Top 10: March 3

Copy-editor: Rob Camp


Paper of the Day

Saadat S, Tehrani ZR, Logue J, et al. Binding and Neutralization Antibody Titers After a Single Vaccine Dose in Health Care Workers Previously Infected With SARS-CoV-2. JAMA. March 1, 2021. doi:10.1001/jama.2021.3341.

Health care workers with previous COVID-19, based on laboratory-confirmed serology testing, had higher antibody titer responses to a single dose of mRNA vaccine (Pfizer-BioNTech or Moderna, depending on personal preference and availability) than those who were not previously infected. Although the groups were small and only 59 volunteers were enrolled (17 in the Ab-negative, 16 in the asymptomatic, and 26 in the symptomatic group), this data indicates that one shot is enough in people with prior infection. Of note, titers did not differ between asymptomatic and symptomatic disease.



Tse H, Lung CD, Wong SC, et al. Emergence of a Severe Acute Respiratory Syndrome Coronavirus 2 virus variant with novel genomic architecture in Hong Kong. Clinical Infectious Diseases 02 March 2021, ciab198,

SARS-CoV-2 lineages have emerged continuously, mostly through the genomic accumulation of substitutions. Herman Tse and colleagues highlight the considerable evolutionary potential of SARS-CoV-2. They report three infections caused by a variant with a novel genomic architecture resulting from deletion of an 882-nucleotide region spanning ORF6 to ORF8 together with duplication and transposition of a 57-nucleotide segment from the 5’-untranslated region (UTR). The tolerance of a major and unusual genomic arrangement led to the formation of ORF6x, which involved recruitment of typically non-coding sequences into the open reading frame. These events greatly increased the genetic diversity of SARS-CoV-2, thereby accelerating the evolution of new potentially advantageous genotypes and compensating for the relatively low mutation rates in coronaviruses. On a more immediate note, caution is warranted when using diagnostic assays targeting only accessory genes or proteins such as Orf8, given the risk of false-negative results.



Rodebaugh TL, Frumkin MR, Reiersen AM, et al.  Acute symptoms of mild to moderate COVID-19 are highly heterogeneous across individuals and over time. Open Forum Infectious Diseases March 1, ofab090,

Thomas L. Rodebaugh from St. Louis, US, and colleagues asked 162 participants with acute COVID-19 to respond to surveys up to 31 times for up to 17 days. Several statistical methods were used to characterize the temporal dynamics of these symptoms. Results: the course of symptoms during the initial weeks of COVID-19 is highly heterogeneous and is neither predictable nor easily characterized using typical survey methods. However, the pattern of symptoms over time suggested a fluctuating course for many patients. Participants who showed clinical deterioration were more likely to present with higher reports of severity of cough and diarrhea.


Cavanaugh AM, Thoroughman D, Miranda H, Spicer K. Suspected Recurrent SARS-CoV-2 Infections Among Residents of a Skilled Nursing Facility During a Second COVID-19 Outbreak — Kentucky, July–November 2020. MMWR Morb Mortal Wkly Rep 2021;70:273–277.

Five residents of a skilled nursing facility received positive PCR results in two separate COVID-19 outbreaks separated by 3 months. Residents received at least four negative test results between the two outbreaks, suggesting the possibility of reinfection. Severity of disease in the five residents during the second outbreak was worse than that during the first outbreak and included one death.



Gacci M, Coppi M, Baldi E, et al. Semen impairment and occurrence of SARS-CoV-2 virus in semen after recovery from COVID-19. Human Reproduction March 1, 2021. Full-text:

Mauro Gacci from Florence, Italy, and colleagues performed a large prospective cross-sectional study on 43 sexually active men who were known to have recovered from SARS-CoV-2 (3-6 weeks after negative swab). One patient had a positive PCR in semen (21 days after the second negative swab). Of note, 11/43 were oligo-crypto-azoospermic and all azoospermic patients reported a previous unimpaired fertility status suggesting that semen impairment was due to COVID-19. However, a main limitation of the study is the lack of samples obtained prior to COVID-19.


Severe COVID-19

Yang P, Zhao Y, Li J. et al. Downregulated miR-451a as a feature of the plasma cfRNA landscape reveals regulatory networks of IL-6/IL-6R-associated cytokine storms in COVID-19 patients. Cell Mol Immunol (2021).

Cell-free circulating RNAs (cfRNAs) in plasma carry information from pathologic sites, and they have been reported to play important roles in disease development. Compared with healthy donors, significantly higher mRNA expression of IL-6R was observed; miR-451a, a known negative regulator of IL-6R translation, was down-regulated, which may promote IL-6R expression at the protein level.



Jee J, Stonestrom AJ, Devlin S, et al. Oncologic immunomodulatory agents in patients with cancer and COVID-19. Sci Rep March 1, 2021, 11, 4814 (2021).

A large single-center, retrospective analysis of 820 cancer patients with COVID-19 treated with various immunomodulatory agents within 90 days prior to SARS-CoV-2 diagnosis, mainly anti-CD20 therapies (rituximab, ofatumumab, or obinutuzumab) and immunotherapy (PD-1, PDL-1, or CTLA-4 blockade). Of note, whereas cytotoxic chemotherapy itself was not a risk for worse outcomes, pre-COVID-19 neutropenia was associated with worse COVID-19. In assessing whether certain oncologic medications are associated with worse COVID-19 outcomes, considering cancer type, degree of effect (i.e. neutropenia or other bone marrow suppression) and other patient-specific factors is crucial.



Janiaud P, Axfors C, Ioannidis JP, et al. Recruitment and Results Reporting of COVID-19 Randomized Clinical Trials Registered in the First 100 Days of the Pandemic. JAMA Netw Open March 1, 2021;4(3):e210330.

All RCTs (n = 516) registered in and the WHO International Clinical Trials Registry Platform between January 1 and April 9, 2020, were included. Overall, 30% of COVID-19 RCTs initiated in the first 100 days of the pandemic did not begin recruitment, and only 10% had results reported by mid-October, suggesting the possibility of substantial research waste.


Li S, Liu S, Jiang Z, et al. Study on the promotion of lymphocytes in patients with COVID-19 by broad-spectrum chemokine receptor inhibitor vMIP-II and its Mechanism of signal transmission in vitro. Sig Transduct Target Ther March2, 2012. 6, 104.

Viral macrophage inflammatory protein (vMIP) is a homologue of a chemokine derived from the recombinant natural human herpes virus 8 gene. It has been proved that vMIP can effectively inhibit the process of HIV infecting target cells through chemokine receptors. In this pilot study, 10 patients and 35 uninfected volunteers from Wuhan were treated with vMIP (given as injection). vMIP-II significantly improved the lymphocyte decrease of COVID-19. It was shown that vMIP-II inhibits multiple chemokine receptors and their related phosphorylation signaling pathways. In other words, this study shows that vMIP-II can reconstruct the cellular immune function lost in acute SARS-CoV-2 infection. The elucidation of the molecular mechanism of vMIP-II increasing CD8+ TCM provides a new strategy for the treatment of COVID-19.



Takefuji Y. Besançon L, Steadson D, Flahault A. Ludvigsson JF. Open Schools, Covid-19, and Child and Teacher Morbidity in Sweden. NEJM March 1, 2021, DOI: 10.1056/NEJMc2101280.

Ludvigsson JF. The first eight months of Sweden’s COVID-19 strategy and the key actions and actors that were involved. Acta Paediatr 2020;109:2459-2471.

Controversial discussion about the Swedish approach. Sweden allowed COVID-19 to spread in the hope that the population would develop “herd immunity.” The younger the patients, the fewer deaths due to COVID-19 were reported by Ludvigsson et al. (Feb. 18 issue). The authors of the correspondence letters don’t believe that this was a good idea.


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