The Short- and Long-Term Clinical, Radiological and Functional Consequences of COVID-19.

As with the rapid increase of the number of patients who have recovered from COVID-19 globally, there needs to be a major shift of the focus from rapid pathogen detection, treatment and prevention to the promotion of better recovery. Notwithstanding the scarcity of our understandings, recent studies have unraveled a plethora of pulmonary and systemic consequences which require medical attention. These consequences remained as of the end of follow-up which ranged from 1 month to 1 year. Here, we review the consequences of COVID-19 in terms of the residual symptoms, radiological and functional manifestations, and identify the potential risk factors that contribute to a prolonged recovery. We also summarize the benefits of clinical interventions (particularly the pulmonary rehabilitation program), and address several undetermined concerns and key future research directions.

Como consecuencia del rápido aumento del número de pacientes que se han recuperado de la COVID-19 en todo el mundo, es necesario cambiar el enfoque de la detección rápida del patógeno, el tratamiento y la prevención para promover una mejor recuperación. A pesar de la escasez de nuestros conocimientos, estudios recientes han desvelado una plétora de consecuencias pulmonares y sistémicas que requieren atención médica. Estas consecuencias se mantienen al final del seguimiento, que oscila entre 1 mes y 1 año. Aquí se hace una revisión de las consecuencias de la COVID-19 en términos de síntomas residuales y manifestaciones radiológicas y funcionales y se identifican los posibles factores de riesgo que contribuyen a una recuperación demorada. También se resumen los beneficios de las intervenciones clínicas (en particular el programa de rehabilitación pulmonar) y se abordan varias preocupaciones no resueltas y direcciones clave de investigación futura.

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.).

Earlier diagnosis improves COVID-19 prognosis: a nationwide retrospective cohort analysis.

BACKGROUND: Risk of adverse outcomes in COVID-19 patients by stratifying by the time from symptom onset to confirmed diagnosis status is still uncertain. METHODS: We included 1,590 hospitalized COVID-19 patients confirmed by real-time RT-PCR assay or high-throughput sequencing of pharyngeal and nasal swab specimens from 575 hospitals across China between 11 December 2019 and 31 January 2020. Times from symptom onset to confirmed diagnosis, from symptom onset to first medical visit and from first medical visit to confirmed diagnosis were described and turned into binary variables by the maximally selected rank statistics method. Then, survival analysis, including a log-rank test, Cox regression, and conditional inference tree (CTREE) was conducted, regarding whether patients progressed to a severe disease level during the observational period (assessed as severe pneumonia according to the Chinese Expert Consensus on Clinical Practice for Emergency Severe Pneumonia, admission to an intensive care unit, administration of invasive ventilation, or death) as the prognosis outcome, the dependent variable. Independent factors included whether the time from symptom onset to confirmed diagnosis was longer than 5 days (the exposure) and other demographic and clinical factors as multivariate adjustments. The clinical characteristics of the patients with different times from symptom onset to confirmed diagnosis were also compared. RESULTS: The medians of the times from symptom onset to confirmed diagnosis, from symptom onset to first medical visit, and from first medical visit to confirmed diagnosis were 6, 3, and 2 days. After adjusting for age, sex, smoking status, and comorbidity status, age [hazard ratio (HR): 1.03; 95% CI: 1.01-1.04], comorbidity (HR: 1.84; 95% CI: 1.23-2.73), and a duration from symptom onset to confirmed diagnosis of >5 days (HR: 1.69; 95% CI: 1.10-2.60) were independent predictors of COVID-19 prognosis, which echoed the CTREE models, with significant nodes such as time from symptom onset to confirmed diagnosis, age, and comorbidities. Males, older patients with symptoms such as dry cough/productive cough/shortness of breath, and prior COPD were observed more often in the patients who procrastinated before initiating the first medical consultation. CONCLUSIONS: A longer time from symptom onset to confirmed diagnosis yielded a worse COVID-19 prognosis.

Chronic Respiratory Diseases and the Outcomes of COVID-19: A Nationwide Retrospective Cohort Study of 39,420 Cases.

BACKGROUND: Chronic respiratory diseases (CRD) are common among patients with coronavirus disease 2019 (COVID-19). OBJECTIVES: We sought to determine the association between CRD (including disease overlap) and the clinical outcomes of COVID-19. METHODS: Data of diagnoses, comorbidities, medications, laboratory results, and clinical outcomes were extracted from the national COVID-19 reporting system. CRD was diagnosed based on International Classification of Diseases-10 codes. The primary endpoint was the composite outcome of needing invasive ventilation, admission to intensive care unit, or death within 30 days after hospitalization. The secondary endpoint was death within 30 days after hospitalization. RESULTS: We included 39,420 laboratory-confirmed patients from the electronic medical records as of May 6, 2020. Any CRD and CRD overlap was present in 2.8% and 0.2% of patients, respectively. Chronic obstructive pulmonary disease (COPD) was most common (56.6%), followed by bronchiectasis (27.9%) and asthma (21.7%). COPD-bronchiectasis overlap was the most common combination (50.7%), followed by COPD-asthma (36.2%) and asthma-bronchiectasis overlap (15.9%). After adjustment for age, sex, and other systemic comorbidities, patients with COPD (odds ratio [OR]: 1.71, 95% confidence interval [CI]: 1.44-2.03) and asthma (OR: 1.45, 95% CI: 1.05-1.98), but not bronchiectasis, were more likely to reach to the composite endpoint compared with those without at day 30 after hospitalization. Patients with CRD were not associated with a greater likelihood of dying from COVID-19 compared with those without. Patients with CRD overlap did not have a greater risk of reaching the composite endpoint compared with those without. CONCLUSION: CRD was associated with the risk of reaching the composite endpoint, but not death, of COVID-19.

Lung transplantation as therapeutic option in acute respiratory distress syndrome for coronavirus disease 2019-related pulmonary fibrosis.

BACKGROUND: Critical patients with the coronavirus disease 2019 (COVID-19), even those whose nucleic acid test results had turned negative and those receiving maximal medical support, have been noted to progress to irreversible fatal respiratory failure. Lung transplantation (LT) as the sole therapy for end-stage pulmonary fibrosis related to acute respiratory distress syndrome has been considered as the ultimate rescue therapy for these patients. METHODS: From February 10 to March 10, 2020, three male patients were urgently assessed and listed for transplantation. After conducting a full ethical review and after obtaining assent from the family of the patients, we performed three LT procedures for COVID-19 patients with illness durations of more than one month and extremely high sequential organ failure assessment scores. RESULTS: Two of the three recipients survived post-LT and started participating in a rehabilitation program. Pearls of the LT team collaboration and perioperative logistics were summarized and continually improved. The pathological results of the explanted lungs were concordant with the critical clinical manifestation, and provided insight towards better understanding of the disease. Government health affair systems, virology detection tools, and modern communication technology all play key roles towards the survival of the patients and their rehabilitation. CONCLUSIONS: LT can be performed in end-stage patients with respiratory failure due to COVID-19-related pulmonary fibrosis. If confirmed positive-turned-negative virology status without organ dysfunction that could contraindicate LT, LT provided the final option for these patients to avoid certain death, with proper protection of transplant surgeons and medical staffs. By ensuring instant seamless care for both patients and medical teams, the goal of reducing the mortality rate and salvaging the lives of patients with COVID-19 can be attained.

Clinical characteristics and outcomes of hospitalised patients with COVID-19 treated in Hubei (epicentre) and outside Hubei (non-epicentre): a nationwide analysis of China.

BACKGROUND: During the outbreak of coronavirus disease 2019 (COVID-19), consistent and considerable differences in disease severity and mortality rate of patients treated in Hubei province compared to those in other parts of China have been observed. We sought to compare the clinical characteristics and outcomes of patients being treated inside and outside Hubei province, and explore the factors underlying these differences. METHODS: Collaborating with the National Health Commission, we established a retrospective cohort to study hospitalised COVID-19 cases in China. Clinical characteristics, the rate of severe events and deaths, and the time to critical illness (invasive ventilation or intensive care unit admission or death) were compared between patients within and outside Hubei. The impact of Wuhan-related exposure (a presumed key factor that drove the severe situation in Hubei, as Wuhan is the epicentre as well the administrative centre of Hubei province) and the duration between symptom onset and admission on prognosis were also determined. RESULTS: At the data cut-off (31 January 2020), 1590 cases from 575 hospitals in 31 provincial administrative regions were collected (core cohort). The overall rate of severe cases and mortality was 16.0% and 3.2%, respectively. Patients in Hubei (predominantly with Wuhan-related exposure, 597 (92.3%) out of 647) were older (mean age 49.7 versus 44.9 years), had more cases with comorbidity (32.9% versus 19.7%), higher symptomatic burden, abnormal radiologic manifestations and, especially, a longer waiting time between symptom onset and admission (5.7 versus 4.5 days) compared with patients outside Hubei. Patients in Hubei (severe event rate 23.0% versus 11.1%, death rate 7.3% versus 0.3%, HR (95% CI) for critical illness 1.59 (1.05-2.41)) have a poorer prognosis compared with patients outside Hubei after adjusting for age and comorbidity. However, among patients outside Hubei, the duration from symptom onset to hospitalisation (mean 4.4 versus 4.7 days) and prognosis (HR (95%) 0.84 (0.40-1.80)) were similar between patients with or without Wuhan-related exposure. In the overall population, the waiting time, but neither treated in Hubei nor Wuhan-related exposure, remained an independent prognostic factor (HR (95%) 1.05 (1.01-1.08)). CONCLUSION: There were more severe cases and poorer outcomes for COVID-19 patients treated in Hubei, which might be attributed to the prolonged duration of symptom onset to hospitalisation in the epicentre. Future studies to determine the reason for delaying hospitalisation are warranted.

Recommended prophylactic and management strategies for severe acute respiratory syndrome coronavirus 2 infection in transplant recipients.

Since December 2019, increasing attention has been paid to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in Wuhan, China. SARS-CoV-2 primarily invades the respiratory tract and lungs, leading to pneumonia and other systemic disorders. The effect of SARS-CoV-2 in transplant recipients has raised significant concerns, especially because there is a large population of transplant recipients in China. Based on the current epidemic situation, this study reviewed publications on this virus and coronavirus disease 2019 (COVID-19), analyzed common features of respiratory viral pneumonias, and presented the currently reported clinical characteristics of COVID-19 in transplant recipients to improve strategies regarding the diagnosis and treatment of COVID-19 in this special population.

Comorbidity and its impact on 1590 patients with COVID-19 in China: a nationwide analysis.

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak is evolving rapidly worldwide. OBJECTIVE: To evaluate the risk of serious adverse outcomes in patients with COVID-19 by stratifying the comorbidity status. METHODS: We analysed data from 1590 laboratory confirmed hospitalised patients from 575 hospitals in 31 provinces/autonomous regions/provincial municipalities across mainland China between 11 December 2019 and 31 January 2020. We analysed the composite end-points, which consisted of admission to an intensive care unit, invasive ventilation or death. The risk of reaching the composite end-points was compared according to the presence and number of comorbidities. RESULTS: The mean age was 48.9 years and 686 (42.7%) patients were female. Severe cases accounted for 16.0% of the study population. 131 (8.2%) patients reached the composite end-points. 399 (25.1%) reported having at least one comorbidity. The most prevalent comorbidity was hypertension (16.9%), followed by diabetes (8.2%). 130 (8.2%) patients reported having two or more comorbidities. After adjusting for age and smoking status, COPD (HR (95% CI) 2.681 (1.424-5.048)), diabetes (1.59 (1.03-2.45)), hypertension (1.58 (1.07-2.32)) and malignancy (3.50 (1.60-7.64)) were risk factors of reaching the composite end-points. The hazard ratio (95% CI) was 1.79 (1.16-2.77) among patients with at least one comorbidity and 2.59 (1.61-4.17) among patients with two or more comorbidities. CONCLUSION: Among laboratory confirmed cases of COVID-19, patients with any comorbidity yielded poorer clinical outcomes than those without. A greater number of comorbidities also correlated with poorer clinical outcomes.