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By Christian Hoffmann &
Bernd S. Kamps
26 August
Epidemiology
Perkins TA, Cavany SM, Moore SM, et al. Estimating unobserved SARS-CoV-2 infections in the United States. PNAS August 21, 2020. Full-text: https://doi.org/10.1073/pnas.2005476117
The authors quantified unobserved infections in the United States during the early weeks of the epidemic. After a national emergency was declared, fewer than 10% of locally acquired, symptomatic infections in the US may were detected over a period of a month. This gap in surveillance during a critical phase of the epidemic resulted in a large, unobserved reservoir by early March. Testing was a major limiting factor in assessing the extent of SARS-CoV-2 transmission during its initial invasion into the US.
Virology, Immunology
To KK, Hung IF, Ip JD, et al. COVID-19 re-infection by a phylogenetically distinct SARS-coronavirus-2 strain confirmed by whole genome sequencing. Clinical Infectious Diseases, 25 August 2020, ciaa1275. Full-text: https://doi.org/10.1093/cid/ciaa1275
The first case of re-infection? During recent weeks, there has been probably no other case report gaining so much media attention as this 33-year old gentleman residing in Hong Kong. By the end of March, a mildly symptomatic SARS-CoV-2 infection was confirmed by a positive posterior oropharyngeal saliva PCR on March 26, 2020. On August 15, 142 days later, the patient returned to Hong Kong from Spain via the United Kingdom and was tested positive by SARS-CoV-2 RT-PCR on the posterior oropharyngeal saliva taken for entry screening at the Hong Kong airport. Of note, the patient remained asymptomatic during the second episode but had elevated CRP, relatively high viral load with gradual decline, and seroconversion of SARS-CoV-2 IgG during the second episode, suggesting that this was a genuine episode of acute infection. Viral genomes from first and second episodes belonged to different clades/lineages. Kwok-Yung Yuen, Kelvin Kai-Wang To and colleagues discuss several implications of this case.
Damas J, Hughes GM, Keough KC, et al. Broad host range of SARS-CoV-2 predicted by comparative and structural analysis of ACE2 in vertebrates. PNAS August 21, 2020 Full-text: https://doi.org/10.1073/pnas.2010146117
Joana Damas and colleagues utilized a unique dataset of ACE2 sequences from 410 vertebrate species, including 252 mammals, to study the conservation of ACE2 and its potential to be used as a receptor by SARS-CoV-2. A large number of mammals were identified that can potentially be infected by SARS-CoV-2 via their ACE2 proteins. Species with the highest risk for SARS-CoV-2 infection were wildlife and endangered species. However, the authors urge caution not to overinterpret their predictions, given the limited infectivity data for the species studied.
Transmission
Rhee C, Kanjilal S, Baker M, et al. Duration of SARS-CoV-2 Infectivity: When is it Safe to Discontinue Isolation? Clinical Infectious Diseases, 25 August 2020, ciaa1249. Full-text: https://doi.org/10.1093/cid/ciaa1249
Persistently positive RT-PCRs generally do not reflect replication-competent virus. SARS-CoV-2 infectivity rapidly decreases thereafter to near-zero after about 10 days in mild-to-moderately-ill patients and 15 days in severely-to-critically-ill and immunocompromised patients. This review summarizes evidence-to-date on the duration of infectivity of SARS-CoV-2.
Singanayagam A, Patel M, Charlett A. Duration of infectiousness and correlation with RT-PCR cycle threshold values in cases of COVID-19, England, January to May 2020. Euro Surveill. 2020;25(32). Full-text: https://doi.org/10.2807/1560-7917.ES.2020.25.32.2001483
More on “viral load” and infectivity. Virus culture was attempted from 324 samples (from 253 cases) that tested positive for SARS-CoV-2 by RT-PCR. RT-PCR cycle threshold (Ct) values correlated strongly with cultivable virus. Probability of culturing virus declined to 8% in samples with Ct > 35 and to 6% (95% CI: 0.9–31.2%) 10 days after onset; it was similar in asymptomatic and symptomatic persons.
Lesho E, Reno L, Newhart D, et al. Temporal, Spatial, and Epidemiologic Relationships of SARS-CoV-2 Gene Cycle Thresholds: A Pragmatic Ambi-directional Observation. Clinical Infectious Diseases, 25 August 2020, ciaa1248. Full-text: https://doi.org/10.1093/cid/ciaa1248
Same direction. This prospective serial sampling of 70 patients revealed clinically relevant cycle thresholds (Ct, “viral load”), namely a Ct of 24 (“high viral load”), 34, and > 40 (“negative”) that occurred 9, 26, and 36 days after symptom onset. Of note, race, gender, or corticosteroids did not appear to influence RNA-positivity. A retrospective analysis of 180 patients revealed that initial Ct did not correlate with requirement for admission or intensive care.
Diagnostics
Ren L, Fan G, Wu W, et al. Antibody Responses and Clinical Outcomes in Adults Hospitalized with Severe COVID-19: A Post hoc Analysis of LOTUS China Trial. Clin Infect Dis. 2020 Aug 25:ciaa1247. PubMed: https://pubmed.gov/32840287. Full-text: https://doi.org/10.1093/cid/ciaa1247
A retrospective analysis of patients from the LOTUS trial which showed no effect of lopinavir/r in patients with severe COVID-19. From 191 patients included in the trial, a total of 576 blood and 576 throat swabs samples were taken at days 1, 5, 10, 14, 21 and 28 after recruitment, until death or discharge, whichever came first. IgM, IgG against N, S and RBD and NAbs developed in most patients but did not correlate clearly with clinical outcomes. The levels of IgG antibodies against N, S and RBD were related to viral clearance.
Del Valle DM, Kim-Schulze S, Huang HH, et al. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat Med. 2020 Aug 24. PubMed: https://pubmed.gov/32839624. Full-text: https://doi.org/10.1038/s41591-020-1051-9
Can inflammatory cytokine levels can help predict disease course? Probably yes. Upon admission to the Mount Sinai Health System in New York, cytokines were measured in 1484 patients. When adjusting for disease severity, common laboratory inflammation markers, hypoxia and other vitals, demographics, and a range of comorbidities, IL-6 and TNF-α serum levels remained independent and significant predictors of disease severity and death. These findings were validated in a second cohort of 231 patients. Diane Marie del Valle and colleagues propose that serum IL-6 and TNF-α levels should be considered in the management and treatment of patients with COVID-19 to stratify prospective clinical trials, guide resource allocation and inform therapeutic options.
Severe COVID-19
Lang C, Jaksch P, Hoda MA, et al. Lung transplantation for COVID-19-associated acute respiratory distress syndrome in a PCR-positive patient. Lancet Resp Med, August 25, 2020. Full-text: https://doi.org/10.1016/S2213-2600(20)30361-1
An incredible case of a brave, otherwise healthy 44-year-old woman from Klagenfurt, Austria. After a battle of 52 days with critical COVID-19, ECMO and several complications, a comprehensive interdisciplinary discussion on the direction of treatment resulted in a consensus that the lungs of the patient had no potential for recovery. On day 58, a suitable donor organ became available and a sequential bilateral lung transplant was performed. At day 144, the patient remained well. Despite the success of this case, Christian Lang and his colleagues emphasize that lung transplantation is an option for only a small proportion of patients.
Cypel M, Keshavjee S. When to consider lung transplantation for COVID-19. Lancet Resp Med, August 25, 2020. Full-text: https://doi.org/10.1016/S2213-2600(20)30393-3
Well written editorial reviewing this case. The authors list ten considerations that they believe should be carefully weighed when assessing a patient with COVID-19-associated ARDS regarding potential candidacy for lung transplantation (< 65 years, only single-organ dysfunction, sufficient time for lung recovery, radiological evidence of irreversible lung disease, such as severe bullous destruction or established fibrosis etc.).