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1.
BMC Med Res Methodol ; 21(1): 165, 2021 08 10.
Article in English | MEDLINE | ID: covidwho-1352645

ABSTRACT

BACKGROUND: A considerable proportion of SARS-CoV-2 transmission occurs from asymptomatic and pre-symptomatic cases. Therefore, different polymerase chain reaction (PCR)- or rapid antigen test (RAT)-based approaches are being discussed and applied to identify infectious individuals that would have otherwise gone undetected. In this article, we provide a framework to estimate the time-dependent risk of being infectious after a negative SARS-CoV-2 test, and we simulate the number of expected infectious individuals over time in populations who initially tested negative. METHODS: A Monte Carlo approach is used to simulate asymptomatic infections over a 10-days period in populations of 1000 individuals following a negative SARS-CoV-2 test. Parameters representing the application of PCR tests or RATs are utilized, and SARS-CoV-2 cumulative 7-day incidences between 25 and 200 per 100,000 people are considered. Simulation results are compared to case numbers predicted via a mathematical equation. RESULTS: The simulations showed a continuous increase in infectious individuals over time in populations of individuals who initially tested SARS-CoV-2 negative. The interplay between false negative rates of PCR tests or RATs, and the time that has passed since testing determines the number of infectious individuals. The simulated and the mathematically predicted number of infectious individuals were comparable. However, Monte Carlo simulations highlight that, due to random variation, theoretically observed infectious individuals can considerably exceed predicted case numbers even shortly after a test was conducted. CONCLUSIONS: This study demonstrates that the number of infectious individuals in a screened group of asymptomatic people can be effectively reduced, and this effect can be described mathematically. However, the false negative rate of a test, the time since the negative test and the underlying SARS-CoV-2 incidence are critical parameters in determining the observed subsequent number of cases in tested population groups.


Subject(s)
COVID-19 , Communicable Diseases , Computer Simulation , Humans , Polymerase Chain Reaction , SARS-CoV-2
2.
Sci Rep ; 11(1): 14471, 2021 07 14.
Article in English | MEDLINE | ID: covidwho-1310815

ABSTRACT

Early detection of severe forms of COVID-19 is absolutely essential for timely triage of patients. We longitudinally followed-up two well-characterized patient groups, hospitalized moderate to severe (n = 26), and ambulatory mild COVID-19 patients (n = 16) at home quarantine. Human D-dimer, C-reactive protein (CRP), ferritin, cardiac troponin I, interleukin-6 (IL-6) levels were measured on day 1, day 7, day 14 and day 28. All hospitalized patients were SARS-CoV-2 positive on admission, while all ambulatory patients were SARS-CoV-2 positive at recruitment. Hospitalized patients had higher D-dimer, CRP and ferritin, cardiac troponin I and IL-6 levels than ambulatory patients (p < 0.001, p < 0.001, p = 0.016, p = 0.035, p = 0.002 respectively). Hospitalized patients experienced significant decreases in CRP, ferritin and IL-6 levels from admission to recovery (p < 0.001, p = 0.025, and p = 0.001 respectively). Cardiac troponin I levels were high during the acute phase in both hospitalized and ambulatory patients, indicating a potential myocardial injury. In summary, D-dimer, CRP, ferritin, cardiac troponin I, IL-6 are predictive laboratory markers and can largely determine the clinical course of COVID-19, in particular the prognosis of critically ill COVID-19 patients.


Subject(s)
COVID-19/blood , COVID-19/diagnosis , Ambulatory Care , Biomarkers/blood , C-Reactive Protein/analysis , Early Diagnosis , Ferritins/blood , Fibrin Fibrinogen Degradation Products/analysis , Follow-Up Studies , Hospitalization , Humans , Interleukin-6/blood , Longitudinal Studies , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , Precision Medicine , Prognosis , Quarantine , SARS-CoV-2 , Severity of Illness Index , Troponin I/blood
3.
Int J Infect Dis ; 106: 265-268, 2021 May.
Article in English | MEDLINE | ID: covidwho-1279605

ABSTRACT

INTRODUCTION: Use of hydroxychloroquine in patients with coronavirus disease 2019 (COVID-19) was widespread and uncontrolled until recently. Patients vulnerable to severe COVID-19 are at risk of hydroxychloroquine interactions with co-morbidities and co-medications contributing to detrimental, including fatal, adverse treatment effects. METHODS: A retrospective survey was undertaken of health conditions and co-medications of patients with COVID-19 who were pre-screened for enrolment in a randomized, double-blind, placebo-controlled hydroxychloroquine multi-centre trial. RESULTS: The survey involved 305 patients [median age 71 (interquartile range 59-81) years]. The majority of patients (n = 279, 92%) considered for inclusion in the clinical trial were not eligible, mainly due to safety concerns caused by health conditions or co-medications. The most common were QT-prolonging drugs (n = 188, 62%) and haematologic/haemato-oncologic diseases (n = 39, 13%) which prohibited the administration of hydroxychloroquine. In addition, 165 (54%) patients had health conditions and 167 (55%) patients were on co-medications that did not prohibit the use of hydroxychloroquine but had a risk of adverse interactions with hydroxychloroquine. The most common were diabetes (n = 86, 28%), renal insufficiency (n = 69, 23%) and heart failure (n = 58, 19%). CONCLUSION: The majority of hospitalized patients with COVID-19 had health conditions or took co-medications precluding safe treatment with hydroxychloroquine. Therefore, hydroxychloroquine should be administered with extreme caution in elderly patients with COVID-19, and only in clinical trials.


Subject(s)
COVID-19/drug therapy , Hydroxychloroquine/adverse effects , SARS-CoV-2 , Aged , Aged, 80 and over , Comorbidity , Contraindications, Drug , Drug Interactions , Female , Germany/epidemiology , Humans , Male , Middle Aged , Retrospective Studies
5.
J Clin Med ; 10(11)2021 May 24.
Article in English | MEDLINE | ID: covidwho-1244046

ABSTRACT

In this study, we directly compared coronavirus disease 2019 (COVID-19) patients hospitalized during the first (27 February-28 July 2020) and second (29 July-31 December 2020) wave of the pandemic at a large tertiary center in northern Germany. Patients who presented during the first (n = 174) and second (n = 331) wave did not differ in age (median [IQR], 59 years [46, 71] vs. 58 years [42, 73]; p = 0.82) or age-adjusted Charlson Comorbidity Index (median [IQR], 2 [1, 4] vs. 2 [0, 4]; p = 0.50). During the second wave, a higher proportion of patients were treated as outpatients (11% [n = 20] vs. 20% [n = 67]), fewer patients were admitted to the intensive care unit (43% [n = 75] vs. 29% [n = 96]), and duration of hospitalization was significantly shorter (median days [IQR], 14 [8, 34] vs. 11 [5, 19]; p < 0.001). However, in-hospital mortality was high throughout the pandemic and did not differ between the two periods (16% [n = 27] vs. 16% [n = 54]; p = 0.89). While novel treatment strategies and increased knowledge about the clinical management of COVID-19 may have resulted in a less severe disease course in some patients, in-hospital mortality remained unaltered at a high level. These findings highlight the unabated need for efforts to hamper severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) transmission, to increase vaccination coverage, and to develop novel treatment strategies to prevent mortality and decrease morbidity.

6.
Nat Commun ; 12(1): 2349, 2021 04 15.
Article in English | MEDLINE | ID: covidwho-1189222

ABSTRACT

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.


Subject(s)
COVID-19/drug therapy , COVID-19/mortality , Chloroquine/adverse effects , Hydroxychloroquine/adverse effects , Pregnancy Complications, Infectious/mortality , Adult , COVID-19/complications , COVID-19/virology , Child , Chloroquine/administration & dosage , Combined Modality Therapy/adverse effects , Combined Modality Therapy/methods , Comorbidity , Female , Humans , Hydroxychloroquine/administration & dosage , International Cooperation , Odds Ratio , Patient Participation/statistics & numerical data , Pregnancy , Pregnancy Complications, Infectious/drug therapy , Pregnancy Complications, Infectious/virology , Randomized Controlled Trials as Topic/statistics & numerical data , SARS-CoV-2
7.
Trop Med Infect Dis ; 6(2)2021 Mar 26.
Article in English | MEDLINE | ID: covidwho-1154500

ABSTRACT

We report a case of Plasmodium falciparum malaria in a patient asymptomatically co-infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the current ongoing coronavirus pandemic, co-infections with unrelated life-threatening febrile conditions may pose a particular challenge to clinicians. The current situation increases the risk for cognitive biases in medical management.

8.
J Clin Virol ; 137: 104782, 2021 04.
Article in English | MEDLINE | ID: covidwho-1116968

ABSTRACT

BACKGROUND: SARS-CoV-2 molecular diagnostics is facing material shortages and long turnaround times due to exponential increase of testing demand. OBJECTIVE: We evaluated the analytic performance and handling of four rapid Antigen Point of Care Tests (AgPOCTs) I-IV (Distributors: (I) Roche, (II) Abbott, (III) MEDsan and (IV) Siemens). METHODS: 100 RT-PCR negative and 84 RT-PCR positive oropharyngeal swabs were prospectively collected and used to determine performance and accuracy of these AgPOCTs. Handling was evaluated by 10 healthcare workers/users through a questionnaire. RESULTS: The median duration from symptom onset to sampling was 6 days (IQR 2-12 days). The overall respective sensitivity were 49.4 % (CI95 %: 38.9-59.9), 44.6 % (CI95 %: 34.3-55.3), 45.8 % (CI95 %: 35.5-56.5) and 54.9 % (CI95 %: 43.4-65.9) for tests I, II, III and IV, respectively. In the high viral load subgroup (containing >106 copies of SARS-CoV-2 /swab, n = 26), AgPOCTs reached sensitivities of 92.3 % or more (range 92.3 %-100 %). Specificity was 100 % for tests I, II (CI95 %: 96.3-100 for both tests) and IV (CI95 %: 96.3-100) and 97 % (CI95 %: 91.5-98.9) for test III. Regarding handling, test I obtained the overall highest scores, while test II was considered to have the most convenient components. Of note, users considered all assays, with the exception of test I, to pose a significant risk for contamination by drips or spills. DISCUSSION: Besides some differences in sensitivity and handling, all four AgPOCTs showed acceptable performance in high viral load samples. However, due to the significantly lower sensitivity compared to RT-qPCR, a careful consideration of pro and cons of AgPOCT has to be taken into account before clinical implementation.


Subject(s)
Antigens, Viral/analysis , COVID-19 Nucleic Acid Testing/methods , COVID-19 Testing/methods , COVID-19/diagnosis , SARS-CoV-2/isolation & purification , COVID-19/immunology , COVID-19/virology , Humans , Nasopharynx/virology , Oropharynx/virology , Point-of-Care Testing , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Sensitivity and Specificity , Serologic Tests/methods , Specimen Handling/methods , Viral Load
9.
Am J Trop Med Hyg ; 103(4): 1640-1641, 2020 10.
Article in English | MEDLINE | ID: covidwho-725539

ABSTRACT

The emergence and international spread of SARS-CoV-2 led to unprecedented challenges for international travelers including health-related concerns and international travel restrictions. Remarkably, overseas travelers consulted at our travel clinic during the first quarter of 2020 were apparently not disconcerted by the evolving pandemic with a continuously high rate of consultations at our center; 85% of travelers did not actively inquire about COVID-19 during the pretravel consultation including individuals with clinically significant immunosuppression constituting a high-risk group for COVID-19-related adverse health outcome. This experience demonstrates the societal responsibility of travel medicine practitioners to proactively provide unbiased information about the health-related and travel-related impact of newly emerging infections.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Immunocompromised Host , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Travel/psychology , Adult , Asia/epidemiology , COVID-19 , Coronavirus Infections/psychology , Coronavirus Infections/virology , Female , Germany/epidemiology , Humans , Male , Pneumonia, Viral/psychology , Pneumonia, Viral/virology , Referral and Consultation/statistics & numerical data , Risk Assessment , SARS-CoV-2 , Travel/statistics & numerical data , Travel Medicine/statistics & numerical data
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