Two elementary parameters for quantifying viral infection and shedding are viral load and whether samples yield a replicating virus isolate in cell culture. We examined 25,381 German SARS-CoV-2 cases, including 6110 from test centres attended by pre-symptomatic, asymptomatic, and mildly-symptomatic (PAMS) subjects, 9519 who were hospitalised, and 1533 B.1.1.7 lineage infections. The youngest had mean log10 viral load 0.5 (or less) lower than older subjects and an estimated ~78% of the peak cell culture replication probability, due in part to smaller swab sizes and unlikely to be clinically relevant. Viral loads above 109 copies per swab were found in 8% of subjects, one-third of whom were PAMS, with mean age 37.6. We estimate 4.3 days from onset of shedding to peak viral load (8.1) and cell culture isolation probability (0.75). B.1.1.7 subjects had mean log10 viral load 1.05 higher than non-B.1.1.7, with estimated cell culture replication probability 2.6 times higher.

Estimating infectiousness throughout SARS-CoV-2 infection course.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory disease coronavirus 2 (SARS-CoV-2), has led to millions of confirmed cases and deaths worldwide. Efficient diagnostic tools are in high demand, as rapid and large-scale testing plays a pivotal role in patient management and decelerating disease spread. This paper reviews current technologies used to detect SARS-CoV-2 in clinical laboratories as well as advances made for molecular, antigen-based, and immunological point-of-care testing, including recent developments in sensor and biosensor devices. The importance of the timing and type of specimen collection is discussed, along with factors such as disease prevalence, setting, and methods. Details of the mechanisms of action of the various methodologies are presented, along with their application span and known performance characteristics. Diagnostic imaging techniques and biomarkers are also covered, with an emphasis on their use for assessing COVID-19 or monitoring disease severity or complications. While the SARS-CoV-2 literature is rapidly evolving, this review highlights topics of interest that have occurred during the pandemic and the lessons learned throughout. Exploring a broad armamentarium of techniques for detecting SARS-CoV-2 will ensure continued diagnostic support for clinicians, public health, and infection prevention and control for this pandemic and provide advice for future pandemic preparedness.

https://cmr.asm.org/content/cmr/34/3/e00228-20.full.pdf

Tools and Techniques for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)/COVID-19 Detection.

The coronavirus disease (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, is leading to unknown and unusual health conditions that are challenging to manage. Post-COVID-19 syndrome is one of those challenges, having become increasingly common as the pandemic evolves. The latest estimates suggest that 10 to 20% of the SARS-CoV-2 patients who undergo an acute symptomatic phase are experiencing effects of the disease beyond 12 weeks after diagnosis. Although research is beginning to examine this new condition, there are still serious concerns about the diagnostic identification, which limits the best therapeutic approach. Exercise programs and physical activity levels are well-known modulators of the clinical manifestations and prognosis in many chronic diseases. This narrative review summarizes the up-to-date evidence on post-COVID-19 syndrome to contribute to a better knowledge of the disease and explains how regular exercise may improve many of these symptoms and could reduce the long-term effects of COVID-19.

Post-COVID-19 Syndrome and the Potential Benefits of Exercise

Clarifying the evidence on SARS-CoV-2 antigen rapid tests in public health responses to COVID-19.

Background Little is known about clusters of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in acute care hospitals Objective To describe the detection, mitigation, and analysis of a large cluster of SARS-CoV-2 infections in an acute care hospital with mature infection control policies Design Descriptive study Setting Brigham and Women's Hospital, Boston, Massachusetts Participants Patients and staff with cluster-related SARS-CoV-2 infections Intervention Close contacts of infected patients and staff were identified and tested every 3 days, patients on affected units were preemptively isolated and repeatedly tested, affected units were cleaned, room ventilation was measured, and specimens were sent for whole-genome sequencing A case-control study was done to compare clinical interactions, personal protective equipment use, and breakroom and workroom practices in SARS-CoV-2-positive versus negative staff Measurements Description of the cluster, mitigation activities, and risk factor analysis Results Fourteen patients and 38 staff members were included in the cluster per whole-genome sequencing and epidemiologic associations The index case was a symptomatic patient in whom isolation was discontinued after 2 negative results on nasopharyngeal polymerase chain reaction testing The patient subsequently infected multiple roommates and staff, who then infected others Seven of 52 (13%) secondary infections were detected only on second or subsequent tests Eight of 9 (89%) patients who shared rooms with potentially contagious patients became infected Potential contributing factors included high viral loads, nebulization, and positive pressure in the index patient's room Risk factors for transmission to staff included presence during nebulization, caring for patients with dyspnea or cough, lack of eye protection, at least 15 minutes of exposure to case patients, and interactions with SARS-CoV-2-positive staff in clinical areas Whole-genome sequencing confirmed that 2 staff members were infected despite wearing surgical masks and eye protection Limitation Findings may not be generalizable Conclusion SARS-CoV-2 clusters can occur in hospitals despite robust infection control policies Insights from this cluster may inform additional measures to protect patients and staff Primary funding source None

A SARS-CoV-2 Cluster in an Acute Care Hospital.

Background The detection of SARS-CoV-2 by real-time polymerase chain reaction (PCR) in respiratory samples collected from persons recovered from COVID-19 does not necessarily indicate shedding of infective virions. By contrast, the isolation of SARS-CoV-2 using cell-based culture likely indicates infectivity, but there are limited data on the correlation between SARS-CoV-2 culture and PCR. Here we review our experience using SARS-CoV-2 culture to determine infectivity and safe de-isolation of COVID-19 patients. Methods 195 patients with diverse severity of COVID-19 were tested (outpatients [n=178]), inpatients [n=12] and ICU [n=5]). SARS-CoV-2 PCR positive samples were cultured in Vero C1008 cells and inspected daily for cytopathic effect (CPE). SARS-CoV-2-induced CPE was confirmed by PCR of culture supernatant. Where no CPE was documented, PCR was performed on day four to confirm absence of virus replication. Cycle threshold (Ct) values of the day four PCR (Ctculture) and the PCR of the original clinical sample (Ctsample) were compared, and positive cultures were defined as a Ctsample - Ctculture value of ≥3. Findings Of 234 samples collected, 228 (97%) were from the upper respiratory tract. SARS-CoV-2 was only successfully isolated from samples with Ctsample values Conclusion SARS-CoV-2 culture may be used as a surrogate marker for infectivity and inform de-isolation protocols.

https://www.medrxiv.org/content/medrxiv/early/2020/07/16/2020.07.14.20153981.full.pdf

Cell-based culture of SARS-CoV-2 informs infectivity and safe de-isolation assessments during COVID-19

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Cell-based culture of SARS-CoV-2 informs infectivity and safe de-isolation assessments during COVID-19