Impact of the COVID-19 Pandemic on Outpatient Service in Primary Healthcare Institutions: An Inspiration From Yinchuan of China.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has posed a great challenge to the healthcare system. This study evaluated the impact of the pandemic on the utilization of primary healthcare (PHC). METHODS: The outpatient data from 158 PHC institutions in Yinchuan from May 1, 2017 to April 30, 2020 were used. The difference in difference (DID) model was used to analyze the difference in the number of outpatient visits per day, total outpatient expenditure per day, and outpatient expenditure per visit between December 2019 and February 2020 compared with the same periods in two previous years. The autoregressive integrated moving average (ARIMA) modelling was used to investigate the association between the outpatient volume and the number of the last week's new COVID-19 cases in Yinchuan, Ningxia, and China. RESULTS: From December 2019 to February 2020, the decline in the number of outpatient visits per day (DID: -367.21 times, P=.004) was larger than that in two previous years, and a similar trend can be seen in the outpatient expenditure per day. However, the rise in the outpatient expenditure per visit (DID: 19.06 thousand yuan, P=.003) was larger than that in two previous years. In 2020, the outpatient visits for most types of diseases decreased from week 3 and rebounded after week 5. The decline and rebound of outpatient visits in the population aged 45 years and older were steeper than in those younger. The outpatient volume was negatively associated with the number of the last week's new COVID-19 cases. CONCLUSION: This study indicated a significant impact of the pandemic on PHC service utilization. Since PHC service is the foundation of the healthcare system in most developing countries, measures should be taken to make PHC help cope with the crisis and relieve the burden of hospital care.

Ambroxol for the treatment of COVID-19 among hospitalized patients: A multicenter retrospective cohort study.

Ambroxol is a commonly used mucolytic agent principally used to treat respiratory diseases, which may have a role as adjunctive therapy for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, but there is lack of evidence about its effectiveness on coronavirus disease-2019 (COVID-19) patients. To study the association between ambroxol use and clinical outcomes among hospitalized patients of COVID-19 infection. We conducted a multicenter retrospective cohort study involving 3,111 patients with confirmed SARS-CoV-2 infection from three hospitals in Wuhan from 19 December 2019 to 15 April 2020, and the primary outcome was in-hospital mortality. COVID-19 patients were classified into ambroxol and non-ambroxol groups based on the administration of ambroxol during hospitalization. Two analyses including propensity score matching (PSM) to obtain a 1:1 balanced cohort and logistic regression were used to control for confounding factors. The average age of 3,111 patients was 57.55 ± 14.93 years old, 127 of them died during hospitalization, and 924 of them used ambroxol. Treatment with ambroxol did not have a significant effect on in-hospital mortality of COVID-19 patients when compared with non-ambroxol in PSM model after adjusting for confounders (8.0% vs. 3.5%, adjusted OR, 1.03 [95% CI, 0.54-1.97], p = 0.936). Adverse events such as nausea/vomiting, headache, and rash were comparable between the two groups. Our results suggest that the use of ambroxol is not significantly associated with in-hospital mortality in COVID-19 patients, which provides evidence for evaluating the effects of ambroxol on COVID-19 patient outcomes and may be helpful for physicians considering medication alternatives for COVID-19 patients.

Preparing for and conducting the National Health and Morbidity Survey in Malaysia amid the COVID-19 pandemic: balancing risks and benefits to participants and society.

PROBLEM: The novel coronavirus disease 2019 (COVID-19) pandemic adversely affected the preparation of Malaysia's National Health and Morbidity Survey for 2020 because conducting it would expose data collectors and participants to an increased risk of infection. CONTEXT: The survey is nationally representative and community based and is conducted by the Institute for Public Health, part of the National Institutes of Health, to generate health-related evidence and to support the Malaysian Ministry of Health in policy-making. Its planned scope for 2020 was the seroprevalence of communicable diseases such as hepatitis B and C. ACTION: Additional components were added to the survey to increase its usefulness, including COVID-19 seroprevalence and facial anthropometric studies to ensure respirator fit. The survey's scale was reduced, and data collection was changed from including only face-to-face interviews to mainly self-administered and telephone interviews. The transmission risk to participants was reduced by screening data collectors before the survey and fortnightly thereafter, using standard droplet and contact precautions, ensuring proper training and monitoring of data collectors, and implementing other administrative infection prevention measures. OUTCOME: Data were collected from 7 August to 11 October 2020, with 5957 participants recruited. Only 4 out of 12 components of the survey were conducted via face-to-face interview. No COVID-19 cases were reported among data collectors and participants. All participants were given their hepatitis and COVID-19 laboratory test results; 73 participants with hepatitis B and 14 with hepatitis C who had been previously undiagnosed were referred for further case management. DISCUSSION: Preparing and conducting the National Health and Morbidity Survey during the COVID-19 pandemic required careful consideration of the risks and benefits, multiple infection prevention measures, strong leadership and strong stakeholder support to ensure there were no adverse events.

Sustaining effective COVID-19 control in Malaysia through large-scale vaccination.

INTRODUCTION: As of 3rd June 2021, Malaysia is experiencing a resurgence of COVID-19 cases. In response, the federal government has implemented various non-pharmaceutical interventions (NPIs) under a series of Movement Control Orders and, more recently, a vaccination campaign to regain epidemic control. In this study, we assessed the potential for the vaccination campaign to control the epidemic in Malaysia and four high-burden regions of interest, under various public health response scenarios. METHODS: A modified susceptible-exposed-infectious-recovered compartmental model was developed that included two sequential incubation and infectious periods, with stratification by clinical state. The model was further stratified by age and incorporated population mobility to capture NPIs and micro-distancing (behaviour changes not captured through population mobility). Emerging variants of concern (VoC) were included as an additional strain competing with the existing wild-type strain. Several scenarios that included different vaccination strategies (i.e. vaccines that reduce disease severity and/or prevent infection, vaccination coverage) and mobility restrictions were implemented. RESULTS: The national model and the regional models all fit well to notification data but underestimated ICU occupancy and deaths in recent weeks, which may be attributable to increased severity of VoC or saturation of case detection. However, the true case detection proportion showed wide credible intervals, highlighting incomplete understanding of the true epidemic size. The scenario projections suggested that under current vaccination rates complete relaxation of all NPIs would trigger a major epidemic. The results emphasise the importance of micro-distancing, maintaining mobility restrictions during vaccination roll-out and accelerating the pace of vaccination for future control. Malaysia is particularly susceptible to a major COVID-19 resurgence resulting from its limited population immunity due to the country's historical success in maintaining control throughout much of 2020.

Sustaining effective COVID-19 control in Malaysia through large-scale vaccination (preprint)

Introduction As of 3rd June 2021, Malaysia is experiencing a resurgence of COVID-19 cases. In response, the federal government has implemented various non-pharmaceutical interventions (NPIs) under a series of Movement Control Orders and, more recently, a vaccination campaign to regain epidemic control. In this study, we assessed the potential for the vaccination campaign to control the epidemic in Malaysia and four high-burden regions of interest, under various public health response scenarios. Methods A modified susceptible-exposed-infectious-recovered compartmental model was developed that included two sequential incubation and infectious periods, with stratification by clinical state. The model was further stratified by age and incorporated population mobility to capture NPIs and micro-distancing (behaviour changes not captured through population mobility). Emerging variants of concern (VoC) were included as an additional strain competing with the existing wild-type strain. Several scenarios that included different vaccination strategies (i.e. vaccines that reduce disease severity and/or prevent infection, vaccination coverage) and mobility restrictions were implemented. Results The national model and the regional models all fit well to notification data but underestimated ICU occupancy and deaths in recent weeks, which may be attributable to increased severity of VoC or saturation of case detection. However, the true case detection proportion showed wide credible intervals, highlighting incomplete understanding of the true epidemic size. The scenario projections suggested that under current vaccination rates complete relaxation of all NPIs would trigger a major epidemic. The results emphasise the importance of micro-distancing, maintaining mobility restrictions during vaccination roll-out and accelerating the pace of vaccination for future control. Malaysia is particularly susceptible to a major COVID-19 resurgence resulting from its limited population immunity due to the historical success of the country in maintaining control throughout much of 2020.

Insights into SARS-CoV-2: Medicinal Chemistry Approaches to Combat Its Structural and Functional Biology.

Coronavirus disease 2019, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still a pandemic around the world. Currently, specific antiviral drugs to control the epidemic remain deficient. Understanding the details of SARS-CoV-2 structural biology is extremely important for development of antiviral agents that will enable regulation of its life cycle. This review focuses on the structural biology and medicinal chemistry of various key proteins (Spike, ACE2, TMPRSS2, RdRp and Mpro) in the life cycle of SARS-CoV-2, as well as their inhibitors/drug candidates. Representative broad-spectrum antiviral drugs, especially those against the homologous virus SARS-CoV, are summarized with the expectation they will drive the development of effective, broad-spectrum inhibitors against coronaviruses. We are hopeful that this review will be a useful aid for discovery of novel, potent anti-SARS-CoV-2 drugs with excellent therapeutic results in the near future.

An analytical study of drug utilization, disease progression, and adverse events among 165 COVID-19 patients.

BACKGROUND: The coronavirus disease 2019 (COVID-19) epidemic has lasted for nearly 4 months by this study was conducted. We aimed to describe drug utilization, disease progression, and adverse drug events of COVID-19. METHODS: A retrospective, single-center case series study enrolled 165 consecutive hospitalized COVID-19 patients who were followed up until March 25, 2020, from a designated hospital in Wuhan. Patients were grouped by a baseline degree of severity: non-severe and severe. An analytical study of drug utilization, disease progression, and adverse events (AEs) of COVID-19 was conducted. RESULTS: Of the 165 COVID-19 cases, antivirals, antibacterials, glucocorticoids, and traditional Chinese medicine (TCM) were administered to 92.7%, 98.8%, 68.5%, and 55.2% of patients, respectively. The total kinds of drugs administered to the severe subgroup [26, interquartile range (IQR) 18-39] were 11 more than the non-severe subgroup (15, IQR 10-24), regardless of comorbidities. The 2 most common combinations of medications in the 165 cases were 'antiviral therapy + glucocorticoids + TCM' (81, 49.1%) and 'antiviral therapy + glucocorticoids' (23, 13.9%). Compared with non-severe cases, severe cases received more glucocorticoids (88.5% vs. 66.2%, P=0.02), but less TCM (50.0% vs. 63.3%, P=0.20), and suffered a higher percentage of death (34.6% vs. 7.2%, P=0.001). At the end of the follow-up, 130 (78.8%) patients had been discharged, and 24 (14.5%) died. There were 13 patients (7.9%) who had elevated liver enzymes, and 49 patients (29.7%) presented with worsening kidney function during the follow-up. CONCLUSIONS: Of the 165 COVID-19 patients, the fatality rate remained high (14.5%). Drug utilization for COVID-19 was diverse and generally complied with the existing guidelines. Combination regimens containing antiviral drugs might be beneficial to assist COVID-19 recovery. Additionally, liver and kidney AEs should not be ignored.

Clinical Features and Risk Factors for Secondary Infection in Critically Ill Patients With COVID-19 (preprint)

Background: To analyze the clinical features and the possible risk factors of secondary infection, and explore their impact on prognosis of COVID-19. Methods: A total of 165 severe and critical hospitalized patients diagnosed with COVID-19 were included. The clinical characteristics, laboratory tests, imaging data, secondary infections and outcomes were analyzed. Results: The mean age of total patients was (57.3±15.2) years, of which 111 were males (67.3%). 108 cases were with basic diseases (65.5%), and 1 death (0.6%). The secondary infection rate in critical patients was significantly higher than in severe patients (P <0.05). The secondary infections were mainly lung infections. The pathogens were principally Burkholderia multivorans, Stenotrophomonas maltophilia, Acinetobacter baumannii and Klebsiella pneumoniae. The recovery rate of 28 days in the infected group was significantly lower than that in the non-infected group (p < 0.001).The utilization rate and usage time of invasive ventilator, and deep vein catheterization, catheter indwelling and ECMO were the risk factors for the secondary infected patients.Conclusion: Secondary infection is an extremely common complication in critically ill patients and a trigger point for exacerbation of the disease. An effective control on the secondary infection will do good to the prognosis of COVID-19 patients.

A scientificity and feasibility evaluation of COVID-19 clinical studies registered in China.

BACKGROUND: An outbreak of novel coronavirus infection in Wuhan, China, in early 2020 has now developed into a worldwide pandemic. Researchers in China and around the world have conducted many clinical studies on the scientific response to infectious diseases. Here, we review and summarize the registration protocols for clinical research of the novel coronavirus disease (COVID-19). METHODS: We searched all the registered studies in all platforms under the International Clinical Trials Registry Platform (ICTRP) of the World Health Organization (WHO) before March 11, 2020, screened the registration scheme for novel coronavirus, extracted the basic research information, research quality, feasibility information, and described the scientificity and feasibility of interventional research. RESULTS: From January 23, 2020 to March 11, 2020, 379 clinical studies were registered, 260 were therapeutic studies among them, and 96.8% studies were conducted in China by Chinese researchers. Some studies were registered 2 weeks just after the virus was identified, and up to 22 studies registered for one day. The number of interventional studies was greater than observational studies (263 vs. 116). Among the interventional studies, nearly 50% studies were funded, 87.7% were randomized, and 79.4% of the primary outcome indicators were objective. However, the sample size of the studies ranged from 60 to 200, with the total sample size accounting for 40% of the confirmed infected population. More than 60% studies might face the problem of insufficient sample size. CONCLUSIONS: COVID-19 clinical study registration has been considerable, rapid, and high quality in study design. However, the feasibility of these studies may still be problematic, especially in such as insufficient sample size, poor coordination among multidisciplinary teams, and weak quality control in the research process.