Progress of the COVID-19: Persistence, Effectiveness, and Immune Escape of the Neutralizing Antibody in Convalescent Serum.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a new coronavirus causing Coronavirus Disease 2019 (COVID-19), is a major topic of global human health concern. The Delta and Omicron variants have caused alarming responses worldwide due to their high transmission rates and a number of mutations. During a one-year follow-up (from June 2020 to June 2021), we included 114 patients with SARS-CoV-2 infection to study the long-term dynamics and the correlative factors of neutralizing antibodies (NAbs) in convalescent patients. The blood samples were collected at two detection time points (at 6 and 12 months after discharge). We evaluated the NAbs response of discharged patients by performing a micro-neutralization assay using a SARS-CoV-2 wild type. In addition, a total of 62 serum samples from discharged COVID-19 patients with Alpha, Beta, Delta, and Omicron variants of infection were enrolled to perform cross-neutralization tests using the original SARS-CoV-2 strain and VOCs variants (including Alpha, Beta, Gamma, Delta, and Omicron variants) and to assess the ability of NAbs against the SARS-CoV-2 variants. NAbs seroconversion occurred in 91.46% of patients (n = 82) in the first timepoint and in 89.29% of patients (n = 84) in the second detection point, and three kinds of NAbs kinetics curves were perceived. The NAbs levels in young patients had higher values than those in elder patients. The kinetics of disease duration was accompanied by an opposite trend in NAbs levels. Despite a declining NAbs response, NAbs activity was still detectable in a substantial proportion of recovered patients one year after discharge. Compared to the wild strain, the Omicron strain could lead to a 23.44-, 3.42-, 8.03-, and 2.57-fold reduction in neutralization capacity in "SAlpha", "SBeta", "SDelta", and "SOmicron", respectively, and the NAbs levels against the Omicron strain were significantly lower than those of the Beta and Delta variants. Remarkably, the NAbs activity of convalescent serum with Omicron strain infection was most obviously detectable against six SARS-CoV-2 strains in our study. The role of the vaccination history in NAbs levels further confirmed the previous study that reported vaccine-induced NAbs as the convincing protection mechanism against SARS-CoV-2. In conclusion, our findings highlighted the dynamics of the long-term immune responses after the disappearance of symptoms and revealed that NAbs levels varied among all types of convalescent patients with COVID-19 and that NAbs remained detectable for one year, which is reassuring in terms of protection against reinfection. Moreover, a moderate correlation between the duration of disease and Nabs titers was observed, whereas age was negatively correlated with Nabs titers. On the other hand, compared with other VOCs, the Omicron variant was able to escape the defenses of the immune system more significantly, and the convalescent serum infected with the Omicron variant played a critical part in protection against different SARS-CoV-2 variants. Recovery serum from individuals vaccinated with inactivated vaccine preceding infection with the Omicron strain had a high efficacy against the original strain and the VOCs variants, whereas the convalescent serum of persons vaccinated by inactivated vaccine prior to infection with the Delta variant was only potent against the wild-type strain.

IL-6 drives T cell death to participate in lymphopenia in COVID-19.

Lymphopenia is a common observation in patients with COVID-19. To explore the cause of T cell lymphopenia in the disease, laboratory results of 64 hospitalized COVID-19 patients were retrospectively analyzed and six patients were randomly selected to trace their changes of T lymphocytes and plasma concentration of IL-6 for the course of disease. Results confirmed that the T-cell lymphopenia, especially CD4+ T cell reduction in COVID-19 patients, was a reliable indicator of severity and hospitalization in infected patients. And CD4+ T cell count below 200 cells/µL predicts critical illness in COVID-19 patients. In vitro assay supported that exposure to key contributors (IL-1ß, IL-6, TNF-α and IFN-γ) of COVID-19 cytokine storm caused substantial death of activated T cells. Among these contributors, IL-6 level was found to probably reversely correlate with T cell counts in patients. And IL-6 alone was potent to induce T cell reduction by gasderminE-mediated pyroptosis, inferring IL-6 took a part in affecting the function and status of T cells in COVID-19 patients. Intervention of IL-6 mediated T cell pryprotosis may effectively delay disease progression, maintain normal immune status at an early stage of infection.

Cellular and molecular atlas of the placenta from a COVID-19 pregnant woman infected at midgestation highlights the defective impacts on foetal health.

OBJECTIVES: The impacts of the current COVID-19 pandemic on maternal and foetal health are enormous and of serious concern. However, the influence of SARS-CoV-2 infection at early-to-mid gestation on maternal and foetal health remains unclear. MATERIALS AND METHODS: Here, we report the follow-up study of a pregnant woman of her whole infective course of SARS-CoV-2, from asymptomatic infection at gestational week 20 to mild and then severe illness state, and finally cured at Week 24. Following caesarean section due to incomplete uterine rupture at Week 28, histological examinations on the placenta and foetal tissues as well as single-cell RNA sequencing (scRNA-seq) for the placenta were performed. RESULTS: Compared with the gestational age-matched control placentas, the placenta from this COVID-19 case exhibited more syncytial knots and lowered expression of syncytiotrophoblast-related genes. The scRNA-seq analysis demonstrated impaired trophoblast differentiation, activation of antiviral and inflammatory CD8 T cells, as well as the tight association of increased inflammatory responses in the placenta with complement over-activation in macrophages. In addition, levels of several inflammatory factors increased in the placenta and foetal blood. CONCLUSION: These findings illustrate a systematic cellular and molecular signature of placental insufficiency and immune activation at the maternal-foetal interface that may be attributed to SARS-CoV-2 infection at the midgestation stage, which highly suggests the extensive care for maternal and foetal outcomes in pregnant women suffering from COVID-19.

The combined regimens of antiviral therapy might not be useful for the viral clearance of severe COVID-19 cases.

BACKGROUND: Severe COVID-19 caused by SARS-CoV-2 should closely be cared because of the relatively high mortality rate. If SARS-CoV-2 could be cleared as soon as possible, the mortality rate might lower. In the present study, we analyzed factors which might be related to the clearance of SARS-CoV-2. METHODS: One hundred and twenty-eight severe COVID-19 cases were enrolled. All of them had been isolated and treated at Shenzhen Third People's Hospital because they were positive for nucleic acid of SARS-CoV-2 tested by qRT-PCR. Their baseline clinical characteristics and antiviral regimens were collected and analyzed, respectively. RESULTS: Of the 128 enrolled severe COVID-19 cases, unfortunately 3 died. The mean viral duration of all patients was 23.5 (range 17-32) days. All patients achieved viral clearance during 9 weeks. 13.4% of patients achieved viral clearance within 2 weeks, and 63.0% of patients achieved viral clearance within 4 weeks. The combined regimens of three or more antiviral drugs, the use of invasive mechanical ventilation, and late admission might be related to the delay of viral clearance within 2 weeks. The use of arbidol, the use of invasive mechanical ventilation, and late admission might be related to the delay of viral clearance within 4 weeks. Patients often had a prolonged course of COVID-19 and hospitalization, and were more likely transferred to intensive care unit (ICU) for treatment, if they could not clear SARS-CoV-2 during 23 days. CONCLUSION: Severe COVID-19 cases should be admitted to hospital as soon as possible. The combined regimens of three or more antiviral drugs might not be useful for viral clearance, and should be performed carefully and cautiously.

Repeat laboratory testing of SARS-CoV-2 is necessary to diagnose COVID-19.

The pandemic of corona virus disease 2019 (COVID-19) caused by SARS-CoV-2 is ravaging the world. Diagnosis and isolation of persons who are infected with SARS-CoV-2 is very important medical emergency to contain the epidemic of COVID-19. To date, the diagnosis of COVID-19 is mainly depending on positive quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) results for SARS-CoV-2. In the present study, we reported that two cases with uncommon symptoms from a family cluster were ultimately diagnosed as COVID-19 after more than twice of collecting samples and qRT-PCR tests were done. It is easily to miss diagnosis of COVID-19 especially for patients with uncommon symptoms. More attention should be paid to observe the clinical characteristics of it and invent more accurate and convenient methods to detect SARS-CoV-2 as soon as possible.

COVID-19: gastrointestinal symptoms from the view of gut-lung axis.

The main symptoms of coronavirus disease 2019 (COVID-19) are respiratory manifestations, while some confirmed patients developed gastrointestinal symptoms or even initially presented digestive symptoms. The link between pneumonia and gastrointestinal symptoms caused by severe acute respiratory symptoms coronavirus 2 focused our attention on the concept of 'gut-lung axis'. In this review, we discuss the inevitability and possible mechanisms of the occurrence of intestinal symptoms or intestinal dysfunction in COVID-19 from the perspective of the gut-lung axis, as well as the influence of the imbalance of intestinal homeostasis on the respiratory symptoms of COVID-19. The interaction between lung and intestine might lead to a vicious cycle of pulmonary and intestinal inflammation which may be a potential factor leading to the death of patients with COVID-19.

Clinical characteristics, laboratory outcome characteristics, comorbidities, and complications of related COVID-19 deceased: a systematic review and meta-analysis.

BACKGROUND: At present, novel coronavirus disease 2019 (COVID-19) has become a serious global public health problem. The current meta-analysis aimed to find risk factors for the COVID-19-related death, helping to enhance the efficacy and reduce the mortality of COVID-19. METHODS: We searched PubMed, Embase, medRxiv, and Cochrane Library for articles published between January 1, 2020, and April 13, 2020. We statistically analyzed the risk factors of the COVID-19 deceased with meta-analysis. RESULTS: A total of 2401 patients in 15 articles were included in this study. Meta-analysis showed that 66.6% of COVID-19 deceased were male, with a median age of 69.9 years. Common symptoms of deceased included fever (70.6-100%), dyspnea (38.89-85.7%), cough (22.4-78%), and fatigue (22-61.9%). The incidence of hypertension, chronic cardiovascular disease, diabetes, and chronic cerebrovascular disease among the COVID-19 deceased were 38.56% (95% confidence interval (CI) 25.84 ~ 52.12%), 17.54% (95% CI 13.38 ~ 21.69%), 22.2% (95% CI 19.30 ~ 25.10%), and 15.58% (95% CI 10.05 ~ 21.12%), respectively. Compared with the surviving COVID-19 patients, the deceased had lower platelet levels (mean difference (MD) = - 39.35, 95% CI - 55.78 ~ - 22.93) and higher C-reactive protein (CRP) (MD = 80.85, 95% CI 62.53 ~ 99.18) and lactate dehydrogenase (LDH) (MD = 246.65, 95% CI 157.43 ~ 335.88) at admission. The most common complications of the deceased were acute respiratory distress syndrome (ARDS) (OR = 100.36, 95% CI 64.44 ~ 156.32) and shock (OR = 96.60, 95% CI 23.80 ~ 392.14). CONCLUSION: Most of the COVID-19 deceased were elderly males. Fever, dyspnea, dry cough, fatigue, hypertension, chronic cardiovascular and cerebrovascular disease, diabetes, and laboratory examinations showed low levels of platelet content, increased CRP and LDH were associated with the risk of dying. ARDS and shock were risk factors for death in COVID-19 patients.

Expert consensus for managing pregnant women and neonates born to mothers with suspected or confirmed novel coronavirus (COVID-19) infection.

OBJECTIVE: To provide clinical management guidelines for novel coronavirus (COVID-19) in pregnancy. METHODS: On February 5, 2020, a multidisciplinary teleconference comprising Chinese physicians and researchers was held and medical management strategies of COVID-19 infection in pregnancy were discussed. RESULTS: Ten key recommendations were provided for the management of COVID-19 infections in pregnancy. CONCLUSION: Currently, there is no clear evidence regarding optimal delivery timing, the safety of vaginal delivery, or whether cesarean delivery prevents vertical transmission at the time of delivery; therefore, route of delivery and delivery timing should be individualized based on obstetrical indications and maternal-fetal status.