Clinical presentation and virological assessment of hospitalized cases of coronavirus disease 2019 in a travel-associated transmission cluster

Roman Woelfel; Victor Max Corman; Wolfgang Guggemos; Michael Seilmaier; Sabine Zange; Marcel A Mueller; Daniela Niemeyer; Patrick Vollmar; Camilla Rothe; Michael Hoelscher; Tobias Bleicker; Sebastian Bruenink; Julia Schneider; Rosina Ehmann; Katrin Zwirglmaier; Christian Drosten; Clemens Wendtner

The serological courses of all patients suggest a timing of seroconversion similar to or slightly earlier than in SARS-CoV infection 18 . Seroconversion in most cases of SARS occurred during the second week of symptoms. As in SARS and MERS, IgM was not detected significantly earlier than IgG in immunofluorescence, which might in part be due to technical reasons as the higher avidity of IgG antibodies outcompetes IgM for viral epitopes in the assay. IgG depletion can only partially alleviate this effect. Because IFA is a laborintensive method, ELISA tests should be developed as a screening test. Neutralization testing is necessary to rule out cross-reactive antibodies directed against endemic human coronaviruses. Based on frequently low neutralizing antibody titers observed in coronavirus infection 12,25 , we have here developed a particularly sensitive plaque reduction neutralization assay. Considering the titers observed, a simpler microneutralization test format is likely to provide sufficient sensitivity in routine application and population studies.