Lessons Learnt From the COVID-19 Pandemic.

The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has been characterized by unprecedented rates of spatio-temporal spread. Here, we summarize the main events in the pandemic's timeline and evaluate what has been learnt by the public health community. We also discuss the implications for future public health policy and, specifically, the practice of epidemic control. We critically analyze this ongoing pandemic's timeline and contrast it with the 2002-2003 SARS outbreak. We identify specific areas (e.g., pathogen identification and initial reporting) wherein the international community learnt valuable lessons from the SARS outbreak. However, we also identify the key areas where international public health policy failed leading to the exponential spread of the pandemic. We outline a clear agenda for improved pandemic control in the future.

Hypoxia: The "Invisible Pusher" of Gut Microbiota.

Oxygen is important to the human body. Cell survival and operations depend on oxygen. When the body becomes hypoxic, it affects the organs, tissues and cells and can cause irreversible damage. Hypoxia can occur under various conditions, including external environmental hypoxia and internal hypoxia. The gut microbiota plays different roles under hypoxic conditions, and its products and metabolites interact with susceptible tissues. This review was conducted to elucidate the complex relationship between hypoxia and the gut microbiota under different conditions. We describe the changes of intestinal microbiota under different hypoxic conditions: external environment and internal environment. For external environment, altitude was the mayor cause induced hypoxia. With the increase of altitude, hypoxia will become more serious, and meanwhile gut microbiota also changed obviously. Body internal environment also became hypoxia because of some diseases (such as cancer, neonatal necrotizing enterocolitis, even COVID-19). In addition to the disease itself, this hypoxia can also lead to changes of gut microbiota. The relationship between hypoxia and the gut microbiota are discussed under these conditions.

The ecological dynamics of the coronavirus epidemics during transmission from outside sources when R 0 is successfully managed below one.

Since COVID-19 spread globally in early 2020 and was declared a pandemic by the World Health Organization (WHO) in March, many countries are managing the local epidemics effectively through intervention measures that limit transmission. The challenges of immigration of new infections into regions and asymptomatic infections remain. Standard deterministic compartmental models are inappropriate for sub- or peri-critical epidemics (reproductive number close to or less than one), so individual-based models are often used by simulating transmission from an infected person to others. However, to be realistic, these models require a large number of parameters, each with its own set of uncertainties and lack of analytic tractability. Here, we apply stochastic age-structured Leslie theory with a long history in ecological research to provide some new insights to epidemic dynamics fuelled by external imports. We model the dynamics of an epidemic when R 0 is below one, representing COVID-19 transmission following the successful application of intervention measures, and the transmission dynamics expected when infections migrate into a region. The model framework allows more rapid prediction of the shape and size of an epidemic to improve scaling of the response. During an epidemic when the numbers of infected individuals are rapidly changing, this will help clarify the situation of the pandemic and guide faster and more effective intervention.

Development and evaluation of a serological test for diagnosis of COVID-19 with selected recombinant spike proteins.

Serological test is a valuable diagnostic tool for coronavirus disease 2019 (COVID-19). However, considerable improvements to these tests are needed, especially in the detection sensitivity. In this study, six recombinant nucleocapsid and spike proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were prepared and evaluated, including three prokaryotic expression nucleocapsid proteins (rN, rN1, rN2) and three eukaryotic expression spike proteins (rS1, rS-RBD, rS-RBD-mFc). The recombinant proteins with the highest ELISA titers (rS1 and rS-RBD-mFc) were selected to develop a double-antigen sandwich colloidal gold immunochromatography assay (GICA) to detect total antibodies against SARS-CoV-2. The clinical evaluation results showed that the sensitivity and specificity of GICA were 92.09% (419/455) and 99.44% (706/710), respectively. Moreover, a significant number (65.63%, 21/32) of COVID-19 patients with undetectable viral RNA were correctly diagnosed by the GICA method. In conclusion, the eukaryotic expression spike proteins (rS1 and rS-RBD-mFc) are more suitable than the prokaryotic expression nucleocapsid proteins for serological diagnosis of SARS-CoV-2. The proposed GICA for detection of total antibodies could be a powerful complement to the current RNA tests for COVID-19.

Viral RNA level, serum antibody responses, and transmission risk in recovered COVID-19 patients with recurrent positive SARS-CoV-2 RNA test results: a population-based observational cohort study.

Managing recovered COVID-19 patients with recurrent-positive SARS-CoV-2 RNA test results is challenging. We performed a population-based observational study to characterize the viral RNA level and serum antibody responses in recurrent-positive patients and evaluate their viral transmission risk. Of 479 recovered COVID-19 patients, 93 (19%) recurrent-positive patients were identified, characterized by younger age, with a median discharge-to-recurrent-positive length of 8 days. After readmission, recurrent-positive patients exhibited mild (28%) or absent (72%) symptoms, with no disease progression. The viral RNA level in recurrent-positive patients ranged from 1.8 to 5.7 log10 copies/mL (median: 3.2), which was significantly lower than the corresponding values at disease onset. There are generally no significant differences in antibody levels between recurrent-positive and non-recurrent-positive patients, or in recurrent-positive patients over time (before, during, or after recurrent-positive detection). Virus isolation of nine representative specimens returned negative results. Whole genome sequencing of six specimens yielded only genomic fragments. 96 close contacts and 1,200 candidate contacts of 23 recurrent-positive patients showed no clinical symptoms; their viral RNA (1,296/1,296) and antibody (20/20) tests were negative. After full recovery (no longer/never recurrent-positive), 60% (98/162) patients had neutralizing antibody titers of ≥1:32. Our findings suggested that an intermittent, non-stable excretion of low-level viral RNA may result in recurrent-positive occurrence, rather than re-infection. Recurrent-positive patients pose a low transmission risk, a relatively relaxed management of recovered COVID-19 patients is recommended.

Short-term high-dose gavage of hydroxychloroquine changes gut microbiota but not the intestinal integrity and immunological responses in mice.

AIMS: Hydroxychloroquine (HCQ), a widely used antimalarial drug, is proposed to treat coronavirus disease 2019 (COVID-19). However, no report is currently available regarding the direct effects of HCQ on gut microbiota, which is associated with the outcomes of elderly patients with COVID-19. Here, we first investigated the effects of HCQ on intestinal microecology in mice. MAIN METHODS: Fifteen female C57BL/6J mice were randomly divided into two groups: HCQ group (n = 10) and control group (n = 5). Mice in the HCQ group were administered with HCQ at dose of 100 mg/kg by gavage daily for 14 days. The feces of mice were collected before and on the 7th and 14th days after HCQ challenge, and then analyzed by 16S rRNA amplicon sequencing. At the end of the experiment, the hematology, serum biochemistry and cytokines were determined, respectively. The mRNA expression of tight junction proteins in colonic tissues were also studied by RT-PCR. KEY FINDINGS: HCQ challenge had no effects on the counts of white blood cells, the levels of serum cytokines, and the gene expression of tight junction proteins in colon. HCQ also did not increase the content of serum d-lactate in mice. Notably, HCQ significantly decreased the diversity of gut microbiota, increased the relative abundance of phylum Bacteroidetes whereas decreased that of Firmicutes. SIGNIFICANCE: Short-term high dose HCQ challenge changes gut microbiota but not the intestinal integrity and immunological responses in mice. Special attention should be paid to the effects of HCQ on intestinal microecology in future clinical use.

An investigation of transmission control measures during the first 50 days of the COVID-19 epidemic in China.

Responding to an outbreak of a novel coronavirus [agent of coronavirus disease 2019 (COVID-19)] in December 2019, China banned travel to and from Wuhan city on 23 January 2020 and implemented a national emergency response. We investigated the spread and control of COVID-19 using a data set that included case reports, human movement, and public health interventions. The Wuhan shutdown was associated with the delayed arrival of COVID-19 in other cities by 2.91 days. Cities that implemented control measures preemptively reported fewer cases on average (13.0) in the first week of their outbreaks compared with cities that started control later (20.6). Suspending intracity public transport, closing entertainment venues, and banning public gatherings were associated with reductions in case incidence. The national emergency response appears to have delayed the growth and limited the size of the COVID-19 epidemic in China, averting hundreds of thousands of cases by 19 February (day 50).