) and wound healing were used to analyze the effects of dihydromyricetin on lung fibrosis mechanisms in Mlg cells. RESULTS: In this study, we found that dihydromyricetin is a potent inhibitor targeting the SARS-CoV-2 Mpro with a half-maximum inhibitory concentration (IC50) of 1.716 ± 0.419 µM, using molecular docking and the FRET-based enzymatic assay. The binding pose of dihydromyricetin with SARS-CoV-2 Mpro was identified using molecular docking method. In the binding pocket of SARS-CoV-2 Mpro, the dihydrochromone ring of dihydromyricetin interact with the imidazole side chain of His163 through π-π stacking. The 1-oxygen of dihydromyricetin forms a hydrogen bond with the backbone nitrogen of Glu166. The 3-, 7-, 3'- and 4'-hydroxyl of dihydromyricetin interact with Gln189, Leu141, Arg188 and Thr190 through hydrogen bonds. Moreover, our results showed that dihydromyricetin can significantly alleviate BLM-induced pulmonary inflammation by inhibiting the infiltration of inflammation cells and the secretion of inflammation factors in the early process and also ameliorate pulmonary fibrosis by improving pulmonary function and down-regulate the expression of α-SMA and fibronectin in vivo. Our results also showed that dihydromyricetin inhibits the migration and activation of myofibroblasts and extracellular matrix production via transforming growth factor (TGF)-ß1/Smad signaling pathways. CONCLUSION: Dihydromyricetin is an effective inhibitor for SARS-CoV-2 Mpro and it prevents BLM-induced pulmonary inflammation and fibrosis in mice. Dihydromyricetin will be a potential medicine for the treatment of COVID-19 and its sequelae.

Pulmonary fibrosis and its related factors in discharged patients with new corona virus pneumonia: a cohort study.

BACKGROUND: Thousands of 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 to 150 days after the onset of the disease, and lung function tests were conducted 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 the COVID-19 patients revealed abnormal conditions 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, higher BMI, severe/critical condition, fever, a longer viral clearance time, pre-existing disease and delayed hospitalization. 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.

Geographic Differences on Clinical Manifestations of COVID-19 Infection Between Overseas Chinese and Local Chinese Patients.

INTRODUCTION: The novel coronavirus (COVID-19) has become a global pandemic with sharp rises in the number of confirmed cases and rapid spread across the world. Here, we looked at the effects of geographic differences on clinical manifestations of SARS-CoV-2 infected patients. METHODS: A total of 114 confirmed COVID-19 patients were included in this study. The epidemiological, demographic, clinical, as well as laboratory findings were extracted from the electronic medical records of these patients. RESULTS: We report the observation that patients from overseas residents diagnosed with COVID-19 were mildly symptomatic with cough and presented with lower inflammatory response and attenuated virus clearance rate, as well as correspondingly prolonged days of hospital stay than local Chinese patients. Moreover, the receiver-operating characteristic (ROC) analysis, performed to provide a measure of the difference between two groups, showed that serum albumin had the highest area under the curve value (0.81, p < 0.001). DISCUSSION: Our results suggested that blood albumin level acted as a predictive value in distinguishing clinical features between local and overseas Chinese. This work underscores the need to identify distinguishably prognostic factors of geographical dissimilarity in COVID-19 patients.

Epidemiology of COVID-19: A systematic review and meta-analysis of clinical characteristics, risk factors, and outcomes.

Coronavirus disease 2019 (COVID-19) has become a pandemic, but its reported characteristics and outcomes vary greatly amongst studies. We determined pooled estimates for clinical characteristics and outcomes in COVID-19 patients including subgroups by disease severity (based on World Health Organization Interim Guidance Report or Infectious Disease Society of America/American Thoracic Society criteria) and by country/region. We searched Pubmed, Embase, Scopus, Cochrane, Chinese Medical Journal, and preprint databases from 1 January 2020 to 6 April 2020. Studies of laboratory-confirmed COVID-19 patients with relevant data were included. Two reviewers independently performed study selection and data extraction. From 6007 articles, 212 studies from 11 countries/regions involving 281 461 individuals were analyzed. Overall, mean age was 46.7 years, 51.8% were male, 22.9% had severe disease, and mortality was 5.6%. Underlying immunosuppression, diabetes, and malignancy were most strongly associated with severe COVID-19 (coefficient = 53.9, 23.4, 23.4, respectively, all P < .0007), while older age, male gender, diabetes, and hypertension were also associated with higher mortality (coefficient = 0.05 per year, 5.1, 8.2, 6.99, respectively; P = .006-.0002). Gastrointestinal (nausea, vomiting, abdominal pain) and respiratory symptoms (shortness of breath, chest pain) were associated with severe COVID-19, while pneumonia and end-organ failure were associated with mortality. COVID-19 is associated with a severe disease course in about 23% and mortality in about 6% of infected persons. Individuals with comorbidities and clinical features associated with severity should be monitored closely, and preventive efforts should especially target those with diabetes, malignancy, and immunosuppression.

Profile of Immunoglobulin G and IgM Antibodies Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

We profiled the serological responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein and spike (S) glycoprotein. The majority of the patients developed robust antibody responses between 17 and 23 days after illness onset. Delayed, but stronger, antibody responses were observed in critical patients.

Thin-section computed tomography findings and longitudinal variations of the residual pulmonary sequelae after discharge in patients with COVID-19: a short-term follow-up study.

OBJECTIVES: This study analyzed and compared CT findings and longitudinal variations after discharge between severe and non-severe coronavirus disease (COVID-19) patients who had residual pulmonary sequelae at pre-discharge. METHODS: A total of 310 patients were included and stratified into severe and non-severe COVID-19 groups. Cross-sectional CT features across different time periods (T0: pre-discharge, T1: 1-4 weeks after discharge, T2: 5-8 weeks after discharge, T3: 9-12 weeks after discharge, T4: > 12 weeks after discharge) were compared, and the longitudinal variations of CT findings were analyzed and compared in both groups. RESULTS: The cumulative absorption rate of fibrosis-like findings in the severe and non-severe groups at T4 was 24.3% (17/70) and 52.0% (53/102), respectively. In both groups, ground-glass opacity (GGO) with consolidation showed a clear decreasing trend at T1, after which they maintained similar lower levels. The GGO in the severe group showed an increasing trend first at T1 and then decreasing at T4; however, the incidence decreased gradually in the non-severe group. Most fibrosis-like findings showed a tendency to decrease rapidly and then remained stable. Bronchial dilatation in the severe group persisted at an intermediate level. CONCLUSIONS: After discharge, the characteristics and changing trends of pulmonary sequelae caused by COVID-19 were significantly different between the two groups. Pulmonary sequelae were more serious and recovery was slower in patients with severe/critical disease than in patients with moderate disease. A portion of the fibrosis-like findings were completely absorbed in patients with moderate and severe/critical diseases. KEY POINTS: • Lung sequelae were more serious and recovery was slower in severe/critical COVID-19 patients. • Complete absorption of fibrosis-like findings after a short-term follow-up was observed in at least 17/70 (24.3%) of COVID-19 patients with severe/critical disease and 53/102 (52.0%) of COVID-19 patients with moderate disease. • The most common fibrosis-like findings was a parenchymal band; irregular interface was a nonspecific sign of COVID-19, and the percentage of bronchial dilatation in patients with severe/critical disease remained at a relatively stable medium level (range, 31.6 to 47.8%) at all stages.

Comparison of patients hospitalized with COVID-19, H7N9 and H1N1.

BACKGROUND: There is an urgent need to better understand the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for that the coronavirus disease 2019 (COVID-19) continues to cause considerable morbidity and mortality worldwide. This paper was to differentiate COVID-19 from other respiratory infectious diseases such as avian-origin influenza A (H7N9) and influenza A (H1N1) virus infections. METHODS: We included patients who had been hospitalized with laboratory-confirmed infection by SARS-CoV-2 (n = 83), H7N9 (n = 36), H1N1 (n = 44) viruses. Clinical presentation, chest CT features, and progression of patients were compared. We used the Logistic regression model to explore the possible risk factors. RESULTS: Both COVID-19 and H7N9 patients had a longer duration of hospitalization than H1N1 patients (P < 0.01), a higher complication rate, and more severe cases than H1N1 patients. H7N9 patients had higher hospitalization-fatality ratio than COVID-19 patients (P = 0.01). H7N9 patients had similar patterns of lymphopenia, neutrophilia, elevated alanine aminotransferase, C-reactive protein, lactate dehydrogenase, and those seen in H1N1 patients, which were all significantly different from patients with COVID-19 (P < 0.01). Either H7N9 or H1N1 patients had more obvious symptoms, like fever, fatigue, yellow sputum, and myalgia than COVID-19 patients (P < 0.01). The mean duration of viral shedding was 9.5 days for SARS-CoV-2 vs 9.9 days for H7N9 (P = 0.78). For severe cases, the meantime from illness onset to severity was 8.0 days for COVID-19 vs 5.2 days for H7N9 (P < 0.01), the comorbidity of chronic heart disease was more common in the COVID-19 patients than H7N9 (P = 0.02). Multivariate analysis showed that chronic heart disease was a possible risk factor (OR > 1) for COVID-19, compared with H1N1 and H7N9. CONCLUSIONS: The proportion of severe cases were higher for H7N9 and SARS-CoV-2 infections, compared with H1N1. The meantime from illness onset to severity was shorter for H7N9. Chronic heart disease was a possible risk factor for COVID-19.The comparison may provide the rationale for strategies of isolation and treatment of infected patients in the future.

Immunological Evaluation on Potential Treatment Window for Hospitalized COVID-19 Patients.

PURPOSE: Novel coronavirus disease has become such an escalating epidemic that the exponential growth of infected patients has overloaded the health-care systems in many countries. Determination of early assessments for patients with a risk of clinical deterioration would benefit the management of COVID-19 outbreaks. PATIENTS AND METHODS: A total of 214 confirmed COVID-19 patients were enrolled from January 11th to February 11th 2020. Medical records including laboratory parameters, clinical outcomes and other characteristics of the admitted patients were analyzed retrospectively. RESULTS: The critical patients experienced a significantly prolonged onset-admission interval and presented with lymphopenia (r=-0.547, p=0.015) and lower albumin level (p<0.001) 6 days after symptom onset. Early admission of critical patients significantly reduced the duration of hormone therapy. Starting from 9 days of hospital stay, the reduced lymphocyte counts exhibited linear growth. Furthermore, on days 9 and 12, significant correlations were demonstrated between immunological manifestations and duration of hormone therapy in critical patients, and length of hospital stay in severe patients. In addition, the virus negative conversion rate was more significantly correlated with increased lymphocytes in critical patients. CONCLUSION: Early intervention, within 6 days of symptom onset, benefited patients' recovery from critical illness. The 9-12 days of hospital care represented a valuable window during which to evaluate the therapeutic effects on physical recovery and virus clearance.

Factors Associated With Prolonged Viral RNA Shedding in Patients with Coronavirus Disease 2019 (COVID-19).

BACKGROUND: An outbreak of coronavirus disease 2019 (COVID-19) is becoming a public health emergency. Data are limited on the duration and host factors related to viral shedding. METHODS: In this retrospective study, risk factors associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA shedding were evaluated in a cohort of 113 symptomatic patients from 2 hospitals outside Wuhan. RESULTS: The median (interquartile range) duration of SARS-CoV-2 RNA detection was 17 (13-22) days as measured from illness onset. When comparing patients with early (<15 days) and late (≥15 days after illness onset) viral RNA clearance, prolonged SARS-CoV-2 RNA shedding was associated with male sex (P = .009), old age (P = .033), concomitant hypertension (P = .009), delayed admission to hospital after illness onset (P = .001), severe illness at admission (P = .049), invasive mechanical ventilation (P = .006), and corticosteroid treatment (P = .025). Patients with longer SARS-CoV-2 RNA shedding duration had slower recovery of body temperature (P < .001) and focal absorption on radiograph images (P < .001) than patients with early SARS-CoV-2 RNA clearance. Male sex (OR, 3.24; 95% CI, 1.31-8.02), delayed hospital admission (OR, 1.30; 95% CI, 1.10-1.54), and invasive mechanical ventilation (OR, 9.88; 95% CI, 1.11-88.02) were independent risk factors for prolonged SARS-CoV-2 RNA shedding. CONCLUSIONS: Male sex, delayed admission to hospital after illness onset, and invasive mechanical ventilation were associated with prolonged SARS-CoV-2 RNA shedding. Hospital admission and general treatments should be started as soon as possible in symptomatic COVID-19 patients, especially male patients.

Effect of Corticosteroid Therapy on the Duration of SARS-CoV-2 Clearance in Patients with Mild COVID-19: A Retrospective Cohort Study.

INTRODUCTION: In December, 2019, an outbreak of the coronavirus disease 2019 (COVID-19), which was caused by a novel coronavirus, started in Wuhan, China. So far, there is limited clinical evidence on the effect of corticosteroid therapy for this disease. This study aims to investigate the association between corticosteroid therapy and the duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance among patients with mild COVID-19. METHODS: Patients with mild COVID-19 were enrolled from two medical centers in China between January 13, 2020 and February 29, 2020. Baseline characteristics and durations of RNA clearance were compared between the corticosteroid and non-corticosteroid therapy groups. The independent effects of corticosteroid therapy on the duration of RNA clearance were estimated by generalized linear models. RESULTS: Of 82 patients with a mild infection, 40 patients were male (48.8%), with a median age of 49 years (interquartile range, IQR 36-61). Among those patients, 36 patients (43.9%) received corticosteroid therapy. The adjusted multivariate models showed that the effects of corticosteroids were non-significant on the durations of onset to first RNA clearance [ß 2.48, 95% CI (95% confidence interval) - 0.42 to 5.38, P = 0.0926] and to persistent RNA clearance (ß 1.54, 95% CI - 1.41 to 4.48, P = 0.3016), and durations of therapy to first RNA clearance (ß 2.16, 95% CI - 0.56 to 4.89, P = 0.1184) and to persistent RNA clearance (ß 1.22, 95% CI - 1.52 to 3.95, P = 0.3787). CONCLUSIONS: Corticosteroid therapy in patients with mild COVID-19 was not associated with the duration of SARS-CoV-2 clearance, suggesting that the use of corticosteroids may not be beneficial for patients with mild COVID-19 and should be prudently recommended in clinical practice. However, further studies are needed to verify the findings.

Clinical characteristics of COVID-19 infection in chronic obstructive pulmonary disease: a multicenter, retrospective, observational study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been a global pandemic disease, with more than 4 million cases and nearly 300,000 deaths. Little is known about COVID-19 in patients with chronic obstructive pulmonary disease (COPD). We aimed to evaluate the influence of preexisting COPD on the progress and outcomes of COVID-19. METHODS: This was a multicenter, retrospective, observational study. We enrolled 1,048 patients aged 40 years and above, including 50 patients with COPD and 998 patients without COPD, and with COVID-19 confirmed via high-throughput sequencing or real-time reverse transcription-polymerase chain reaction, between December 11, 2019 and February 20, 2020. We collected data of demographics, pathologic test results, radiologic imaging, and treatments. The primary outcomes were composite endpoints determined by admission to an intensive care unit, the use of mechanical ventilation, or death. RESULTS: Compared with patients who had COVID-19 but not COPD, those with COPD had higher rates of fatigue (56.0% vs. 40.2%), dyspnea (66.0% vs. 26.3%), diarrhea (16.0% vs. 3.6%), and unconsciousness (8.0% vs. 1.7%) and a significantly higher proportion of increased activated partial thromboplastin time (23.5% vs. 5.2%) and D-dimer (65.9% vs. 29.3%), as well as ground-glass opacities (77.6% vs. 60.3%), local patchy shadowing (61.2% vs. 41.4%), and interstitial abnormalities (51.0% vs. 19.8%) on chest computed tomography. Patients with COPD were more likely to develop bacterial or fungal coinfection (20.0% vs. 5.9%), acute respiratory distress syndrome (ARDS) (20.0% vs. 7.3%), septic shock (14.0% vs. 2.3%), or acute renal failure (12.0% vs. 1.3%). Patients with COPD and COVID-19 had a higher risk of reaching the composite endpoints [hazard ratio (HR): 2.17, 95% confidence interval (CI): 1.40-3.38; P=0.001] or death (HR: 2.28, 95% CI: 1.15-4.51; P=0.019), after adjustment. CONCLUSIONS: In this study, patients with COPD who developed COVID-19 showed a higher risk of admission to the intensive care unit, mechanical ventilation, or death.

The correlation between viral clearance and biochemical outcomes of 94 COVID-19 infected discharged patients.

OBJECTIVE: This study aims to evaluate the correlation between viral clearance and blood biochemical index of 94 discharged patients with COVID-19 infection in Shenzhen Third People's Hospital, enrolled from Jan 5 to Feb 13, 2020. METHODS: The clinical and laboratory findings were extracted from the electronic medical records of the patients. The data were analysed and reviewed by a trained team of physicians. Information on clinical signs and symptoms, medical treatment, virus clearance, and laboratory parameters including interleukin 6 (IL-6) and C-reactive protein were collected. RESULTS: COVID-19 mRNA clearance ratio was identified significantly correlated with the decline of serum creatine kinase (CK) and lactate dehydrogenase (LDH) levels. Furthermore, COVID-19 mRNA clearance time was positively correlated with the length of hospital stay in patients treated with either IFN-α + lopinavir/ritonavir or IFN-α + lopinavir/ritonavir + ribavirin. CONCLUSIONS: Therapeutic regimens of IFN-α + lopinavir/ritonavir and IFN-α + lopinavir/ritonavir + ribavirin might be beneficial for treatment of COVID-19. Serum LDH or CK decline may predict a favorable response to treatment of COVID-19 infection.

Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study.

There is currently an outbreak of respiratory disease caused by a novel coronavirus. The virus has been named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the disease it causes has been named coronavirus disease 2019 (COVID-19). More than 16% of patients developed acute respiratory distress syndrome, and the fatality ratio was 1%-2%. No specific treatment has been reported. Herein, we examined the effects of favipiravir (FPV) versus lopinavir (LPV)/ritonavir (RTV) for the treatment of COVID-19. Patients with laboratory-confirmed COVID-19 who received oral FPV (Day 1: 1600 mg twice daily; Days 2-14: 600 mg twice daily) plus interferon (IFN)-α by aerosol inhalation (5 million international unit (IU) twice daily) were included in the FPV arm of this study, whereas patients who were treated with LPV/RTV (Days 1-14: 400 mg/100 mg twice daily) plus IFN-α by aerosol inhalation (5 million IU twice daily) were included in the control arm. Changes in chest computed tomography (CT), viral clearance, and drug safety were compared between the two groups. For the 35 patients enrolled in the FPV arm and the 45 patients in the control arm, all baseline characteristics were comparable between the two arms. A shorter viral clearance median time was found for the FPV arm versus the control arm (4 d (interquartile range (IQR): 2.5-9) versus 11 d (IQR: 8-13), P < 0.001). The FPV arm also showed significant improvement in chest CT compared with the control arm, with an improvement rate of 91.43% versus 62.22% (P = 0.004). After adjustment for potential confounders, the FPV arm also showed a significantly higher improvement rate in chest CT. Multivariable Cox regression showed that FPV was independently associated with faster viral clearance. In addition, fewer adverse events were found in the FPV arm than in the control arm. In this open-label before-after controlled study, FPV showed better therapeutic responses on COVID-19 in terms of disease progression and viral clearance. These preliminary clinical results provide useful information of treatments for SARS-CoV-2 infection.