key: cord-305788-z75yv88e
authors: Agergaard, Charlotte Nielsen; Lis-Tønder, Joanna; Olsen, Dorte Aalund; Kierkegaard, Helene; Møller, Jens Kjølseth
title: Challenging diagnostics in familial transmission from asymptomatic COVID-19 carrier. Should we group SARS-CoV-2 samples from households?
date: 2020-09-28
journal: Int J Infect Dis
DOI: 10.1016/j.ijid.2020.09.1442
sha: 
doc_id: 305788
cord_uid: z75yv88e

nan

Dear Editor in Chief, By March 8, 85 COVID-19 cases had been diagnosed in Denmark and mid-March an estimated 50% of imported cases derived from Austria [https://files.ssi.dk/COVID19-overvaagningsrapport-12032020, Correa-Martínez et al., 2020] . March 3 to 8 a 49-year-old, man went skiing in Ischgl, Austria accompanied by 11 male friends. Few days after returning to Denmark, six travel companions developed symptoms of COVID-19 and were tested SARS-CoV-2 PCR positive. According to the Danish guidelines at that time, none of the six asymptomatic individuals was tested. However, one of these, the 49-year-old man and his family of four arranged a self-imposed two-week home quarantine on March 11. Approximately one week later his wife and 18-year-old daughter developed influenza-like symptoms. The following week the 15-year-old daughter developed ageusia while the 8-year-old old daughter presented her usual recurrent cough.

Extension of the national COVID-19 testing April 1 led the family to the local test-center, where the indexperson and the daughter presenting ageusia tested SARS-CoV-2 PCR positive. The wife and two other daughters tested negative. The three negative specimens together with 197 SARS-CoV-2 negative samples from other patients were retested at an external laboratory. All samples remained negative; but the specimens from the wife and youngest daughter were found weakly positive. Their initial PCR curves were reassessed and found equally irregular with Ct-values of 32 and 35.

Three weeks later, all five displayed a serologic SARS-CoV-2 N/S IgG response. The asymptomatic indexperson and the youngest daughter presenting the highest IgG-titers (chemiluminescence immunoassay (CLIA), iFlash1800 Shenzhen YHLO). Comparative testing with the SARS-CoV-2 S1/S2 IgG assay (CLIA, DiaSorin, Liaison) found the index-person and three daughters positive and the wife just below cut-off (Table 1) .

This family cluster incorporates several aspects of the challenges surrounding COVID-19 and SARS-CoV-2 diagnostics. The familial transmission from an asymptomatic carrier who displayed a positive SARS-CoV-2 PCR four weeks after infestation and a subsequent immunologic response. The wife and three daughters, who J o u r n a l P r e -p r o o f had mild symptoms of COVID-19, presented diverse and divergent SARS-CoV-2 PCR results, yet displayed an immunologic response.

This family case implies the importance of duration of infectiousness from an asymptomatic carrier [Chan et al., 2020 , Huang et al., 2020 . Secondly, that symptoms and generation of specific antibodies varies even among closely related family members, supporting the potential benefit of SARS-CoV-2 detection from a combination of nucleic acid testing and time-related serology [Fafi-kremer et al., 2020 , Flodgren 2020 , Okba et al., 2020 . Finally, that COVID-19 diagnostics and containment measures might benefit from grouping samples from households in order to collectively assess results and potential need of repeat sampling [Winichakoon et al., 2020] .

Oral and written informed consent to describe this family cluster was obtained from the father on behalf of the family. 

A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster

A pandemic in times of global tourism: super spreading and exportation of COVID-19 cases from a ski area in Austria

Serologic responses to SARS-CoV-2 infection among hospital staff with mild disease in eastern France

Immunity after SARS-CoV-2 infection, 1st update -a rapid review 2020

SSI. COVID-19 in Denmark, an epidemiological surveillance report

A family cluster of SARS-CoV-2 infection involving 11 patients in Nanjing, China

Severe acute respiratory syndrome Coronavirus 2−specific antibody responses in Coronavirus Disease 2019 patients

Negative nasopharyngeal and oropharyngeal swabs do not rule out COVID-19

The authors declare that there are no conflicts of interests.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-forprofit sectors.

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.J o u r n a l P r e -p r o o f