Ferritin and C-reactive protein (CRP) significantly declined as compared to pre-transfusion whereas the lymphocyte count returned to normal. SARS-CoV-2 infected patients, uncertainty remains in those patients with underlying immunodeficiency. Walsh et?al. included a total of 15 relevant studies, but only two of them identified immunosuppressed patients from whom SARS-CoV-2 was isolated for up to 20 days beyond onset of disease.4 , 5 Here, we report SARS-CoV-2 positive viral Apremilast (CC 10004) culture 7 weeks after onset of COVID-19 in a patient with an underlying immunosuppressive disorder, so-called X chromosome-linked agammaglobulinemia (XLA), demonstrating the potential of prolonged SARS-CoV-2 spreading beyond widely accepted isolation precautions. Our patient had been tested positive for SARS-CoV-2 ribonucleic acid (RNA) by reverse transcription real-time polymerase Apremilast (CC 10004) chain reaction (RT-PCR) from upper respiratory specimen first on March 11 2020,. At this point of time, symptoms comprised fever and fatigue. In the patient’s medical history, XLA, obstructive respiratory disorder, impaired alveolar diffusion capacity and non-cystic fibrosis bronchiectasis were recorded. Due to worsening of fever, cough and dyspnea, the patient required for hospitalization 16 days after the initial diagnosis of COVID-19. The patient received antibiotic treatment with amoxicillin/clavulanic acid and azithromycin, was switched to piperacillin/tazobactam, followed by moxifloxacin and meropenem. Based on local recommendations valid at this point of time, the patient was treated with hydroxychloroquine and then by an antiretroviral combination of lopinavir/ritonavir. Furthermore, posaconazole was administered for Aspergillus positive sputum culture and intravenous immunoglobulin substitution (IVIG) was performed regarding the absence of endogenous antibody production in underlying XLA. Due to persistent fever up to 40.4?C, progressive respiratory insufficiency and deterioration of laboratory parameters expressing an increasing inflammatory activity, the patient was transmitted to the Intensive Care Unit (ICU) on April 9. Interleukin-6 (IL-6) receptor blockade by tocilizumab and convalescent plasma were administered on April 10. No adverse effects related to this treatment regimen were recorded. The rationale behind this approach was to restrain the inflammatory response Tmem33 by IL-6 blockade and to provide neutralizing COVID-19 immunoglobulins by convalescent Apremilast (CC 10004) plasma. Afterwards, we observed a rapid recovery regarding clinical and laboratory parameters. Ferritin and C-reactive protein (CRP) significantly declined as compared to pre-transfusion whereas the lymphocyte count returned to normal. We observed an increase in IL-6 after treatment followed by a fast and almost complete decline within the next days. Body temperature did not exceed a limit of 38?C as compared to measurements of up to 40.4?C pre-transfusion. Oxygen demand decreased resulting in an increase of Apremilast (CC 10004) PaO2/FiO2 ratio (143 before versus 223 after treatment).? A chest radiograph showed a significant decline in infiltrative opacities. On Apremilast (CC 10004) April 15, five days after tocilizumab and convalescent plasma administration and five weeks after the initial diagnosis of COVID-19, SARS-CoV-2 RNA was not detectable for the first time.? The patient showed progressive clinical recovery, but an alternating course of three negative followed by three positive SARS-CoV-2 RT-PCR results was subsequently observed. Convalescent plasma transfusion was repeated on April 21. Despite full clinical recovery, SARS-CoV-2 RT-PCR showed six positive and also six negative SARS-CoV-2 RT-PCR results in an alternating order in the time span between April 23 and May 4. SARS-CoV-2 PCR from oropharyngeal swabs and sputum obtained on April 24 showed 103 (sputum) to 105 (oropharyngeal swabs) SARS-CoV-2 copies/mL. A SARS-CoV-2 PCR-positive oropharyngeal swab with a low cycle threshold (Ct) value of 25 was inoculated onto Vero E6 cells for viral culture. A cytopathic effect was observed four days after inoculation, and the presence of SARS-CoV-2 in the cell culture supernatant was confirmed by RT-PCR (Ct value of 16 at a 10-fold higher dilution than the original swab). In contrast to this finding, previously published reports revealed that the viral burden measured in respiratory specimens obtained from mild coronavirus disease 2019 (COVID-19) cases declined after onset of symptoms and was considered without infectious potential beyond day 9 or 10 of symptoms with less than 105 viral ribonucleic acid (RNA) copies/mL of sputum.6 , 7 Based on the clinical improvement and three negative follow up SARS-CoV-2 PCR results the patient was discharged on May 5 and isolated at home. Almost 2 weeks later a SARS-CoV-2 PCR showed 500 copies/mL in transport medium (containing the oropharyngeal swab) and the viral culture was negative. Fig.?1 presents an overview by timeline from the initial diagnosis of COVID-19 up until negative viral culture. Open in a separate window Fig. 1 Timeline presenting milestones of disease from onset of COVID 19 up until negative virus culture. Our patient was diagnosed with COVID-19 based on a positive result from SARS-CoV-2 RT-PCR first on March 11. Admission to the hospital was.