Feasible intervention combinations for achieving a safe exit of the Zero-COVID policy in China and its determinants: an individual-based model study.

BACKGROUND: Although several pathways have been proposed as the prerequisite for a safe phase-out in China, it is not clear which of them are the most important for keeping the mortality rate low, what thresholds should be achieved for these most important interventions, and how the thresholds change with the assumed key epidemiological parameters and population characteristics. METHODS: We developed an individual-based model (IBM) to simulate the transmission of the Omicron variant in the synthetic population, accounting for the age-dependent probabilities of severe clinical outcomes, waning vaccine-induced immunity, increased mortality rates when hospitals are overburdened, and reduced transmission when self-isolated at home after testing positive. We applied machine learning algorithms on the simulation outputs to examine the importance of each intervention parameter and the feasible intervention parameter combinations for safe exits, which is defined as having mortality rates lower than that of influenza in China (14.3 per 100, 000 persons). RESULTS: We identified vaccine coverage in those above 70 years old, number of ICU beds per capita, and the availability of antiviral treatment as the most important interventions for safe exits across all studied locations, although the thresholds required for safe exits vary remarkably with the assumed vaccine effectiveness, as well as the age structure, age-specific vaccine coverage, community healthcare capacity of the studied locations. CONCLUSIONS: The analytical framework developed here can provide the basis for further policy decisions that incorporate considerations about economic costs and societal impacts. Achieving safe exits from the Zero-COVID policy is possible, but challenging for China's cities. When planning for safe exits, local realities such as the age structure and current age-specific vaccine coverage must be taken into consideration.

Comparison of infection and human immune responses of two SARS-CoV-2 strains in a humanized AdV-hACE2 NIKO mouse model (preprint)

The COVID-19 pandemic has sickened millions, cost lives and has devastated the global economy. Various animal models for experimental infection with SARS-CoV-2 have played a key role in many aspects of COVID-19 research. Here, we describe a humanized AdV-hACE2 NOD-SCID IL2Rγ-/- (NIKO) mouse model and compared infection with ancestral and mutant (SARS-CoV-2-∆382) strains of SARS-CoV-2. Immune cell infiltration, inflammation, lung damage and pro-inflammatory cytokines and chemokines was observed in humanized AdV-hACE2 NIKO mice. Humanized AdV-hACE2 NIKO mice infected with the WT and mutant SARS-CoV-2 strain had lung inflammation and production of pro-inflammatory cytokines and chemokines. This model can aid in examining the pathological basis of SARS-CoV-2 infection in a human immune environment and evaluation of therapeutic interventions.

Comparable bidirectional neutrophil immune dysregulation between Kawasaki disease and severe COVID-19.

Kawasaki disease (KD), a multisystem inflammatory syndrome that occurs in children, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-19) may share some overlapping mechanisms. The purpose of this study was to analyze the differences in single-cell RNA sequencing between KD and COVID-19. We performed single-cell RNA sequencing in KD patients (within 24 hours before IVIG treatment) and age-matched fever controls. The single-cell RNA sequencing data of COVID-19, influenza, and health controls were downloaded from the Sequence Read Archive (GSE149689/PRJNA629752). In total, 22 single-cell RNA sequencing data with 102,355 nuclei were enrolled in this study. After performing hierarchical and functional clustering analyses, two enriched gene clusters demonstrated similar patterns in severe COVID-19 and KD, heightened neutrophil activation, and decreased MHC class II expression. Furthermore, comparable dysregulation of neutrophilic granulopoiesis representing two pronounced hyperinflammatory states was demonstrated, which play a critical role in the overactivated and defective aging program of granulocytes, in patients with KD as well as those with severe COVID-19. In conclusion, both neutrophil activation and MHC class II reduction play a crucial role and thus may provide potential treatment targets for KD and severe COVID-19.

Dysregulation of Innate and Adaptive Immune Responses in Asymptomatic SARS-CoV-2 Infection with Delayed Viral Clearance.

Asymptomatic infection with SARS-CoV-2 is a major concern in the control of the COVID-19 pandemic. Many questions concerning asymptomatic infection remain to be answered, for example, what are the differences in infectivity and the immune response between asymptomatic and symptomatic infections? In this study, based on a cohort established by the Wuchang District Health Bureau of Wuhan in the early stage of the COVID-19 pandemic in Wuhan in 2019, we conducted a comprehensive analysis of the clinical, virological, immunological, and epidemiological data of asymptomatic infections. The major findings of this study included: 1) the asymptomatic cohort enrolled this study exhibited low-grade but recurrent activity of viral replication; 2) despite a lack of overt clinical symptoms, asymptomatic infections exhibited ongoing innate and adaptive immune responses; 3) however, the immune response from asymptomatic infections was not activated adequately, which may lead to delayed viral clearance. Given the fragile equilibrium between viral infection and host immunity, and the delayed viral clearance in asymptomatic individuals, close viral monitoring should be scheduled, and therapeutic intervention may be needed.

Evaluation of Immunogenicity and Safety of Vero Cell-Derived Inactivated COVID-19 Vaccine in Older Patients with Hypertension and Diabetes Mellitus.

BACKGROUND: To evaluate the immunogenicity and safety of the COVID-19 vaccine (Vero cell), inactivated, in a population aged ≥60 years with hypertension or(/and) diabetes mellitus. METHODS: A total of 1440 participants were enrolled and divided into four groups, 330 in the hypertension group, 330 in the diabetes group, 300 in the hypertensive combined with diabetes group (combined disease group), and 480 in the healthy population group. Two doses of the COVID-19 vaccine (Vero cell), inactivated, were administered at a 21-day interval and blood samples were collected before vaccination and 28 days after the second dose to evaluate the immunogenicity. The adverse events and changes in blood pressure and blood glucose levels after vaccination were recorded. RESULTS: The seroconversion rate of the COVID-19 neutralizing antibodies was 100% for all participants. The post-inoculation geometric mean titer (GMT) in the four groups of the hypertension, diabetes, combined disease, and healthy populations were 73.41, 69.93, 73.84, and 74.86, respectively. The seroconversion rates and post-vaccination GMT in the hypertension, diabetes, and combined disease groups were non-inferior to the healthy population group. The rates of vaccine-related adverse reactions were 11.93%, 14.29%, 12.50%, and 9.38%, respectively. No serious adverse events were reported during the study. No apparent abnormal fluctuations in blood pressure and blood glucose values were observed after vaccination in participants with hypertension or(/and) diabetes. CONCLUSIONS: The COVID-19 vaccine (Vero cell), inactivated, showed good immunogenicity and safety in patients aged ≥60 years suffering from hypertension or(/and) diabetes mellitus.

Progress in prevention and control of Delta coronavirus variant

With the spread of SARS-CoV-2 virus worldwide, mutant strains are constantly emerging. The Delta strain has quickly become the dominant strain because of its powerful transmission, high viral load, and strong pathogenicity. It has brought new challenges to the global epidemic prevention and control, and the effectiveness of the existing vaccines have also been significantly reduced. The single-strand RNA characteristics of the virus mean that the mutation will continue to occur, and how to deal with the prevalence of mutant strains has also become a widespread concern. More stringent protection and control strategies have been developed for Delta strains at home and abroad. At the same time, it has progressed in the research and development of specific drugs and variant vaccines for SARS-CoV-2 virus and its mutant strains, which will provide more references for the future dissemination of SARS-CoV-2 virus and its variant strains. In this paper, we summarized the prevention and control measures of Delta at home and abroad, and reviewed the research progress on the treatment of SARS-CoV-2 virus and its mutant strains, in order to provide a scientific basis for formulating more scientific and perfect prevention and control strategies.

Efficacy and Safety of Anticoagulation Treatment in COVID-19 Patient Subgroups Identified by Clinical-Based Stratification and Unsupervised Machine Learning: A Matched Cohort Study.

Objective: To explore the efficacy of anticoagulation in improving outcomes and safety of Coronavirus disease 2019 (COVID-19) patients in subgroups identified by clinical-based stratification and unsupervised machine learning. Methods: This single-center retrospective cohort study unselectively reviewed 2,272 patients with COVID-19 admitted to the Tongji Hospital between Jan 25 and Mar 23, 2020. The association between AC treatment and outcomes was investigated in the propensity score (PS) matched cohort and the full cohort by inverse probability of treatment weighting (IPTW) analysis. Subgroup analysis, identified by clinical-based stratification or unsupervised machine learning, was used to identify sub-phenotypes with meaningful clinical features and the target patients benefiting most from AC. Results: AC treatment was associated with lower in-hospital death risk either in the PS matched cohort or by IPTW analysis in the full cohort. A higher incidence of clinically relevant non-major bleeding (CRNMB) was observed in the AC group, but not major bleeding. Clinical subgroup analysis showed that, at admission, severe cases of COVID-19 clinical classification, mild acute respiratory distress syndrome (ARDS) cases, and patients with a D-dimer level ≥0.5 µg/mL, may benefit from AC. During the hospital stay, critical cases and severe ARDS cases may benefit from AC. Unsupervised machine learning analysis established a four-class clustering model. Clusters 1 and 2 were non-critical cases and might not benefit from AC, while clusters 3 and 4 were critical patients. Patients in cluster 3 might benefit from AC with no increase in bleeding events. While patients in cluster 4, who were characterized by multiple organ dysfunction (neurologic, circulation, coagulation, kidney and liver dysfunction) and elevated inflammation biomarkers, did not benefit from AC. Conclusions: AC treatment was associated with lower in-hospital death risk, especially in critically ill COVID-19 patients. Unsupervised learning analysis revealed that the most critically ill patients with multiple organ dysfunction and excessive inflammation might not benefit from AC. More attention should be paid to bleeding events (especially CRNMB) when using AC.

Efficacy and Safety of Anticoagulation Treatment in COVID-19 Patient Subgroups Identified by Clinical-Based Stratification and Unsupervised Machine Learning: A Matched Cohort Study

Objective: To explore the efficacy of anticoagulation in improving outcomes and safety of Coronavirus disease 2019 (COVID-19) patients in subgroups identified by clinical-based stratification and unsupervised machine learning. Methods: This single-center retrospective cohort study unselectively reviewed 2,272 patients with COVID-19 admitted to the Tongji Hospital between Jan 25 and Mar 23, 2020. The association between AC treatment and outcomes was investigated in the propensity score (PS) matched cohort and the full cohort by inverse probability of treatment weighting (IPTW) analysis. Subgroup analysis, identified by clinical-based stratification or unsupervised machine learning, was used to identify sub-phenotypes with meaningful clinical features and the target patients benefiting most from AC. Results: AC treatment was associated with lower in-hospital death risk either in the PS matched cohort or by IPTW analysis in the full cohort. A higher incidence of clinically relevant non-major bleeding (CRNMB) was observed in the AC group, but not major bleeding. Clinical subgroup analysis showed that, at admission, severe cases of COVID-19 clinical classification, mild acute respiratory distress syndrome (ARDS) cases, and patients with a D-dimer level ≥0.5 μg/mL, may benefit from AC. During the hospital stay, critical cases and severe ARDS cases may benefit from AC. Unsupervised machine learning analysis established a four-class clustering model. Clusters 1 and 2 were non-critical cases and might not benefit from AC, while clusters 3 and 4 were critical patients. Patients in cluster 3 might benefit from AC with no increase in bleeding events. While patients in cluster 4, who were characterized by multiple organ dysfunction (neurologic, circulation, coagulation, kidney and liver dysfunction) and elevated inflammation biomarkers, did not benefit from AC. Conclusions: AC treatment was associated with lower in-hospital death risk, especially in critically ill COVID-19 patients. Unsupervised learning analysis revealed that the most critically ill patients with multiple organ dysfunction and excessive inflammation might not benefit from AC. More attention should be paid to bleeding events (especially CRNMB) when using AC.

Epidemiological, Virological and Serological Features of Coronavirus Disease 2019 (COVID-19) Cases in People Living With Human Immunodeficiency Virus in Wuhan: A Population-based Cohort Study.

BACKGROUND: We aimed to describe the epidemiological, virological, and serological features of coronavirus disease 2019 (COVID-19) cases in people living with human immunodeficiency virus (HIV; PLWH). METHODS: This population-based cohort study identified all COVID-19 cases among all PLWH in Wuhan, China, by 16 April 2020. The epidemiological, virological, and serological features were analyzed based on the demographic data, temporal profile of nucleic acid test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the disease, and SARS-CoV-2-specific immunoglobin (Ig) M and G after recovery. RESULTS: From 1 January to 16 April 2020, 35 of 6001 PLWH experienced COVID-19, with a cumulative incidence of COVID-19 of 0.58% (95% confidence interval [CI], .42-.81%). Among the COVID-19 cases, 15 (42.86) had severe illness, with 2 deaths. The incidence, case-severity, and case-fatality rates of COVID-19 in PLWH were comparable to those in the entire population in Wuhan. There were 197 PLWH who had discontinued combination antiretroviral therapy (cART), 4 of whom experienced COVID-19. Risk factors for COVID-19 were age ≥50 years old and cART discontinuation. The median duration of SARS-CoV-2 viral shedding among confirmed COVID-19 cases in PLWH was 30 days (interquartile range, 20-46). Cases with high HIV viral loads (≥20 copies/mL) had lower IgM and IgG levels than those with low HIV viral loads (<20 copies/ml; median signal value divided by the cutoff value [S/CO] for IgM, 0.03 vs 0.11, respectively [P < .001]; median S/CO for IgG, 10.16 vs 17.04, respectively [P = .069]). CONCLUSIONS: Efforts are needed to maintain the persistent supply of antiretroviral treatment to elderly PLWH aged 50 years or above during the COVID-19 epidemic. The coinfection of HIV and SARS-CoV-2 might change the progression and prognosis of COVID-19 patients in PLWH.

Association of Public Health Interventions With the Epidemiology of the COVID-19 Outbreak in Wuhan, China.

IMPORTANCE: Coronavirus disease 2019 (COVID-19) has become a pandemic, and it is unknown whether a combination of public health interventions can improve control of the outbreak. OBJECTIVE: To evaluate the association of public health interventions with the epidemiological features of the COVID-19 outbreak in Wuhan by 5 periods according to key events and interventions. DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, individual-level data on 32 583 laboratory-confirmed COVID-19 cases reported between December 8, 2019, and March 8, 2020, were extracted from the municipal Notifiable Disease Report System, including patients' age, sex, residential location, occupation, and severity classification. EXPOSURES: Nonpharmaceutical public health interventions including cordons sanitaire, traffic restriction, social distancing, home confinement, centralized quarantine, and universal symptom survey. MAIN OUTCOMES AND MEASURES: Rates of laboratory-confirmed COVID-19 infections (defined as the number of cases per day per million people), across age, sex, and geographic locations were calculated across 5 periods: December 8 to January 9 (no intervention), January 10 to 22 (massive human movement due to the Chinese New Year holiday), January 23 to February 1 (cordons sanitaire, traffic restriction and home quarantine), February 2 to 16 (centralized quarantine and treatment), and February 17 to March 8 (universal symptom survey). The effective reproduction number of SARS-CoV-2 (an indicator of secondary transmission) was also calculated over the periods. RESULTS: Among 32 583 laboratory-confirmed COVID-19 cases, the median patient age was 56.7 years (range, 0-103; interquartile range, 43.4-66.8) and 16 817 (51.6%) were women. The daily confirmed case rate peaked in the third period and declined afterward across geographic regions and sex and age groups, except for children and adolescents, whose rate of confirmed cases continued to increase. The daily confirmed case rate over the whole period in local health care workers (130.5 per million people [95% CI, 123.9-137.2]) was higher than that in the general population (41.5 per million people [95% CI, 41.0-41.9]). The proportion of severe and critical cases decreased from 53.1% to 10.3% over the 5 periods. The severity risk increased with age: compared with those aged 20 to 39 years (proportion of severe and critical cases, 12.1%), elderly people (≥80 years) had a higher risk of having severe or critical disease (proportion, 41.3%; risk ratio, 3.61 [95% CI, 3.31-3.95]) while younger people (<20 years) had a lower risk (proportion, 4.1%; risk ratio, 0.47 [95% CI, 0.31-0.70]). The effective reproduction number fluctuated above 3.0 before January 26, decreased to below 1.0 after February 6, and decreased further to less than 0.3 after March 1. CONCLUSIONS AND RELEVANCE: A series of multifaceted public health interventions was temporally associated with improved control of the COVID-19 outbreak in Wuhan, China. These findings may inform public health policy in other countries and regions.

A Systematic Review of Youth and Teen Mental Health First Aid: Improving Adolescent Mental Health.

PURPOSE: Adolescent mental illness often goes undetected. Youth and teen Mental Health First Aid (MHFA) are variations of adult MHFA that aims to help adults and adolescents recognize the signs and provide help where appropriate. We conducted a systematic review to summarize the current evidence for youth and teen MHFA, providing direction for future training and research. METHODS: A systematic search was performed on September 12, 2020 on PubMed, Embase, PsycINFO, ERIC, and Cochrane using keywords related to teen or youth MHFA, adolescents, and mental health. A narrative synthesis was then carried out. RESULTS: Of the 695 articles identified, 14 studies were included. All studies were from the U.S. and Australia. All studies demonstrated significant improvements in knowledge, recognition, stigmatizing attitudes, confidence, helping intentions, and helping behavior in both adult and youth participants. Improvement in knowledge and confidence was most reported, and improvement in helping behavior was the least reported. There is encouraging evidence of long-term benefits after the training. CONCLUSIONS: More studies need to be conducted in non-Western countries, high-risk populations, and different professional settings. Future interventions could also consider different modes of learning, longer-term follow-up, and the measurement of outcomes that evaluate the quality of helping behavior.

Chemosensory Dysfunction Induced by Environmental Pollutants and Its Potential As a Novel Neurotoxicological Indicator: A Review.

Air pollution composed of the complex interactions among particular matter, chemicals, and pathogens is an emerging and global environmental issue that closely correlates with a variety of diseases and adverse health effects, especially increasing incidences of neurodegenerative diseases. However, as one of the prevalent health outcomes of air pollution, chemosensory dysfunction has not attracted enough concern until recently. During the COVID-19 pandemic, multiple scientific studies emphasized the plausibly essential roles of the chemosensory system in the airborne transmission airway of viruses into the human body, which can also be utilized by pollutants. In this Review, in addition to summarizing current progress regarding the contributions of traditional air pollutants to chemosensory dysfunction, we highlight the roles of emerging contaminants. We not only sum up clarified mechanisms, such as inflammation and apoptosis but also discuss some not yet completely identified mechanisms, e.g., disruption of olfactory signal transduction. Although the existing evidence is not overwhelming, the chemosensory system is expected to be a useful indicator in neurotoxicology and neural diseases based on accumulating studies that continually excavate the deep link between chemosensory dysfunction and neurodegenerative diseases. Finally, we argue the importance of studies concerning chemosensory dysfunction in understanding the health effects of air pollution and provide comments for some future directions of relevant research.

Role of Prealbumin in Predicting the Prognosis of Severely and Critically Ill COVID-19 Patients.

Most critically ill patients experience malnutrition, resulting in a poor prognosis. This study aimed to evaluate the association of prealbumin (PAB) with the prognosis for severely and critically ill coronavirus disease 2019 (COVID-19) patients and explore factors related to this association. Patients with laboratory-confirmed COVID-19 from West Campus of Union Hospital in Wuhan from January 29, 2020 to March 31, 2020 were enrolled in this study. Patients were classified into the PAB1 (150-400 mg/L; N = 183) and PAB2 (< 150 mg/L; N = 225) groups. Data collection was performed using the hospital's electronic medical records system. The predictive value of PAB was evaluated by measuring the area under the receiver-operating characteristic (AUROC) curve. Patients were defined as severely or critically ill based on the Guidance for COVID-19 (7th edition) by the National Health Commission of China. During this analysis, 316 patients had severe cases and 65 had critical cases. A reduced PAB level was associated with a higher risk of mortality and a longer hospital stay. The AUROC curve for the prognosis based on the PAB level was 0.93, with sensitivity of 97.2% and specificity of 77.6%. For severe cases, a lower level of PAB was associated with a higher risk of malnutrition, higher NK cell counts, and lower B lymphocyte counts; these factors were not significant in critical cases. C-reactive protein and nutritional status mediated the association between PAB and prognosis. This retrospective analysis suggests that the PAB level on admission is an indicator of the prognosis for COVID-19.

Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials.

Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/ ). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I² = 0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I² = 0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.

Clinical characteristics on admission predict in-hospital fatal outcome in patients aged ≥75 years with novel coronavirus disease (COVID-19): a retrospective cohort study.

BACKGROUND: Novel coronavirus disease 2019 (COVID-19) has become a worldwide pandemic and precise fatality data by age group is needed urgently. This study to delineate the clinical characteristics and outcome of COVID-19 patients aged ≥75 years and identify the risk factors of in-hospital death. METHODS: A total of 141 consecutive patients aged ≥75 years who were admitted to the hospital between 12th and 19th February 2020. In-hospital death, clinical characteristics and laboratory findings on admission were obtained from medical records. The final follow-up observation was on the 31st March 2020. RESULTS: The median age was 81 years (84 female, 59.6%). Thirty-eight (27%) patients were classified as severe or critical cases. 18 (12.8%) patients had died in hospital and the remaining 123 were discharged. Patients who died were more likely to present with fever (38.9% vs. 7.3%); low percutaneous oxygen saturation (SpO2) (55.6% vs. 7.3%); reduced lymphocytes (72.2% vs. 35.8%) and platelets (27.8% vs. 4.1%); and increased D-dimer (94.4% vs. 42.3%), creatinine (50.0% vs. 22.0%), lactic dehydrogenase (LDH) (77.8% vs. 30.1%), high sensitivity troponin I (hs-TnI) (72.2% vs. 14.6%), and N-terminal pro-brain natriuretic peptide (NT-proBNP) (72.2% vs. 6.5%; all P < 0.05) than patients who recovered. Male sex (odds ratio [OR] = 13.1, 95% confidence interval [CI] 1.1 to 160.1, P = 0.044), body temperature > 37.3 °C (OR = 80.5, 95% CI 4.6 to 1407.6, P = 0.003), SpO2 ≤ 90% (OR = 70.1, 95% CI 4.6 to 1060.4, P = 0.002), and NT-proBNP> 1800 ng/L (OR = 273.5, 95% CI 14.7 to 5104.8, P < 0.0001) were independent risk factors of in-hospital death. CONCLUSIONS: In-hospital fatality among elderly COVID-19 patients can be estimated by sex and on-admission measurements of body temperature, SpO2, and NT-proBNP.

A multicenter, randomized, open-label, controlled trial to evaluate the efficacy and tolerability of hydroxychloroquine and a retrospective study in adult patients with mild to moderate coronavirus disease 2019 (COVID-19).

OBJECTIVE: In this study, we evaluated the efficacy of hydroxychloroquine (HCQ) against coronavirus disease 2019 (COVID-19) via a randomized controlled trial (RCT) and a retrospective study. METHODS: Subjects admitted to 11 designated public hospitals in Taiwan between April 1 and May 31, 2020, with COVID-19 diagnosis confirmed by pharyngeal real-time RT-PCR for SARS-CoV-2, were randomized at a 2:1 ratio and stratified by mild or moderate illness. HCQ (400 mg twice for 1 d or HCQ 200 mg twice daily for 6 days) was administered. Both the study and control group received standard of care (SOC). Pharyngeal swabs and sputum were collected every other day. The proportion and time to negative viral PCR were assessed on day 14. In the retrospective study, medical records were reviewed for patients admitted before March 31, 2020. RESULTS: There were 33 and 37 cases in the RCT and retrospective study, respectively. In the RCT, the median times to negative rRT-PCR from randomization to hospital day 14 were 5 days (95% CI; 1, 9 days) and 10 days (95% CI; 2, 12 days) for the HCQ and SOC groups, respectively (p = 0.40). On day 14, 81.0% (17/21) and 75.0% (9/12) of the subjects in the HCQ and SOC groups, respectively, had undetected virus (p = 0.36). In the retrospective study, 12 (42.9%) in the HCQ group and 5 (55.6%) in the control group had negative rRT-PCR results on hospital day 14 (p = 0.70). CONCLUSIONS: Neither study demonstrated that HCQ shortened viral shedding in mild to moderate COVID-19 subjects.

Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19: an international collaborative meta-analysis of randomized trials (preprint)

Background: Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aimed to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. Methods: Rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/). We systematically identified published and unpublished RCTs by September 14, 2020 (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, PubMed, Cochrane COVID-19 registry). All-cause mortality was extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine/chloroquine. Prespecified subgroup analyses included patient setting, diagnostic confirmation, control type, and publication status. Results: Sixty-two trials were potentially eligible. We included 16 unpublished trials (1596 patients) and 10 publications/preprints (6317 patients). The combined summary OR on all-cause mortality for hydroxychloroquine was 1.08 (95%CI: 0.99, 1.18; I-square=0%; 24 trials; 7659 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I-square=0%; 4 trials; 307 patients). We identified no subgroup effects. Conclusions: We found no benefit of hydroxychloroquine or chloroquine on the survival of COVID-19 patients. For hydroxychloroquine, the confidence interval is compatible with increased mortality (OR 1.18) or negligibly reduced mortality (OR 0.99). Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.