Vaccination is reasonably effective in limiting the spread of COVID-19 infections, hospitalizations and deaths with COVID-19

This paper uses large cross-country data for 110 countries to examine the effectiveness of COVID vaccination coverage. Our results confirm that vaccines are reasonably effective in both limiting the spread of infections and containing more severe disease progression in symptomatic patients. First, the results show that full vaccination rate is consistently negatively correlated with the number of new COVID cases, whereby a 10 percent increase in vaccination rate is associated with a 1.3 to 1.7 percent decrease in new COVID cases. Second, the magnitude of vaccination is shown to contribute significantly to moderating severe disease progression. On average, a 10 percent increase in the rate of vaccination leads to a reduction of about 5 percent in the number of new hospitalizations, 12 percent decrease in the number of new intensive care patients and 2 percent reduction in the number of new deaths. Finally, by comparing the data for the same period between 2020 and 2021, we also check how good is vaccination as a substitute for lockdowns or other stringent government protection measures. Results suggest that vaccination does not appear to be an effective substitute for more stringent government safety measures to contain the spread of COVID infections until a high vaccination coverage threshold (more than 70 percent) has been achieved. On the other hand, vaccination is shown to be quite effective in limiting the more severe course of the disease in symptomatic patients already at moderate vaccination coverage (between 40 and 70 percent). This suggests that vaccination can also help to reduce pressure on the health system and thus benefit the overall public health of society.

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Vaccination is reasonably effective in limiting the spread of COVID-19 infections, hospitalizations and deaths with COVID-19

10.21203/rs.3.rs-1129457/v1 ◽

2021 ◽

Author(s):

Joze Damijan ◽

Sandra Damijan ◽

Crt Kostevc

Keyword(s):

Disease Progression ◽

Vaccination Coverage ◽

Severe Disease ◽

Vaccination Rate ◽

Safety Measures ◽

Protection Measures ◽

Intensive Care Patients ◽

Percent Increase ◽

Cross Country ◽

Percent Decrease

Abstract This paper uses large cross-country data for 110 countries to examine the effectiveness of COVID vaccination coverage. Our results confirm that vaccines are reasonably effective in both limiting the spread of infections and containing more severe disease progression in symptomatic patients. First, the results show that full vaccination rate is consistently negatively correlated with the number of new COVID cases, whereby a 10 percent increase in vaccination rate is associated with a 1.3 to 1.7 percent decrease in new COVID cases. Second, the magnitude of vaccination is shown to contribute significantly to moderating severe disease progression. On average, a 10 percent increase in the rate of vaccination leads to a reduction of about 5 percent in the number of new hospitalizations, 12 percent decrease in the number of new intensive care patients and 2 percent reduction in the number of new deaths. Finally, by comparing the data for the same period between 2020 and 2021, we also check how good is vaccination as a substitute for lockdowns or other stringent government protection measures. Results suggest that vaccination does not appear to be an effective substitute for more stringent government safety measures to contain the spread of COVID infections until a high vaccination coverage threshold (more than 70 percent) has been achieved. On the other hand, vaccination is shown to be quite effective in limiting the more severe course of the disease in symptomatic patients already at moderate vaccination coverage (between 40 and 70 percent). This suggests that vaccination can also help to reduce pressure on the health system and thus benefit the overall public health of society.

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The hemocyte counts as a potential biomarker for predicting disease progression in COVID-19: a retrospective study

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2020-0377 ◽

2020 ◽

Vol 58 (7) ◽

pp. 1106-1115 ◽

Cited By ~ 14

Author(s):

Yufen Zheng ◽

Ying Zhang ◽

Hongbo Chi ◽

Shiyong Chen ◽

Minfei Peng ◽

...

Keyword(s):

Risk Factors ◽

Platelet Count ◽

Disease Progression ◽

Neutrophil Count ◽

Calibration Curve ◽

Lymphocyte Count ◽

Severe Disease ◽

Clinical Impact ◽

Predictive Tool ◽

Potential Biomarker

AbstractObjectivesIn December 2019, there was an outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, and since then, the disease has been increasingly spread throughout the world. Unfortunately, the information about early prediction factors for disease progression is relatively limited. Therefore, there is an urgent need to investigate the risk factors of developing severe disease. The objective of the study was to reveal the risk factors of developing severe disease by comparing the differences in the hemocyte count and dynamic profiles in patients with severe and non-severe COVID-19.MethodsIn this retrospectively analyzed cohort, 141 confirmed COVID-19 patients were enrolled in Taizhou Public Health Medical Center, Taizhou Hospital, Zhejiang Province, China, from January 17, 2020 to February 26, 2020. Clinical characteristics and hemocyte counts of severe and non-severe COVID patients were collected. The differences in the hemocyte counts and dynamic profiles in patients with severe and non-severe COVID-19 were compared. Multivariate Cox regression analysis was performed to identify potential biomarkers for predicting disease progression. A concordance index (C-index), calibration curve, decision curve and the clinical impact curve were calculated to assess the predictive accuracy.ResultsThe data showed that the white blood cell count, neutrophil count and platelet count were normal on the day of hospital admission in most COVID-19 patients (87.9%, 85.1% and 88.7%, respectively). A total of 82.8% of severe patients had lymphopenia after the onset of symptoms, and as the disease progressed, there was marked lymphopenia. Multivariate Cox analysis showed that the neutrophil count (hazard ratio [HR] = 4.441, 95% CI = 1.954–10.090, p = 0.000), lymphocyte count (HR = 0.255, 95% CI = 0.097–0.669, p = 0.006) and platelet count (HR = 0.244, 95% CI = 0.111–0.537, p = 0.000) were independent risk factors for disease progression. The C-index (0.821 [95% CI, 0.746–0.896]), calibration curve, decision curve and the clinical impact curve showed that the nomogram can be used to predict the disease progression in COVID-19 patients accurately. In addition, the data involving the neutrophil count, lymphocyte count and platelet count (NLP score) have something to do with improving risk stratification and management of COVID-19 patients.ConclusionsWe designed a clinically predictive tool which is easy to use for assessing the progression risk of COVID-19, and the NLP score could be used to facilitate patient stratification management.

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THU0070 DEFINING SYNOVIAL SIGNATURES IN THE RAT CIA MODEL: WHAT CAN WE LEARN ABOUT RA PROGRESSION?

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3695 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 247.2-248

Author(s):

D. Ruelas ◽

R. LI ◽

C. Franci ◽

V. Lira ◽

D. Lopez ◽

...

Keyword(s):

Disease Progression ◽

Synovial Tissue ◽

Current Knowledge ◽

Severe Disease ◽

Unmet Need ◽

Poor Response ◽

Multiple Time ◽

Combination Therapies ◽

Course Of Disease ◽

Time Point

Background:Patients showing inadequate or no response to current therapies represent a key unmet need in rheumatoid arthritis (RA). To address this, novel or combination therapies are of high clinical interest. Identification of novel therapeutic targets requires a greater understanding of the pathogenic molecular drivers in the RA synovium. However, our current knowledge of human molecular patterns that emerge as a result of disease progression is complicated by patient-to-patient heterogeneity and access to synovial tissue.Objectives:Here we use the current knowledge of human synovial heterogeneity to conduct a longitudinal study of global molecular responses in the rat collagen-induced arthritis (CIA) model to better understand synovial biology, improve the preclinical modeling of human disease, and discover novel targets for RA.Methods:A rat CIA model was performed as previously described.1RNA-Seq was performed on 56 knee synovial tissues collected at multiple time points throughout the course of disease. Differential gene expression was determined at each individual time point and longitudinally with disease progression. Published human synovial datasets were used to categorize these genes into myeloid, lymphoid, fibroid, and low inflammatory signatures.2Differentially expressed genes (DEGs) at each time point were compared to human synovial datasets of RA patients before and after treatment. In addition, we compared disease-driven genes in CIA to genes in RA patients that are unchanged following therapy to identify possible combination therapies.Results:Disease pathology in the rat CIA natural history study progressed as expected: significant decreases were seen in body weight, as well as increases in ankle diameter, paw weight, and histopathology scores of joints in collagen-injected vs noninjected rats. There were 1900 DEGs identified between diseased and naïve rats over the course of disease, representing disease-induced gene signatures (Fig. 1). Comparing these DEGs to reported human RA synovial signatures, both the lymphoid and myeloid signatures were found to be highly upregulated. Interestingly, there were no significant DEGs representing the human fibroid and low inflammatory synovial signatures identified in the CIA rat model. This suggests that the rat CIA model most closely models RA patients with an immune synovial phenotype. In addition, we examined the overlap between disease-driven genes in CIA and genes in RA patients that are unchanged following therapy to identify signaling pathways that may be of utility in combination therapy. Of genes that were upregulated in CIA, 94% of genes that mapped to extracellular matrix-receptor pathways remained unchanged in the synovial tissue of RA patients following tocilizumab treatment.Conclusion:Previous studies have shown that nearly 30% of treatment-naïve early RA patients exhibit a strong fibroid phenotype that correlates with less severe disease and a relatively poor response to disease-modifying anti-rheumatic drugs.3These data indicate that the synovial biology associated with such patients (fibroid or pauci-immune) is not well captured in CIA, the most common preclinical RA model. To assess potential new therapies targeting these patients, it will be necessary to develop alternative animal models with more intact fibroid signatures. In addition to these findings, we also characterized the global molecular changes that occur with disease progression in the CIA rat and made a comparison to RA patients on treatment, providing an overall understanding of disease-relevant pathways in the synovium that may point to possible combination therapies.References:[1]Trentham DE, et al.J Exp Med. 1977;146(3):857-868.[2]Dennis G Jr, et al.Arthritis Res Ther. 2014;16(2):R90.[3]Humby F, et al.Ann Rheum Dis. 2019;78(6):761-772.Disclosure of Interests:Debbie Ruelas Employee of: Gilead, Ruidong Li Employee of: Gilead, Christian Franci Employee of: Gilead, Victor Lira Employee of: Gilead, David Lopez Employee of: Gilead, Li Li Employee of: Gilead, Gundula Min-Oo Employee of: Gilead, Julie A. Di Paolo Employee of: Gilead

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Donor Smoking Negatively Affects Donor and Recipient Renal Function following Living Donor Nephrectomy

Advances in Urology ◽

10.1155/2011/929263 ◽

2011 ◽

Vol 2011 ◽

pp. 1-5 ◽

Cited By ~ 16

Author(s):

Jonathan Heldt ◽

Robert Torrey ◽

Daniel Han ◽

Pedro Baron ◽

Christopher Tenggardjaja ◽

...

Keyword(s):

Renal Function ◽

Patient Survival ◽

Linear Regression Analysis ◽

Multiple Linear Regression Analysis ◽

Tobacco Exposure ◽

Kidney Donor ◽

Chi Square ◽

Living Donor Nephrectomy ◽

Percent Increase ◽

Percent Decrease

Background.While tobacco use by a renal transplant recipient has been shown to negatively affect graft and patient survival, the effect of smoking on the part of the kidney donor remains unknown.Methods.29 smoking donors (SD) and their recipients (SD-R) as well as 71 non-smoking donors (ND) and their recipients (ND-R) were retrospectively reviewed. Preoperative demographics and perioperative variables including serum creatinine (Cr) and glomerular filtration rate (GFR) were calculated and stratified by amount of tobacco exposure in pack-years. Clinical outcomes were analyzed with a Student'st-test, chi-square, and multiple linear regression analysis ().Results.At most recent followup, SD-R's had a significantly smaller percent decrease in postoperative Cr than ND-R's (−57% versus −81%; ) and lower calculated GFR's (37.0 versus 53.0 mL/min per 1.73 m2; . SD's had a larger percent increase in Cr than ND's at most recent followup (57% versus 40%; ), with active smokers having a larger increase than those who quit, although this difference was not statistically significant (68% versus 52%; ).Conclusions.Use of tobacco by kidney donors is associated with decreased posttransplant renal function, although smoking cessation can improve outcomes. Kidneys from donors who smoke should be used with caution.

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Modeling the spread of porcine reproductive and respiratory syndrome virus (PRRSV) in a swine population: transmission dynamics, immunity information, and optimal control strategies

Advances in Difference Equations ◽

10.1186/s13662-019-2351-6 ◽

2019 ◽

Vol 2019 (1) ◽

Cited By ~ 4

Author(s):

Phithakdet Phoo-ngurn ◽

Chanakarn Kiataramkul ◽

Farida Chamchod

Keyword(s):

Mathematical Model ◽

Vaccination Coverage ◽

Control Strategies ◽

Vaccination Rate ◽

Transmission Dynamics ◽

Respiratory Syndrome Virus ◽

Respiratory Problems ◽

Prrs Virus ◽

Swine Population ◽

Swine Disease

Abstract Porcine reproductive and respiratory syndrome (PRRS) is an important swine disease that affects many swine industries worldwide. The disease can cause reproductive failure and respiratory problems in a swine population. As vaccination is an important tool to control the spread of PRRS virus (PRRSV), we employ a mathematical model to investigate the transmission dynamics of PRRSV and the effects of immunity information, as well as vaccination control strategies. We also explore optimal vaccination coverage and vaccination rate to minimize the number of infected swines and vaccination efforts. Our results suggest that: (i) higher vaccination coverage and vaccination rate together with prior knowledge about immunity may help reduce the prevalence of PRRSV, and (ii) longer maximum vaccination efforts are required when swines stay longer in a population and it takes them longer time to recover from PRRS infections.

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Mandatory vaccination against COVID-19 would be supported by less than fifty per cent: A Twitter poll analysis on public health opinion. (Preprint)

10.2196/preprints.35754 ◽

2021 ◽

Author(s):

Valentin Ritschl ◽

Fabian Eibensteiner ◽

Erika Mosor ◽

Maisa Omara ◽

Lisa Sperl ◽

...

Keyword(s):

Public Health ◽

Social Media ◽

Vaccination Coverage ◽

Digital Health ◽

Developed Countries ◽

Vaccination Rate ◽

World Health ◽

Vaccination Coverage Rate ◽

Twitter Users ◽

Mandatory Vaccination

BACKGROUND On January 30, 2020, the World Health Organization (WHO) Emergency Committee declared the rapid worldwide spread of Coronavirus Disease 2019 (COVID-19) a global health emergency. By December 2020, the safety and efficacy of the first COVID-19 vaccines had been demonstrated. However, global vaccination coverage rates have remained below expectations. Mandatory vaccination is now being controversially discussed and has been enacted in some developed countries, while the vaccination rate is very low in many developing countries. We used the Twitter survey system as a viable method to quickly and comprehensively gather international public health insights on mandatory vaccination against COVID-19. OBJECTIVE The purpose of this study was to understand better the public's perception of mandatory COVID-19 vaccination in real-time utilizing Twitter polls. METHODS Two Twitter polls were developed to seek the public's opinion on the possibility of mandatory vaccination. The polls were pinned to the Digital Health and Patient Safety Platform's Twitter timeline for one week in mid-November 2021, three days after the official public announcement of mandatory COVID-19 vaccination in Austria. Twitter users were asked to participate and retweet the polls to reach the largest possible audience. RESULTS Our Twitter polls revealed two extremes on the topic of mandatory vaccination against COVID-19. Almost half of the respondents (49% [1,246/2,545]) favour mandatory vaccination, at least in certain areas. This attitude is in contrast to the 45.7% (1,162/2,545) who categorically reject mandatory vaccination. 26.3% (621/2,365) of participating Twitter users said they would never get vaccinated, which is reflected by the current vaccination coverage rate. Concatenating interpretation of these two polls needs to be done cautiously as participating populations might greatly differ. CONCLUSIONS Mandatory vaccination against COVID-19 (in at least certain areas) is favoured by less than 50%, whereas it is vehemently opposed by almost half of the surveyed Twitter users. Since (social) media strongly influences public perceptions and views through and social media discussions and surveys specifically susceptible to the "echo chamber effect", the results can be seen as a momentary snapshot. Therefore, the results of this study need to be complemented by long-term surveys to maintain their validity.

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Disease Progression in Frontotemporal Dementia and Alzheimer Disease: The Contribution of Staging Scales

Journal of Geriatric Psychiatry and Neurology ◽

10.1177/0891988720944239 ◽

2020 ◽

pp. 089198872094423

Author(s):

Thaís Bento Lima-Silva ◽

Eneida Mioshi ◽

Valéria Santoro Bahia ◽

Mário Amore Cecchini ◽

Luciana Cassimiro ◽

...

Keyword(s):

Alzheimer Disease ◽

Disease Progression ◽

Frontotemporal Dementia ◽

Rating Scale ◽

Severe Disease ◽

Primary Progressive Aphasia ◽

Behavioral Changes ◽

Clinical Dementia Rating ◽

Dementia Rating Scale ◽

Disease Stages

Introduction: There is a shortage of validated instruments to estimate disease progression in frontotemporal dementia (FTD). Objectives: To evaluate the ability of the FTD Rating Scale (FTD-FRS) to detect functional and behavioral changes in patients diagnosed with the behavioral variant of FTD (bvFTD), primary progressive aphasia (PPA), and Alzheimer disease (AD) after 12 months of the initial evaluation, compared to the Clinical Dementia Rating scale−frontotemporal lobar degeneration (CDR-FTLD) and the original Clinical Dementia Rating scale (CDR). Methods: The sample consisted of 70 individuals, aged 40+ years, with at least 2 years of schooling, 31 with the diagnosis of bvFTD, 12 with PPA (8 with semantic variant and 4 with non-fluent variant), and 27 with AD. The FTD-FRS, the CDR, and the 2 additional CDR-FTLD items were completed by a clinician, based on the information provided by the caregiver with frequent contact with the patient. The Addenbrooke Cognitive Examination-Revised was completed by patients. After 12 months, the same protocol was applied. Results: The FTD-FRS, CDR-FTLD, and CDR detected significant decline after 12 months in the 3 clinical groups (exception: FTD-FRS for PPA). The CDR was less sensitive to severe disease stages. Conclusions: The FTD-FRS and the CDR-FTLD are especially useful tools for dementia staging in AD and in the FTD spectrum.

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Longitudinal Metabolomics Reveals Ornithine Cycle Dysregulation Correlates With Inflammation and Coagulation in COVID-19 Severe Patients

Frontiers in Microbiology ◽

10.3389/fmicb.2021.723818 ◽

2021 ◽

Vol 12 ◽

Author(s):

Tao Li ◽

Nianzhi Ning ◽

Bo Li ◽

Deyan Luo ◽

Enqiang Qin ◽

...

Keyword(s):

Amino Acids ◽

Disease Progression ◽

Metabolic Disorders ◽

Acid Metabolism ◽

Severe Disease ◽

Essential Amino Acids ◽

Dynamic Changes ◽

Metabolic Recovery ◽

Global Pandemic ◽

Highly Correlated

COVID-19 is a severe disease in humans, as highlighted by the current global pandemic. Several studies about the metabolome of COVID-19 patients have revealed metabolic disorders and some potential diagnostic markers during disease progression. However, the longitudinal changes of metabolomics in COVID-19 patients, especially their association with disease progression, are still unclear. Here, we systematically analyzed the dynamic changes of the serum metabolome of COVID-19 patients, demonstrating that most of the metabolites did not recover by 1–3 days before discharge. A prominent signature in COVID-19 patients comprised metabolites of amino acids, peptides, and analogs, involving nine essential amino acids, 10 dipeptides, and four N-acetylated amino acids. The levels of 12 metabolites in amino acid metabolism, especially three metabolites of the ornithine cycle, were significantly higher in severe patients than in mild ones, mainly on days 1–3 or 4–6 since onset. Integrating blood metabolomic, biochemical, and cytokine data, we uncovered a highly correlated network, including 6 cytokines, 13 biochemical parameters, and 49 metabolites. Significantly, five ornithine cycle-related metabolites (ornithine, N-acetylornithine, 3-amino-2-piperidone, aspartic acid, and asparagine) highly correlated with “cytokine storms” and coagulation index. We discovered that the ornithine cycle dysregulation significantly correlated with inflammation and coagulation in severe patients, which may be a potential mechanism of COVID-19 pathogenicity. Our study provided a valuable resource for detailed exploration of metabolic factors in COVID-19 patients, guiding metabolic recovery, understanding the pathogenic mechanisms, and creating drugs against SARS-CoV-2 infection.

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Epidemiological impact of SARS-CoV-2 vaccination: mathematical modeling analyses

10.1101/2020.04.19.20070805 ◽

2020 ◽

Cited By ~ 5

Author(s):

Monia Makhoul ◽

Houssein H. Ayoub ◽

Hiam Chemaitelly ◽

Shaheen Seedat ◽

Ghina R Mumtaz ◽

...

Keyword(s):

Decision Making ◽

Disease Progression ◽

Vaccine Development ◽

Severe Disease ◽

Herd Immunity ◽

Social Contact ◽

Population Level ◽

Contact Rate ◽

Disease Case ◽

Vaccine Impact

AbstractBackgroundSeveral SARS-CoV-2 vaccine candidates are currently in the pipeline. This study aims to inform SARS-CoV-2 vaccine development, licensure, decision-making, and implementation by determining key preferred vaccine product characteristics and associated population-level impact.MethodsVaccination impact was assessed at various efficacies using an age-structured mathematical model describing SARS-CoV-2 transmission and disease progression, with application for China.ResultsA prophylactic vaccine with efficacy against acquisition (VES) of ≥70% is needed to eliminate this infection. A vaccine with VES <70% will still have a major impact, and may control the infection if it reduces infectiousness or infection duration among those vaccinated who acquire the infection, or alternatively if supplemented with a moderate social-distancing intervention (<20% reduction in contact rate), or complemented with herd immunity. Vaccination is cost-effective. For a vaccine with VES of 50%, number of vaccinations needed to avert one infection is only 2.4, one severe disease case is 25.5, one critical disease case is 33.2, and one death is 65.1. Gains in effectiveness are achieved by initially prioritizing those ≥60 years. Probability of a major outbreak is virtually zero with a vaccine with VES ≥70%, regardless of number of virus introductions. Yet, an increase in social contact rate among those vaccinated (behavior compensation) can undermine vaccine impact.ConclusionsEven a partially-efficacious vaccine can offer a fundamental solution to control SARS-CoV-2 infection and at high cost-effectiveness. In addition to the primary endpoint on infection acquisition, developers should assess natural history and disease progression outcomes and/or proxy biomarkers, since such secondary endpoints may prove critical in licensure, decision-making, and vaccine impact.

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Treating COVID-19 With Hydroxychloroquine (TEACH): A Multicenter, Double-Blind Randomized Controlled Trial in Hospitalized Patients

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa446 ◽

2020 ◽

Vol 7 (10) ◽

Cited By ~ 5

Author(s):

Robert J Ulrich ◽

Andrea B Troxel ◽

Ellie Carmody ◽

Jaishvi Eapen ◽

Martin Bäcker ◽

...

Keyword(s):

Randomized Controlled Trials ◽

Disease Progression ◽

Severe Disease ◽

Small Sample ◽

Hospitalized Patients ◽

Controlled Trials ◽

Double Blind ◽

Randomized Controlled ◽

End Point ◽

Clinical Scores

Abstract Background Effective therapies to combat coronavirus 2019 (COVID-19) are urgently needed. Hydroxychloroquine (HCQ) has in vitro antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the clinical benefit of HCQ in treating COVID-19 is unclear. Randomized controlled trials are needed to determine the safety and efficacy of HCQ for the treatment of hospitalized patients with COVID-19. Methods We conducted a multicenter, double-blind randomized clinical trial of HCQ among patients hospitalized with laboratory-confirmed COVID-19. Subjects were randomized in a 1:1 ratio to HCQ or placebo for 5 days and followed for 30 days. The primary efficacy outcome was a severe disease progression composite end point (death, intensive care unit admission, mechanical ventilation, extracorporeal membrane oxygenation, and/or vasopressor use) at day 14. Results A total of 128 patients were included in the intention-to-treat analysis. Baseline demographic, clinical, and laboratory characteristics were similar between the HCQ (n = 67) and placebo (n = 61) arms. At day 14, 11 (16.4%) subjects assigned to HCQ and 6 (9.8%) subjects assigned to placebo met the severe disease progression end point, but this did not achieve statistical significance (P = .350). There were no significant differences in COVID-19 clinical scores, number of oxygen-free days, SARS-CoV-2 clearance, or adverse events between HCQ and placebo. HCQ was associated with a slight increase in mean corrected QT interval, an increased D-dimer, and a trend toward an increased length of stay. Conclusions In hospitalized patients with COVID-19, our data suggest that HCQ does not prevent severe outcomes or improve clinical scores. However, our conclusions are limited by a relatively small sample size, and larger randomized controlled trials or pooled analyses are needed.

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