Initial Severe Acute Respiratory Syndrome Coronavirus 2 Viral Load Is Associated With Disease Severity: A Retrospective Cohort Study.

Background: We assessed the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load and hospital admission, intensive care unit (ICU) admission, and in-hospital mortality. Methods: All SARS-CoV-2-positive persons with a combined nasopharyngeal and oropharyngeal swab that was collected between 17 March 2020 and 31 March 2021 in public health testing facilities were included. Results: From 20 207 SARS-CoV-2-positive persons, 310 (1.5%) were hospitalized within 30 days. High viral loads (crossing point [Cp] <25) were associated with an increased risk of hospitalization as compared to low viral loads (Cp >30), adjusted for age and sex (adjusted odds ratio [aOR], 1.57 [95% confidence interval {CI}, 1.11-2.26]). The same association was seen for ICU admission (aOR, 7.06 [95% CI, 2.15-43.57]). The median [interquartile range] Cp value of the 17 patients who died in hospital was significantly lower compared to the 226 survivors (22.7 [3.4] vs 25.0 [5.2]). Conclusions: Higher initial SARS-CoV-2 viral load is associated with an increased risk of hospital admission, ICU admission, and in-hospital mortality. Our findings emphasize the added value of reporting SARS-CoV-2 viral load or cycle threshold/Cp values to identify persons who are at the highest risk of adverse outcomes such as hospital or ICU admission and who therefore may benefit from more intensive monitoring or early initiation of antiviral therapy.

SARS-CoV-2 viral-load distribution reveals that viral loads increase with age: a retrospective cross-sectional cohort study.

BACKGROUND: Describing the SARS-CoV-2 viral-load distribution in different patient groups and age categories. METHODS: All results from first nasopharyngeal (NP) and oropharyngeal (OP) swabs from unique patients tested via SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) collected between 1 January and 1 December 2020 predominantly in the Public Health Services regions Kennemerland and Hollands Noorden, province of North Holland, the Netherlands, were included in this study. SARS-CoV-2 PCR crossing-point (Cp)-values were used to estimate viral loads. RESULTS: In total, 278 455 unique patients were tested, of whom 9.1% (n = 25.374) were SARS-CoV-2-positive. PCRs performed by Public Health Services (n = 211 914), in which sampling and inclusion were uniform, revealed a clear relation between age and SARS-CoV-2 viral load, with especially children aged <12 years showing lower viral loads than adults (ß: -0.03, 95% confidence interval: -0.03 to -0.02, p < 0.001), independently of sex and/or symptom duration. Interestingly, the median Cp-values between the >79- and <12-year-old populations differed by more than four PCR cycles, suggesting an ∼16-fold difference in viral load. In addition, the proportion of children aged <12 years with a low load (Cp-value >30) was higher compared with other patients (31.1% vs 17.2%, p-value < 0.001). CONCLUSIONS: In patients tested by Public Health Services, SARS-CoV-2 viral load increases with age. Further studies should elucidate whether the lower viral load in children is indeed related to their suggested limited role in SARS-CoV-2 transmission. Moreover, as rapid antigen tests are less sensitive than PCR, these results suggest that SARS-CoV-2 antigen tests have lower sensitivity in children than in adults.

QTc Prolongation in COVID-19 Patients Using Chloroquine.

Chloroquine is used in the treatment of patients with COVID-19 infection, although there is no substantial evidence for a beneficial effect. Chloroquine is known to prolong the QRS and QTc interval on the ECG. To assess the effect of chloroquine on QRS and QTc intervals in COVID-19 patients, we included all inpatients treated with chloroquine for COVID-19 in the Spaarne Gasthuis (Haarlem/Hoofddorp, the Netherlands) and had an ECG performed both in the 72 h before and during or at least 48 h after treatment. We analyzed the (change in) QRS and QTc interval using the one-sample t-test. Of the 106 patients treated with chloroquine, 70 met the inclusion criteria. The average change in QRS interval was 6.0 ms (95% CI 3.3-8.7) and the average change in QTc interval was 32.6 ms (95% CI 24.9-40.2) corrected with the Bazett's formula and 38.1 ms (95% CI 30.4-45.9) corrected with the Fridericia's formula. In 19 of the 70 patients (27%), the QTc interval was above 500 ms after start of chloroquine treatment or the change in QTc interval was more than 60 ms. A heart rate above 90 bpm, renal dysfunction, and a QTc interval below 450 ms were risk factors for QTc interval prolongation. Chloroquine prolongs the QTc interval in a substantial number of patients, potentially causing rhythm disturbances. Since there is no substantial evidence for a beneficial effect of chloroquine, these results discourage its use in COVID-19 patients.

Ciprofloxacin does not Prolong the QTc Interval: A Clinical Study in ICU Patients and Review of the Literature.

PURPOSE: Ciprofloxacin may prolong the QT interval and increase the risk of Torsade de Pointes (TdP). Intravenous administration of ciprofloxacin in patients with additional risks may elevate the risk of QTc interval prolongation. We prospectively assessed whether intravenous ciprofloxacin prolongs the QT interval in patients with additional co-morbidities and risk factors. We also reviewed the literature on the QT prolonging effect or TdP inducing effect of ciprofloxacin. METHODS: ICU Patients who were treated with intravenous ciprofloxacin as part of their therapy were recruited. ECG was recorded within 60 min before start and in the last 30 min of 1 h infusion, or within 30 min after the end of ciprofloxacin infusion. QT interval was corrected for the heart rate using both Bazett's and Fridericia's formula. The changes were analyzed using the paired Student's t-test. RESULTS: Ten patients were included in the study (average age 74-y, 6 males). The average baseline QTc interval corrected with Bazett's formula was 448 ms that was shortened during or after ciprofloxacin infusion by 3 ms and 2 ms based on Bazett's  (p=0.67) and Fridericia's (p=0.68) formula, respectively. No observational study  or cohort study thus far has shown that ciprofloxacin has a QT prolonging effect or increases the risk of TdP or (cardiovascular) mortality.  Conclusion. Based on our results and the results of previous studies, it is unlikely that ciprofloxacin has a clinically relevant QT prolonging effect or an increased risk of TdP. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.