Virological and serological characterization of critically ill patients with COVID-19 in the UK: a special focus on variant detection
Ratcliff J., Nguyen D., Fish M., Rhynne J., Jennings A., Williams S., Al-Beidh F., Bonsall D., Evans A., Golubchik T., Gordon AC., Lamikanra A., Tsang P., Ciccone N., Leuscher U., Slack W., Laing E., Mouncey PR., Ziyenge S., Olivera M., Ploeg R., Rowan KM., Shankar-Hari M., Roberts DJ., Menon DK., Estcourt L., Simmonds P., Harvala H.
<jats:title>ABSTRACT</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Treatment of COVID-19 patients with convalescent plasma containing neutralising antibody to SARS-CoV-2 is under investigation as a means of reducing viral loads, ameliorating disease outcomes, and reducing mortality. However, its efficacy might be reduced in those infected with the emerging B.1.1.7 SARS-CoV-2 variant. Here, we report the diverse virological characteristics of UK patients enrolled in the Immunoglobulin Domain of the REMAP-CAP randomised controlled trial.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>SARS-CoV-2 viral RNA was detected and quantified by real-time PCR in nasopharyngeal swabs obtained from study subjects within 48 hours of admission to intensive care unit. Antibody status was determined by spike-protein ELISA. B.1.1.7 strain was differentiated from other SARS-CoV-2 strains by two novel typing methods detecting the B.1.1.7-associated D1118H mutation with allele-specific probes and by restriction site polymorphism (SfcI).</jats:p></jats:sec><jats:sec><jats:title>Findings</jats:title><jats:p>Of 1260 subjects, 90% were PCR-positive with viral loads in nasopharyngeal swabs ranging from 72 international units [IUs]/ml to 1.7×10<jats:sup>11</jats:sup> IU/ml. Median viral loads were 45-fold higher in those who were seronegative for IgG antibodies (n=314; 28%) compared to seropositives (n=804; 72%), reflecting in part the latter group’s possible later disease stage on enrolment. Frequencies of B.1.1.7 infection increased from early November (<1%) to December 2020 (>60%). Anti-SARS-CoV-2 seronegative individuals infected with wild-type SARS-CoV-2 had significantly higher viral loads than seropositives (medians of 1.2×10<jats:sup>6</jats:sup> and 3.4 ×10<jats:sup>4</jats:sup> IU/ml respectively; p=2×10<jats:sup>−9</jats:sup>). However, viral load distributions were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (13.4×10<jats:sup>6</jats:sup> and 7.6×10<jats:sup>6</jats:sup> IU/ml; p=0.18).</jats:p></jats:sec><jats:sec><jats:title>Interpretation</jats:title><jats:p>High viral loads in seropositive B.1.1.7-infected subjects are consistent with increased replication capacity and/or less effective clearance by innate or adaptive immune response of B.1.1.7 strain than wild-type. As viral genotype was associated with diverse virological and immunological phenotypes, metrics of viral load, antibody status and infecting strain should be used to define subgroups for analysis of treatment efficacy.</jats:p></jats:sec>