The SARS-CoV-2 Antibody and Drug Research Based on the Structure of the Spike Protein and the Mechanism of Cell Entry.

COVID-19 is a severe acute respiratory syndrome caused by a novel coronavirus, SARS-CoV- 2.COVID-19 is now a pandemic, and is not yet fully under control.As the surface spike protein (S) mediates the recognition between the virus and cell membrane and the process of cell entry, it plays an important role in the course of disease transmission.The study on the S protein not only elucidates the structure and function of virus-related proteins and explains their cellular entry mechanism, but also provides valuable information for the prevention, diagnosis and treatment of COVII)-19.Concentrated on the S protein of SARS-CoV-2, this review covers four aspects: (1 ) The structure of the S protein and its binding with angiotensin converting enzyme II (ACE2) , the specific receptor of SARS-CoV-2, is introduced in detail.Compared with SARS-CoV, the receptor binding domain (RBD) of the SARS-CoV- 2 S protein has a higher affinity with ACE2, while the affinity of the entire S protein is on the contrary.(2) Currently, the cell entry mechanism of SARS-CoV-2 meditated by the S protein is proposed to include endosomal and non-endosomal pathways.With the recognition and binding between the S protein and ACE2 or after cell entry, transmembrane protease serine 2(TMPRSS2) , lysosomal cathepsin or the furin enzyme can cleave S protein at S1/S2 cleavage site, facilitating the fusion between the virus and target membrane.(3) For the progress in SARS-CoV-2 S protein antibodies, a collection of significant antibodies are introduced and compared in the fields of the target, source and type.(4) Mechanisms of therapeutic treatments for SARS-CoV-2 varied.Though the antibody and medicine treatments related to the SARS-CoV-2 S protein are of high specificity and great efficacy, the mechanism, safety, applicability and stability of some agents are still unclear and need further assessment.Therefore, to curb the pandemic, researchers in all fields need more cooperation in the development of SARS-CoV-2 antibodies and medicines to face the great challenge.Copyright © Palaeogeography (Chinese Edition).All right reserved.

Surveillance of anti-SARS-CoV-2 antibodies in plasma pools and in immunoglobulin medicinal products manufactured since 2020 has shown high neutralizing activity against SARS-CoV-2 and current variants

Background: Patients with primary and secondary immunodeficiencies have shown an impaired humoral immune response to COVID-19 vaccination. It is therefore of paramount importance to investigate anti-SARS-CoV-2 antibody levels in plasma pools and in immunoglobulin (IgG) products used to treat these patients. AIM: To assess the evolution of anti-SARS-CoV-2 antibodies (S protein) in plasma pools and IgG products and its neutralizing activity to original-type virus (Wuhan) and the variants of concern (VOC), including Omicron. Method(s): Healthy donors plasma pools collected in the US and Europe, and the subsequent intravenous (Flebogamma DIFand Gamunex-C, Grifols) and subcutaneous (Xembify, Grifols) IgG manufactured batches were followed from March 2020. Anti-SARS-CoV-2 S protein IgG titers were determined in plasma pools and in IgG batches by ELISA. Neutralization assays analyzed the capacity of IgG products to neutralize original-type virus and VOC (Alpha, Beta, Delta, Omicron BA.1 and BA.5), using pseudo viruses expressing S protein. Results were expressed as the dilution producing 50% neutralization (ID50). Result(s): In plasma pools, anti-SARS-CoV-2 S antibodies continuously increased throughout the study period regardless of the geographic origin. In the US, the first positive plasma pools were collected at the end of 2020. Since July 2021, an exponential increase over 30-fold of anti-SARS-CoV-2 S antibodies was reported. This trend continued increasing until the end of study period. Similarly, IgG products showed a similar evolution of anti-SARS-CoV-2 S antibodies. As expected, IgG batches released at the end of 2020 presented low SARS-CoV-2 neutralization activity. However, IgG products manufactured since August 2021 showed high neutralization activity against original-type virus and the rest of VOC. Regarding Omicron BA.5, a 5 to 10-fold increase was observed over time. Conclusion(s): This study reported the onset of elevated anti-SARS-CoV-2 antibody titers in plasma pools and IgG products since mid-2021, reflecting the evolution of the pandemic and vaccine campaigns. Intravenous and subcutaneous IgG products efficiently neutralized the current circulating VOC, Omicron BA.5. Further research is warranted to assess whether a clinical protective titer against SARS-CoV-2 and passive immunization is achieved in patients with immunodeficiencies treated with IgG products.Copyright © 2023 Elsevier Inc.

Anti-SARS-CoV-2 antibodies important in diagnostics of acute hepatitis in children

The most common causes of acute hepatitis in children are hepatitis A and autoimmune hepatitis. Hepatitis in the course of Wilson's disease is sporadically registered in adolescents. An increase of activity of aminotransferases both in the course of multisystem inflammatory syndrome in children (MIS-C) and in the course of COVID-19 has been observed. Hepatitis is common in children with MIS-C and is associated with a more severe presentation and persistent elevation of liver function tests. To date, no cases of acute hepatitis in children due to COVID-19 have been reported. We present 2 cases of acute hepatitis in children where the only cause seems to be a previous asymptomatic SARS-CoV-2 infection.Copyright © 2023 Termedia Publishing House Ltd.. All rights reserved.

Research Article Molecular Docking and Drug Likeness Prediction of New Potent Sars Cov-2 Main Protease Inhibitors

The novel corona virus whose outbreak took place in December 2019 continues to spread at a rapid rate worldwide. The Main protease (Mpro) plays critical role in the SARS-CoV-2 life cycle through virus replication and transcription process making it as an attractive drug target. Herein, molecular docking study followed by drug-Likeness prediction, were performed in order to identify new potent Mpro inhibitors. Indeed, molecular docking of 1880 compounds into the Mpro active site reveals compounds S1 and S2 as promising inhibitors of this enzyme with binding energy of -39,22 KJ/mol, -36.27 KJ/mol respectively. These two compounds were also predicted to have satisfying drug likeness properties, indicating that they might be promising lead compounds for further anti-SARS CoV-2 drug research.Copyright © KESS All rights reserved.

A third dose of the BNT162b2 mRNA vaccine sufficiently improves the neutralizing activity against SARS-CoV-2 variants in liver transplant recipients.

Introduction: We examined the neutralizing antibody production efficiency of the second and third severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine doses (2nd- and 3rd-dose) and neutralizing activity on mutant strains, including, the Ancestral, Beta and Omicron strains using green fluorescent protein-carrying recombinant SARS-CoV-2, in living-donor liver transplantation (LDLT) recipients. Methods: The patients who were administered vaccines other than Pfizer- BioNTechBNT162b2 and who had coronavirus disease 2019 in this study period were excluded. We enrolled 154 LDLT recipients and 50 healthy controls. Result: The median time were 21 days (between 1st and 2nd vaccination) and 244 days (between 2nd and 3rd vaccination). The median neutralizing antibody titer after 2nd-dose was lower in LDLT recipients than in controls (0.46 vs 1.00, P<0.0001). All controls had SARS-CoV-2 neutralizing antibodies, whereas 39 LDLT recipients (25.3%) had no neutralizing antibodies after 2nd-dose; age at vaccination, presence of ascites, multiple immunosuppressive treatments, and mycophenolate mofetil treatment were significant risk factors for nonresponder. The neutralizing activities of recipient sera were approximately 3-fold and 5-fold lower than those of control sera against the Ancestral and Beta strains, respectively. The median antibody titer after 3rd-dose was not significantly different between recipients and controls (1.02 vs 1.22, p=0.0758); only 5% recipients was non-responder. The neutralizing activity after third dose to Omicron strains were enhanced and had no significant difference between two groups. Conclusion: Only the 2nd-dose was not sufficiently effective in recipients; however, 3rd-dose had sufficient neutralizing activity against the mutant strain and was as effective as that in healthy controls.

Humoral and cellular immune response to SARS-CoV-2 mRNA BNT162b2 vaccine in pediatric kidney transplant recipients compared with dialysis patients and healthy children.

BACKGROUND: Compared with the general population, the immune response to COVID-19 mRNA vaccines is lower in adult kidney transplant recipients (KTRs). However, data is limited for pediatric KTRs. In this study, we aimed to assess humoral and cellular immune responses to the COVID-19 mRNA vaccine in pediatric KTRs. METHODS: This multicenter, prospective, case-control study included 63 KTRs (37 male, aged 12-21 years), 19 dialysis patients, and 19 controls. Humoral (anti-SARS-CoV2 IgG, neutralizing Ab (nAb)) and cellular (interferon-gamma release assay (IGRA)) immune responses were assessed at least one month after two doses of BNT162b2 mRNA vaccine. RESULTS: Among COVID-19 naïve KTRs (n = 46), 76.1% tested positive for anti-SARS-CoV-2 IgG, 54.3% for nAb, and 63% for IGRA. Serum levels of anti-SARS-CoV-2 IgG and nAb activity were significantly lower in KTRs compared to dialysis and control groups (p < 0.05 for all). Seropositivity in KTRs was independently associated with shorter transplant duration (p = 0.005), and higher eGFR (p = 0.007). IGRA titer was significantly lower than dialysis patients (p = 0.009). Twenty (43.4%) KTRs were positive for all immune parameters. Only four of 11 seronegative KTRs were IGRA-positive. COVID-19 recovered KTRs had significantly higher anti-SARS-CoV-2 IgG and nAb activity levels than COVID-19 naïve KTRs (p = 0.018 and p = 0.007, respectively). CONCLUSIONS: The humoral and cellular immune responses to SARS-CoV-2 mRNA BNT162b2 vaccine are lower in pediatric KTRs compared to dialysis patients. Further prospective studies are required to demonstrate the clinical efficacy of the mRNA vaccine in KTRs. This prospective study was registered in ClinicalTrials.gov (NCT05465863, registered retrospectively at 20.07.2022). A higher resolution version of the Graphical abstract is available as Supplementary information.

Age, Sex and BMI Relations with Anti-SARS-CoV-2-Spike IgG Antibodies after BNT162b2 COVID-19 Vaccine in Health Care Workers in Northern Greece.

The aim of this work was to study age, sex, and BMI (Body Mass Index)-related differences in the development of anti-SARS-CoV-2-Spike IgG antibodies, after vaccination with the BNT162b2 COVID-19 vaccine, in health care workers of a General Hospital in a city in Northern Greece. Blood sampling was drawn two to four weeks following the second dose of the vaccine, and six months after the first blood sample collection. Measurement of serum IgG antibodies against the spike domain of SARS-CoV-2 was performed using the SARS-CoV-2 IgG II Quant assay. All participants had sufficient serum IgG titers in the first measurement. Women developed higher IgG titers than men. The IgG titers were inversely related to age in both sexes; there was also a small, insignificant tendency to be inversely related to BMI. Six months after the first measurement, the IgG titers decreased dramatically to values less than 5% of the initial. This decrease was observed in both men and women and was inversely related to age. Multivariate regression analysis showed that age and sex explained with statistical significance 9% of the variance in SARS-CoV-2 IgG titers in our study population; the role of BMI was limited and insignificant.

A higher number of SARS-COV-2 infections in quilombola communities than in the local population in Brazil.

The historical and social vulnerability of quilombola communities in Brazil can make them especially fragile in the face of COVID-19, considering that several individuals have precarious health systems and inadequate access to water. This work aimed to characterize the frequency of SARS-COV-2 infections and the presence of IgM and IgG SARS-CoV-2 antibodies in quilombola populations and their relationship with the presence of risk factors or preexisting chronic diseases in the quilombola communities. We analyzed the sociodemographic and clinical characteristics, serological status, comorbidities, and symptoms of 1,994 individuals (478 males and 1,536 females) from 18 Brazilian municipalities in the State of Sergipe of quilombola communities, which were evaluated at different epidemiological weeks, starting at the 32nd (August 6th) and ending at the 40th (October 3rd) epidemiological week. More than 70% of studied families live in rural areas and they have an extreme poverty social status. Although we found a higher number of SARS-COV-2 infections in quilombola communities than in the local population, their SARS-CoV-2 reactivity and IgM and IgG positivity varied across the communities investigated. Arterial hypertension was the most risk factor, being found in 27.8% of the individuals (9.5% in stage 1, 10.8% in stage 2, and 7.5% in stage 3). The most common COVID-19 symptoms and comorbidities were headache, runny nose, flu, and dyslipidemia. However, most individuals were asymptomatic (79.9%). Our data indicate that mass testing must be incorporated into public policy to improve the health care system available to quilombola populations during a future pandemic or epidemic.

Impact of COVID-19 Vaccination on Women During Pregnancy and Breastfeeding.

Rapid development of anti-SARS-CoV-2 vaccinations in the late 2020s has significantly altered the trajectory in which the virus affects various patient demographics, especially the most susceptible ones. In light of ethical and conceptual safety considerations, pregnant women were initially barred from participating in clinical studies for the coronavirus disease 2019 (COVID-19) vaccination programs. However, the steady accumulation of reliable observational data from cohorts of pregnant women who received vaccinations enabled the research establishments to quickly address a number of open questions. Still, more than a year after vaccines were widely available, the safety concerns of expectant or nursing mothers are cited as the primary justification for refusing COVID-19 vaccination, and notably, the rate of vaccination in the said populations is known to be consistently lower than those of the general populace. In light of such a scenario, we have made an attempt to garner relevant studies that evaluated the effect of COVID-19 vaccination on pregnant and lactating mothers which may prove to be supporting evidence for its wide usage among the said population.

Long COVID and Hybrid Immunity among Children and Adolescents Post-Delta Variant Infection in Thailand.

This study aimed to assess long COVID, and describe immunogenicity against Omicron variants following BNT162b2 vaccination. A prospective cohort study was conducted among children (aged 5-11) and adolescents (aged 12-17) who had SARS-CoV-2 infection from July to December 2021 (Delta predominant period). Long COVID symptoms were assessed by questionnaires at 3 months after infection. Immunogenicity was evaluated by using a surrogate virus-neutralizing antibody test (sVNT) against the Omicron variant. We enrolled 97 children and 57 adolescents. At 3 months, 30 children (31%) and 34 adolescents (60%) reported at least one long COVID symptom, with respiratory symptoms prevailing (25% children and 32% adolescents). The median time from infection to vaccination was 3 months in adolescents and 7 months in children. At 1 month following vaccination, in children who received one-dose and two-dose BNT162b2 vaccines, the median (IQR) sVNT against Omicron was 86.2% inhibition (71.1-91.8) and 79.2% inhibition (61.5-88.9), respectively (p = 0.26). Among adolescents who received one-dose and two-dose BNT162b2 vaccines, the median (IQR) sVNT against Omicron was 64.4% inhibition (46.8-88.8) and 68.8% inhibition (65.0-91.2) (p = 0.64). Adolescents had a higher prevalence of long COVID than children. Immunogenicity against the Omicron variant after vaccination was high and did not vary between one or two doses of the vaccine in either children or adolescents.

The Kinetics of Anti-SARS-CoV-2 Antibodies in Pediatric Patients and the Characterization of Post-COVID-19 Condition at 6 Months After Infection: Protocol for a Longitudinal Observational Study.

BACKGROUND: Data regarding the kinetics of anti-SARS-CoV-2 antibodies and information about post-COVID-19 condition (colloquially known as "long COVID") in children are scarce, especially in low-income countries. Even though cases of COVID-19 in children are less prevalent than adults, post-COVID-19 condition cases in children are high and have a burden that may impact their growth and development. There are other features of antibody kinetics in connection with SARS-CoV-2 infection that are yet unknown as of this writing, especially in children following infection. Furthermore, the long-term results, risk factors, and underlying pathophysiology are still uncertain. To better understand post-COVID-19 condition in children, it is necessary to further investigate the impact of clinically significant factors such multisystem inflammatory syndrome and disease severity among hospitalized survivors through their SARS-CoV-2 antibody response. OBJECTIVE: We aim to analyze anti-receptor-binding domain SARS-CoV-2 immunoglobulin G antibodies over time and characterize the signs and symptoms of post-COVID-19 condition in pediatric patients at the time of diagnosis and at 2 weeks and 1, 3, and 6 months following infection. METHODS: This is a longitudinal observational study in Indonesia. Pediatric patients diagnosed with COVID-19 by positive molecular assay using nasopharyngeal swab will be tested for anti-SARS-CoV-2 antibodies using the Roche Elecsys Anti-SARS-CoV-2 S assay at the time of diagnosis and at 2 weeks and 1, 3, and 6 months following infection. Antibody titer data will be reported as means and SDs. The respondents' signs and symptoms will be observed up to 6 months after the onset of infection, including the vaccination event, reinfection, rehospitalization, and mortality. The clinical features will be reported as frequencies and percentages. RESULTS: Participant enrollment began in February 2022. As of September 30, 2022, a total of 58 patients were enrolled. After data collection, results are expected to be analyzed in August 2023. CONCLUSIONS: This study will allow us to know the kinetics of anti-receptor-binding domain SARS-CoV-2 immunoglobulin G antibodies and data regarding post-COVID-19 condition up to 6 months following infection in the Indonesian pediatric population. Furthermore, this study has the potential to serve as a foundation for government decisions about vaccination programs and prevention measures. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/43344.

Triple combination therapy with two antivirals and monoclonal antibodies for persistent or relapsed SARS-CoV-2 infection in immunocompromised patients.

INTRODUCTION: Severely immunocompromised patients are at risk for prolonged or relapsed COVID-19 leading to increased morbidity and mortality. We aimed to evaluate efficacy and safety of combination treatment in immunocompromised COVID-19 patients. METHODS: We included all immunocompromised patients with prolonged/relapsed COVID-19 treated with combination therapy with two antivirals (remdesivir plus nirmatrelvir/ritonavir, or molnupiravir in case of renal failure) plus, if available, anti-spike monoclonal antibodies (Mabs), between February and October 2022. The main outcomes were virological response at day 14 (negative SARS-CoV-2 swab) and virological and clinical response (alive, asymptomatic, with negative SARS-CoV-2 swab) at day 30 and the last follow-up. RESULTS: Overall, 22 patients (Omicron variant in 17/18) were included: 18 received full combination of two antivirals and Mabs and 4 received two antivirals only; in 20/22 (91%) two antivirals were nirmatrelvir/ritonavir plus remdesivir. Nineteen (86%) patients had hematological malignancy, 15 (68%) had received anti-CD20 therapy. All were symptomatic; 8 (36%) required oxygen. Four patients received second course of combination treatment. Response rate at day 14, 30 and last follow-up was, respectively, 75% (15/20 evaluable), 73% (16/22) and 82% (18/22). Day 14 and 30 response rates were significantly higher when combination therapy included Mabs. Higher number of vaccine doses was associated with better final outcome. Two patients (9%) developed severe side effects: bradycardia leading to remdesivir discontinuation and myocardial infarction. CONCLUSION: Combination therapy including two antivirals (mainly remdesivir and nirmatrelvir/ritonavir) and Mabs was associated with high rate of virological and clinical response in immunocompromised patients with prolonged/relapsed COVID-19.

IDWeek 2022

IDWeek is the joint annual meeting of the Infectious Diseases Society of America (IDSA), Society for Healthcare Epidemiology of America (SHEA), the HIV Medicine Association (HIVMA), the Pediatric Infectious Diseases Society (PIDS) and the Society of Infectious Diseases Pharmacists (SIDP). For the first time since the COVID-19 public health emergency began, IDWeek 2022 returned to in-person attendance. It was held in Washington, D.C., and the meeting comprised 5 days of live sessions and on-demand content that included posters and oral presentations.Copyright © 2023 Clarivate.

Rapid Detection of SARS-CoV-2 Antigens and Antibodies Using OFET Biosensors Based on a Soft and Stretchable Semiconducting Polymer.

In the midst of the COVID-19 pandemic, adaptive solutions are needed to allow us to make fast decisions and take effective sanitation measures, e.g., the fast screening of large groups (employees, passengers, pupils, etc.). Although being reliable, most of the existing SARS-CoV-2 detection methods cannot be integrated into garments to be used on demand. Here, we report an organic field-effect transistor (OFET)-based biosensing device detecting of both SARS-CoV-2 antigens and anti-SARS-CoV-2 antibodies in less than 20 min. The biosensor was produced by functionalizing an intrinsically stretchable and semiconducting triblock copolymer (TBC) film either with the anti-S1 protein antibodies (S1 Abs) or receptor-binding domain (RBD) of the S1 protein, targeting CoV-2-specific RBDs and anti-S1 Abs, respectively. The obtained sensing platform is easy to realize due to the straightforward fabrication of the TBC film and the utilization of the reliable physical adsorption technique for the molecular immobilization. The device demonstrates a high sensitivity of about 19%/dec and a limit of detection (LOD) of 0.36 fg/mL for anti-SARS-Cov-2 antibodies and, at the same time, a sensitivity of 32%/dec and a LOD of 76.61 pg/mL for the virus antigen detection. The TBC used as active layer is soft, has a low modulus of 24 MPa, and can be stretched up to 90% with no crack formation of the film. The TBC is compatible with roll-to-roll printing, potentially enabling the fabrication of low-cost wearable or on-skin diagnostic platforms aiming at point-of-care concepts.

AI-Driven De Novo Design and Molecular Modeling for Discovery of Small-Molecule Compounds as Potential Drug Candidates Targeting SARS-CoV-2 Main Protease.

Over the past three years, significant progress has been made in the development of novel promising drug candidates against COVID-19. However, SARS-CoV-2 mutations resulting in the emergence of new viral strains that can be resistant to the drugs used currently in the clinic necessitate the development of novel potent and broad therapeutic agents targeting different vulnerable spots of the viral proteins. In this study, two deep learning generative models were developed and used in combination with molecular modeling tools for de novo design of small molecule compounds that can inhibit the catalytic activity of SARS-CoV-2 main protease (Mpro), an enzyme critically important for mediating viral replication and transcription. As a result, the seven best scoring compounds that exhibited low values of binding free energy comparable with those calculated for two potent inhibitors of Mpro, via the same computational protocol, were selected as the most probable inhibitors of the enzyme catalytic site. In light of the data obtained, the identified compounds are assumed to present promising scaffolds for the development of new potent and broad-spectrum drugs inhibiting SARS-CoV-2 Mpro, an attractive therapeutic target for anti-COVID-19 agents.

Spread of SARS-CoV-2 Infection in Adult Populations in Cameroon: A Repeated Cross-Sectional Study Among Blood Donors in the Cities of Yaoundé and Douala.

Over a period of about 9 months, we conducted three serosurveys in the two major cities of Cameroon to determine the prevalence of SARS-COV-2 antibodies and to identify factors associated with seropositivity in each survey. We conducted three independent cross-sectional serosurveys of adult blood donors at the Central Hospital in Yaoundé (CHY), the Jamot Hospital in Yaoundé (JHY) and at the Laquintinie Hospital in Douala (LHD) who consented in writing to participate. Before blood sampling, a short questionnaire was administered to participants to collect their sociodemographic and clinical characteristics. We included a total of 743, 1202, and 1501 participants in the first (January 25-February 15, 2021), second (May 03-28, 2021), and third (November 29-December 31, 2021) surveys, respectively. The adjusted seroprevalence increased from 66.3% (95% CrI 61.1-71.3) in the first survey to 87.2% (95% CrI 84.0-90.0) in the second survey, and 98.4% (95% CrI 96.8-99.7) in the third survey. In the first survey, study site, participant occupation, and comorbid conditions were associated with SARS-CoV-2 seropositivity, whereas only study site remained associated in the second survey. None of the factors studied was significantly associated with seropositivity in the third survey. Together, the data suggest a rapid initial spread of SARS-CoV-2 in the study population, independent of the sociodemographic parameters assessed.

Efficacy and Safety of Anti-SARS-CoV-2 Monoclonal Antibodies: An Updated Review.

Monoclonal antibodies (mAbs) had received emergency use authorization for mild-to-moderate coronavirus disease 2019 (COVID-19) or for prophylaxis against COVID-19, including casirivimab plus imdevimab (C+I), bamlanivimab plus etesevimab (B+E), tixagevimab plus cilgavimab (T+CG), and sotrovimab (S) and bebtelovimab (BEB). This systematic review was done to assess the efficacy and safety of the same. PubMed, Embase, Scopus, medRxiv, bioRxiv, and FDA fact sheets were searched for the studies published between January 2021 and May 2022, and appropriate search terms related to the mentioned mAbs were used for data collection. Review included original research including randomized clinical trials and observational studies published or preprints. Studies included in the review had compared with placebo or standard of care or no treatment or mAbs with each other and also of various doses. Data extraction was done and reviewed the same for both efficacy and safety. Total of 20 studies were included in this review. The rate of hospitalization within 30 days showed ∼2% in comparison to ∼7% with placebo. Significant reduction in viral load was more observed with combination mAbs. Combination therapy showed faster virological cure against the Gamma variant. With C + I as postexposure prophylaxis (PEP), 29.0% of asymptomatic participants developed symptomatic COVID-19. Pre-exposure prophylaxis with T+CG reduced the incidence of infection by 77%. Infusion-related reaction was the most common adverse event (AE). The neutralizing mAbs reduced hospitalization in mild-to-moderate patients with infusion-related reactions as common AE. The response was better in the seronegative patients. Most of these studies were conducted in unvaccinated individuals and against Alpha, Gamma, and Delta variants.

Distinct clinical features of post COVID-19 vaccination early-onset Graves' disease (PoVEO GD).

CONTEXT: Several case reports of Graves' disease (GD) occurrence after COVID-19 vaccination were recently published and possibly related to the autoimmune syndrome induced by adjuvants (ASIA). The aim of our study was to evaluate possible distinctive features in the presentation and clinical course of patients with GD occurring early (within 4 weeks) after COVID-19 vaccination who attended our Endocrine Unit in 2021. DESIGN: Patients with first episode of GD attending a tertiary endocrine center between January 1st and December 31st 2021 were included. RESULTS: Sixty-four patients with first episode of GD were seen in 2021: 20 (31.2%) of them had onset within 4 weeks following vaccine administration. Compared to the other 44 patients, the 20 patients with post-vaccine early-onset (PoVEO) GD were older (median age: 51 years vs 35 years, p = 0.003) and more likely male (40.0% vs 13.6%, p = 0.018). At diagnosis, the biochemical and immune profiles were similar between the two groups. However, at 3 months after starting methimazole, PoVEO GD patients had significantly lower TRAb titer and were taking lower doses of methimazole than the other GD patients. None in the PoVEO group had sustained fT3 elevation. CONCLUSIONS: This relatively large series suggests that in 2021, PoVEO GD may be a new nosological entity representing one third of patients evaluated for new-onset GD in our center. Distinctive features included older age at onset, higher male prevalence and a better initial biochemical and immunological response to treatment. Further studies are warranted to clinically and biochemically differentiate these cases from sporadically occurred GD.

Anti-N SARS-CoV-2 assays for evaluation of natural viral infection.

BACKGROUND: The 2019 coronavirus (COVID-19) epidemic, required the development of different diagnostic tests. While reverse transcriptase real-time PCR (RT-PCR) remains the first-line test of choice in acute infection diagnosis, anti-N antibodies serological assays provide a valuable tool to differentiate natural SARS-CoV-2 immunological response from that induced by vaccination, thus the goal of our study was to evaluate three serological tests agreement for these antibodies detection. METHODS: Three anti-N different tests were examined in 74 sera from patients referred or not COVID infection: immunochromatographic rapid test (Panbio™ COVID-19 IgG/IgM Rapid Test Device Abbott, Germany), ELISA kit (NovaLisa® SARS-CoV-2 IgG and IgM NovaTech Immunodiagnostic GmbH, Germany) and ECLIA immunoassay (Elecsys® Anti-SARS-CoV-2 Roche Diagnostics, Manheim, Germany). RESULTS: Qualitative comparison of the three analytical methods revealed a moderate agreement between ECLIA immunoassay and immunochromatographic rapid test (Cohen kappa coefficient κ = 0.564). Correlation analysis indicated weak positive correlation between total Ig (IgT) detected by ECLIA immunoassay and IgG by ELISA test (p < 0.0001), the analysis of ECLIA IgT and IgM ELISA detected, showed no statistical correlation. CONCLUSION: Comparison between of three analytical systems available for anti-N SARS-CoV-2 IgG and IgM antibodies showed a general agreement when compared to detect total and G class immunoglobulins, while doubtful or discordant results have been highlighted for IgT and IgM class. Anyway, all the tests examined provide reliable results to assess the serological status of SARS-CoV-2 infected patients.

Research progress in antiviral therapy for novel coronavirus pneumonia.

Since the outbreak of novel coronavirus pneumonia (COVID-19), a number of clinical studies have been carried out globally in order to explore efficacy and safety of drugs for novel coronavirus (2019-nCoV). These studies were mainly focused on drugs with anti-2019-nCoV activity tested in vitro and those previously used for the treatment of SARS and Middle East respiratory syndrome, including remdesivir, lopinavir/ritonavir, chloroquine, hydroxychloroquine, arbidol, interferon, ribavirin, and etc. The recent clinical studies on anti-2019-nCoV drugs are reviewed in this article, but the current research results are inconsistent, which are insufficient to constitute evidence for the efficacy and safety of these drugs in the treatment of COVID-19. In the absence of specific antiviral agents, remdesivir can be a treatment option for patients with critical illness or rapid progress. Some clinical studies are still in progress. We are looking forward to more large-scale and multicenter clinical trials to provide safe and effective evidence for antiviral treatment in the future.Copyright © 2020 by the Chinese Medical Association.