Lettter to the editor: N Engl J Med 2020; 383:2291-2293 DOI: 10.1056/NEJMc2031364
A 45-year-old man with severe antiphospholipid syndrome complicated by diffuse alveolar hemorrhage,1 who was receiving anticoagulation therapy, glucocorticoids, cyclophosphamide, and intermittent rituximab and eculizumab, was admitted to the hospital with fever (Fig. S1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org). On day 0, Covid-19 was diagnosed by SARS-CoV-2 reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay of a nasopharyngeal swab specimen, and the patient received a 5-day course of remdesivir (Fig. S2). Glucocorticoid doses were increased because of suspected diffuse alveolar hemorrhage. He was discharged on day 5 without a need for supplemental oxygen.
From day 6 through day 68, the patient quarantined alone at home, but during the quarantine period, he was hospitalized three times for abdominal pain and once for fatigue and dyspnea. The admissions were complicated by hypoxemia that caused concern for recurrent diffuse alveolar hemorrhage and was treated with increased doses of glucocorticoids. SARS-CoV-2 RT-PCR cycle threshold (Ct) values increased to 37.8 on day 39, which suggested resolving infection (Table S1).2,3
On day 72 (4 days into another hospital admission for hypoxemia), RT-PCR assay of a nasopharyngeal swab was positive, with a Ct value of 27.6, causing concern for a recurrence of Covid-19. The patient again received remdesivir (a 10-day course), and subsequent RT-PCR assays were negative.
On day 105, the patient was admitted for cellulitis. On day 111, hypoxemia developed, ultimately requiring treatment with high-flow oxygen. Given the concern for recurrent diffuse alveolar hemorrhage, the patient’s immunosuppression was escalated (Figs. S1 through S3). On day 128, the RT-PCR Ct value was 32.7, which caused concern for a second Covid-19 recurrence, and the patient was given another 5-day course of remdesivir. A subsequent RT-PCR assay was negative. Given continued respiratory decline and concern for ongoing diffuse alveolar hemorrhage, the patient was treated with intravenous immunoglobulin, intravenous cyclophosphamide, and daily ruxolitinib, in addition to glucocorticoids.
On day 143, the RT-PCR Ct value was 15.6, which caused concern for a third recurrence of Covid-19. The patient received a SARS-CoV-2 antibody cocktail against the SARS-CoV-2 spike protein (Regeneron).4 On day 150, he underwent endotracheal intubation because of hypoxemia. A bronchoalveolar-lavage specimen on day 151 revealed an RT-PCR Ct value of 15.8 and grew Aspergillus fumigatus. The patient received remdesivir and antifungal agents. On day 154, he died from shock and respiratory failure.
We performed quantitative SARS-CoV-2 viral load assays in respiratory samples (nasopharyngeal and sputum) and in plasma, and the results were concordant with RT-PCR Ct values, peaking at 8.9 log10 copies per milliliter (Fig. S2 and Table S1). Tissue studies showed the highest SARS-CoV-2 RNA levels in the lungs and spleen (Figs. S4 and S5).
SARS-CoV-2 Whole-Genome Viral Sequencing from Longitudinally Collected Nasopharyngeal Swabs.
Phylogenetic analysis was consistent with persistent infection and accelerated viral evolution (Figures 1A and S6). Amino acid changes were predominantly in the spike gene and the receptor-binding domain, which make up 13% and 2% of the viral genome, respectively, but harbored 57% and 38% of the observed changes (Figure 1B). Viral infectivity studies confirmed infectious virus in nasopharyngeal samples from days 75 and 143 (Fig. S7). Immunophenotyping and SARS-CoV-2–specific B-cell and T-cell responses are shown in Table S2 and Figures S8 through S11.
Although most immunocompromised persons effectively clear SARS-CoV-2 infection, this case highlights the potential for persistent infection5 and accelerated viral evolution associated with an immunocompromised state.
This happened in 2020 - before vaccinations.
Suspect it has happened many times in 2021 with vaccinated immunocompromized persons
The person is a "test laboratory" for the virus
The virus is able to "try" many mutations
- Mutations of SARS-CoV-2 spike protein: Implications on immune evasion and vaccine-induced immunity - Nov 20, 2021 https://doi.org/10.1016/j.smim.2021.101533 FREE PDF
- COVID-19 mRNA Vaccine Immunogenicity in Immunosuppressed Individuals Nov 20, 2021 https://doi.org/10.1093/infdis/jiab569 FREE PDF -Vaccinated persons
- Treatment of chronic or relapsing COVID-19 in immunodeficiency - Nov 12, 2021 https://doi.org/10.1016/j.jaci.2021.10.031 FREE PDF
- Persistent SARS-CoV-2 infection with repeated clinical recurrence in a patient with common variable immunodeficiency - Nov10 2021 https://doi.org/10.1016/j.cmi.2021.10.021 FREE PDF
- Immunocompromised Host: Persistent Shedding of Viable SARS-CoV-2 and Emergence of Multiple Mutations, a Case Report. - Oct 29, 2021 https://doi.org/10.1016/j.ijid.2021.10.045 FREE PDF
- COVID-19 in an Immunocompromised Host: Persistent Shedding of Viable SARS-CoV-2 and Emergence of Multiple Mutations, a Case Report.- Oct 29 ,2 021 https://doi.org/10.1016/j.ijid.2021.10.045 FREE PDF