Chinese expert consensus on intestinal microecology and management of digestive tract complications related to tumor treatment (version 2022).

The human gut microbiota represents a complex ecosystem that is composed of bacteria, fungi, viruses, and archaea. It affects many physiological functions including metabolism, inflammation, and the immune response. The gut microbiota also plays a role in preventing infection. Chemotherapy disrupts an organism's microbiome, increasing the risk of microbial invasive infection; therefore, restoring the gut microbiota composition is one potential strategy to reduce this risk. The gut microbiome can develop colonization resistance, in which pathogenic bacteria and other competing microorganisms are destroyed through attacks on bacterial cell walls by bacteriocins, antimicrobial peptides, and other proteins produced by symbiotic bacteria. There is also a direct way. For example, Escherichia coli colonized in the human body competes with pathogenic Escherichia coli 0157 for proline, which shows that symbiotic bacteria compete with pathogens for resources and niches, thus improving the host's ability to resist pathogenic bacteria. Increased attention has been given to the impact of microecological changes in the digestive tract on tumor treatment. After 2019, the global pandemic of novel coronavirus disease 2019 (COVID-19), the development of novel tumor-targeting drugs, immune checkpoint inhibitors, and the increased prevalence of antimicrobial resistance have posed serious challenges and threats to public health. Currently, it is becoming increasingly important to manage the adverse effects and complications after chemotherapy. Gastrointestinal reactions are a common clinical presentation in patients with solid and hematologic tumors after chemotherapy, which increases the treatment risks of patients and affects treatment efficacy and prognosis. Gastrointestinal symptoms after chemotherapy range from nausea, vomiting, and anorexia to severe oral and intestinal mucositis, abdominal pain, diarrhea, and constipation, which are often closely associated with the dose and toxicity of chemotherapeutic drugs. It is particularly important to profile the gastrointestinal microecological flora and monitor the impact of antibiotics in older patients, low immune function, neutropenia, and bone marrow suppression, especially in complex clinical situations involving special pathogenic microbial infections (such as clostridioides difficile, multidrug-resistant Escherichia coli, carbapenem-resistant bacteria, and norovirus).

Dysregulated hematopoiesis in bone marrow marks severe COVID-19.

Severe coronavirus disease 2019 (COVID-19) is often indicated by lymphopenia and increased myelopoiesis; however, the underlying mechanism is still unclear, especially the alteration of hematopoiesis. It is important to explore to what extent and how hematopoietic stem cells contribute to the impairment of peripheral lymphoid and myeloid compartments in COVID-19 patients. In this study, we used single-cell RNA sequencing to assess bone marrow mononuclear cells from COVID-19 patients with peripheral blood mononuclear cells as control. The results showed that the hematopoietic stem cells in these patients were mainly in the G1 phase and prone to apoptosis, with immune activation and anti-viral responses. Importantly, a significant accumulation of immature myeloid progenitors and a dramatic reduction of lymphoid progenitors in severe cases were identified, along with the up-regulation of transcription factors (such as SPI1, LMO4, ETS2, FLI1, and GATA2) that are important for the hematopoietic stem cell or multipotent progenitor to differentiate into downstream progenitors. Our results indicate a dysregulated hematopoiesis in patients with severe COVID-19.

The time-varying transmission dynamics of COVID-19 and synchronous public health interventions in China.

OBJECTIVES: We aimed to estimate the time-varying transmission dynamics of COVID-19 in China, Wuhan City, and Guangdong province, and compare to that of severe acute respiratory syndrome (SARS). METHODS: Data on COVID-19 cases in China up to 20 March 2020 was collected from epidemiological investigations or official websites. Data on SARS cases in Guangdong Province, Beijing, and Hong Kong during 2002-3 was also obtained. We estimated the doubling time, basic reproduction number (R0), and time-varying reproduction number (Rt) of COVID-19 and SARS. RESULTS: As of 20 March 2020, 80,739 locally acquired COVID-19 cases were identified in mainland China, with most cases reported between 20 January and 29 February 2020. The R0 value of COVID-19 in China and Wuhan was 5.0 and 4.8, respectively, which was greater than the R0 value of SARS in Guangdong (R0 = 2.3), Hong Kong (R0 = 2.3), and Beijing (R0 = 2.6). At the start of the COVID-19 epidemic, the Rt value in China peaked at 8.4 and then declined quickly to below 1.0 in one month. With SARS, the Rt curve saw fluctuations with more than one peak, the highest peak was lower than that for COVID-19. CONCLUSIONS: COVID-19 has much higher transmissibility than SARS, however, a series of prevention and control interventions to suppress the outbreak were effective. Sustained efforts are needed to prevent the rebound of the epidemic in the context of the global pandemic.

Clinical characteristics of recovered COVID-19 patients with re-detectable positive RNA test.

BACKGROUND: The characteristics, significance and potential cause of positive SARS-CoV-2 diagnoses in recovered coronavirus disease 2019 (COVID-19) patients post discharge (re-detectable positive, RP) remained elusive. METHODS: A total of 262 COVID-19 patients discharged from January 23 to February 25, 2020 were enrolled into this study. RP and non-RP (NRP) patients were grouped according to disease severity, and the characterization at re-admission was analyzed. SARS-CoV-2 RNA and plasma antibody levels were measured, and all patients were followed up for at least 14 days, with a cutoff date of March 10, 2020. RESULTS: A total of 14.5% of RP patients were detected. These patients were characterized as young and displayed mild and moderate conditions compared to NRP patients while no severe patients were RP. RP patients displayed fewer symptoms but similar plasma antibody levels during their hospitalization compared to NRP patients. Upon hospital readmission, these patients showed no obvious symptoms or disease progression. All 21 close contacts of RP patients were tested negative for viral RNA and showed no suspicious symptoms. Eighteen out of 24 of RNA-negative samples detected by the commercial kit were tested positive for viral RNA using a hyper-sensitive method, suggesting that these patients were potential carriers of the virus after recovery from COVID-19. CONCLUSIONS: Our results indicated that young patients, with a mild diagnosis of COVID-19 are more likely to display RP status after discharge. These patients show no obvious symptoms or disease progression upon re-admission. More sensitive RNA detection methods are required to monitor these patients. Our findings provide information and evidence for the management of convalescent COVID-19 patients.

Clinical, immunological and virological characterization of COVID-19 patients that test re-positive for SARS-CoV-2 by RT-PCR.

BACKGROUND: Some COVID-19 cases test positive again for SARS-CoV-2 RNA following negative test results and discharge, raising questions about the meaning of virus detection. Better characterization of re-positive cases is urgently needed. METHODS: Clinical data were obtained through Guangdong's COVID-19 surveillance network. Neutralization antibody titre was determined using microneutralization assays. Potential infectivity of clinical samples was evaluated by cell inoculation. SARS-CoV-2 RNA was detected using three different RT-PCR kits and multiplex PCR with nanopore sequencing. FINDINGS: Among 619 discharged COVID-19 cases, 87 re-tested as SARS-CoV-2 positive in circumstances of social isolation. All re-positive cases had mild or moderate symptoms at initial diagnosis and were younger on average (median, 28). Re-positive cases (n = 59) exhibited similar neutralization antibodies (NAbs) titre distributions to other COVID-19 cases (n = 218) tested here. No infectious strain could be obtained by culture and no full-length viral genomes could be sequenced from re-positive cases. INTERPRETATION: Re-positive SARS-CoV-2 cases do not appear to be caused by active reinfection and were identified in ~14% of discharged cases. A robust NAb response and potential virus genome degradation were detected in almost all re-positive cases, suggesting a substantially lower transmission risk, especially through respiratory routes.

Risk factors associated with COVID-19 infection: a retrospective cohort study based on contacts tracing.

This study aimed to estimate the attack rates, and identify the risk factors of COVID-19 infection. Based on a retrospective cohort study, we investigated 11,580 contacts of COVID-19 cases in Guangdong Province from 10 January to 15 March 2020. All contacts were tested by RT-PCR to detect their infection of SARS-COV-2. Attack rates by characteristics were calculated. Logistic regression was used to estimate the risk factors of infection for COVID-19. A total of 515 of 11,580 contacts were identified to be infected with SARS-COV-2. Compared to young adults aged 20-29 years, the infected risk was higher in children (RR: 2.59, 95%CI: 1.79-3.76), and old people aged 60-69 years (RR: 5.29, 95%CI: 3.76-7.46). Females also had higher infected risk (RR: 1.66, 95%CI: 1.39-2.00). People having close relationship with index cases encountered higher infected risk (RR for spouse: 20.68, 95%CI: 14.28-29.95; RR for non-spouse family members: 9.55, 95%CI: 6.73-13.55; RR for close relatives: 5.90, 95%CI: 4.06-8.59). Moreover, contacts exposed to index case in symptomatic period (RR: 2.15, 95%CI: 1.67-2.79), with critically severe symptoms (RR: 1.61, 95%CI: 1.00-2.57), with symptoms of dizzy (RR: 1.58, 95%CI: 1.08-2.30), myalgia (RR: 1.49, 95%CI: 1.15-1.94), and chill (RR: 1.42, 95%CI: 1.05-1.92) had higher infected risks. Children, old people, females, and family members are susceptible of COVID-19 infection, while index cases in the incubation period had lower contagiousness. Our findings will be helpful for developing targeted prevention and control strategies to combat the worldwide pandemic.