Detection of Antibodies Against the SARS-CoV-2 Spike Protein and Analysis of the Peripheral Blood Mononuclear Cell Transcriptomic Profile, 15 Years After Recovery From SARS.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shows a high degree of homology with SARS-CoV. They share genes, protein sequences, clinical manifestations, and cellular entry patterns. Thus, SARS research may serve helpful in gaining a better understanding of the current coronavirus disease 2019 (COVID-19) pandemic. Serum antibodies from convalescent patients with SARS collected in 2018 were used to target the recombinant SARS-CoV-2 spike protein via a chemiluminescence microsphere immunoassay. Antibodies of convalescent patients with SARS exhibited serous immune cross-reactivity with the SARS-CoV-2 spike protein. The serous antibodies, excluding S22 of convalescent patients with SARS, did not competitively inhibit the binding of SARS-CoV-2 spike protein to ACE2. T cellular immunity research was conducted in vitro using peripheral blood mononuclear cells (PBMCs) stimulated by pooled peptide epitopes 15 years post-infection. Interferon gamma was detected and the PBMC transcriptomic profile was obtained. The heatmap of the transcriptomic profile showed that mRNAs and circRNAs of the SARS group clustered together after being stimulated by the peptide epitope pool. Differentially expressed mRNAs were most significantly enriched in immunity and signal transduction (P < 0.01). SARS elicits cytokine and chemokine responses, partially consistent with previously published data about COVID-19. Overall, our results indicate that antibodies from convalescent patients with SARS persisted for 15 years and displayed immune cross-reactivity with the SARS-CoV-2 spike protein. The immune status of patients with SARS 15 years post-infection may provide a better understanding of the future immune status of patients with COVID-19.

Correction: Long-term bone and lung consequences associated with hospital-acquired severe acute respiratory syndrome: a 15-year follow-up from a prospective cohort study.

[This corrects the article DOI: 10.1038/s41413-020-0084-5.].

Long-term bone and lung consequences associated with hospital-acquired severe acute respiratory syndrome: a 15-year follow-up from a prospective cohort study.

The most severe sequelae after rehabilitation from SARS are femoral head necrosis and pulmonary fibrosis. We performed a 15-year follow-up on the lung and bone conditions of SARS patients. We evaluated the recovery from lung damage and femoral head necrosis in an observational cohort study of SARS patients using pulmonary CT scans, hip joint MRI examinations, pulmonary function tests and hip joint function questionnaires. Eighty medical staff contracted SARS in 2003. Two patients died of SARS, and 78 were enrolled in this study from August 2003 to March 2018. Seventy-one patients completed the 15-year follow-up. The percentage of pulmonary lesions on CT scans diminished from 2003 (9.40 ± 7.83)% to 2004 (3.20 ± 4.78)% (P < 0.001) and remained stable thereafter until 2018 (4.60 ± 6.37)%. Between 2006 and 2018, the proportion of patients with interstitial changes who had improved pulmonary function was lower than that of patients without lesions, as demonstrated by the one-second ratio (FEV1/FVC%, t = 2.21, P = 0.04) and mid-flow of maximum expiration (FEF25%-75%, t = 2.76, P = 0.01). The volume of femoral head necrosis decreased significantly from 2003 (38.83 ± 21.01)% to 2005 (30.38 ± 20.23)% (P = 0.000 2), then declined slowly from 2005 to 2013 (28.99 ± 20.59)% and plateaued until 2018 (25.52 ± 15.51)%. Pulmonary interstitial damage and functional decline caused by SARS mostly recovered, with a greater extent of recovery within 2 years after rehabilitation. Femoral head necrosis induced by large doses of steroid pulse therapy in SARS patients was not progressive and was partially reversible.

The clinical characteristics and prognosis of COVID-19 patients with comorbidities: a retrospective analysis of the infection peak in Wuhan.

BACKGROUND: This study aims to determine the clinical characteristics and prognosis of COVID-19 patients with comorbidities and to identify survival factors. METHODS: A retrospective study was conducted in Wuhan, China, between February 8, 2020, and March 9, 2020. Based on underlying diseases, patients were assigned to either the comorbidity group or the non-comorbidity group. The clinical characteristics and outcomes of COVID-19 were analyzed and a Kaplan-Meier survival analysis was used to evaluate the prognosis predictive value of each comorbidity. RESULTS: During the study period, 278 COVID-19 patients were enrolled, 175 (62.95%) were assigned to the comorbidity group, and 103 (37.05%) to the non-comorbidity group. Of the patients in the comorbidity group, 34.86% were classified as critical. Further, patients in the comorbidity group had lower lymphocyte cell counts, and higher concentrations of D-dimer, high sensitivity C-reactive protein, interleukin 6, and serum ferritin as well as higher critical illness severity scores than patients in the non-comorbidity group (P<0.05). Patients in the comorbidity group also had higher mortality, acute respiratory distress syndrome, and ventilation treatment rates than patients in the non-comorbidity group (P<0.05). The length of hospital stay was longer in the comorbidity group than in the non-comorbidity group (P<0.05). The most common underlying diseases included hypertension (40.65%), diabetes mellitus (20.5%), and cardiovascular disease (19.42%). Patients with comorbidities were more likely to develop cardiovascular sequelae associated with COVID-19, shock, acute kidney injury, and multiple organ dysfunction syndrome (30.86% vs. 12.62%, P=0.001; 18.86% vs. 8.74%, P=0.023; 24.57% vs. 11.65%, P=0.009; 33.71% vs. 14.56%, P=0.000, respectively). In the Kaplan-Meier survival analysis, older patients (¡Ý65 years) (log-rank test: χ2=4.202, P=0.040) and patients with chronic obstructive pulmonary disease (COPD) (log-rank test: χ2=4.839, P=0.028) or diabetes mellitus (log-rank test: χ2=4.377, P=0.036) had shorter survival than those without comorbidities. CONCLUSIONS: Patients with comorbidities were more severely affected and had a higher mortality rate. Age, COPD and diabetes mellitus were the main factors affecting the survival of patients.

Ultrasonic Characteristics and Severity Assessment of Lung Ultrasound in COVID-19 Pneumonia in Wuhan, China: A Retrospective, Observational Study.

The clinical application of lung ultrasound (LUS) in the assessment of coronavirus disease 2019 (COVID-19) pneumonia severity remains limited. Herein, we investigated the role of LUS imaging in COVID-19 pneumonia patients and the relationship between LUS findings and disease severity. This was a retrospective, observational study at Tongji Hospital in Wuhan, on 48 recruited patients with COVID-19 pneumonia, including 32 non-critically ill patients and 16 critically ill patients. LUS was performed and the respiratory rate oxygenation (ROX) index, disease severity, and confusion, blood urea nitrogen, respiratory rate, blood pressure, and age (CURB-65) score were recorded on days 0-7, 8-14, and 15-21 after symptom onset. Lung images were divided into 12 regions, and the LUS score (0-36 points) was calculated. Chest computed tomography (CT) scores (0-20 points) were also recorded on days 0-7. Correlations between the LUS score, ROX index, and CURB-65 scores were examined. LUS detected COVID-19 pneumonia in 38 patients. LUS signs included B lines (34/38, 89.5%), consolidations (6/38, 15.8%), and pleural effusions (2/38, 5.3%). Most cases showed more than one lesion (32/38, 84.2%) and involved both lungs (28/38, 73.7%). Compared with non-critically ill patients, the LUS scores of critically ill patients were higher (12 (10-18) vs 2 (0-5), p < 0.001). The LUS score showed significant negative correlations with the ROX index on days 0-7 (r = -0.85, p < 0.001), days 8-14 (r = -0.71, p < 0.001), and days 15-21 (r = -0.76, p < 0.001) after symptom onset. However, the LUS score was positively correlated with the CT score (r = 0.82, p < 0.001). The number of patients with LUS-detected lesions decreased from 27 cases (81.8%) to 20 cases (46.5%), and the LUS scores significantly decreased from 4 (2-10) to 0 (0-5) (p < 0.001) from days 0-7 to 17-21. We conclude that LUS can detect lung lesions in COVID-19 pneumonia patients in a portable, real-time, and safe manner. Thus, LUS is helpful in assessing COVID-19 pneumonia severity in critically ill patients.

Increasing SARS-CoV-2 nucleic acid testing capacity during the COVID-19 epidemic in Beijing: experience from a general hospital.

Under the ongoing COVID-19 prevention and control measures in China, increasing the laboratory severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid testing capacity has become the top priority. Since the COVID-19 outbreak in Xinfadi market in Beijing in June 2020, large-scale screening of key populations has been carried out, challenging the nucleic acid testing capabilities of hospital laboratories. Therefore, within 48 hours, Peking University People's Hospital (PKUPH) transformed a non-nucleic acid testing laboratory into a SARS-CoV-2 nucleic acid testing laboratory. Based on the original structure of the building, we adapted measures to local conditions, sorted out a new testing process, and quickly started testing for COVID-19. The nucleic acid testing process has been optimized, including quality control, personal operating specifications, and the timeliness of the release of LIS results to form closed-loop management. This high-throughput COVID-19 testing optimization process provides a reference model for other countries that are fighting the epidemic.

A four-compartment model for the COVID-19 infection-implications on infection kinetics, control measures, and lockdown exit strategies.

Objective: To analyse the impact and repercussions of the surge in healthcare demand in response to the COVID-19 pandemic, assess the potential effectiveness of various infection/disease control measures, and make projections on the best approach to exit from the current lockdown. Design: A four-compartment model was constructed for SARS-CoV-2 infection based on the Wuhan data and validated with data collected in Italy, the UK, and the US. The model captures the effectiveness of various disease suppression measures in three modifiable factors: (a) the per capita contact rate (ß) that can be lowered by means of social distancing, (b) infection probability upon contacting infectious individuals that can be lowered by wearing facemasks, personal hygiene, etc., and (c) the population of infectious individuals in contact with the susceptible population, which can be lowered by quarantine. The model was used to make projections on the best approach to exit from the current lockdown. Results: The model was applied to evaluate the epidemiological data and hospital burden in Italy, the UK, and the US. The control measures were identified as the key drivers for the observed epidemiological data through sensitivity analyses. Analysing the different lockdown exit strategies showed that a lockdown exit strategy with a combination of social separation/general facemask use may work, but this needs to be supported by intense monitoring which would allow re-introduction/tightening of the control measures if the number of new infected subjects increases again. Conclusions and relevance: Governments should act early in a swift and decisive manner for containment policies. Any lockdown exit will need to be monitored closely, with regards to the potential of lockdown reimplementation. This mathematical model provides a framework for major pandemics in the future.