Viral dynamics of SARS-CoV-2 variants in vaccinated and unvaccinated individuals

Background The alpha and delta SARS-CoV-2 variants have been responsible for major recent waves of COVID-19 despite increasing vaccination rates. The reasons for the increased transmissibility of these variants and for the reduced transmissibility of vaccine breakthrough infections are unclear. Methods We quantified the course of viral proliferation and clearance for 173 individuals with acute SARS-CoV-2 infections using longitudinal quantitative RT-PCR tests conducted using anterior nares/oropharyngeal samples ( n = 199,941) as part of the National Basketball Association’s (NBA) occupational health program between November 28th, 2020, and August 11th, 2021. We measured the duration of viral proliferation and clearance and the peak viral concentration separately for individuals infected with alpha, delta, and non-variants of interest/variants of concern (non-VOI/VOC), and for vaccinated and unvaccinated individuals. Results The mean viral trajectories of alpha and delta infections resembled those of non-VOI/VOC infections. Vaccine breakthrough infections exhibited similar proliferation dynamics as infections in unvaccinated individuals (mean peak Ct: 20.5, 95% credible interval [19.0, 21.0] vs . 20.7 [19.8, 20.2], and mean proliferation time 3.2 days [2.5, 4.0] vs . 3.5 days [3.0, 4.0]); however, vaccinated individuals exhibited faster clearance (mean clearance time: 5.5 days [4.6, 6.6] vs . 7.5 days [6.8, 8.2]). Conclusions Alpha, delta, and non-VOI/VOC infections feature similar viral trajectories. Acute infections in vaccinated and unvaccinated people feature similar proliferation and peak Ct, but vaccinated individuals cleared the infection more quickly. Viral concentrations do not fully explain the differences in infectiousness between SARS-CoV-2 variants, and mitigation measures are needed to limit transmission from vaccinated individuals. ### Competing Interest Statement JW is an employee of Quest Diagnostics. JW is an employee of Bioreference Laboratories. NDG has a consulting agreement for Tempus and receives financial support from Tempus to develop SARS-CoV-2 diagnostic tests. SMK, SWO, and YHG have a consulting agreement with the NBA. ### Funding Statement Huffman Family Donor Advised Fund (NDG); Fast Grant funding from the Emergent Ventures at 85 the Mercatus Center; George Mason University (NDG); the Morris-Singer Fund for the Center for 86 Communicable Disease Dynamics at the Harvard T.H. Chan School of Public Health (YHG). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Residual de-identified viral transport media from anterior nares and oropharyngeal swabs collected from players, staff, vendors, and associated household members from a professional sports league were obtained from BioReference Laboratories. In accordance with the guidelines of the Yale Human Investigations Committee, this work with de-identified samples was approved for research not involving human subjects by the Yale Intitutional Review Board (HIC protocol # 2000028599). This project was designated exempt by the Harvard IRB (IRB20-1407). All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data and code are available online at