Persistent while declined neutralizing antibody responses in the convalescents of COVID-19 across clinical spectrum during the 16 months follow up (preprint)

Elucidation the kinetics of neutralizing antibody response in the coronavirus disease 2019 (COVID-19) convalescents is crucial for the future control of the COVID-19 pandemic and vaccination strategies. Here we tested 411 sequential plasma samples collected up to 480 days post symptoms onset (d.a.o) from 214 convalescents of COVID-19 across clinical spectrum without re-exposure history after recovery and vaccination of SARS-CoV-2, using authentic SARS-CoV-2 microneutralization (MN) assays. COVID-19 convalescents free of re-exposure and vaccination could maintain relatively stable anti-RBD IgG and MN titers during 400[~]480 d.a.o after the peak at around 120 d.a.o and the subsequent decrease. Undetectable neutralizing activity started to occur in mild and asymptomatic infections during 330 to 480 d.a.o with an overall rate of 14.29% and up to 50% for the asymptomatic infections. Significant decline in MN titers was found in 91.67% COVID-19 convalescents with [≥] 50% decrease in MN titers when comparing the available peak and current MN titers ([≥] 300 d.a.o). Antibody-dependent immunity could also provide protection against most of circulating variants after one year, while significantly decreased neutralizing activities against the Beta, Delta and Lambda variants were found in most of individuals. In summary, our results indicated that neutralizing antibody responses could last at least 480 days in most COVID-19 convalescents despite of the obvious decline of neutralizing activity, while the up to 50% undetectable neutralizing activity in the asymptomatic infections is of great concern.

Effects of Different Anti-hypertensive Drugs on Hospitalized Patients With COVID-19 and Hypertension in China (preprint)

Background and aims: Calcium channel blockers (CCBs) and angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) are commonly used in the treatment of hypertension. However, it is still not clear whether there are differences among different anti-hypertensive drugs in the treatment of patients with coronavirus disease 2019 (COVID-19) and hypertension. Herein, we aimed to assess the relation between different anti-hypertensive medications and COVID-19 outcomes. Materials and methods: We conducted a retrospective analysis of 58 hypertensive patients with COVID-19 who were treated with different anti-hypertensive drugs and reviewed the clinical data obtained from electronic medical records, including epidemiological, clinical, laboratory, and the treatment and progression of the disease. Results: There was no obvious difference in clinical prognosis after using any anti-hypertensive drugs in patients with COVID-19 and hypertension, but the different anti-hypertensive drugs were associated with the use of non-invasive ventilator treatment at admission comparing two groups between ACEIs/ARBs and CCBs+ACEIs/ARBs. Conclusion: there is no evidence showing that the different use of anti-hypertensive drugs is related to outcomes of patients with COVID-19 and hypertension, even between single drug regimen and combined therapy (with at least two anti-hypertensive drugs as combined therapy).

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.

The Architecture of Inactivated SARS-CoV-2 with Postfusion Spikes Revealed by CryoEM and CryoET (preprint)

The outbreak of SARS-CoV-2 in December 2019, led to the ongoing global pandemic of coronavirus disease 2019 (COVID‑19), which has claimed more than a half million lives in a few months. Enormous efforts are being made in developing vaccines and therapeutic treatment to fight against COVID-19. Inactivated SARS-CoV-2 viruses are currently used as vaccine candidates; therefore, it is important to understand the architecture of SARS-CoV-2. We have propagated and purified a clinical strain of SARS-CoV-2 and genetically and structurally characterized β-propiolactone inactivated viruses. We observed that the virus particles are roughly spherical or moderately pleiomorphic. Although a small fraction of prefusion spikes are observed, the majority of viral spikes appear nail-shaped resembling a postfusion state, where S1 protein of the spike has disassociated. Cryo-electron tomography and subtomogram averaging of these spikes yielded a density map which closely matches the overall structure of SARS-CoV S2 spike and their corresponding glycosylation sites. Our findings have major implications in SARS-CoV-2 vaccine design owing to the critical importance of prefusion immunogens.Funding: This work was supported by the Science and Technology Innovation Committee of Shenzhen Municipality(202002073000002), the National Institutes of Health grant P50AI150481 (P.Z.), the UK Wellcome Trust Investigator Award 206422/Z/17/Z(P.Z.), and the UK Biotechnology and Biological Sciences Research Council grant BB/S003339/1 (P.Z.). Conflict of Interest: The authors declare no competing financial or non-financial interests. Ethical Approval: The research received approval from the Research Ethics Committee of Shenzhen Third People's Hospital, China (approval number: 2020-038). The Research Ethics Committee waived the requirement informed consent before the study started because of the urgent need to collect epidemiological and clinical data. We analyzed the data anonymously.

Viral RNA level, serum antibody responses, and transmission risk in discharged COVID-19 patients with recurrent positive SARS-CoV-2 RNA test results: a population-based observational cohort study (preprint)

SummaryO_ST_ABSBackgroundC_ST_ABSManaging discharged COVID-19 (DC) patients with recurrent positive (RP) SARS-CoV-2 RNA test results is challenging. We aimed to comprehensively characterize the viral RNA level and serum antibody responses in RP-DC patients and evaluate their viral transmission risk. MethodsA population-based observational cohort study was performed on 479 DC patients discharged from February 1 to May 5, 2020 in Shenzhen, China. We conducted RT-qPCR, antibody assays, neutralisation assays, virus isolation, whole genome sequencing (WGS), and epidemiological investigation of close contacts. FindingsOf 479 DC patients, the 93 (19%) RP individuals, including 36 with multiple RP results, were characterised by young age (median age: 34 years, 95% confidence interval [CI]: 29-38 years). The median discharge-to-RP length was 8 days (95% CI: 7-14 days; maximum: 90 days). After readmission, RP-DC patients exhibited mild (28%) or absent (72%) symptoms, with no disease progression. The viral RNA level in RP-DC patients ranged from 1{middle dot}9-5{middle dot}7 log10 copies/mL (median: 3{middle dot}2, 95% CI: 3{middle dot}1-3{middle dot}5). At RP detection, the IgM, IgG, IgA, total antibody, and neutralising antibody (NAb) seropositivity rates in RP-DC patients were 38% (18/48), 98% (47/48), 63% (30/48), 100% (48/48), and 91% (39/43), respectively. Regarding antibody levels, there was no significant difference between RP-DC and non-RP-DC patients. The antibody level remained constant in RP-DC patients pre- and post-RP detection. Virus isolation of nine representative specimens returned negative results. WGS of six specimens yielded only genomic fragments. No clinical symptoms were exhibited by 96 close contacts of 23 RP-DC patients; their viral RNA (96/96) and antibody (20/20) test results were negative. After full recovery, 60% of patients (n=162, 78 no longer RP RP-DC and 84 non-RP-DC) had NAb titres of [≥]1:32. InterpretationRP may occur in DC patients following intermittent and non-stable excretion of low viral RNA levels. RP-DC patients pose a low risk of transmitting SARS-CoV-2. An NAb titre of [≥] 1:32 may provide a reference indicator for evaluating humoral responses in COVID-19 vaccine clinical trials. FundingSanming Project of Medicine in Shenzhen, China National Science and Technology Major Projects Foundation, Special Foundation of Science and Technology Innovation Strategy of Guangdong Province of China, and Shenzhen Committee of Scientific and Technical Innovation grants.

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.

Development and validation of a prognostic risk score system for COVID-19 inpatients: A multi-center retrospective study in China (preprint)

Coronavirus Disease 2019 (COVID-19) has become a world-wide pandemic. Hospitalized patients of COVID-19 suffer from a high mortality rate, motivating the development of convenient and practical methods for clinicians to promptly identify high-risk patients. Here we developed a risk score using clinical data from 1,479 inpatients admitted to Tongji Hospital, Wuhan, China (development cohort) and externally validated with data from two other centers: 141 inpatients from Jinyintan Hospital in Wuhan (validation cohort 1) and 432 inpatients from the Third People’s Hospital Shenzhen (validation cohort 2). The risk score is based on three biomarkers readily available in routine blood samples and can be easily translated into a probability of death. The risk score can predict the mortality of individual patients more than 12 days in advance with more than 90% accuracy across all cohorts. Moreover, the Kaplan-Meier score shows that patients upon admission can clearly be differenciated into low, medium or high risk, with an AUC score of 0.9551. In summary, a simple risk score was validated to predict death in patients infected with COVID-19 and was validated in independent cohorts.

First-Generation Corona Virus Disease 2019 (COVID-19) Patients with a Wuhan-Traveling History are Prone to More Severe Diseases (preprint)

Wuhan has the highest number of deaths and mortality from COVID-19 in China to date, but the reason remains unknown. Here we compared patients with COVID-19 with a history of traveling in Wuhan with those who did not travel in Wuhan in the early stage of pandemic with respect to a series of clinical characteristics and laboratory parameters. We observed that patients who had traveled in Wuhan had an increased rate of severe disease and longer viral duration along with fewer CD4+ and CD8+ T cells, although there was no significant difference in viral load between the two groups.

Analysis of Functional Indices Indicates Multiple Organ Function Damage in Patients with Severe Coronavirus Disease 2019 (COVID-19) Pneumonia (preprint)

Background: This study aims to analyze the changes and significance of organ function indices in patients with severe Coronavirus Disease 2019 (COVID-19) pneumonia for prediction of major organ damages and guiding treatment schemes. Methods: 63 patients with severe COVID-19 pneumonia were selected as the severe group and 73 patients with mild syndromes were selected as the mild group. SAS9.4 software was used for statistical analysis of the data. Results: Levels of ALT, AST, cTnI, Cr, PT, APTT and D-DIC of the severe group were significantly higher while PLT was lower than those of the mild group. The data of all quantitative variables were converted into categorical variables. Significantly higher levels of AST, ALB, D-DIC and higher proportion of bilateral lung involvement were observed from the severe group comparing to those in the mild group, while the difference in the other indices between the two groups was insignificant in statistical perspective. Conclusions: There are significant differences in the levels of multiple organ function indices between the severe group and the mild group of patients with COVID-19 pneumonia infection. Through examining the relevant indices, conditions of patients’ multiple organ function damage could be predicted and used as guidance of treatment.

FDA-approved Pralatrexate identified by virtual drug screening inhibits SARS-CoV-2 replication in vitro (preprint)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic poses serious threats to the global public health and leads to an unprecedented worldwide crisis. Unfortunately, no effective drugs or vaccines are available till now. Since the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 is a promising therapeutic target, a deep learning and molecular simulation based hybrid drug screening procedure was proposed and applied to identify potential drug candidates targeting RdRp from 1906 approved drugs. Among the four selected FDA-approved drug candidates, Pralatrexate and Azithromycin were confirmed to effectively inhibit SARS-CoV-2 replication in vitro with EC50 values of 0.008µM and 9.453 µM, respectively. For the first time, our study discovered that Pralatrexate is able to potently inhibit SARS-CoV-2 replication with a stronger inhibitory activity than Remdesivir within the same experimental conditions. The paper demonstrates the feasibility of accurate virtual drug screening for inhibitors of SARS-CoV-2 and provides potential therapeutic agents against COVID-19.

Analysis of functional indices indicates multiple organ function damage in patients with severe Coronavirus Disease 2019 (COVID-19) pneumonia (preprint)

Background: This study aims to analyze the changes and significance of organ function indices in patients with severe Coronavirus Disease 2019 (COVID-19) pneumonia for prediction of major organ damages and guiding treatment schemes.Methods: 63 patients with severe COVID-19 pneumonia were selected as the severe group and 73 patients with mild syndromes were selected as the mild group. SAS9.4 software was used for statistical analysis of the data.Results: Levels of ALT, AST, cTnI, Cr, PT, APTT and D-DIC of the severe group were significantly higher while PLT was lower than those of the mild group. The data of all quantitative variables were converted into categorical variables. Significantly higher levels of AST, ALB, D-DIC and higher proportion of bilateral lung involvement were observed from the severe group comparing to those in the mild group, while the difference in the other indices between the two groups was insignificant in statistical perspective.Discussion: There are significant differences in the levels of multiple organ function indices between the severe group and the mild group of patients with COVID-19 pneumonia infection. Through examining the relevant indices, conditions of patients’ multiple organ function damage could be predicted and used as guidance of treatment.

Recurrence of SARS-CoV-2 PCR positivity in COVID-19 patients: a single center experience and potential implications (preprint)

IMPORTANCE How to appropriately care for patients who become PCR-negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still not known. Patients who have recovered from coronavirus disease 2019 (COVID-19) could profoundly impact the health care system if a subset were to be PCR-positive again with reactivated SARS-CoV-2. OBJECTIVE To characterize a single center COVID-19 cohort with and without recurrence of PCR positivity, and develop an algorithm to identify patients at high risk of retest positivity after discharge to inform health care policy and case management decision-making. DESIGN, SETTING, AND PARTICIPANTS A cohort of 414 patients with confirmed SARS-CoV-2 infection, at The Second Affiliated Hospital of Southern University of Science and Technology in Shenzhen, China from January 11 to April 23, 2020. EXPOSURES Polymerase chain reaction (PCR) and IgM-IgG antibody confirmed SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES Univariable and multivariable statistical analysis of the clinical, laboratory, radiologic image, medical treatment, and clinical course of admission/quarantine/readmission data to develop an algorithm to predict patients at risk of recurrence of PCR positivity. RESULTS 16.7% (95CI: 13.0%-20.3%) patients retest PCR positive 1 to 3 times after discharge, despite being in strict quarantine. The driving factors in the recurrence prediction model included: age, BMI; lowest levels of the blood laboratory tests during hospitalization for cholinesterase, fibrinogen, albumin, prealbumin, calcium, eGFR, creatinine; highest levels of the blood laboratory tests during hospitalization for total bilirubin, lactate dehydrogenase, alkaline phosphatase; the first test results during hospitalization for partial pressure of oxygen, white blood cell and lymphocyte counts, blood procalcitonin; and the first test episodic Ct value and the lowest Ct value of the nasopharyngeal swab RT PCR results. Area under the ROC curve is 0.786. CONCLUSIONS AND RELEVANCE This case series provides clinical characteristics of COVID-19 patients with recurrent PCR positivity, despite strict quarantine, at a 16.7% rate. Use of a recurrence prediction algorithm may identify patients at high risk of PCR retest positivity of SARS-CoV-2 and help modify COVID-19 case management and health policy approaches.

A non-competing pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2 (preprint)

Neutralizing antibodies could be antivirals against COVID-19 pandemics. Here, we report the isolation of four human-origin monoclonal antibodies from a convalescent patient in China. All of these isolated antibodies display neutralization abilities in vitro. Two of them (B38 and H4) block the binding between RBD and vial cellular receptor ACE2. Further competition assay indicates that B38 and H4 recognize different epitopes on the RBD, which is ideal for a virus-targeting mAb-pair to avoid immune escape in the future clinical applications. Moreover, therapeutic study on the mouse model validated that these two antibodies can reduce virus titers in the infected mouse lungs. Structure of RBD-B38 complex revealed that most residues on the epitope are overlapped with the RBD-ACE2 binding interface, which explained the blocking efficacy and neutralizing capacity. Our results highlight the promise of antibody-based therapeutics and provide the structural basis of rational vaccine design. One Sentence SummaryA pair of human neutralizing monoclonal antibodies against COVID-19 compete cellular receptor binding but with different epitopes, and with post-exposure viral load reduction activity.

Development and validation of an early warning score (EWAS) for predicting clinical deterioration in patients with coronavirus disease 2019 (preprint)

Background: Since the pandemic outbreak of coronavirus disease 2019 (COVID-19), the health system capacity in highly endemic areas has been overwhelmed. Approaches to efficient management are urgently needed. We aimed to develop and validate a score for early prediction of clinical deterioration of COVID-19 patients. Methods: In this retrospective multicenter cohort study, we included 1138 mild to moderate COVID-19 patients admitted to 33 hospitals in Guangdong Province from December 27, 2019 to March 4, 2020 (N =818; training cohort), as well as two hospitals in Hubei Province from January 21 to February 22, 2020 (N =320; validation cohort) in the analysis. Results: The 14-day cumulative incidences of clinical deterioration were 7.9% and 12.1% in the training and validation cohorts, respectively. An Early WArning Score (EWAS) (ranging from 0 to 4.5), comprising of age, underlying chronic disease, neutrophil to lymphocyte ratio, C-reactive protein, and D-dimer levels, was developed (AUROC: 0.857). By applying the EWAS, patients were categorized into low-, medium-, and high risk groups (cut-off values: two and three). The 14-day cumulative incidence of clinical deterioration in the low-risk group was 1.8%, which was significantly lower than the incidence rates in the medium- (14.4%) and high-risk (40.9%) groups (P

ECMO application of patients with Critical Corona Virus Disease 2019 and fulminant myocarditis / 中华实验和临床病毒学杂志

Objective To evaluate the clinical experience of extracorporeal membrane oxygenation (ECMO) treatment on two cases of infection with the critical Corona Virus Disease 2019 (COVID-19) complicated by fulminant myocarditis (FM) . Methods This study selects two COVID-19 cases comorbid with fulminant myocarditis and had been treated with ECMO in Shenzhen Third People's Hospital from January 2020 to February 2020. We compare the index of inflammation, immunization, D-dimer and lactic acid before and after ECMO treatment in 24 and 96 hours, cardiopulmonary function before and after ECMO treatment in 24, 48, 72, 96 hours,. We also analyze the complications and clinical outcomes of the two cases during the ECMO treatment. Results Both patients were elderly obese men with chronic cardiopulmonary disease. Comparing the laboratory test results and imaging data of the two patients, the acute lung injury score, oxygenation index, albumin level, hypersensitive C-reactive protein, lactate and lactate dehydrogenase levels in 2 patients after ECMO treatment were improved as compared with those before ECMO treatment. Finally, case 1 died of multiple organ failure and his cardiac function continued to deteriorate, while, case 2 successfully withdrew and his cardiac function gradually improved. Conclusions For critical COVID-19 patients with fulminant myocarditis, ECMO treatment can improve pulmonary function in the short term, provide valuable time for rescuing COVID-19 patients with fulminant myocarditis.

Obesity and COVID-19 Severity in a Designated Hospital in Shenzhen, China (preprint)

Background: Patients with obesity are at increased risk of exacerbations from viral respiratory infections. However, the association of obesity with severity of corona virus disease 2019 (COVID-19) is unclear. We hereby examined this association using data from the only referral hospital in Shenzhen, China.Methods: 383 COVID-19 patients admitted from 11 January to 16 February 2020 in the Third People’s Hospital of Shenzhen, China were included. Underweight was defined by body mass index (BMI) lower than 18·5 kg/m2, normal weight by 18·5-23·9 kg/m2 , overweight by 24·0- 27·9 kg/m2 and obesity as ≥28 kg/m2.Findings: Of them, 53·1% were normal weight, 4·2% were underweight, 32·0% were overweight, and 10·7% were obese. Patients with obesity, versus without, were tended to have cough (P=0·03) and fever (P=0·06). After adjusting for potential confounders, compared to normal weight, overweight showed 86% higher, and obesity group showed 2·42-fold higher odds of developing severe pneumonia. Despite a non-significant sex interaction was found (P=0·09), the association appeared to be more pronounced in men than in women. The odds ratios (95% confidence intervals) for severe pneumonia in overweight and obesity was 1·96 (0·78-4·98) and 5·70 (1·83-17·76) in men, and 1·51 (0·57-4·01) and 0·71 (0·07-7·3) in women, respectively.Interpretation: This is the first study showing that obesity, especially in men, significantly increases the risk of developing severe pneumonia in COVID-19 patients. As the 2019n-Cov may continue to spread worldwide, clinicians should maintain a high level of attention in obese patients. Obese patients should be carefully managed with prompt and aggressive treatment.Funding Statement: Sanming Project of Medicine in Shenzhen (SZSM201412003, SZSM201512005) and Bill & Melinda Gates Foundations, Shenzhen Science and Technology Research and Development Project (202002073000001).Declaration of Interests: All authors declare no competing interests.Ethics Approval Statement: This study was approved by the Ethics Committee of The Third People’s Hospital of Shenzhen (2020 108). All patients provided signed informed consent at admission.