Safety and immunogenicity of a mosaic vaccine booster against Omicron and other SARS-CoV-2 variants: a randomized phase 2 trial.

An ongoing randomized, double-blind, controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of a mosaic-type recombinant vaccine candidate, named NVSI-06-09, as a booster dose in subjects aged 18 years and older from the United Arab Emirates (UAE), who had administered two or three doses of inactivated vaccine BBIBP-CorV at least 6 months prior to enrollment. The participants were randomly assigned with 1:1 to receive a booster dose of NVSI-06-09 or BBIBP-CorV. The primary outcomes were immunogenicity and safety against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, and the exploratory outcome was cross-immunogenicity against other circulating strains. Between May 25 and 30, 2022, 516 adults received booster vaccination with 260 in NVSI-06-09 group and 256 in BBIBP-CorV group. Interim results showed a similar safety profile between two booster groups, with low incidence of adverse reactions of grade 1 or 2. For immunogenicity, by day 14 post-booster, the fold rises in neutralizing antibody geometric mean titers (GMTs) from baseline elicited by NVSI-06-09 were remarkably higher than those by BBIBP-CorV against the prototype strain (19.67 vs 4.47-fold), Omicron BA.1.1 (42.35 vs 3.78-fold), BA.2 (25.09 vs 2.91-fold), BA.4 (22.42 vs 2.69-fold), and BA.5 variants (27.06 vs 4.73-fold). Similarly, the neutralizing GMTs boosted by NVSI-06-09 against Beta and Delta variants were also 6.60-fold and 7.17-fold higher than those by BBIBP-CorV. Our findings indicated that a booster dose of NVSI-06-09 was well-tolerated and elicited broad-spectrum neutralizing responses against divergent SARS-CoV-2 variants, including Omicron and its sub-lineages.

Mucormycosis-related osteomyelitis of the maxilla in a post-COVID-19 patient.

Mucormycosis is a rare, invasive fungal infection that progresses aggressively and requires prompt surgery and appropriate treatment. The number of cases of mucormycosis in coronavirus disease 2019 (COVID-19) patients has recently increased, and patients with uncontrolled diabetes mellitus are particularly at an elevated risk of infection. This report presents a case of mucormycosis-related osteomyelitis of the maxilla in a 37-year-old man with diabetes mellitus. The patient complained of severe and persistent pain in the right maxilla, accompanied by increased tooth mobility and headache. On contrast-enhanced computed tomographic images, gas-forming osteomyelitis of the right maxilla was observed. Destruction of the maxilla and palatine bone then proceeded aggressively. Sequestrectomy was performed on the right maxilla, and the histopathological diagnosis was mucormycosis. Further investigation after the first operation revealed the patient's history of COVID-19 infection.

Safety and immunogenicity of a hybrid-type vaccine booster in BBIBP-CorV recipients in a randomized phase 2 trial.

NVSI-06-08 is a potential broad-spectrum recombinant COVID-19 vaccine that integrates the antigens from multiple SARS-CoV-2 strains into a single immunogen. Here, we evaluate the safety and immunogenicity of NVSI-06-08 as a heterologous booster dose in BBIBP-CorV recipients in a randomized, double-blind, controlled, phase 2 trial conducted in the United Arab Emirates (NCT05069129). Three groups of healthy adults over 18 years of age (600 participants per group) who have administered two doses of BBIBP-CorV 4-6-month, 7-9-month and >9-month earlier, respectively, are randomized 1:1 to receive either a homologous booster of BBIBP-CorV or a heterologous booster of NVSI-06-08. The incidence of adverse reactions is low, and the overall safety profile is quite similar between two booster regimens. Both Neutralizing and IgG antibodies elicited by NVSI-06-08 booster are significantly higher than those by BBIBP-CorV booster against not only SARS-CoV-2 prototype strain but also multiple variants of concerns (VOCs). Especially, the neutralizing antibody GMT against Omicron variant induced by heterologous NVSI-06-08 booster reaches 367.67, which is substantially greater than that boosted by BBIBP-CorV (GMT: 45.03). In summary, NVSI-06-08 is safe and immunogenic as a booster dose following two doses of BBIBP-CorV, which is immunogenically superior to the homologous boost with another dose of BBIBP-CorV.

Immunogenicity and safety of NVSI-06-07 as a heterologous booster after priming with BBIBP-CorV: a phase 2 trial.

The increased coronavirus disease 2019 (COVID-19) breakthrough cases pose the need of booster vaccination. We conducted a randomised, double-blinded, controlled, phase 2 trial to assess the immunogenicity and safety of the heterologous prime-boost vaccination with an inactivated COVID-19 vaccine (BBIBP-CorV) followed by a recombinant protein-based vaccine (NVSI-06-07), using homologous boost with BBIBP-CorV as control. Three groups of healthy adults (600 individuals per group) who had completed two-dose BBIBP-CorV vaccinations 1-3 months, 4-6 months and ≥6 months earlier, respectively, were randomly assigned in a 1:1 ratio to receive either NVSI-06-07 or BBIBP-CorV boost. Immunogenicity assays showed that in NVSI-06-07 groups, neutralizing antibody geometric mean titers (GMTs) against the prototype SARS-CoV-2 increased by 21.01-63.85 folds on day 28 after vaccination, whereas only 4.20-16.78 folds of increases were observed in control groups. For Omicron variant, the neutralizing antibody GMT elicited by homologous boost was 37.91 on day 14, however, a significantly higher neutralizing GMT of 292.53 was induced by heterologous booster. Similar results were obtained for other SARS-CoV-2 variants of concerns (VOCs), including Alpha, Beta and Delta. Both heterologous and homologous boosters have a good safety profile. Local and systemic adverse reactions were absent, mild or moderate in most participants, and the overall safety was quite similar between two booster schemes. Our findings indicated that NVSI-06-07 is safe and immunogenic as a heterologous booster in BBIBP-CorV recipients and was immunogenically superior to the homologous booster against not only SARS-CoV-2 prototype strain but also VOCs, including Omicron.

Clinical Experience with Ropeginterferon Alfa-2b in the Off-Label Use for the Treatment of COVID-19 Patients in Taiwan.

INTRODUCTION: This study, for the first time to our knowledge, evaluated the efficacy of ropeginterferon alfa-2b, a long-acting pegylated interferon (IFN)-alfa, in the treatment of COVID-19. METHODS: We retrospectively evaluated ropeginterferon alfa-2b administered subcutaneously at a single dose of 250 µg for the treatment of mild and moderate COVID-19. Primary outcome was to compare the overall negative conversion time from the confirmed, last positive SARS-CoV-2 RT-PCR to the first RT-PCR negative conversion between patients receiving ropeginterferon alfa-2b plus standard of care (SOC) and those receiving SOC alone. RESULTS: Thirty-five patients with mild COVID-19 and 37 patients with moderate disease were included. Of them, 19 patients received SOC plus ropeginterferon alfa-2b and 53 patients received SOC alone. All patients with moderate disease in the ropeginterferon alfa-2b group showed RT-PCR negative conversion within 8 days, while a significant portion of patients in the SOC alone group failed to do so. For patients with moderate disease and age ≤ 65 years old, the ropeginterferon alfa-2b group had statistically significant shorter median RT-PCR conversion time than the SOC alone group (7 vs. 11.5 days, p < 0.05). CONCLUSIONS: Ropeginterferon alfa-2b showed the potential for the treatment of moderate COVID-19 patients. A randomized, controlled Phase III study is planned to further assess the effectiveness of ropeginterferon alfa-2b in COVID-19 patients.

Diagnostic Accuracy of SARS-CoV-2 Antigen Tests for Community Transmission Screening: A Systematic Review and Meta-Analysis.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) caused the global pandemic of coronavirus disease 2019 (COVID-19). Rapid identification and isolation of infectious patients are critical methods to block COVID-19 transmission. Antigen tests can contribute to prompt identification of infectious individuals. This meta-analysis aims to evaluate the diagnostic accuracy of antigen tests for SARS-CoV-2. We conducted a literature search in PubMed, Embase, the Cochrane Library, and Biomed Central databases. Studies evaluating the diagnostic accuracy of antigen tests for SARS-CoV-2 in community participants were included. Only English-language articles were reviewed. We included eligible studies that provided available data to construct a 2 × 2 table on a per-patient basis. Overall sensitivity and specificity for antigen tests were generated using a bivariate random-effects model. Eighteen studies with 34,865 participants were retrieved. The meta-analysis for SARS-CoV-2 antigen tests generated a pooled sensitivity of 0.82 and a pooled specificity of 1.00. A subgroup analysis of ten studies that reported outcomes for 5629 symptomatic participants generated a pooled sensitivity of 0.87 and a pooled specificity of 1.00. Antigen tests might have higher sensitivity in detecting SARS-CoV-2 in symptomatic patients in the community and may be an effective tool to identify patients to be quarantined to prevent further SARS-CoV-2 transmission.

COVID-19 in South Korea: Proper Timing for Easing Mask Mandates After COVID-19 Vaccination.

OBJECTIVE: As of July 25, 2021, the Korea Disease Control and Prevention Agency reported 1,422 new coronavirus disease 2019 (COVID-19) cases, 188,848 total cases, and 2,073 total deaths (1.10% fatality rates). Since the first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) case was reported, efforts to find a treatment and vaccine against COVID-19 have been widespread. METHODS: Four vaccines are on the World Health Organization's (WHO's) emergency use listing and are approved of their usage; BNT162b2, mRNA-1273, AZD1222, and Ad26.COV2.S. Vaccines against SARS-CoV-2 need at least 14 d to achieve effectiveness. Thus, people should abide by prevention and control measures, including wearing masks, washing hands, and social distancing. RESULTS: However, a lot of new cases were reported after vaccinations, as many people did not follow the prevention control measures before the end of the 14-d period. There is no doubt we need to break free from mask mandates. CONCLUSIONS: But let us not decide the timing in haste. Even if the mask mandates are eased, they should be changed depending on the number of reported cases, vaccinations, as well as prevention and control measures on how circumstances are changing under the influence of mutant coronavirus.

Alteration in angiotensin-converting enzyme 2 by PM1 during the development of emphysema in rats.

INTRODUCTION: Angiotensin-converting enzyme 2 (ACE2) provides an adhesion site for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients with COPD could have severe outcomes after SARS-CoV-2 infection. The objective of this study was to investigate ACE2 regulation by air pollution during the development of COPD. METHODS: Sprague Dawley rats were exposed to unconcentrated traffic-related air pollution for 3 and 6 months. We examined lung injury markers, oxidative stress, inflammation, emphysema, ACE2 and angiotensin II receptor type 1 (AT1) and 2 (AT2) in the lungs after exposure. RESULTS: Lung injury occurred due to an increase in permeability and lactate dehydrogenase cytotoxicity was observed after 6 months of exposure to fine particulate matter of <1 µm in aerodynamic diameter (PM1). An α1-antitrypsin deficiency and neutrophil elastase production with emphysema development were observed after 6 months of PM1 exposure. 8-isoprostane and interleukin-6 were increased after 3 and 6 months of PM1 exposure. Caspase-3 was increased after exposure to PM1 for 6 months. Upregulation of ACE2 was found after 3 months of PM1 exposure; however, ACE2 had decreased by 6 months of PM1 exposure. AT1 and AT2 had significantly decreased after exposure to PM1 for 6 months. Furthermore, smooth muscle hypertrophy had occurred after 6 months of PM1 exposure. CONCLUSIONS: In conclusion, short-term exposure to PM1 increased the ACE2 overexpression in lungs. Long-term exposure to PM1 decreased the ACE2 overexpression in emphysema. Air pollution may be a risk for SARS-CoV-2 adhesion during the development of COPD.

Profiling of T Cell Repertoire in SARS-CoV-2-Infected COVID-19 Patients Between Mild Disease and Pneumonia.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a public health emergency. The most common symptoms of COVID-19 are fever, cough, and fatigue. While most patients with COVID-19 present with mild illness, some patients develop pneumonia, an important risk factor for mortality, at early stage of viral infection, putting these patients at increased risk of death. So far, little has been known about differences in the T cell repertoires between COVID-19 patients with and without pneumonia during SARS-CoV-2 infection. Herein, we aimed to investigate T cell receptor (TCR) repertoire profiles and patient-specific SARS-CoV-2-associated TCR clusters between COVID-19 patients with mild disease (no sign of pneumonia) and pneumonia. The TCR sequencing was conducted to characterize the peripheral TCR repertoire profile and diversity. The TCR clustering and CDR3 annotation were exploited to further discover groups of patient-specific TCR clonotypes with potential SARS-CoV-2 antigen specificities. Our study indicated a slight decrease in the TCR repertoire diversity and a skewed CDR3 length usage in patients with pneumonia compared to those with mild disease. The SARS-CoV-2-associated TCR clusters enriched in patients with mild disease exhibited significantly higher TCR generation probabilities and most of which were highly shared among patients, compared with those from pneumonia patients. Importantly, using similarity network-based clustering followed by the sequence conservation analysis, we found different patterns of CDR3 sequence motifs between mild disease- and pneumonia-specific SARS-CoV-2-associated public TCR clusters. Our results showed that characteristics of overall TCR repertoire and SARS-CoV-2-associated TCR clusters/clonotypes were divergent between COVID-19 patients with mild disease and patients with pneumonia. These findings provide important insights into the correlation between the TCR repertoire and disease severity in COVID-19 patients.

South Korea's COVID-19 Infection Status: From the Perspective of Re-positive Test Results After Viral Clearance Evidenced by Negative Test Results.

Coronavirus disease (COVID-19) started to occur in South Korea by means of inflow of the virus from abroad, when a case from Wuhan, China, was first confirmed on January 19, 2020. Although South Korea has drastically reduced the number of new confirmed cases and is stabilizing the situation with its exemplary disease prevention policies, there remains a problem. These are cases that had shown negative results to polymerase chain reaction (PCR) (gene amplification) tests as the COVID-19 virus had become undetectable but turned re-positive after a short period. The Central Clinical Committee determined that these re-positive cases after COVID-19 viral clearance are due to the limits of the test method; it is considered that the genetic material of the "dead virus" remaining in a recovered patient's body is amplified during the test process. Comprehending the above evidence, re-positive cases of COVID-19 are not infectious; the virus is not even reactivated. However, further research is required as we lack research results on this subject. Until we can be sure, social distancing and other such policies should be maintained.

Lessons Learned From Cases of COVID-19 Infection in South Korea.

On December 31, 2019, the Chinese government officially announced that the country had a single pneumonia case with an unknown cause. In the weeks after, South Korea had 24 confirmed cases by February 8, and the number has increased steadily since then. The highly contagious virus known as coronavirus disease 2019 (COVID-19) infected Case No. 31 in Daegu; she was the first patient related to Sincheonji Church. Later, the number of cases involved with Sincheonji skyrocketed. On March 6, 2020, the number of confirmed cases was 6284, with 42 dead. This study, through collecting epidemiological data about various COVID-19 infection cases, discovered that getting together in large groups leads to mass infection, and that paying close attention to personal hygiene by means of wearing masks, sanitary gloves, etc., can prevent the spread of COVID-19. Additional epidemiological data and related studies on COVID-19 infections in South Korea are likely to support or slightly modify this conclusion. However, this study is significant in that it emphasizes the precautionary principle in preventing and managing infectious diseases, and has a suggestion for public health policies, which are currently in high demand.

Surviving the Rookie Virus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2): The Immunopathology of a SARS-CoV2 Infection.

Until July 29th, the number of confirmed coronavirus (COVID-19) cases worldwide has risen to over 16 million, within which 655 k deaths. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) emerges as the 11th global pandemic disease, showing the highest infectivity and lowest infection fatality rate. In this review, we compare the immunopathology among SARS-CoV, Middle East respiratory syndrome coronavirus, and SARS-CoV2. SARS-CoV2 is similar to SARS-CoV; it can cause lymphocytopenia and a rising granulocyte count. Here we point out the human body and concentrated society make for an excellent incubator for virus evolution. Most research energies put into developing the SARS-CoV2 vaccine are trying to block virus infection. Sixty-five percent of severe patients die with multiple organ failure, inflammation, and cytokine storm, which indicates that the patient's immune system maintains functionality. Finding a way to trigger the specific T cell subset and plasmablast in our body is the best shot to get away with SARS-CoV2.

Transcriptome network analyses in human coronavirus infections suggest a rational use of immunomodulatory drugs for COVID-19 therapy.

The recent outbreak of coronavirus disease 2019 (COVID-19) by SARS-CoV-2 has led to uptodate 24.3 M cases and 0.8 M deaths. It is thus in urgent need to rationalize potential therapeutic targets against the progression of diseases. An effective, feasible way is to use the pre-existing ΔORF6 mutant of SARS-CoV as a surrogate for SARS-CoV-2, since both lack the moiety responsible for interferon antagonistic effects. By analyzing temporal profiles of upregulated genes in ΔORF6-infected Calu-3 cells, we prioritized 55 genes and 238 ligands to reposition currently available medications for COVID-19 therapy. Eight of them are already in clinical trials, including dexamethasone, ritonavir, baricitinib, tofacitinib, naproxen, budesonide, ciclesonide and formoterol. We also pinpointed 16 drug groups from the Anatomical Therapeutic Chemical classification system, with the potential to mitigate symptoms of SARS-CoV-2 infection and thus to be repositioned for COVID-19 therapy.

Mortality Rate of Infection With COVID-19 in Korea From the Perspective of Underlying Disease.

On December 31, 2019 the China National Health Commission (NHC) reported that an unknown cause of pneumonia had been detected in Wuhan in Hubei province. On February 12, the disease caused by the novel coronavirus (2019-nCoV) was given a formal name, COVID-19. On January 20, 2020, the first case of COVID-19 was confirmed in Korea. The age-specific death rate was the highest among patients over 70 years of age, with underlying diseases in their circulatory system, such as myocardial infarction, cerebral infraction, arrythmia, and hypertension. Patients with underlying disease who are 70 years of age or older should recognize that there is a high possibility of developing a serious disease in case of viral infection and follow strict precautions.

A mathematical model for the impacts of face mask, hospitalization and quarantine on the dynamics of COVID-19 in India: deterministic vs. stochastic.

In this paper, we propose a mathematical model to assess the impacts of using face masks, hospitalization of symptomatic individuals and quarantine of asymptomatic individuals in combating the COVID-19 pandemic in India. We calibrate the proposed model to fit the four data sets, viz. data for the states of Maharashtra, Delhi, Tamil Nadu and overall India, and estimate the rate of infection of susceptible with symptomatic population and recovery rate of quarantined individuals. We also estimate basic reproduction number to illustrate the epidemiological status of the regions under study. Our simulations infer that the infective population will be on increasing curve for Maharashtra and India, and settling for Tamil Nadu and Delhi. Sophisticated techniques of sensitivity analysis are employed to determine the impacts of model parameters on basic reproduction number and symptomatic infected individuals. Our results reveal that to curtail the disease burden in India, specific control strategies should be implemented effectively so that the basic reproduction number is decreased below unity. The three control strategies are shown to be important preventive measures to lower disease transmission rate. The model is further extended to its stochastic counterpart to encapsulate the variation or uncertainty observed in the disease transmissibility. We observe the variability in the infective population and found their distribution at certain fixed time, which shows that for small populations, the stochasticity will play an important role.

Dynamics of an SIS network model with a periodic infection rate.

Seasonal forcing and contact patterns are two key features of many disease dynamics that generate periodic patterns. Both features have not been ascertained deeply in the previous works. In this work, we develop and analyze a non-autonomous degree-based mean field network model within a Susceptible-Infected-Susceptible (SIS) framework. We assume that the disease transmission rate being periodic to study synergistic impacts of the periodic transmission and the heterogeneity of the contact network on the infection threshold and dynamics for seasonal diseases. We demonstrate both analytically and numerically that (1) the disease free equilibrium point is globally asymptotically stable if the basic reproduction number is less than one; and (2) there exists a unique global periodic solution that both susceptible and infected individuals coexist if the basic reproduction number is larger than one. We apply our framework to Scale-free contact networks for the simulation. Our results show that heterogeneity in the contact networks plays an important role in accelerating disease spreading and increasing the amplitude of the periodic steady state solution. These results confirm the need to address factors that create periodic patterns and contact patterns in seasonal disease when making policies to control an outbreak.

South Korea's COVID-19 Infection Status: From the Perspective of Reconfirmation after Complete Recovery

COVID-19 started to occur in South Korea by an inflow of the virus from abroad, when a traveler from Wuhan, China, was first confirmed on January 19th, 2020. Although South Korea reduced the number of newly confirmed cases and is on the way to stabilizing the situation with its disease prevention policies, problems remain. The main issue is the reconfirmation of the virus after recovery. South Korean experts believe the reconfirmed cases are caused by reactivation of the virus inside the patients' body, rather than by virus reinfection after recovery. When considering reconfirmed COVID-19 cases, it is important to keep social distancing even after treating the infection. Despite no cases of reconfirmed patients infecting others having been reported yet, reexamination of patients after recovery is thought to be pivotal to prevent reactivation.

The diagnostic value of detecting sudden smell loss among asymptomatic COVID-19 patients in early stage: The possible early sign of COVID-19.

IMPORTANCE: The newly emerged coronavirus disease 19 (COVID-19), is threatening the world. Olfactory or gustatory dysfunction is reported as one of the symptoms worldwide. As reported so far, different clinical features have been reported according to outbreak sites and gender; most of the patients, who complained of anosmia or hyposmia, were Europeans. We had a fast review for novel articles about COVID-19 infection and olfactory function. OBSERVATIONS: Rapid reviews for COVID-19 or other viral infection and olfactory and/or gustatory dysfunctions were done in this review. Up to date, a lot of reports have shown that olfactory dysfunction is related to viral infections but no exact mechanism, clinical course, and definite treatment have been discovered, which is also same in COVID-19. In general, intranasal steroid (INS) and oral steroid for short time help improve the recovery of the olfactory function in case of olfactory dysfunction after virus infection. Considering severe respiratory complications and immunocompromised state of COVID-19, the use of steroid should be limited and cautious because we do not have enough data to support the usage of steroid to treat olfactory dysfunction in the clinical course of COVID-19. CONCLUSIONS AND RELEVANCE: In the days of pandemic COVID-19, we should keep in mind that olfactory dysfunctions, even without other upper respiratory infection or otolaryngologic symptoms, might be the early signs of COVID-19.

Characteristics of the COVID-19 Outbreak in Korea From the Mass Infection Perspective.

On December 31, 2019, the Chinese government officially announced that the country had some cases of pneumonia with an unknown cause. By February 8, 2020, there were 24 confirmed cases in Korea, and the number of cases has steadily increased since then. On March 9, 2020, the cumulative number of confirmed cases in Korea was 7382, with 51 deaths. This study examines the characteristics of the coronavirus disease 2019 (COVID-19) outbreak from the perspective of the large-scale number of confirmed COVID-19 cases and deaths. This study is significant in that it emphasizes the precautionary principle in preventing and managing infectious diseases, and makes suggestions for urgently needed public health policies.

Impact of human mobility on the transmission dynamics of infectious diseases.

Spatial heterogeneity is an important aspect to be studied in infectious disease models. It takes two forms: one is local, namely diffusion in space, and other is related to travel. With the advancement of transportation system, it is possible for diseases to move from one place to an entirely separate place very quickly. In a developing country like India, the mass movement of large numbers of individuals creates the possibility of spread of common infectious diseases. This has led to the study of infectious disease model to describe the infection during transport. An SIRS-type epidemic model is formulated to illustrate the dynamics of such infectious disease propagation between two cities due to population dispersal. The most important threshold parameter, namely the basic reproduction number, is derived, and the possibility of existence of backward bifurcation is examined, as the existence of backward bifurcation is very unsettling for disease control and it is vital to know from modeling analysis when it can occur. It is shown that dispersal of populations would make the disease control difficult in comparison with nondispersal case. Optimal vaccination and treatment controls are determined. Further to find the best cost-effective strategy, cost-effectiveness analysis is also performed. Though it is not a case study, simulation work suggests that the proposed model can also be used in studying the SARS epidemic in Hong Kong, 2003.