Alterations in Gut Microbiota of Patients With COVID-19 During Time of Hospitalization.

The linkage of individuals with obesity and COVID-19 is controversial and lacks systematic reviews. After a systematic search of the Chinese and English language literature on COVID-19, 75 studies were used to conduct a series of meta-analyses on the relationship of individuals with obesity-COVID-19 over the full spectrum from risk to mortality. A systematic review of the mechanistic pathways for COVID-19 and individuals with obesity is presented. Pooled analysis show individuals with obesity were more at risk for COVID-19 positive, >46.0% higher (OR = 1.46; 95% CI, 1.30-1.65; p < 0.0001); for hospitalization, 113% higher (OR = 2.13; 95% CI, 1.74-2.60; p < 0.0001); for ICU admission, 74% higher (OR = 1.74; 95% CI, 1.46-2.08); and for mortality, 48% increase in deaths (OR = 1.48; 95% CI, 1.22-1.80; p < 0.001). Mechanistic pathways for individuals with obesity are presented in depth for factors linked with COVID-19 risk, severity and their potential for diminished therapeutic and prophylactic treatments among these individuals. Individuals with obesity are linked with large significant increases in morbidity and mortality from COVID-19. There are many mechanisms that jointly explain this impact. A major concern is that vaccines will be less effective for the individuals with obesity.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/obr.13128

Individuals with obesity and COVID-19: A global perspective on the epidemiology and biological relationships.

The pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused an unprecedented global social and economic impact, and high numbers of deaths. Many risk factors have been identified in the progression of COVID-19 into a severe and critical stage, including old age, male gender, underlying comorbidities such as hypertension, diabetes, obesity, chronic lung diseases, heart, liver and kidney diseases, tumors, clinically apparent immunodeficiencies, local immunodeficiencies, such as early type I interferon secretion capacity, and pregnancy. Possible complications include acute kidney injury, coagulation disorders, thoromboembolism. The development of lymphopenia and eosinopenia are laboratory indicators of COVID-19. Laboratory parameters to monitor disease progression include lactate dehydrogenase, procalcitonin, high-sensitivity C-reactive protein, proinflammatory cytokines such as interleukin (IL)-6, IL-1β, Krebs von den Lungen-6 (KL-6), and ferritin. The development of a cytokine storm and extensive chest computed tomography imaging patterns are indicators of a severe disease. In addition, socioeconomic status, diet, lifestyle, geographical differences, ethnicity, exposed viral load, day of initiation of treatment, and quality of health care have been reported to influence individual outcomes. In this review, we highlight the scientific evidence on the risk factors of severity of COVID-19.

Risk factors for severe and critically ill COVID-19 patients: A review.

Background & aims New York is the current epicenter of Coronavirus disease 2019 (COVID-19) pandemic. The underrepresented minorities, where the prevalence of obesity is higher, appear to be affected disproportionately. Our objectives were to assess the characteristics and early outcomes of patients hospitalized with COVID-19 in the Bronx and investigate whether obesity is associated with worse outcomes independently from age, gender and other comorbidities. Methods This retrospective study included the first 200 patients admitted to a tertiary medical center with COVID-19. The electronic medical records were reviewed at least three weeks after admission. The primary endpoint was in-hospital mortality. Results 200 patients were included (female sex: 102, African American: 102). The median BMI was 30 kg/m2. The median age was 64 years. Hypertension (76%), hyperlipidemia (46.2%), and diabetes (39.5%) were the three most common comorbidities. Fever (86%), cough (76.5%), and dyspnea (68%) were the three most common symptoms. 24% died during hospitalization (BMI  Conclusions In this cohort of hospitalized patients with COVID-19 in a minority-predominant population, severe obesity, increasing age, and male sex were independently associated with higher in-hospital mortality and in general worse in-hospital outcomes.

Severe obesity, increasing age and male sex are independently associated with worse in-hospital outcomes, and higher in-hospital mortality, in a cohort of patients with COVID-19 in the Bronx, New York.

SARS-CoV-2 enters cells using its Spike protein, which is also the main target of neutralizing antibodies. Therefore, assays to measure how antibodies and sera affect Spike-mediated viral infection are important for studying immunity. Because SARS-CoV-2 is a biosafety-level-3 virus, one way to simplify such assays is to pseudotype biosafety-level-2 viral particles with Spike. Such pseudotyping has now been described for single-cycle lentiviral, retroviral, and vesicular stomatitis virus (VSV) particles, but the reagents and protocols are not widely available. Here, we detailed how to effectively pseudotype lentiviral particles with SARS-CoV-2 Spike and infect 293T cells engineered to express the SARS-CoV-2 receptor, ACE2. We also made all the key experimental reagents available in the BEI Resources repository of ATCC and the NIH. Furthermore, we demonstrated how these pseudotyped lentiviral particles could be used to measure the neutralizing activity of human sera or plasma against SARS-CoV-2 in convenient luciferase-based assays, thereby providing a valuable complement to ELISA-based methods that measure antibody binding rather than neutralization.

Protocol and Reagents for Pseudotyping Lentiviral Particles with SARS-CoV-2 Spike Protein for Neutralization Assays.

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.

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

Background: The novel coronavirus SARS-CoV-2 is a newly emerging virus. The antibody response in infected patient remains largely unknown, and the clinical values of antibody testing have not been fully demonstrated.

Methods: A total of 173 patients with confirmed SARS-CoV-2 infection were enrolled. Their serial plasma samples (n = 535) collected during the hospitalization period were tested for total antibodies (Ab), IgM and IgG against SARS-CoV-2 using immunoassays. The dynamics of antibodies with the progress and severity of disease was analyzed.

Findings: Among 173 patients, the seroconversion rate for Ab, IgM and IgG was 93.1% (161/173), 82.7% (143/173) and 64.7% (112/173), respectively. Twelve patients who had not seroconverted were those only blood samples at the early stage of illness were collected. The seroconversion sequentially appeared for Ab, IgM and then IgG, with a median time of 11, 12 and 14 days, respectively. The presence of antibodies was < 40% among patients in the first 7 days of illness, and then rapidly increased to 100.0%, 94.3% and 79.8% for Ab, IgM and IgG respectively since day 15 after onset. In contrast, the positive rate of RNA decreased from 66.7% (58/87) in samples collected before day 7 to 45.5% (25/55) during days 15 to 39. Combining RNA and antibody detections significantly improved the sensitivity of pathogenic diagnosis for COVID-19 patients (p < 0.001), even in early phase of 1-week since onset (p = 0.007). Moreover, a higher titer of Ab was independently associated with a worse clinical classification (p = 0.006).

Interpretation: The antibody detection offers vital clinical information during the course of SARS-CoV-2 infection. The findings provide strong empirical support for the routine application of serological testing in the diagnosis and management of COVID-19 patients.

Funding Statement: This study was supported by National Key R&D Program of China (SQ2020YFC080015), and the Science and Technology Major Project of Shenzhen, Fujian (2020YZ0106), Xiamen (3502Z2020YJ01) and Bill & Melinda Gates Foundation.

Declaration of Interests: The authors declare no competing interests.

Ethics Approval Statement: This study was reviewed and approved by the Medical Ethical Committee of Shenzhen Third People’s Hospital (approval number 2020-0018). Written informed consent was obtained from each enrolled patient.

https://papers.ssrn.com/sol3/Delivery.cfm/THELANCET-D-20-02366.pdf?abstractid=3546052&mirid=1

He Qing

Papers

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

Antibody Responses to SARS-CoV-2 in Patients of Novel Coronavirus Disease 2019