Association between a low response to rubella vaccination and reduced anti-severe acute respiratory syndrome coronavirus 2 immune response after vaccination with BNT162b2: a cross-sectional study

ObjectivesSome vaccinated individuals fail to acquire an adequate immune response against infection. We aimed to determine whether mRNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination could induce a sufficient immune response against SARS-CoV-2 in low responders to other vaccinations.MethodsUsing data from health-care workers who received two doses of the BNT162b2 vaccine (BioNTech/Pfizer), we conducted a single-centre, cross-sectional study to determine whether low responders to measles, rubella, and hepatitis B virus (HBV) vaccinations could acquire sufficient antibodies after SARS-CoV-2 vaccination. From May 2021 to June 2021, participants were tested for anti-SARS-CoV-2 spike (anti-S) IgG antibodies at least 2 weeks after the second dose of BNT162b2. The association between a low response to measles, rubella, and HBV vaccinations and the post-vaccination anti-S IgG titre was evaluated using the multivariable linear regression analysis.ResultsAll 714 participants were positive for the anti-S IgG titre (≥50.0 AU/mL) after two doses of BNT162b2 (median, 7126.8 AU/mL; interquartile range, 4496.2–11 296.8). There were 323 (45.2%), 131 (18.3%), and 43 (6.0%) low responders to measles, rubella, and HBV vaccinations, respectively. In the multivariable linear regression analysis, low responders to rubella vaccination had significantly low acquisition of the anti-S IgG titre after two doses of the BNT162b2 vaccine (standardized coefficient β, ?0.110; 95% CI, ?0.175 to ?0.044).ConclusionsA low response to rubella vaccination is a potential predictor of a reduced response to SARS-CoV-2 vaccination. Further studies are needed to determine whether a low response to rubella vaccination is associated with the durability of SARS-CoV-2 vaccination-induced immune response.     

Immunization against severe acute respiratory syndrome Coronavirus 2: an overview

In the past years, numerous new fatal infections have emerged, including Ebola, Nipah, and Zika viruses, as well as coronaviruses. Recently, infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged in China, and were then transmitted all over the world, causing the coronavirus disease-19 (COVID-19) pandemic, which is transmitted at a higher rate than other diseases caused by coronaviruses. At the time of writing this review, COVID-19 is not contained in most countries in spite of quarantine, physical distancing, and enhanced hygiene measures. In this review, I address different methods for passive and active immunization against this virus, which is known to cause fatal respiratory disease, including natural passive immunization by breast milk, natural active immunization by herd immunization, artificial passive immunization by convalescent plasma or monoclonal antibodies, and artificial active immunization by vaccination. I hope this review will help design a prophylactic approach against outbreaks and pandemics of related coronaviruses in the future.     

Immunopathology and immunotherapeutic strategies in severe acute respiratory syndrome coronavirus 2 infection

The outbreak of coronavirus disease 2019 (COVID‐19) and pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has become a major concern globally. As of 14 April 2020, more than 1.9 million COVID‐19 cases have been reported in 185 countries. Some patients with COVID‐19 develop severe clinical manifestations, while others show mild symptoms, suggesting that dysregulation of the host immune response contributes to disease progression and severity. In this review, we have summarized and discussed recent immunological studies focusing on the response of the host immune system and the immunopathology of SARS‐CoV‐2 infection as well as immunotherapeutic strategies for COVID‐19. Immune evasion by SARS‐CoV‐2, functional exhaustion of lymphocytes, and cytokine storm have been discussed as part of immunopathology mechanisms in SARS‐CoV‐2 infection. Some potential immunotherapeutic strategies to control the progression of COVID‐19, such as passive antibody therapy and use of interferon αβ and IL‐6 receptor (IL‐6R) inhibitor, have also been discussed. This may help us to understand the immune status of patients with COVID‐19, particularly those with severe clinical presentation, and form a basis for further immunotherapeutic investigations.     

一种新型冠状病毒假病毒的制备及初步应用

目的 制备一种新型冠状病毒(SARS-CoV-2)假病毒,并将其应用于抗体中和能力检测和抗体广谱性评估.方法 整合2种近期出现的SARS-CoV-2变异病毒株(20A.EU1和B1.1.7)刺突(spike,S)蛋白的突变序列、以及对胞浆区肽段19个氨基酸进行局部缺失突变,构建突变型S蛋白表达质粒,转染293T细胞进行...     

Good perceived sleep quality protects against the raised risk of respiratory infection during sleep restriction in young adults

Study ObjectivesProspectively examine the association between sleep restriction, perceived sleep quality (PSQ) and upper respiratory tract infection (URTI).MethodsIn 1318 military recruits (68% males) self-reported sleep was assessed at the beginning and end of a 12-week training course. Sleep restriction was defined as an individualized reduction in sleep duration of ≥2 hours/night compared with civilian life. URTIs were retrieved from medical records.ResultsOn commencing training, approximately half of recruits were sleep restricted (52%; 2.1 ± 1.6 h); despite the sleep debt, 58% of recruits with sleep restriction reported good PSQ. Regression adjusted for covariates showed that recruits commencing training with sleep restriction were more likely to suffer URTI during the course (OR = 2.93, 95% CI 1.29–6.69, p = .011). Moderation analysis showed this finding was driven by poor PSQ (B = −1.12, SE 0.50, p = .023), as no significant association between sleep restriction and URTI was observed in recruits reporting good PSQ, despite a similar magnitude of sleep restriction during training. Associations remained in the population completing training, accounting for loss to follow-up. Recruits reporting poor PSQ when healthy at the start and end of training were more susceptible to URTI (OR = 3.16, 95% CI 1.31–7.61, p = .010, vs good PSQ).ConclusionGood perceived sleep quality was associated with protection against the raised risk of respiratory infection during sleep restriction. Studies should determine whether improvements in sleep quality arising from behavioral sleep interventions translate to reduced respiratory infection during sleep restriction.     

Characteristics and roles of severe acute respiratory syndrome coronavirus 2-specific antibodies in patients with different severities of coronavirus 19

The diagnosis of coronavirus 19 (COVID-19) relies mainly upon viral nucleic acid detection, but false negatives can lead to missed diagnosis and misdiagnosis; severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody detection is convenient, safe and highly sensitive. Immunoglobulin (Ig)M and IgG are commonly used to serologically diagnose COVID-19; however, the role of IgA is not well known. We aimed to quantify the levels of SARS-CoV-2-specific IgM, IgA and IgG antibodies, identify changes in them based on COVID-19 severity, and establish the significance of combined antibody detection. COVID-19 patients, divided into a severe and critical group and a moderate group, and non-COVID-19 patients with respiratory disease were included in this study. A chemiluminescence method was used to detect the levels of SARS-CoV-2-specific IgM, IgA and IgG in the blood samples from the three groups. Epidemiological characteristics, symptoms, blood test results and other data were recorded for all patients. Compared to the traditional IgM–IgG combined antibodies, IgA–IgG combined antibodies are more effective for diagnosing COVID-19. During the disease process, IgA appeared first and disappeared last. All three antibodies had significantly higher levels in COVID-19 patients than in non-COVID-19 patients. IgA and IgG were also higher for severe and critical disease than for moderate disease. All antibodies were at or near low levels at the time of tracheal extubation in critical patients. Detection of SARS-CoV-2-specific combined IgA–IgG antibodies is advantageous in diagnosing COVID-19. IgA detection is suitable during early and late stages of the disease. IgA and IgG levels correspond to disease severity.     

Low placental weight and altered metabolic scaling after severe acute respiratory syndrome coronavirus type 2 infection during pregnancy: a prospective multicentric study

ObjectivesA higher risk of adverse pregnancy outcomes is associated with SARS-CoV-2 infection; this could be partially explained by an altered placental function. Because histopathology is often unspecific, we aimed to assess placental weight, birthweight/placental weight (b/p) ratio, and the metabolic scaling exponent ß, an indicator of normal fetal-placental growth, to analyze placental function.MethodsWe included 153 singleton pregnancies with SARS-CoV-2–positive PCR result who delivered at three referring hospitals in Switzerland. Placental weight and b/p ratio were compared to published reference charts. Logistic regression analysis investigated the role of time of infection and other confounding factors on placental weight. The scaling exponent β was compared to the reference value of 0.75.ResultsPlacental weight was inferior or equal to the tenth centile in 42.5% (65 of 153) and to the third centile in 19% (29 of 153) of the cases. The risk of low placental weight was not influenced by the trimester in which infection occurred. The b/p ratio was >50th centile in 80.4% (123 of 153) of the cases. The incidence of foetal growth restriction, preeclampsia, and gestational diabetes was 11.8% (18 of 153), 3.3% (5 of 153), and 19.6% (30 of 153). Linear regression modelling revealed a pathologic metabolic scaling exponent β of 0.871 ± 0.064 (R² = 0.56).DiscussionSARS-CoV-2 infection during pregnancy was associated with a higher incidence of low placental weight, an increased b/p ratio, and an abnormal scaling exponent β in our cohort. This could be particularly relevant for the still controversial issue of an increased stillbirth rate in SARS-CoV-2 infection during pregnancy. In this regard, intensified foetal surveillance should be mandatory in these pregnancies.     

Current infection prevention and control strategies of COVID-19 in hospitals

Background/aim Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has been appeared first in China since December 2019. Transmission of SARS-CoV-2 occurs primarily with droplets through coughing and sneezing and also occurs through inhalation of aerosolized secretions, which travel, remain suspended in the air longer.Materials and methodsSince early stages of the outbreak, COVID-19 cases have been described in healthcare workers (HCWs). However, in the early stages, the disease may be asymptomatic. This may lead to incorrect diagnosis or delayed diagnosis and may lead to the nosocomial spread of the virus. One of the most important causes of transmission among HCWs is being exposed to an aerosolized virus in a closed environment for a long time. It is possible to prevent and control the spread of COVID-19 in hospitals with outpatient treatment and triage.ResultsInfection control measures, including wearing surgical masks, hand hygiene, and social distance are considered essential in preventing human-to-human transmissions of SARS-CoV-2. Immediate response and practices of infection control measures are critical for saving lives during an epidemic inside and outside the hospital.ConclusionAnalyzing current knowledge about the features of SARS-CoV-2 infection, screening, personal protection protocols, triage and psychological support practices for healthcare professionals can be promising in terms of controlling the infection.     

Association of hostility with sleep duration and sleep disturbances in an employee population

Background: Sleep disturbances are common among the general population, and hostile persons have been proposed to be at greater risk of several serious health problems and diseases. Purpose: This study examined the relationships between hostility, sleep disturbances, and sleep duration in a large non-clinical sample of 5,433 employees working in 12 Finnish hospitals. Method: Data were collected by questionnaire surveys in 1998 and 2000. Results: Higher hostility was cross-sectionally associated with increased sleep disturbances but not with sleep duration after adjustment for gender, age, marital status, education, shift work, smoking, alcohol consumption, physical activity, body mass index, psychiatric morbidity, and somatic disease. A stratified analysis distinguishing individuals with stable hostility across the two measurements and those with transient hostility (>0.5 SD difference between measurements) replicated the association with increased sleep disturbance in both groups, but among those with transient hostility, there additionally was a cross-sectional association between higher hostility and shorter sleep duration. Conclusion: Our evidence suggests that hostility is an independent risk factor for sleep disturbances and that transient hostility may also predispose shorter sleep duration. However, the effect sizes for all these associations were small, suggesting limited clinical significance for our findings.     

Association of HLA class I with severe acute respiratory syndrome coronavirus infection

Background

The human leukocyte antigen (HLA) system is widely used as a strategy in the search for the etiology of infectious diseases and autoimmune disorders. During the Taiwan epidemic of severe acute respiratory syndrome (SARS), many health care workers were infected. In an effort to establish a screening program for high risk personal, the distribution of HLA class I and II alleles in case and control groups was examined for the presence of an association to a genetic susceptibly or resistance to SARS coronavirus infection.

Methods

HLA-class I and II allele typing by PCR-SSOP was performed on 37 cases of probable SARS, 28 fever patients excluded later as probable SARS, and 101 non-infected health care workers who were exposed or possibly exposed to SARS coronavirus. An additional control set of 190 normal healthy unrelated Taiwanese was also used in the analysis.

Results

Woolf and Haldane Odds ratio (OR) and corrected P-value (Pc) obtained from two tails Fisher exact test were used to show susceptibility of HLA class I or class II alleles with coronavirus infection. At first, when analyzing infected SARS patients and high risk health care workers groups, HLA-B*4601 (OR = 2.08, P = 0.04, Pc = n.s.) and HLA-B*5401 (OR = 5.44, P = 0.02, Pc = n.s.) appeared as the most probable elements that may be favoring SARS coronavirus infection. After selecting only a "severe cases" patient group from the infected "probable SARS" patient group and comparing them with the high risk health care workers group, the severity of SARS was shown to be significantly associated with HLA-B*4601 (P = 0.0008 or Pc = 0.0279).

Conclusions

Densely populated regions with genetically related southern Asian populations appear to be more affected by the spreading of SARS infection. Up until recently, no probable SARS patients were reported among Taiwan indigenous peoples who are genetically distinct from the Taiwanese general population, have no HLA-B* 4601 and have high frequency of HLA-B* 1301. While increase of HLA-B* 4601 allele frequency was observed in the "Probable SARS infected" patient group, a further significant increase of the allele was seen in the "Severe cases" patient group. These results appeared to indicate association of HLA-B* 4601 with the severity of SARS infection in Asian populations. Independent studies are needed to test these results.     

Omicron variant and change of electrostatic interactions between receptor binding domain of severe acute respiratory syndrome coronavirus 2 with the angiotensin-converting enzyme 2 receptor

BACKGROUNDSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are currently a new hazard. Since the first appearance of classical SARS-CoV-2 in late 2019, pathogen genetic alterations have continued to occur, and some new hazardous forms have already emerged. The underlying pathophysiological process leading to clinical issue is molecular change caused by genetic mutation. AIMTo determine the change in the interaction between receptor binding domain of omicron variant SARS-CoV-2 and the angiotensin-converting enzyme 2 (ACE2). METHODSThe researchers investigated how alterations in the binding area of the SARS receptor CoV2 interacted electrostatically with the ACE2 receptor. In this report, three important coronavirus disease 2019 variants, beta, delta, and omicron, were investigated. RESULTSAccording to this study, there was a change of electrostatic interactions between the receptor binding domain of SARS-CoV-2 with the ACE2 receptor due to each studied variant. The most change was detected in omicron variant followed by delta variant and beta variant.CONCLUSIONOur results may support the clinical finding that the omicron variant is more transmissible than the wild type and other variants.     

Antibody response induced by the BNT162b2 mRNA COVID-19 vaccine in a cohort of health-care workers,with or without prior SARS-CoV-2 infection: a prospective study

ObjectivesTo assess the antibody response to BNT162b2 mRNA COVID-19 vaccine in a cohort of health-care workers (HCW), comparing individuals with previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and SARS-CoV-2-naive individuals.MethodsHCW were tested at T0 (day of first dose), T1 (day of second dose) and T2 (2–3 weeks after second dose) for IgG anti-nucleocapsid protein, IgM anti-spike protein and IgG anti-receptor binding domain (IgG-RBD-S). The antibody response was compared between four main groups: group A, individuals with previous infection and positive antibodies at baseline; group B, individuals with the same history but negative antibodies; group C, individuals with no infection history but positive antibodies; group D, naive individuals. Repeated measures analysis was used to compare results over time-points.ResultsA total of 1935 HCW were included. Median IgG-RBD-S titre was significantly higher for group A (232 individuals) than for group B (56 individuals) both at T1 (A: 22 763 AU/mL, interquartile range (IQR) 14 222–37 204 AU/mL; B: 1373 AU/mL, IQR 783–3078 AU/mL, p 0.0003) and T2 (A: 30 765 AU/mL, IQR 19 841–42 813 AU/mL; B: 13 171 AU/mL, IQR 2324–22 688 AU/mL, p 0.0038) and for group D (1563 individuals; 796 AU/mL, IQR 379–1510 AU/mL at T1; 15 494 AU/mL, IQR 9122–23 916 AU/mL at T2, p < 0.0001 for both time-points). T1 values of group A were also significantly higher than T2 values of group D (p < 0.0001). Presence of symptoms, younger age and being female were associated with stronger antibody response. HCW infected in March showed a significantly stronger response (T1: 35 324 AU/mL, IQR 22 003–44 531 AU/mL; T2: 37 648 AU/mL, IQR 27 088–50 451 AU/mL) than those infected in November (T1: 18 499 AU/mL, IQR 11 492–27 283 AU/mL; T2: 23 210 AU/mL, IQR 18 074–36 086 AU/mL, p < 0.0001 for both time-points.ConclusionsIndividuals with past SARS-CoV-2 infection had a strong antibody response after one single vaccine shot. A single dose might be sufficient for this group, regardless of the time elapsed since infection; however, the clinical correlation with antibody response needs to be studied.     

Heterologous ChAdOx1 and Bnt162b2 vaccination induces strong neutralizing antibody responses against SARS-CoV-2 including delta variant with tolerable reactogenicity

ObjectivesWe assessed humoral responses and reactogenicity following the heterologous vaccination compared to the homologous vaccination groups.MethodsWe enrolled healthcare workers (HCWs) who were either vaccinated with ChAdOx1 followed by BNT162b2 (heterologous group) or 2 doses of ChAdOx1 (ChAdOx1 group) or BNT162b2 (BNT162b2 group). Immunogenicity was assessed by measuring antibody titers against receptor-binding domain (RBD) of SARS-CoV-2 spike protein in all participants and neutralizing antibody titer in 100 participants per group. Reactogenicity was evaluated by a questionnaire-based survey.ResultsWe enrolled 499 HCWs (ChAdOx1, n = 199; BNT162b2, n = 200; heterologous ChAdOx1/BNT162b2, n = 100). The geometric mean titer of anti–receptor-binding domain antibody at 14 days after the booster dose was significantly higher in the heterologous group (11 780.55 binding antibody unit (BAU)/mL [95% CI, 10 891.52–12 742.14]) than in the ChAdOx1 (1561.51 [95% CI, 1415.03–1723.15]) or BNT162b2 (2895.90 [95% CI, 2664.01–3147.98]) groups (both p < 0.001). The neutralizing antibody titer of the heterologous group (geometric mean ND₅₀, 2367.74 [95% CI, 1970.03–2845.74]) was comparable to that of the BNT162b2 group (2118.63 [95% CI, 1755.88–2556.32]; p > 0.05) but higher than that of the ChAdOx1 group (391.77 [95% CI, 326.16–470.59]; p < 0.001). Compared with those against wild-type SARS-CoV-2, the geometric mean neutralizing antibody titers against the Delta variant at 14 days after the boosting were reduced by 3.0-fold in the heterologous group (geometric mean ND₅₀, 872.01 [95% CI, 685.33–1109.54]), 4.0-fold in the BNT162b2 group (337.93 [95% CI, 262.78–434.57]), and 3.2-fold in the ChAdOx1 group (206.61 [95% CI, 144.05–296.34]). The local or systemic reactogenicity after the booster dose in the heterologous group was higher than that of the ChAdOx1 group but comparable to that of the BNT162b2 group.DiscussionHeterologous ChAdOx1 followed by BNT162b2 vaccination with a 12-week interval induced a robust humoral immune response against SARS-CoV-2, including the Delta variant, that was comparable to the homologous BNT162b2 vaccination and stronger than the homologous ChAdOx1 vaccination, with a tolerable reactogenicity profile.     

Detection and infectivity potential of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) environmental contamination in isolation units and quarantine facilities

ObjectivesEnvironmental surfaces have been suggested as likely contributors in the transmission of COVID-19. This study assessed the infectivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contaminating surfaces and objects in two hospital isolation units and a quarantine hotel.MethodsSARS-CoV-2 virus stability and infectivity on non-porous surfaces was tested under controlled laboratory conditions. Surface and air sampling were conducted at two COVID-19 isolation units and in a quarantine hotel. Viral RNA was detected by RT-PCR and infectivity was assessed by VERO E6 CPE test.ResultsIn laboratory-controlled conditions, SARS-CoV-2 gradually lost its infectivity completely by day 4 at ambient temperature, and the decay rate of viral viability on surfaces directly correlated with increase in temperature. Viral RNA was detected in 29/55 surface samples (52.7%) and 16/42 surface samples (38%) from the surroundings of symptomatic COVID-19 patients in isolation units of two hospitals and in a quarantine hotel for asymptomatic and very mild COVID-19 patients. None of the surface and air samples from the three sites (0/97) were found to contain infectious titres of SARS-Cov-2 on tissue culture assay.ConclusionsDespite prolonged viability of SARS-CoV-2 under laboratory-controlled conditions, uncultivable viral contamination of inanimate surfaces might suggest low feasibility for indirect fomite transmission.     

Asymptomatic carrier state,acute respiratory disease,and pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): Facts and myths

Since the emergence of coronavirus disease 2019 (COVID-19) (formerly known as the 2019 novel coronavirus [2019-nCoV]) in Wuhan, China in December 2019, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), more than 75,000 cases have been reported in 32 countries/regions, resulting in more than 2000 deaths worldwide. Despite the fact that most COVID-19 cases and mortalities were reported in China, the WHO has declared this outbreak as the sixth public health emergency of international concern. The COVID-19 can present as an asymptomatic carrier state, acute respiratory disease, and pneumonia. Adults represent the population with the highest infection rate; however, neonates, children, and elderly patients can also be infected by SARS-CoV-2. In addition, nosocomial infection of hospitalized patients and healthcare workers, and viral transmission from asymptomatic carriers are possible. The most common finding on chest imaging among patients with pneumonia was ground-glass opacity with bilateral involvement. Severe cases are more likely to be older patients with underlying comorbidities compared to mild cases. Indeed, age and disease severity may be correlated with the outcomes of COVID-19. To date, effective treatment is lacking; however, clinical trials investigating the efficacy of several agents, including remdesivir and chloroquine, are underway in China. Currently, effective infection control intervention is the only way to prevent the spread of SARS-CoV-2.     

SARS CoV-2 infections in healthcare workers with a pre-existing T-cell response: a prospective cohort study

ObjectiveT-cell responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are observed in unexposed individuals. We evaluated the impact of this pre-existing cellular response on incident SARS-CoV-2 infections.MethodsThis was a follow-up study of 38 seronegative healthcare workers (HCWs) with previous evaluation of CD8+ and CD4+ T-cell responses after stimulation with SARS-CoV-2 structural proteins. Infection was considered in the presence of a positive RT-PCR test and/or confirmed seroconversion.ResultsTwenty of the 38 HCWs included (53%) had a previous specific CD8+ T-cell response to peptides encompassing the spike protein (S) in 13 (34%), the membrane (M) in 17 (45%), or/and the nucleocapsid (N) in three (8%). During a follow-up of 189 days (interquartile range (IQR) 172–195), 11 HCWs (29%) had an RT-PCR-positive test (n = 9) or seroconverted (n = 2). Median duration of symptoms was 2 days (IQR 0–7), and time to negative RT-PCR was 9 days (IQR 4–10). Notably, six incident infections (55%) occurred in HCWs with a pre-existing T-cell response (30% of those with a cellular response), who showed a significantly lower duration of symptoms (three were asymptomatic). Three of the six HCWs having a previous T-cell response continued to test seronegative. All the infected patients developed a robust T-cell response to different structural SARS-CoV-2 proteins, especially to protein S (91%).ConclusionA pre-existing T-cell response does not seem to reduce incident SARS-CoV-2 infections, but it may contribute to asymptomatic or mild disease, rapid viral clearance and differences in seroconversion.