Aim The objective of this observational study was to investigate the association between SARS-CoV-2 transmission risk, RT-PCR Cycle threshold (Ct) values, and age of infected cases in Danish households.
Background The Covid-19 pandemic is one of the most serious global public health threats in recent times. Understanding transmission of SARS-CoV-2 is of utmost importance to be able to respond to outbreaks and take action against the spread of the disease. Viral load is generally thought to correlate with transmission risk.
Methods We used comprehensive administrative register data from Denmark, comprising the full population and all SARS-CoV-2 tests (August 25, 2020 to February 10, 2021), to estimate household transmission risk.
Results We found that the transmission risk was negatively associated—approximately linear—with the Ct values of the tested primary cases. Also, we found that even for relatively high Ct values, the risk of transmission was not negligible; e.g., for primary cases with a Ct value of 38, we found a transmission risk of 8%. This implies that there is no obvious cut-off for Ct values for risk of transmission.
We estimated the transmission risk according to age and found an almost linearly increasing transmission risk with the age of the primary cases for adults (≥20 years) and negatively for children (<20 years). Age had a higher impact than Ct value on the risk of transmission.
Conclusions Lower Ct values (indicating higher viral load) are associated with higher risk of SARS-CoV-2 transmission. However, even at high Ct values, transmission occurs. In addition, we found a strong association between age and transmission risk, and this dominated the Ct value association.
Antiviral treatment of immunocompromised patients with prolonged influenza virus infection can lead to multidrug resistance. This study reveals the selection of antiviral resistance mutations in influenza A(H1N1)pdm09 virus in an immunocompromised patient during a 6-month period. The patient was treated with two courses of oseltamivir (5 days and 2 months, respectively), with the first course starting at symptom onset, and subsequently zanamivir (2 months and 10 days, respectively). Respiratory samples were investigated by Sanger and next generation sequencing (NGS) and, for NGS data, low-frequency-variant-detection analysis was performed. Neuraminidase-inhibition tests were conducted for samples isolated in Madin-Darby canine kidney cells. In a sample collected 15 days after the end of the first treatment with oseltamivir (Day 20 post-symptom onset), oseltamivir resistance was detected (mutation H275Y with 60.3% frequency by NGS). Day 149 when the patient had almost completed the second zanamivir treatment, mixes of the following resistance mutations were detected; H275Y(65.1%), I223R(9.2%), and E119G(89.6%), accompanied by additional mutations, showing a more complex viral population in the long-term treated patient. Two samples obtained on Day 151 from bronchoalveolar lavage (BAL) and nasopharyngeal swab, respectively, showed different mutation profiles, with a higher frequency of antiviral resistance mutations in BAL. The results emphasise the importance of timely antiviral resistance testing both for treatment of individual patients as well as for preventive measures to control the development and transmission of antiviral resistant viruses.
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