key: cord-0961238-ht3wwjyf authors: Rodríguez‐Grande, Cristina; Catalán, Pilar; Alcalá, Luis; Buenestado‐Serrano, Sergio; Adán‐Jiménez, Javier; Rodríguez‐Maus, Sandra; Herranz, Marta; Sicilia, Jon; Acosta, Fermín; Pérez‐Lago, Laura; Muñoz, Patricia; García de Viedma, Darío title: Different dynamics of mean SARS‐CoV‐2 RT‐PCR Ct values between the first and second COVID‐19 waves in the Madrid population date: 2021-03-05 journal: Transbound Emerg Dis DOI: 10.1111/tbed.14045 sha: 8313aaa70b775b9c7ff62f102d6318ac3fa742ea doc_id: 961238 cord_uid: ht3wwjyf SARS‐CoV‐2 RT‐PCR cycle threshold values from 18,803 cases (2 March–4 October) in Madrid define three stages: (i) initial ten weeks with sustained reduction in viral load (Ct: 23.4–32.3), (ii) stability with low viral loads (Ct: 31.9–35.5) in the next nine weeks and (iii) sudden increase with progressive higher viral loads until reaching stability at high levels in the next twelve weeks, coinciding with an increased percentage of positive cases and reduced median age. These data indicate differential virological/epidemiological patterns between the first and second COVID‐19 waves in Madrid. COVID-19 pandemic, covering the first and second waves, in the population of 650,000 inhabitants covered by a tertiary hospital in Madrid, Spain. The study period included the 18,803 cases, with a Ct value available, diagnosed in our laboratory from Week 10 to Week 40 (2 March-4 October). The first COVID-19 case was diagnosed by RT-PCR on 29 February. We stopped at Week 40 of our observation period because antigenic rapid tests started to be applied at the emergency room in our hospital and at the health centres covering our population. It meant a marked reduction in the number of COVID-19 cases which were diagnosed by RT-PCR which would have biased the data if prolonging our study beyond Week 40 (a reduction of 41.7% in the number of RT-PCRs was registered for Week 41). RNA was extracted and purified from 300 μl of nasopharyngeal exudates by using for most of the specimens the KingFisher (Thermo Fisher Scientific, Waltham, Massachusetts) system and, alternatively, the EasyMag (Biomerieux, France) equipment. 20 µl of purified RNA was used as template for the RT-PCR. Along the first COVID wave, due to frequent shortages of reagents, different RT-PCR systems were used: TaqMan In all reactions, we included as controls a SARS-CoV-2 RT-PCRpositive specimen and a negative clinical specimen, which were reextracted and tested in parallel with the clinical problem specimens. Samples were considered positive if the cycle threshold (Ct) value was ≤40. (Armengaud et al., 2020) , could explain the progressive reduction in viral load and subsequent stabilization at values associated with low viral burden seen for the two first stages. However, the sharp increase in viral load observed in the last stage rules out this hypothesis. Alternatively, the dynamics may be explained by an increased efficiency in early diagnosis not only of the most severe cases, but also progressively the mild ones. The dynamics for the third current stage are worrying. The low viral load value plateau observed in the previous weeks was interrupted, and a new stage emerged characterized by an alarming progressive increase towards the highest viral load ever registered amongst our population. The median age of patients showed a decreasing trend throughout the study period. Linear regression analysis revealed that this trend adjusted to the function Age = −0.9*Week + 73.5, which corresponds to a mean reduction of 0.9 years per analysed week (Figure 2 ). The combination of high viral loads plus younger ages was not observed in the two first stages. Higher transmission rates are expected due to this new pattern and consequently a cause of alarm. We must assume the limitations of using Ct values as a proxy to estimate viral load. Samples used for COVID-19 diagnosis are mainly nasopharyngeal; thus, different biases, related to the quality and efficiency of the sampling, may influence Ct values, besides the viral load itself (Mathers, 2020) . However, our sample size, providing data of nearly 10,000 cases diagnosed in the whole pandemic, should compensate this potential bias. We believe that, despite not being very precise, the information extracted from Ct data may be useful cases in younger subjects. These two points seem to point to marked differential epidemiological features characterizing the consecutive COVID-19 waves in Madrid. The authors would like to thank José María Bellón from the Methodology and Biostatistics Unit of Instituto de Investigación Sanitaria Gregorio Marañón for performing the statistical analysis. We are grateful to Dainora Jaloveckas (cienciatraducida.com) for editing and proofreading assistance. No author declared a conflict of interest. Sergio Buenestado-Serrano https://orcid.org/0000-0003-1739-4459 Laura Pérez-Lago https://orcid.org/0000-0001-5249-7619 Darío García de Viedma https://orcid.org/0000-0003-3647-7110 The importance of naturally attenuated SARS-CoV-2 in the fight against COVID-19 Author Correction: Temporal dynamics in viral shedding and transmissibility of COVID-19 Virus shedding dynamics in asymptomatic and mildly symptomatic patients infected with SARS-CoV-2 Viral dynamics in mild and severe cases of COVID-19. The Lancet Infectious Diseases Impact of SARS-CoV-2 viral load on risk of intubation and mortality among hospitalized patients with Coronavirus disease 2019 The practical challenges of making clinical use of the quantitative value for SARS-CoV-2 viral load across several dynamics A narrative systematic review of the clinical utility of cycle threshold values in the context of COVID-19 Duration of infectiousness and correlation with RT-PCR cycle threshold values in cases of COVID-19 How to cite this article Different dynamics of mean SARS-CoV-2 Ct values between the first and second COVID-19 waves in the Madrid population