From Outbreak to Near Disappearance: How Did Non-pharmaceutical Interventions Against COVID-19 Affect the Transmission of Influenza Virus?

Influenza shares the same putative transmission pathway with coronavirus disease 2019 (COVID-19), and causes tremendous morbidity and mortality annually globally. Since the transmission of COVID-19 in China, a series of non-pharmaceutical interventions (NPIs) against to the disease have been implemented to contain its transmission. Based on the surveillance data of influenza, Search Engine Index, and meteorological factors from 2011 to 2021 in Xi'an, and the different level of emergence responses for COVID-19 from 2020 to 2021, Bayesian Structural Time Series model and interrupted time series analysis were applied to quantitatively assess the impact of NPIs in sequent phases with different intensities, and to estimate the reduction of influenza infections. From 2011 to 2021, a total of 197,528 confirmed cases of influenza were reported in Xi'an, and the incidence of influenza continuously increased from 2011 to 2019, especially, in 2019–2020, when the incidence was up to 975.90 per 100,000 persons;however, it showed a sharp reduction of 97.68% in 2020–2021, and of 87.22% in 2021, comparing with 2019–2020. The highest impact on reduction of influenza was observed in the phase of strict implementation of NPIs with an inclusion probability of 0.54. The weekly influenza incidence was reduced by 95.45%, and an approximate reduction of 210,100 (95% CI: 125,100–329,500) influenza infections was found during the post-COVID-19 period. The reduction exhibited significant variations in the geographical, population, and temporal distribution. Our findings demonstrated that NPIs against COVID-19 had a long-term impact on the reduction of influenza transmission.

Acute Mesenteric Ischemia in Patients with COVID-19: Review of the literature.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a global health emergency. In addition to common respiratory symptoms, some patients with COVID-19 infections may experience a range of extra-pulmonary manifestations, such as digestive system involvement. Patients with COVID-19 have been reported to suffer from acute mesenteric ischemia (AMI) that is associated with disease-related severity and mortality. However, in the context of COVID-19, the exact cause of AMI has yet to be clearly defined. This review provides a comprehensive overview of the available data and elucidates the possible underlying mechanisms linking COVID-19 to AMI, in addition to highlighting therapeutic approaches for clinicians. Finally, given the severe global impact of COVID-19, we emphasize the importance of coordinated vaccination programs.

Early Viral Clearance and Antibody Kinetics of COVID-19 Among Asymptomatic Carriers.

Asymptomatic carriers contribute to the spread of Coronavirus Disease 2019 (COVID-19), but their clinical characteristics, viral kinetics, and antibody responses remain unclear. A total of 56 COVID-19 patients without symptoms at admission and 19 age-matched symptomatic patients were enrolled. RNA of SARS-CoV-2 was tested using transcriptase quantitative PCR, and the total antibodies (Ab), IgG, IgA, and IgM against the SARS-CoV-2 were tested using Chemiluminescence Microparticle Immuno Assay. Among 56 patients without symptoms at admission, 33 cases displayed symptoms and 23 remained asymptomatic throughout the follow-up period. 43.8% of the asymptomatic carriers were children and none of the asymptomatic cases had recognizable changes in C-reactive protein or interleukin-6, except one 64-year-old patient. The initial threshold cycle value of nasopharyngeal SARS-CoV-2 in asymptomatic carriers was similar to that in pre-symptomatic and symptomatic patients, but the positive viral nucleic acid detection period of asymptomatic carriers (9.63 days) was shorter than pre-symptomatic patients (13.6 days). There were no obvious differences in the seropositive conversion rate of total Ab, IgG, and IgA among the three groups, though the rates of IgM varied largely. The average peak IgG and IgM COI of asymptomatic cases was 3.5 and 0.8, respectively, which is also lower than those in symptomatic patients with peaked IgG and IgM COI of 4.5 and 2.4 (p < 0.05). Young COVID-19 patients seem to be asymptomatic cases with early clearance of SARS-CoV-2 and low levels of IgM generation but high total Ab, IgG, and IgA. Our findings provide empirical information for viral clearance and antibody kinetics of asymptomatic COVID-19 patients.

Antibody Responses to SARS-CoV-2 in Patients With Novel Coronavirus Disease 2019.

BACKGROUND: The novel coronavirus SARS-CoV-2 is a newly emerging virus. The antibody response in infected patients remains largely unknown, and the clinical value of antibody testing has not been fully demonstrated. METHODS: 173 patients with SARS-CoV-2 infection were enrolled. Their serial plasma samples (n = 535) collected during hospitalization were tested for total antibodies (Ab), IgM, and IgG against SARS-CoV-2. The dynamics of antibodies with disease progress were analyzed. RESULTS: Among 173 patients, the seroconversion rates for Ab, IgM, and IgG were 93.1%, 82.7%, and 64.7%, respectively. The reason for the negative antibody findings in 12 patients might be due to the lack of blood samples at the later stage of illness. The median seroconversion times for Ab, IgM, and then IgG were days 11, 12, and 4, respectively. The presence of antibodies was <40% among patients within 1 week of onset, and rapidly increased to 100.0% (Ab), 94.3% (IgM), and 79.8% (IgG) by day 15 after onset. In contrast, RNA detectability decreased from 66.7% (58/87) in samples collected before day 7 to 45.5% (25/55) during days 15-39. Combining RNA and antibody detection significantly improved the sensitivity of pathogenic diagnosis for COVID-19 (P < .001), even in the early phase of 1 week from onset (P = .007). Moreover, a higher titer of Ab was independently associated with a worse clinical classification (P = .006). CONCLUSIONS: Antibody detection offers vital clinical information during the course of SARS-CoV-2 infection. The findings provide strong empirical support for the routine application of serological testing in the diagnosis and management of COVID-19 patients.

Family-centered care management strategies for term and near-term neonates with brief hospitalization in a level III NICU in Shenzhen, China during the time of COVID-19 pandemic.

BACKGROUND: Adopting the family-centered care (FCC) approach in the neonatal care has been shown to improve breastfeeding rate and parental satisfaction. To minimize the transmission of COVID-19, family visit in neonatal intensive care unit (NICU) was suspended in China. In order to maintain the benefits of FCC, the Hong Kong University-Shenzhen Hospital NICU modified FCC strategies. We evaluated the effects of new strategies and aimed to share our results and experience with other NICUs during the COVID-19 pandemic. METHODS: Using prospectively collected hospital databases, we retrospectively compared the demographic and clinical data of neonates, rates of breastfeeding at discharge, nosocomial infection and parental satisfaction one month before (open group) and after (closed group) the implementation of alternative FCC management strategies when family visit was suspended during COVID-19 pandemic. RESULTS: During the COVID-19 pandemic, we organized a multidisciplinary task force and adopted strategies of triage and screening, management of suspected infants, and breastfeeding promotion with effective communication. The nosocomial infection rate and parental satisfaction for open and closed groups (144 and 108 term and near-term neonates with brief hospitalization, respectively) were not different (1% vs. 0%, p = 1.00; 98.6 vs. 98.8, p = .80; respectively). Breastfeeding rate at discharge decreased but the difference was not significant (74% vs. 80%, p = .29). CONCLUSIONS: In our experience, in term and near-term neonates with brief hospitalization, the alternative FCC strategies maintained high parental satisfaction without increased nosocomial infection rate, but strong support for breastfeeding was needed. Through multidisciplinary collaboration, the continuation of "modified" FCC in a level III NICU is feasible in the context of COVID-19 pandemic with reduced family visitation and participation in the care.

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.

Tocilizumab exerts anti-inflammatory activity in six critically ill COVID-19 patients: a retrospective analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a worldwide pandemic, affecting countries across the globe. With no current vaccine, treatment is still a critical intervention for minimizing morbidity and preventing disease-specific mortality. This study aimed to assess the clinical outcomes of critically ill COVID-19 patients using Tocilizumab treatment to provide recommendations for the treatment of COVID-19 patients with severe disease. METHODS: This was a retrospective analysis of medical records of six critically ill patients admitted to the Third People's Hospital of Shenzhen, China, from January 11 to February 26, 2020. Patient-related outcomes, including demographic, clinical, and laboratory characteristics before and after the initiation of Tocilizumab, were descriptively analyzed. Four to eight milligrams (mg)/kilogram (kg) of Tocilizumab was prescribed, with Chinese treatment guidelines. RESULTS: By the end of the last follow-up, Patient 1 and Patient 2 developed complications and died after using Tocilizumab for three to four days. Patient 4 died of multiple organ failure caused by cerebral infarction after using Tocilizumab for 39 days. Patient 3 and Patient 6 were discharged after 29 days and 33 days on Tocilizumab, respectively. Clinical symptoms, including fever, heart rate, and oxygen levels, improved after Tocilizumab use. Two patients appeared transient abnormal of liver or renal function indicator, and they can gradually recover. All elevated serum levels of inflammatory factors gradually decreased, except in Patient 2. Patient 3 and Patient 6's inflammatory lesions also significantly improved after initiating Tocilizumab. CONCLUSIONS: Anti-inflammatory treatment with Tocilizumab was found to improve inflammatory responses in critically ill COVID-19 patients. Although some side reactions will occur, patients can gradually recover without affecting the efficacy of the therapy. However, the proper timing to start patients on Tocilizumab patients should be explored. Further prospective, randomized controlled clinical trials are called for.

Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses.

The new coronavirus (SARS-CoV-2) outbreak from December 2019 in Wuhan, Hubei, China, has been declared a global public health emergency. Angiotensin I converting enzyme 2 (ACE2), is the host receptor by SARS-CoV-2 to infect human cells. Although ACE2 is reported to be expressed in lung, liver, stomach, ileum, kidney and colon, its expressing levels are rather low, especially in the lung. SARS-CoV-2 may use co-receptors/auxiliary proteins as ACE2 partner to facilitate the virus entry. To identify the potential candidates, we explored the single cell gene expression atlas including 119 cell types of 13 human tissues and analyzed the single cell co-expression spectrum of 51 reported RNA virus receptors and 400 other membrane proteins. Consistent with other recent reports, we confirmed that ACE2 was mainly expressed in lung AT2, liver cholangiocyte, colon colonocytes, esophagus keratinocytes, ileum ECs, rectum ECs, stomach epithelial cells, and kidney proximal tubules. Intriguingly, we found that the candidate co-receptors, manifesting the most similar expression patterns with ACE2 across 13 human tissues, are all peptidases, including ANPEP, DPP4 and ENPEP. Among them, ANPEP and DPP4 are the known receptors for human CoVs, suggesting ENPEP as another potential receptor for human CoVs. We also conducted "CellPhoneDB" analysis to understand the cell crosstalk between CoV-targets and their surrounding cells across different tissues. We found that macrophages frequently communicate with the CoVs targets through chemokine and phagocytosis signaling, highlighting the importance of tissue macrophages in immune defense and immune pathogenesis.

Community Transmission of Severe Acute Respiratory Syndrome Coronavirus 2, Shenzhen, China, 2020.

Since early January 2020, after the outbreak of coronavirus infection in Wuhan, China, ≈365 confirmed cases have been reported in Shenzhen, China. The mode of community and intrafamily transmission is threatening residents in Shenzhen. Strategies to strengthen prevention and interruption of these transmissions should be urgently addressed.

The Impact of the COVID-19 Outbreak on the Medical Treatment of Chinese Children with Chronic Kidney Disease (CKD)：A Multicenter Cross-section Study in the Context of a Public Health Emergency of International Concern (preprint)

Objective: To investigate the impact of the COVID-19 outbreak on the medical advice seeking of Chinese children with chronic kidney disease (CKD). Materials and Methods: An anonymous online questionnaire survey was conducted in 17 pediatric nephropathy diagnosis and treatment centers in China. The questions collected basic information on the patients and their parents and data on changes in the approach to medical treatment and their needs in the context of the outbreak etc. This is a Multicenter Cross-section Study. Results: A total of 735 valid questionnaires were collected. 555 patients (75.5%) and their parents said that the outbreak had a significant influence on their medical treatment: 264 patients (47.6%) said that it would be delayed by 2 to 4 weeks and 199 patients (35.9%) by 4 to 8 weeks. 510 patients (84.16%) hoped to get in touch with specialists through online consultation, and 528 patients (84.5%) hoped that online consultation could be implemented and that medication could be delivered to them.. A total of 458 patients (62.3%) said that their greatest concern was that the CKD would be aggravated or that they would experience a relapse; only 203 patients were infected by 2019-nCoV. A total of 313 patients (42.5%) experienced anxiety and thus required the intervention of psychologists. Conclusion: The COVID-19 outbreak has affected the medical treatment of children with CKD. Online consultation, medication delivery and psychological counselling are the greatest needs reported by patients and their families and could especially provide solutions for the management of low income children with CKD in remote rural areas in the context of the COVID-19 epidemic.