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1.
Clin Infect Dis ; 73(11): 2055-2064, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1561261

ABSTRACT

BACKGROUND: Emerging evidence suggests many people have persistent symptoms after acute coronavirus disease 2019 (COVID-19) illness. Our objective was to estimate the prevalence and correlates of post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC). METHODS: We used a population-based probability survey of adults with COVID-19 in Michigan. Living noninstitutionalized adults aged ≥18 in the Michigan Disease Surveillance System with COVID-19 onset through mid-April 2020 were eligible for selection (N = 28 000). Among 2000 selected, 629 completed the survey between June-December 2020. We estimated PASC prevalence, defined as persistent symptoms ≥30 (30-day COVID-19) or ≥60 (60-day COVID-19) days post-COVID-19 onset, overall and by sociodemographic and clinical factors. We used modified Poisson regression to produce adjusted prevalence ratios (aPRs) for potential risk factors. RESULTS: The analytic sample (n = 593) was predominantly female (56.1%), aged ≥45 years (68.2%), and non-Hispanic White (46.3%) or Black (34.8%). Thirty- and 60-day COVID-19 were highly prevalent (52.5% and 35.0%), even among nonhospitalized respondents (43.7% and 26.9%) and respondents reporting mild symptoms (29.2% and 24.5%). Respondents reporting very severe (vs mild) symptoms had 2.25 times higher prevalence of 30-day COVID-19 (aPR, 2.25; 95% CI, 1.46-3.46) and 1.71 times higher prevalence of 60-day COVID-19 (aPR, 1.71; 95% CI: 1.02-2.88). Hospitalized (vs nonhospitalized) respondents had ~40% higher prevalence of both 30-day (aPR, 1.37; 95% CI: 1.12-1.69) and 60-day (aPR, 1.40; 95% CI: 1.02-1.93) COVID-19. CONCLUSIONS: PASC is highly prevalent among cases reporting severe initial symptoms and, to a lesser extent, cases reporting mild and moderate symptoms.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Disease Progression , Female , Hospitalization , Humans , Prevalence
2.
Clin Infect Dis ; 73(11): e4058-e4063, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1560027

ABSTRACT

BACKGROUND: Little is known about long-term recovery from coronavirus disease 2019 (COVID-19) disease, especially in nonhospitalized individuals. In this longitudinal study we present symptoms registered during the acute phase as well as long COVID (ie, long-lasting COVID-19 symptoms) in patients from the Faroe Islands. METHODS: All consecutive patients with confirmed reverse transcription-polymerase chain reaction testing from April to June 2020 were invited to participate in this study for the assessment of long COVID. Demographic and clinical characteristics and self-reported acute and persistent symptoms were assessed using a standardized detailed questionnaire administered at enrollment and at repeated phone interviews in the period 22 April to 16 August. RESULTS: Of the 180 participants (96.3% of the 187 eligible COVID-19 patients), 53.1% reported persistence of at least 1 symptom after a mean of 125 days after symptoms onset, 33.0% reported 1 or 2 symptoms, and 20.1% reported 3 or more symptoms. At the last follow-up, 46.9% were asymptomatic compared with 4.4% during the acute phase. The most prevalent persistent symptoms were fatigue, loss of smell and taste, and arthralgias. CONCLUSIONS: Our results show that it might take months for symptoms to resolve, even among nonhospitalized persons with mild illness course in the acute phase. Continued monitoring for long COVID is needed.


Subject(s)
COVID-19 , COVID-19/complications , Fatigue , Humans , Longitudinal Studies , SARS-CoV-2
3.
PLoS One ; 16(5): e0245031, 2021.
Article in English | MEDLINE | ID: covidwho-1314324

ABSTRACT

SARS-CoV-2 infection causing the novel coronavirus disease 2019 (COVID-19) has been responsible for more than 2.8 million deaths and nearly 125 million infections worldwide as of March 2021. In March 2020, the World Health Organization determined that the COVID-19 outbreak is a global pandemic. The urgency and magnitude of this pandemic demanded immediate action and coordination between local, regional, national, and international actors. In that mission, researchers require access to high-quality biological materials and data from SARS-CoV-2 infected and uninfected patients, covering the spectrum of disease manifestations. The "Biobanque québécoise de la COVID-19" (BQC19) is a pan-provincial initiative undertaken in Québec, Canada to enable the collection, storage and sharing of samples and data related to the COVID-19 crisis. As a disease-oriented biobank based on high-quality biosamples and clinical data of hospitalized and non-hospitalized SARS-CoV-2 PCR positive and negative individuals. The BQC19 follows a legal and ethical management framework approved by local health authorities. The biosamples include plasma, serum, peripheral blood mononuclear cells and DNA and RNA isolated from whole blood. In addition to the clinical variables, BQC19 will provide in-depth analytical data derived from the biosamples including whole genome and transcriptome sequencing, proteome and metabolome analyses, multiplex measurements of key circulating markers as well as anti-SARS-CoV-2 antibody responses. BQC19 will provide the scientific and medical communities access to data and samples to better understand, manage and ultimately limit, the impact of COVID-19. In this paper we present BQC19, describe the process according to which it is governed and organized, and address opportunities for future research collaborations. BQC19 aims to be a part of a global communal effort addressing the challenges of COVID-19.


Subject(s)
Biological Specimen Banks/organization & administration , COVID-19/pathology , COVID-19/epidemiology , COVID-19/genetics , COVID-19/metabolism , Humans , Information Dissemination/methods , Pandemics , Quebec/epidemiology , SARS-CoV-2/isolation & purification
4.
Philos Trans R Soc Lond B Biol Sci ; 376(1829): 20200274, 2021 07 19.
Article in English | MEDLINE | ID: covidwho-1309692

ABSTRACT

The dynamics of immunity are crucial to understanding the long-term patterns of the SARS-CoV-2 pandemic. Several cases of reinfection with SARS-CoV-2 have been documented 48-142 days after the initial infection and immunity to seasonal circulating coronaviruses is estimated to be shorter than 1 year. Using an age-structured, deterministic model, we explore potential immunity dynamics using contact data from the UK population. In the scenario where immunity to SARS-CoV-2 lasts an average of three months for non-hospitalized individuals, a year for hospitalized individuals, and the effective reproduction number after lockdown ends is 1.2 (our worst-case scenario), we find that the secondary peak occurs in winter 2020 with a daily maximum of 387 000 infectious individuals and 125 000 daily new cases; threefold greater than in a scenario with permanent immunity. Our models suggest that longitudinal serological surveys to determine if immunity in the population is waning will be most informative when sampling takes place from the end of the lockdown in June until autumn 2020. After this period, the proportion of the population with antibodies to SARS-CoV-2 is expected to increase due to the secondary wave. Overall, our analysis presents considerations for policy makers on the longer-term dynamics of SARS-CoV-2 in the UK and suggests that strategies designed to achieve herd immunity may lead to repeated waves of infection as immunity to reinfection is not permanent. This article is part of the theme issue 'Modelling that shaped the early COVID-19 pandemic response in the UK'.


Subject(s)
COVID-19/epidemiology , Communicable Disease Control/trends , Pandemics , SARS-CoV-2/pathogenicity , Basic Reproduction Number/statistics & numerical data , COVID-19/virology , Humans , United Kingdom/epidemiology
5.
PLoS One ; 16(5): e0245031, 2021.
Article in English | MEDLINE | ID: covidwho-1234580

ABSTRACT

SARS-CoV-2 infection causing the novel coronavirus disease 2019 (COVID-19) has been responsible for more than 2.8 million deaths and nearly 125 million infections worldwide as of March 2021. In March 2020, the World Health Organization determined that the COVID-19 outbreak is a global pandemic. The urgency and magnitude of this pandemic demanded immediate action and coordination between local, regional, national, and international actors. In that mission, researchers require access to high-quality biological materials and data from SARS-CoV-2 infected and uninfected patients, covering the spectrum of disease manifestations. The "Biobanque québécoise de la COVID-19" (BQC19) is a pan-provincial initiative undertaken in Québec, Canada to enable the collection, storage and sharing of samples and data related to the COVID-19 crisis. As a disease-oriented biobank based on high-quality biosamples and clinical data of hospitalized and non-hospitalized SARS-CoV-2 PCR positive and negative individuals. The BQC19 follows a legal and ethical management framework approved by local health authorities. The biosamples include plasma, serum, peripheral blood mononuclear cells and DNA and RNA isolated from whole blood. In addition to the clinical variables, BQC19 will provide in-depth analytical data derived from the biosamples including whole genome and transcriptome sequencing, proteome and metabolome analyses, multiplex measurements of key circulating markers as well as anti-SARS-CoV-2 antibody responses. BQC19 will provide the scientific and medical communities access to data and samples to better understand, manage and ultimately limit, the impact of COVID-19. In this paper we present BQC19, describe the process according to which it is governed and organized, and address opportunities for future research collaborations. BQC19 aims to be a part of a global communal effort addressing the challenges of COVID-19.


Subject(s)
Biological Specimen Banks/organization & administration , COVID-19/pathology , COVID-19/epidemiology , COVID-19/genetics , COVID-19/metabolism , Humans , Information Dissemination/methods , Pandemics , Quebec/epidemiology , SARS-CoV-2/isolation & purification
6.
Clin Infect Dis ; 73(11): 2055-2064, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1233845

ABSTRACT

BACKGROUND: Emerging evidence suggests many people have persistent symptoms after acute coronavirus disease 2019 (COVID-19) illness. Our objective was to estimate the prevalence and correlates of post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC). METHODS: We used a population-based probability survey of adults with COVID-19 in Michigan. Living noninstitutionalized adults aged ≥18 in the Michigan Disease Surveillance System with COVID-19 onset through mid-April 2020 were eligible for selection (N = 28 000). Among 2000 selected, 629 completed the survey between June-December 2020. We estimated PASC prevalence, defined as persistent symptoms ≥30 (30-day COVID-19) or ≥60 (60-day COVID-19) days post-COVID-19 onset, overall and by sociodemographic and clinical factors. We used modified Poisson regression to produce adjusted prevalence ratios (aPRs) for potential risk factors. RESULTS: The analytic sample (n = 593) was predominantly female (56.1%), aged ≥45 years (68.2%), and non-Hispanic White (46.3%) or Black (34.8%). Thirty- and 60-day COVID-19 were highly prevalent (52.5% and 35.0%), even among nonhospitalized respondents (43.7% and 26.9%) and respondents reporting mild symptoms (29.2% and 24.5%). Respondents reporting very severe (vs mild) symptoms had 2.25 times higher prevalence of 30-day COVID-19 (aPR, 2.25; 95% CI, 1.46-3.46) and 1.71 times higher prevalence of 60-day COVID-19 (aPR, 1.71; 95% CI: 1.02-2.88). Hospitalized (vs nonhospitalized) respondents had ~40% higher prevalence of both 30-day (aPR, 1.37; 95% CI: 1.12-1.69) and 60-day (aPR, 1.40; 95% CI: 1.02-1.93) COVID-19. CONCLUSIONS: PASC is highly prevalent among cases reporting severe initial symptoms and, to a lesser extent, cases reporting mild and moderate symptoms.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Disease Progression , Female , Hospitalization , Humans , Prevalence
7.
J Med Virol ; 93(5): 3033-3046, 2021 May.
Article in English | MEDLINE | ID: covidwho-1062111

ABSTRACT

We primarily quantified exposure patterns, transmission characteristics, and the clinical spectrum of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among household contacts of individuals with severe coronavirus disease-2019 (COVID-19). We conducted a retrospective cohort study of 20 index patients hospitalized with severe COVID-19 and 79 of their household contacts. We determined the transmission frequency, range of manifestations of SARS-CoV-2 infection, and factors associated with infection in household settings. Of the 79 household contacts, 53 (67%) developed SARS-CoV-2 infection (49 [62%] symptomatic, 4 [5%] asymptomatic). Eight patients (10%) developed severe COVID-19, and one died of COVID-19 pneumonia (case-fatality rate: 1.9%). The probability of SARS-CoV-2 infection was similar in children and adults (55% vs. 72%, p = .14), with children being less likely to develop the symptomatic disease (46% vs. 68%, p = .06). Handwashing ≥ 5 times/day was associated with reduced infection risk (52.8% vs. 76.9%, p = .04). SARS-CoV-2 has a high frequency of transmission among household contacts. Nonhospitalized individuals with SARS-CoV-2 infection should be quarantined in patient care facilities rather than at home to minimize spread, if possible, and frequent handwashing should be practiced to prevent transmission.


Subject(s)
COVID-19/epidemiology , COVID-19/transmission , Contact Tracing/statistics & numerical data , SARS-CoV-2/pathogenicity , Adolescent , Adult , Asymptomatic Infections/epidemiology , COVID-19/diagnosis , COVID-19/prevention & control , Child , Child, Preschool , Cohort Studies , Family Characteristics , Female , Hand Disinfection , Humans , Incidence , Infant , Male , Middle Aged , Quarantine , Retrospective Studies , Risk Factors , SARS-CoV-2/isolation & purification , Young Adult
8.
Infect Drug Resist ; 13: 4577-4587, 2020.
Article in English | MEDLINE | ID: covidwho-999915

ABSTRACT

PURPOSE: A multitude of randomized controlled trials (RCTs) have emerged in response to the novel coronavirus disease (COVID-19) pandemic. Understanding the distribution of trials among various settings is important to guide future research priorities and efforts. The purpose of this review was to describe the emerging evidence base of COVID-19 RCTs by stages of disease progression, from pre-exposure to hospitalization. METHODS: We collated trial data across international registries: ClinicalTrials.gov; International Standard Randomised Controlled Trial Number Registry; Chinese Clinical Trial Registry; Clinical Research Information Service; EU Clinical Trials Register; Iranian Registry of Clinical Trials; Japan Primary Registries Network; German Clinical Trials Register (up to 7 October 2020). Active COVID-19 RCTs in international registries were eligible for inclusion. We extracted trial status, intervention(s), control, sample size, and clinical context to generate descriptive frequencies, network diagram illustrations, and statistical analyses including odds ratios and the Mann-Whitney U-test. RESULTS: Our search identified 11503 clinical trials registered for COVID-19 and identified 2388 RCTs. After excluding 45 suspended RCTs and 480 trials with unclear or unreported disease stages, 1863 active RCTs were included and categorized into four broad disease stages: pre-exposure (n=107); post-exposure (n=208); outpatient treatment (n=266); hospitalization, including the intensive care unit (n=1376). Across all disease stages, most trials had two arms (n=1500/1863, 80.52%), most often included (hydroxy)chloroquine (n=271/1863, 14.55%) and were US-based (n=408/1863, 21.90%). US-based trials had lower odds of including (hydroxy)chloroquine than trials in other countries (OR: 0.63, 95% CI: 0.45-0.90) and similar odds of having two arms compared to other geographic regions (OR: 1.05, 95% CI: 0.80-1.38). CONCLUSION: There is a marked difference in the number of trials across settings, with limited studies on non-hospitalized persons. Focus on pre- and post-exposure, and outpatients, is worthwhile as a means of reducing infections and lessening the health, social, and economic burden of COVID-19.

9.
Chest ; 159(3): 949-958, 2021 03.
Article in English | MEDLINE | ID: covidwho-996766

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 pandemic poses extraordinary challenges. The tremendous number of coronavirus disease 2019 (COVID-19) cases in the United States has resulted in a large population of survivors with prolonged postinfection symptoms. The creation of multidisciplinary post-COVID-19 clinics to address both persistent symptoms and potential long-term complications requires an understanding of the acute disease and the emerging data regarding COVID-19 outcomes. Experience with severe acute respiratory syndrome and Middle East respiratory syndrome, post-acute respiratory distress syndrome complications, and post-intensive care syndrome also informs anticipated sequelae and clinical program design. Post-COVID-19 clinical programs should be prepared to care for individuals previously hospitalized with COVID-19 (including those who required critical care support), nonhospitalized individuals with persistent respiratory symptoms following COVID-19, and individuals with preexisting lung disease complicated by COVID-19. Effective multidisciplinary collaboration models leverage lessons learned during the early phases of the pandemic to overcome the unique logistical challenges posed by pandemic circumstances. Collaboration between physicians and researchers across disciplines will provide insight into survivorship that may shape the treatment of both acute disease and chronic complications. In this review, we discuss the aims, general principles, elements of design, and challenges of a successful multidisciplinary model to address the needs of COVID-19 survivors.


Subject(s)
COVID-19 , Critical Illness/rehabilitation , Recovery of Function , COVID-19/complications , COVID-19/epidemiology , COVID-19/rehabilitation , COVID-19/therapy , Critical Care , Humans , Interdisciplinary Research , Rehabilitation Research , Risk Factors
10.
Glob Health Med ; 2(6): 346-349, 2020 Dec 31.
Article in English | MEDLINE | ID: covidwho-790247

ABSTRACT

The COVID-19 pandemic has unleashed an unprecedented effort to identify efficacious treatments for persons infected with SARS-CoV-2. As of September 2020, more than 750 completed, ongoing, or planned clinical trials of drugs intended to inhibit SARS-CoV-2 replication have been registered on the ClinicalTrials.gov or WHO International Clinical Trials Platform websites. Most of the treatments studied in these trials are repurposed licensed or investigational drugs targeting viral proteins or cellular pathways required for virus replication. The use of repurposed compounds is understandable because with the exception of monoclonal antibodies, it will be several months before novel SARS-CoV-2-specific drugs will be available for human testing. This editorial describes those compounds that I believe should be prioritized for clinical testing: i) viral RNA polymerase inhibitors including GS-441524, its prodrug remdesivir, and EIDD-2801; ii) entry inhibitors including monoclonal antibodies, ACE2 molecular decoys, and peptide fusion inhibitors; iii) parenteral and inhalational preparations of interferon ß and λ; and iv) inhibitors of host transmembrane protease serine 2 (TMPRSS2), endosomal trafficking, and pyrimidine synthesis. As SARS-CoV-2 is pandemic and as its most severe consequences result from a dysregulated immunological response to infection, the ideal therapies should be inexpensive and should be able to be administered to non-hospitalized persons at the time of their initial diagnosis.

11.
Cell Metab ; 32(4): 537-547.e3, 2020 10 06.
Article in English | MEDLINE | ID: covidwho-741151

ABSTRACT

The safety and efficacy of anti-diabetic drugs are critical for maximizing the beneficial impacts of well-controlled blood glucose on the prognosis of individuals with COVID-19 and pre-existing type 2 diabetes (T2D). Metformin is the most commonly prescribed first-line medication for T2D, but its impact on the outcomes of individuals with COVID-19 and T2D remains to be clarified. Our current retrospective study in a cohort of 1,213 hospitalized individuals with COVID-19 and pre-existing T2D indicated that metformin use was significantly associated with a higher incidence of acidosis, particularly in cases with severe COVID-19, but not with 28-day COVID-19-related mortality. Furthermore, metformin use was significantly associated with reduced heart failure and inflammation. Our findings provide clinical evidence in support of continuing metformin treatment in individuals with COVID-19 and pre-existing T2D, but acidosis and kidney function should be carefully monitored in individuals with severe COVID-19.


Subject(s)
Acidosis/chemically induced , Coronavirus Infections/complications , Diabetes Mellitus, Type 2/complications , Metformin/adverse effects , Pneumonia, Viral/complications , Acidosis, Lactic/chemically induced , Aged , COVID-19 , China/epidemiology , Coronavirus Infections/mortality , Coronavirus Infections/physiopathology , Diabetes Mellitus, Type 2/drug therapy , Female , Hospitalization , Humans , Kidney/physiopathology , Male , Middle Aged , Pandemics , Pneumonia, Viral/mortality , Pneumonia, Viral/physiopathology , Retrospective Studies
12.
JMIR Public Health Surveill ; 6(3): e21866, 2020 09 18.
Article in English | MEDLINE | ID: covidwho-640263

ABSTRACT

BACKGROUND: Understanding the occurrence of symptoms resembling those of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a large nonhospitalized population at the peak of the epidemic in Italy is of paramount importance; however, data are currently scarce. OBJECTIVE: The aims of this study were to evaluate the association of self-reported symptoms with SARS-CoV-2 nasopharyngeal swab (NPS) test results in nonhospitalized individuals and to estimate the occurrence of symptoms associated with coronavirus disease (COVID-19) in a larger nontested population. METHODS: EPICOVID19 is a self-administered cross-sectional voluntary web-based survey of adults throughout Italy who completed an anonymous questionnaire in the period of April 13 to 21, 2020. The associations between symptoms potentially related to SARS-CoV-2 infection and NPS results were calculated as adjusted odds ratios (aORs) with 95% CIs by multiple logistic regression analysis controlling for age, sex, education, smoking habits, and number of comorbidities. Thereafter, for each symptom and for combinations of the symptoms, we calculated the sensitivity, specificity, accuracy, and areas under the curve (AUCs) in a receiver operating characteristic (ROC) analysis to estimate the occurrence of COVID-19-like infection in the nontested population. RESULTS: A total of 171,310 people responded to the survey, of whom 102,543 (59.9%) were women; mean age 47.4 years. Out of the 4785 respondents with known NPS test results, 4392 were not hospitalized. Among the 4392 nonhospitalized respondents, those with positive NPS tests (856, 19.5%) most frequently reported myalgia (527, 61.6%), olfactory and taste disorders (507, 59.2%), cough (466, 54.4%), and fever (444, 51.9%), whereas 7.7% were asymptomatic. Multiple regression analysis showed that olfactory and taste disorders (aOR 10.3, 95% CI 8.4-12.7), fever (aOR 2.5, 95% CI 2.0-3.1), myalgia (aOR 1.5, 95% CI 1.2-1.8), and cough (aOR 1.3, 95% CI 1.0-1.6) were associated with NPS positivity. Having two to four of these symptoms increased the aOR from 7.4 (95% CI 5.6-9.7) to 35.5 (95% CI 24.6-52.2). The combination of the four symptoms showed an AUC of 0.810 (95% CI 0.795-0.825) in classifying positive NPS test results and then was applied to the nonhospitalized and nontested sample (n=165,782). We found that 7739 to 20,103 of these 165,782 respondents (4.4% to 12.1%) had experienced symptoms suggestive of COVID-19 infection. CONCLUSIONS: Our results suggest that self-reported symptoms are reliable indicators of SARS-CoV-2 infection in a pandemic context. A nonnegligible number of symptomatic respondents (up to 12.1%) were undiagnosed and potentially contributed to the spread of the infection. TRIAL REGISTRATION: ClinicalTrials.gov NCT04471701; https://clinicaltrials.gov/ct2/show/NCT04471701.


Subject(s)
Coronavirus Infections/complications , Health Status , Pneumonia, Viral/complications , Population Surveillance/methods , Adolescent , Adult , Aged , Aged, 80 and over , Area Under Curve , Betacoronavirus , COVID-19 , Coronavirus , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Cross-Sectional Studies , Female , Health Surveys , Humans , Italy/epidemiology , Male , Middle Aged , Odds Ratio , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Prevalence , ROC Curve , SARS-CoV-2 , Self Report , Severe Acute Respiratory Syndrome , Young Adult
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