Super Dominant Pathobiontic Bacteria in the Nasopharyngeal Microbiota Cause Secondary Bacterial Infection in COVID-19 Patients.

Coronavirus disease 2019 (COVID-19) is a respiratory infectious disease responsible for many infections worldwide. Differences in respiratory microbiota may correlate with disease severity. Samples were collected from 20 severe and 51 mild COVID-19 patients. High-throughput sequencing of the 16S rRNA gene was used to analyze the bacterial community composition of the upper and lower respiratory tracts. The indices of diversity were analyzed. When one genus accounted for >50% of reads from a sample, it was defined as a super dominant pathobiontic bacterial genus (SDPG). In the upper respiratory tract, uniformity indices were significantly higher in the mild group than in the severe group (P < 0.001). In the lower respiratory tract, uniformity indices, richness indices, and the abundance-based coverage estimator were significantly higher in the mild group than in the severe group (P < 0.001). In patients with severe COVID-19, SDPGs were detected in 40.7% of upper and 63.2% of lower respiratory tract samples. In patients with mild COVID-19, only 10.8% of upper and 8.5% of lower respiratory tract samples yielded SDPGs. SDPGs were present in both upper and lower tracts in seven patients (35.0%), among which six (30.0%) patients possessed the same SDPG in the upper and lower tracts. However, no patients with mild infections had an SDPG in both tracts. Staphylococcus, Corynebacterium, and Acinetobacter were the main SDPGs. The number of SDPGs identified differed significantly between patients with mild and severe COVID-19 (P < 0.001). SDPGs in nasopharyngeal microbiota cause secondary bacterial infection in COVID-19 patients and aggravate pneumonia. IMPORTANCE The nasopharyngeal microbiota is composed of a variety of not only the true commensal bacterial species but also the two-face pathobionts, which are one a harmless commensal bacterial species and the other a highly invasive and deadly pathogen. In a previous study, we found that the diversity of nasopharyngeal microbiota was lost in severe influenza patients. We named the genus that accounted for over 50% of microbiota abundance as super dominant pathobiontic genus, which could invade to cause severe pneumonia, leading to high fatality. Similar phenomena were found here for SARS-CoV-2 infection. The diversity of nasopharyngeal microbiota was lost in severe COVID-19 infection patients. SDPGs in nasopharyngeal microbiota were frequently detected in severe COVID-19 patients. Therefore, the SDPGs in nasopharynx microbiota might invade into low respiratory and be responsible for secondary bacterial pneumonia in patients with SARS-CoV-2 infection.

Preliminary Study of the Protectiveness of Vaccination Against the COVID-19 in the Outbreak of VOC Omicron BA.2 - Jilin City, Jilin Province, China, March 3-April 12, 2022.

What is already known about this topic?: An outbreak of coronavirus disease 2019 (COVID-19) of Omicron BA.2 emerged in Jilin City since March 3, 2022, which involved in 27,036 cases by April 12. The vaccination program with inactivated COVID-19 vaccines has been implemented since the beginning of 2021. What is added by this report?: The incidences of moderate, severe, and critical cases in the whole population of the group of 0+1 dose were 1.82-, 9.49-, and 3.85-fold higher than those in the group of 2 doses, and 5.03-, 44.47-, and ∞-fold higher than those received 3 doses vaccination. For the population ≥60 years, the incidences of moderate, severe, and critical cases in the group of 0+1 dose were 29.92, 9.62, and 4.27 per 100,000, showing 4.13-, 43.72-, and 4.85-fold higher than 2 doses, as well as 13.28-, 22.37-, and ∞-fold higher than 3 doses. What are the implications for public health practice?: The incidences of each type of COVID-19 in the population who were fully vaccinated or booster vaccinated in Jilin City were significantly lower than those who were unvaccinated and/or partially vaccinated. Booster vaccination with homologous inactivated vaccines induces stronger protectiveness for COVID-19 caused by variant of concern (VOC) Omicron.

Establishment of a rapid diagnosis assay for SARS-CoV-2 infection based on MALDI-TOF MS

Objective: To establish a rapid, high-throughput detection assay of serum peptidome profiling for the diagnosis of SARS-CoV-2 infection based on matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS).

A Novel Strategy for the Detection of SARS-CoV-2 Variants Based on Multiplex PCR-Mass Spectrometry Minisequencing Technology.

The objective of this study was to construct a novel strategy for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants using multiplex PCR-mass spectrometry minisequencing technique (mPCR-MS minisequencing). Using the nucleic acid sequence of a SARS-CoV-2 nonvariant and a synthetic SARS-CoV-2 variant-carrying plasmid, a matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) method based on the single-base mass probe extension of multiplex PCR amplification products was established to detect 9 mutation types in 7 mutated sites (HV6970del, N501Y, K417N, P681H, D614G, E484K, L452R, E484Q, and P681R) in the receptor-binding domain of the spike protein of SARS-CoV-2 variants. Twenty-one respiratory tract pathogens (9 bacteria and 12 respiratory viruses) and nucleic acid samples from non-COVID-19 patients were selected for specific validation. Twenty samples from COVID-19 patients were used to verify the accuracy of this method. The 9 mutation types could be detected simultaneously by triple PCR amplification coupled with MALDI-TOF MS. SARS-CoV-2 and six variants, B.1.1.7 (Alpha), B.1.351 (Beta), B.1.429 (Epsilon), B.1.526 (Iota), P.1 (Gamma) and B.1.617.2 (Delta), could be identified. The detection limit for all 9 sites was 1.5 × 103 copies. The specificity of this method was 100%, and the accuracy of real-time PCR cycle threshold (CT) values less than 27 among positive samples was 100%. This method is open and extensible, and can be used in a high-throughput manner, easily allowing the addition of new mutation sites as needed to identify and track new SARS-CoV-2 variants as they emerge. mPCR-MS minisequencing provides a new detection option with practical application value for SARS-CoV-2 and its variant infection. IMPORTANCE The emergence of SARS-CoV-2 variants is the key factor in the second wave of the COVID-19 pandemic. An all-in-one SARS-CoV-2 variant identification method based on a multiplex PCR-mass spectrometry minisequencing system was developed in this study. Six SARS-CoV-2 variants (Alpha, Beta, Epsilon, Iota, Gamma, and Delta) can be identified simultaneously. This method can not only achieve the multisite simultaneous detection that cannot be realized by PCR coupled with first-generation sequencing technology and quantitative PCR (qPCR) technology but also avoid the shortcomings of time-consuming, high-cost, and high technical requirements of whole-genome sequencing technology. As a simple screening assay for monitoring the emergence and spread of SARS-CoV-2 and variants, mPCR-MS minisequencing is expected to play an important role in the detection and monitoring of SARS-CoV-2 infection as a supplementary technology.

A COVID-19 Outbreak - Nangong City, Hebei Province, China, January 2021.

WHAT IS KNOWN ABOUT THIS TOPIC?: Coronavirus disease 2019 (COVID-19) is widespread globally. In China, COVID-19 has been well controlled and has appeared only in importation-related cases. Local epidemics occur sporadically in China and have been contained relatively quickly. WHAT IS ADDED BY THIS REPORT?: Epidemiological investigation with genome sequence traceability analysis showed that the first case of COVID-19 in Nangong City acquired infection from a confirmed case from Shijiazhuang City; infection subsequently led to 76 local cases. All cases were associated with the index case, and most were located in Fenggong Street and did not spread outside of Nangong City. The main routes of transmission were family clusters, intra-unit transmission, and nosocomial transmission. WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE?: This study highlights new techniques for rapidly tracing cases and identifying COVID-19 transmission chains. The different epidemiological characteristics in Nangong City, from the earliest stages of the outbreak, suggest that allocation of health sources for prevention and treatment were reasonable. Preventing transmission within medical institutions and isolation facilities and strengthening management in the community should be priorities for COVID-19 control during a city lockdown.

Development of an inactivated vaccine candidate for SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. Because of the novelty of the virus, there are currently no SARS-CoV-2-specific treatments or vaccines available. Therefore, rapid development of effective vaccines against SARS-CoV-2 are urgently needed. Here, we developed a pilot-scale production of PiCoVacc, a purified inactivated SARS-CoV-2 virus vaccine candidate, which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats, and nonhuman primates. These antibodies neutralized 10 representative SARS-CoV-2 strains, suggesting a possible broader neutralizing ability against other strains. Three immunizations using two different doses, 3 or 6 micrograms per dose, provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without observable antibody-dependent enhancement of infection. These data support the clinical development and testing of PiCoVacc for use in humans.