Memory B cell development after asymptomatic or mild symptomatic SARS-CoV-2 infection.

BACKGROUND: The development of memory B cells after asymptomatic SARS-CoV-2 infection is not well understood. METHODS: We compared Spike antibody titers, pseudovirus neutralizing antibody titers, and memory B cell responses among SARS-CoV-2 PCR positive Marine recruits who either reported asymptomatic or symptomatic infection. RESULTS: 36 asymptomatic participants exhibited similar Spike IgG titers, Spike IgA titers, and pseudovirus neutralization titers compared to 30 symptomatic participants. Pseudovirus neutralization and Spike IgG titers showed significant positive correlations with frequency of memory B cells. CONCLUSIONS: Among young adults, asymptomatic SARS-CoV-2 infection induced antibody and memory B cell responses comparable to mild symptomatic infection.

Antibody Responses to the SARS-CoV-2 Ancestral Strain and Omicron Variants in Moderna mRNA-1273 Vaccinated Active-Duty US Navy Sailors and Marines.

Omicron and its subvariants have steadily gained greater capability of immune escape compared to other variants of concern, resulting in an increased incidence of reinfections even among vaccinated individuals. We evaluated the antibody response to Omicron BA.1, BA.2, and BA.4/5 in US military members vaccinated with the primary 2-dose series of Moderna mRNA-1273 in a cross-sectional study. While nearly all vaccinated participants had sustained spike (S) IgG and neutralizing antibodies (ND50) to the ancestral strain, only 7.7% participants had detectable ND50 to Omicron BA.1 at 8 months postvaccination. The neutralizing antibody response to BA.2 and BA.5 was similarly reduced. The reduced antibody neutralization of Omicron correlated with the decreased antibody binding to the receptor-binding domain. The participants' seropositivity to the nuclear protein positively correlated with ND50. Our data emphasizes the need for continuous vigilance in monitoring for emerging variants and the need to identify potential alternative targets for vaccine design.

A field epidemiological investigation and emergency response of a confirmed COVID-19 case of a foreign airline cargo service personnel in Shanghai's international airport

Objective: To conduct on-site epidemiological investigation, emergency response, tracing of infection source and analysis of a confirmed COVID-19 case of a foreign airline cargo service staff member in Shanghai's international airport, aiming to provide reference for prevention of imported COVID-19 cases under regular prevention and control of COVID-19.

Comparison of Neutralizing Antibody Response Kinetics in Patients with Hand, Foot, and Mouth Disease Caused by Coxsackievirus A16 or Enterovirus A71: A Longitudinal Cohort Study of Chinese Children, 2017-2019.

Hand, foot, and mouth disease (HFMD), which is mainly caused by coxsackievirus A16 (CVA16) or enterovirus A71 (EV-A71), poses a serious threat to children's health. However, the long-term dynamics of the neutralizing Ab (NAb) response and ideal paired-serum sampling time for serological diagnosis of CVA16-infected HFMD patients were unclear. In this study, 336 CVA16 and 253 EV-A71 PCR-positive HFMD inpatients were enrolled and provided 452 and 495 sera, respectively, for NAb detection. Random-intercept modeling with B-spline was conducted to characterize NAb response kinetics. The NAb titer of CVA16 infection patients was estimated to increase from negative (2.1, 95% confidence interval [CI]: 1.4-3.3) on the day of onset to a peak of 304.8 (95% CI: 233.4-398.3) on day 21 and then remained >64 until 26 mo after onset. However, the NAb response level of EV-A71-infected HFMD patients was much higher than that of CVA16-infected HFMD patients throughout. The geometric mean titer was significantly higher in severe EV-A71-infected patients than in mild patients, with a 2.0-fold (95% CI: 1.4-3.2) increase. When a 4-fold rise in titer was used as the criterion for serological diagnosis of CVA16 and EV-A71 infection, acute-phase serum needs to be collected at 0-5 d, and the corresponding convalescent serum should be respectively collected at 17.4 (95% CI: 9.6-27.4) and 24.4 d (95% CI: 15.3-38.3) after onset, respectively. In conclusion, both CVA16 and EV-A71 infection induce a persistent humoral immune response but have different NAb response levels and paired-serum sampling times for serological diagnosis. Clinical severity can affect the anti-EV-A71 NAb response.

Long-term immune responses in patients with confirmed novel coronavirus disease-2019: a 9-month prospective cohort study in Shanghai, China.

BACKGROUND: The duration of antibodies against SARS-CoV-2 in Covid-19 patients remains uncertain. Longitudinal serological studies are needed to prevent disease and transmission of the virus. METHODS: In 2020, 414 blood samples were tested, obtained from 157 confirmed Covid-19 patients, in a prospective cohort study in Shanghai. RESULTS: The seropositive rate of IgM peaked at 40.5% (17/42) within 1 month after illness onset and then declined. The seropositive rate of IgG was 90.6% (58/64) after 2 months, remained above 85% from 2 to 9 months and was 90.9% (40/44) after 9 months. Generalized estimating equations models suggested that IgM (P < 0.001) but not IgG significantly decreased over time. Age ≥ 40 years (adjusted odds ratio [aOR] 4.531; 95% confidence interval [CI] 1.879-10.932), and cigarette smoking (aOR 0.344; 95% CI 0.124-0.951) were associated with IgG, and age ≥ 40 years (aOR 2.820; 95% CI 1.579-5.036) was associated with IgM. After seroconversion, over 90% and 75.1% of subjects were estimated to remain IgG-positive 220 and 254 days, respectively. Of 1420 self-reported symptoms questionnaires, only 5% reported symptoms 9 months after onset. CONCLUSIONS: In patients with a history of natural infection, anti-SARS-CoV-2 IgG is long-lived, being present for at least 9 months after illness onset. The long duration of natural immunity can mitigate and eliminate Covid-19 and the ongoing pandemic.

mtor Haploinsufficiency Ameliorates Renal Cysts and Cilia Abnormality in Adult Zebrafish tmem67 Mutants.

BACKGROUND: Although zebrafish embryos have been used to study ciliogenesis and model polycystic kidney disease (PKD), adult zebrafish remain unexplored. METHODS: Transcription activator-like effector nucleases (TALEN) technology was used to generate mutant for tmem67, the homolog of the mammalian causative gene for Meckel syndrome type 3 (MKS3). Classic 2D and optical-clearing 3D imaging of an isolated adult zebrafish kidney were used to examine cystic and ciliary phenotypes. A hypomorphic mtor strain or rapamycin was used to inhibit mTOR activity. RESULTS: Adult tmem67 zebrafish developed progressive mesonephric cysts that share conserved features of mammalian cystogenesis, including a switch of cyst origin with age and an increase in proliferation of cyst-lining epithelial cells. The mutants had shorter and fewer distal single cilia and greater numbers of multiciliated cells (MCCs). Absence of a single cilium preceded cystogenesis, and expansion of MCCs occurred after pronephric cyst formation and was inversely correlated with the severity of renal cysts in young adult zebrafish, suggesting a primary defect and an adaptive action, respectively. Finally, the mutants exhibited hyperactive mTOR signaling. mTOR inhibition ameliorated renal cysts in both the embryonic and adult zebrafish models; however, it only rescued ciliary abnormalities in the adult mutants. CONCLUSIONS: Adult zebrafish tmem67 mutants offer a new vertebrate model for renal cystic diseases, in which cilia morphology can be analyzed at a single-nephron resolution and mTOR inhibition proves to be a candidate therapeutic strategy.

Epidemiological and co-infection characteristics of common human coronaviruses in Shanghai, 2015-2020: a retrospective observational study.

The coronavirus disease (COVID-19) pandemic is a major challenge worldwide. However, the epidemic potential of common human coronaviruses (HCoVs) remains unclear. This study aimed to determine the epidemiological and co-infection characteristics of common HCoVs in individuals with influenza-like illness (ILI) and severe acute respiratory infection (SARI). This retrospective, observational, multicentre study used data collected from patients admitted to nine sentinel hospitals with ILI and SARI from January 2015 through December 2020 in Shanghai, China. We prospectively tested patients for a total of 22 respiratory pathogens using multi-real-time polymerase chain reaction. Of the 4541 patients tested, 40.37% (1833/4541) tested positive for respiratory pathogens and 3.59% (163/4541) tested positive for common HCoVs. HCoV infection was more common in the non-endemic season for respiratory pathogens (odds ratio: 2.33, 95% confidence interval: 1.64-3.31). HCoV-OC43 (41.72%, 68/163) was the most common type of HCoV detected. The co-infection rate was 31.29% (51/163) among 163 HCoV-positive cases, with HCoV-229E (53.13%, 17/32), the HCoV type that was most frequently associated with co-infection. Respiratory pathogens responsible for co-infections with HCoVs included parainfluenza virus, rhinovirus/enterovirus, influenza A virus, and adenovirus. Furthermore, we identified one patient co-infected with HCoV-OC43 and HCoV-NL63/HKU1. The prevalence of common HCoVs remains low in ILI/SARI cases, in Shanghai. However, the seasonal pattern of HCoVs may be opposite to that of other respiratory pathogens. Moreover, HCoVs are likely to co-exist with specific respiratory pathogens. The potential role of co-infections with HCoVs and other pathogenic microorganisms in infection and pathogenesis of ILI and SARI warrants further study.

ß-Coronaviruses Use Lysosomes for Egress Instead of the Biosynthetic Secretory Pathway.

ß-Coronaviruses are a family of positive-strand enveloped RNA viruses that includes the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Much is known regarding their cellular entry and replication pathways, but their mode of egress remains uncertain. Using imaging methodologies and virus-specific reporters, we demonstrate that ß-coronaviruses utilize lysosomal trafficking for egress rather than the biosynthetic secretory pathway more commonly used by other enveloped viruses. This unconventional egress is regulated by the Arf-like small GTPase Arl8b and can be blocked by the Rab7 GTPase competitive inhibitor CID1067700. Such non-lytic release of ß-coronaviruses results in lysosome deacidification, inactivation of lysosomal degradation enzymes, and disruption of antigen presentation pathways. ß-Coronavirus-induced exploitation of lysosomal organelles for egress provides insights into the cellular and immunological abnormalities observed in patients and suggests new therapeutic modalities.

42 cases of coronavirus disease 2019 of the ordinary type with the adjuvant treatment of heat-sensitive moxibustion 42.

OBJECTIVE: To observe the clinical therapeutic effect of adjuvant treatment with heat-sensitive moxibustion for coronavirus disease 2019 (COVID-19) of the ordinary type. METHODS: A total of 42 patients with COVID-19 of the ordinary type were adopted. Shénquè ( CV8) and Tianshu ( ST25) were selected. Heat-sensitive moxibustion was operated according to the required standard, 40 min to 60 min each time, once daily. Before and after moxibustion, the improvements in clinical symptoms were evaluated, such as chest oppression, poor appetite, lassitude and negative emotions. RESULTS: (1) The number of cases and the incidence was 21 cases (50.0%), 24 cases (57.1%) and 26 cases (61.9%) for chest oppression, poor appetite and lassitude before heat-sensitive moxibustion. The number of cases was reduced to be 10 cases (23.8%), 7 cases (16.7%) and 4 cases (9.5%) after the 1st treatment of heat-sensitive moxibustion for chest oppression, poor appetite, and lassitude. It was reduced to be 11 cases (26.2%), 8 cases (19.0%) and 4 cases (9.5%) after the 2nd treatment of moxibustion and it was reduced to be 18 cases (42.9%), 10 cases (23.8%) and 6 cases (14.3%) after the 3rd treatment of moxibustion. The incidences of the symptoms were all reduced obviously as compared with those before treatment. (2) Before treatment with heat-sensitive moxibustion, there were 24 cases of negative emotions (57.1%). It was reduced to be 16 cases (38.1%), 11 cases (26.2%) and 3 cases (7.1%) after the 1st, 2nd and 3rd treatment of heat-sensitive moxibustion successively. The incidences were all reduced obviously as compared with those before treatment. (3) After the 1st treatment, the active acceptance rate of heat-sensitive moxibustion was 100% (42/42) in the patients, higher than 11.9% (5/42) before treatment. CONCLUSION: Adjuvant treatment with heat-sensitive moxibustion effectively relieves the symptoms of COVID-19 such as chest oppression, poor appetite and lassitude, and alleviates the negative emotions, such as tension and anxiety. This therapy improves the therapeutic effect of COVID-19 and deserves to be promoted in clinical practice.

[Clinical observation of heat-sensitive moxibustion treatment for coronavirus disease 2019].

OBJECTIVE: To observe clinical effect of heat-sensitive moxibustion on coronavirus disease 2019 (COVID-19) and to discusses the effective moxibustion treatment program. METHODS: A total of 42 patients with COVID-19 (general type) were treated with heat-sensitive moxibustion at the acupoint area of Shenque (CV 8) and Tianshu (ST 25). The treatment was conducted under the standards of heat-sensitive moxibustion manipulation, which were "locating acupoint by feeling, moxibustion by differentiate sensation, dosage varies individually, ending after sufficient dosage". The incidence of deqi after first heat-sensitive moxibustion, the reduction of negative emotions, the improvement of chest distress and impaired appetite, and the active acceptance rate of moxibustion before and after treatment were observed. RESULTS: ① The deqi rate of heat-sensitive moxibustion for 20 min、40 min、1 h were respectively 52.4% (22/42), 90.5% (38/42), 100.0% (42/42). ② The incidences of feeling relaxed and comfortable immediately after the first, second, and third heat-sensitive moxibustion were 61.9% (26/42), 73.8% (31/42), and 92.9% (39/42), which were higher than 42.9% (18/42) before heat-sensitive moxibustion treatment (P<0.05). ③ The incidences of chest distress after the first, second, and third heat-sensitive moxibustion were 23.8% (10/42), 16.7% (7/42), and 9.5% (4/42), which were lower than 50.0% (21/42) before heat-sensitive moxibustion treatment (P<0.05); the incidences of impaired appetite after the first, second, and third heat-sensitive moxibustion were 26.2% (11/42), 19.0% (8/42), 9.5% (4/42), which were lower than 57.1% (24/42) before heat-sensitive moxibustion treatment (P<0.05). ④ After the first treatment, the active acceptance rate of patients for heat-sensitive moxibustion was 100.0% (42/42), which was higher than 11.9% (5/42) before heat-sensitive moxibustion (P<0.05). CONCLUSION: The heat-sensitive moxibustion can effectively reduce the negative emotions and improve the symptoms of chest distress and impaired appetite with COVID-19. It is generally accepted by patients, and worthy of popularization and application in clinical treatment.

Case fatality risk of the first pandemic wave of novel coronavirus disease 2019 (COVID-19) in China

OBJECTIVE: To assess the case fatality risk (CFR) of COVID-19 in mainland China, stratified by region and clinical category, and estimate key time-to-event intervals. METHODS: We collected individual information and aggregated data on COVID-19 cases from publicly available official sources from December 29, 2019 to April 17, 2020. We accounted for right-censoring to estimate the CFR and explored the risk factors for mortality. We fitted Weibull, gamma, and lognormal distributions to time-to-event data using maximum-likelihood estimation. RESULTS: We analyzed 82,719 laboratory-confirmed cases reported in mainland China, including 4,632 deaths, and 77,029 discharges. The estimated CFR was 5.65% (95%CI: 5.50%-5.81%) nationally, with highest estimate in Wuhan (7.71%), and lowest in provinces outside Hubei (0.86%). The fatality risk among critical patients was 3.6 times that of all patients, and 0.8-10.3 fold higher than that of mild-to-severe patients. Older age (OR 1.14 per year;95%CI: 1.11-1.16), and being male (OR 1.83;95%CI: 1.10-3.04) were risk factors for mortality. The time from symptom onset to first healthcare consultation, time from symptom onset to laboratory confirmation, and time from symptom onset to hospitalization were consistently longer for deceased patients than for those who recovered. CONCLUSIONS: Our CFR estimates based on laboratory-confirmed cases ascertained in mainland China suggest that COVID-19 is more severe than the 2009 H1N1 influenza pandemic in hospitalized patients, particularly in Wuhan. Our study provides a comprehensive picture of the severity of the first wave of the pandemic in China. Our estimates can help inform models and the global response to COVID-19.