The CoLab score is associated with SARS-CoV-2 viral load during admission in individuals admitted to the intensive care unit: the CoLaIC cohort study.

OBJECTIVES: The present study examines the temporal association between the changes in SARS-CoV-2 viral load during infection and whether the CoLab-score can facilitate de-isolation. METHODS: Nasal swabs and blood samples were collected from ICU-admitted SARS-CoV-2 positive patients at Maastricht UMC+ from March 25, 2020 to October 1, 2021. The CoLab-score was calculated based on 10 blood parameters and age and can range from -43 to 6. Three mixed effects analyses compared patient categories based on initial PCR Ct values (low; Ct≤20, mid; 20>Ct≤30, high; Ct>30), serial PCR Ct values to CoLab-scores over time, and the association between within-patient delta Ct values and CoLab-scores. RESULTS: In 324 patients, the median Ct was 33, and the median CoLab-score was -1.78. Mid (n=110) and low (n=41) Ct-categories had higher CoLab-scores over time (+0.60 points, 95 % CI; 0.04-1.17, and +0.28 points, 95 % CI -0.49 to 1.04) compared to the high Ct (n=87) category. Over time, higher serial Ct values were associated with lower serial CoLab-scores, decreasing by -0.07 points (95 % CI; -0.11 to -0.02) per day. Increasing delta Ct values were associated with a decreasing delta CoLab-score of -0.12 (95 % CI; -0.23; -0.01). CONCLUSIONS: The study found an association between lower viral load on admission and reduced CoLab-score. Additionally, a decrease in viral load over time was associated with a decrease in CoLab-score. Therefore, the CoLab-score may make patient de-isolation an option based on the CoLab-score.

Advancing COVID-19 diagnostics: rapid detection of intact SARS-CoV-2 using viability RT-PCR assay.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). Commonly used methods for both clinical diagnosis of SARS-CoV-2 infection and management of infected patients involve the detection of viral RNA, but the presence of infectious virus particles is unknown. Viability PCR (v-PCR) uses a photoreactive dye to bind non-infectious RNA, ideally resulting in the detection of RNA only from intact virions. This study aimed to develop and validate a rapid v-PCR assay for distinguishing intact and compromised SARS-CoV-2. Propidium monoazide (PMAxx) was used as a photoreactive dye. Mixtures with decreasing percentages of intact SARS-CoV-2 (from 100% to 0%) were prepared from SARS-CoV-2 virus stock and a clinical sample. Each sample was divided into a PMAxx-treated part and a non-PMAxx-treated part. Reverse transcription-PCR (RT-PCR) using an in-house developed SARS-CoV-2 viability assay was then applied to both sample sets. The difference in intact SARS-CoV-2 was determined by subtracting the cycle threshold (Ct) value of the PMAxx-treated sample from the non-PMAxx-treated sample. Mixtures with decreasing concentrations of intact SARS-CoV-2 showed increasingly lower delta Ct values as the percentage of intact SARS-CoV-2 decreased, as expected. This relationship was observed in both high and low viral load samples prepared from cultured SARS-CoV-2 virus stock, as well as for a clinical sample prepared directly from a SARS-CoV-2 positive nasopharyngeal swab. In this study, a rapid v-PCR assay has been validated that can distinguish intact from compromised SARS-CoV-2. The presence of intact virus particles, as determined by v-PCR, may indicate SARS-CoV-2 infectiousness. IMPORTANCE: This study developed a novel method that can help determine whether someone who has been diagnosed with coronavirus disease 2019 (COVID-19) is still capable of spreading the virus to others. Current tests only detect the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, but cannot tell whether the particles are still intact and can thus infect cells. The researchers used a dye that selectively blocks the detection of damaged virions and free RNA. They showed that this viability PCR reliably distinguishes intact SARS-CoV-2 capable of infecting from damaged SARS-CoV-2 or free RNA in both cultured virus samples and a clinical sample. Being able to quickly assess contagiousness has important implications for contact tracing and safely ending isolation precautions. This viability PCR technique provides a simple way to obtain valuable information, beyond just positive or negative test results, about the actual risk someone poses of transmitting SARS-CoV-2 through the air or surfaces they come into contact with.

The laboratory parameters-derived CoLab score as an indicator of the host response in ICU COVID-19 patients decreases over time: a prospective cohort study.

The CoLab score was developed and externally validated to rule out COVID-19 among suspected patients presenting at the emergency department. We hypothesized a within-patient decrease in the CoLab score over time in an intensive care unit (ICU) cohort. Such a decrease would create the opportunity to potentially rule out the need for isolation when the infection is overcome. Using linear mixed-effects models, data from the Maastricht Intensive Care COVID (MaastrICCht) cohort were used to investigate the association between time and the CoLab score. Models were adjusted for sex, APACHE II score, ICU mortality, and daily SOFA score. The CoLab score decreased by 0.30 points per day (95% CI - 0.33 to - 0.27), independent of sex, APACHE II, and Mortality. With increasing SOFA score over time, the CoLab score decreased more strongly (- 0.01 (95% CI - 0.01 to - 0.01) additional decrease per one-point increase in SOFA score.) The CoLab score decreased in ICU patients on mechanical ventilation for COVID-19, with a one-point reduction per three days, independent of sex, APACHE II, and ICU mortality, and somewhat stronger with increasing multi-organ failure over time. This suggests that the CoLab score would decrease below a threshold where COVID-19 can be excluded.

Validating a clinical laboratory parameter-based deisolation algorithm for patients with COVID-19 in the intensive care unit using viability PCR: the CoLaIC multicentre cohort study protocol.

INTRODUCTION: To investigate whether biochemical and haematological changes due to the patient's host response (CoLab algorithm) in combination with a SARS-CoV-2 viability PCR (v-PCR) can be used to determine when a patient with COVID-19 is no longer infectious.We hypothesise that the CoLab algorithm in combination with v-PCR can be used to determine whether or not a patient with COVID-19 is infectious to facilitate the safe release of patients with COVID-19 from isolation. METHODS AND ANALYSIS: This study consists of three parts using three different cohorts of patients. All three cohorts contain clinical, vital and laboratory parameters, as well as logistic data related to isolated patients with COVID-19, with a focus on intensive care unit (ICU) stay. The first cohort will be used to develop an algorithm for the course of the biochemical and haematological changes of the host response of the COVID-19 patient. Simultaneously, a second prospective cohort will be used to investigate the algorithm derived in the first cohort, with daily measured laboratory parameters, next to conventional SARS-CoV-2 reverse transcriptase PCRs, as well as v-PCR, to confirm the presence of intact SARS-CoV-2 particles in the patient. Finally, a third multicentre cohort, consisting of retrospectively collected data from patients with COVID-19 admitted to the ICU, will be used to validate the algorithm. ETHICS AND DISSEMINATION: This study was approved by the Medical Ethics Committee from Maastricht University Medical Centre+ (cohort I: 2020-1565/300523) and Zuyderland MC (cohorts II and III: METCZ20200057). All patients will be required to provide informed consent. Results from this study will be disseminated via peer-reviewed journals and congress/consortium presentations.