Copy-editor: Rob Camp
Immunology
Zhang J, Wu Q, Liu Z, et al. Spike-specific circulating T follicular helper cell and cross-neutralizing antibody responses in COVID-19-convalescent individuals. Nat Microbiol (2020). Full-text: https://doi.org/10.1038/s41564-020-00824-5
T follicular help (TFH) cells, a subset of T cells, have been identified as professional B helper T cells in past decades and are required for T-dependent antibody production. Convalescent individuals who experienced severe COVID-19 showed higher neutralizing antibody titers, a faster increase in lymphocyte counts and a higher frequency of CXCR3+ TFH cells compared with COVID-19-convalescent individuals who experienced non-severe disease. Circulating TFH cells were spike specific and functional, and the frequencies of CXCR3+ TFH cells were positively associated with neutralizing antibody titers in COVID-19-convalescent individuals.
Dayarathna S, Jeewandara C, Gomes L, et al. Similarities and differences between the ‘cytokine storms’ in acute dengue and COVID-19. Sci Rep 10, 19839 (2020). Full-text: https://doi.org/10.1038/s41598-020-76836-2
Severe COVID-19 and dengue hemorrhagic fever (DHF) are two diseases that can associate with an altered immune response to the infecting virus. In both infections, a cytokine storm is thought to play a role in disease pathogenesis. Shashika Dayarathna and colleagues from Sri Lanka found similarities between the cytokines that are elevated in early illness in those who progress to severe illness but also many differences. Those who developed severe pneumonia in COVID-19 had high levels of many inflammatory cytokines and chemokines but low IFN-γ levels. Patients who proceeded to develop DHF also had high cytokine and chemokine levels, but most strikingly very high IL-10 levels. Low IFN-γ response to SARS-CoV-2 and high levels of immunosuppressive cytokines such as IL-10 in both COVID-19 and dengue during early illness is likely to result in an altered antiviral response.
Vaccine
Halstead SB, Katzelnick L. COVID-19 Vaccines: Should We Fear ADE? J Infect Dis. 2020 Nov 13;222(12):1946-1950. PubMed: https://pubmed.gov/32785649. Full-text: https://doi.org/10.1093/infdis/jiaa518
Scott B. Halstead and Leah Katzelnick say no. Antibody-dependent enhanced (ADE) breakthrough infections are unlikely because coronavirus diseases in humans lack the clinical, epidemiological, biological, or pathological attributes of ADE disease exemplified by dengue viruses (DENV). In contrast to DENV, SARS and MERS CoVs predominantly infect respiratory epithelium, not macrophages.
Diagnostics
Escribano P, Álvarez-Uría A, Alonso R, et al. Detection of SARS-CoV-2 antibodies is insufficient for the diagnosis of active or cured COVID-19. Sci Rep 10, 19893 2020. Full-text: https://doi.org/10.1038/s41598-020-76914-5
Using Abbott´s SARS-CoV-2 IgG assay and the PanbioTM COVID-19 IgG/IgM device, the authors found that serum IgG detection alone is insufficient for the diagnosis of active or cured COVID-19, with sensitivity values that range between 60 and 75%, respectively. Detection of IgM adds limited value to the performance of serological strategies.
Wang H, Hogan CA, Miller JA, et al. Performance of nucleic acid amplification tests for detection of severe acute respiratory syndrome coronavirus 2 in prospectively pooled specimens. Emerg Infect Dis. 2012 Jan. Full-text: https://doi.org/10.3201/eid2701.203379
Pooled nucleic acid amplification tests (NATs) could increase availability of testing at a decreased cost. However, it is not that trivial, and the effect of dilution on analytical sensitivity through sample pooling has not been well characterized. Hannah Wang and colleagues from Stanford tested 1648 prospectively pooled specimens by using 3 different NATs. Positive percent agreement (PPA) of pooled versus individual testing ranged from 71,7% to 82,6% for pools of 8 and from 82,9% to 100,0% for pools of 4. PPA was dependent on the proportion of tests with positive results, cycle threshold distribution, and assay limit of detection. False negative results occurred exclusively in pools containing samples with low estimated viral load (Ct > 34).
Manabe YC, Sharfstein JS, Armstrong K. The Need for More and Better Testing for COVID-19. JAMA November 13, 2020. Full-text: https://doi.org/10.1001/jama.2020.21694
In their viewpoint, Yukari C. Manabe, Joshua S. Sharfstein and Katrina Armstrong argue that it is more accurate to consider testing less of a prevention strategy than a mitigation strategy. Testing in the absence of other proven prevention strategies is unable to prevent outbreaks. Even as tests become faster with higher sensitivity and specificity, social distancing, mask wearing, and avoidance of large indoor and outdoor gatherings must remain central to any public health strategy. Even the perfect test cannot go it alone.
Clinical
Chopra C, Flanders Sa, O’Malley M, et al. Sixty-Day Outcomes Among Patients Hospitalized With COVID-19. Annals Int Med 11 November 2020. Full-text: https://doi.org/10.7326/M20-5661
The toll of COVID-19 extends well beyond hospitalization. In this cohort study of 1648 patients with COVID-19 admitted to 38 hospitals in Michigan, 398 (24%) died during hospitalization and 1250 (76%) survived. Of these, 975 (78%) went home whereas 158 (13%) were discharged to a skilled nursing or rehabilitation facility. By 60 days after discharge, an additional 84 patients (7% of hospital survivors and 10% of ICU-treated hospital survivors) had died. Within 60 days of discharge, 189 patients (15% of hospital survivors) were re-hospitalized. Of patients alive 60 days after discharge, 488 (41.8%) completed a telephone survey. For most patients who survived, ongoing morbidity, including the inability to return to normal activities, physical and emotional symptoms, and financial loss, was common.
Griffith GJ, Morris TT, Tudball MJ, et al. Collider bias undermines our understanding of COVID-19 disease risk and severity. Nat Commun 11, 5749 (2020). Full-text: https://doi.org/10.1038/s41467-020-19478-2
Numerous observational studies have attempted to identify risk factors for infection with SARS-CoV-2 and COVID-19 disease outcomes. Studies have used datasets sampled from patients admitted to hospital, people tested for active infection, or people who volunteered to participate. Here, Gareth J. Griffith and colleagues from Bristol highlight the challenge of interpreting observational evidence from such non-representative samples. Read how the collider bias (a variable that is influenced by two other variables, for example when a risk factor and an outcome both affect the likelihood of being sampled) can have a dramatic impact on the results and what approaches are available to explore and mitigate this problem.
Treatment
Schwaiger J, Karbiener M, Aberham C, Farcet MR, Kreil TR. No SARS-CoV-2 Neutralization by Intravenous Immunoglobulins Produced From Plasma Collected Before the 2020 Pandemic. J Infect Dis. 2020 Nov 13;222(12):1960-1964. PubMed: https://pubmed.gov/32941626. Full-text: https://doi.org/10.1093/infdis/jiaa593
Julia Schwaiger and colleagues from Baxter AG tested 54 intravenous immunoglobulin preparations, produced from plasma collected in Europe and the US. Although highly potent neutralization of a seasonal coronavirus HCoV-229E was seen, there was no cross-neutralization of the new SARS-CoV-2.
Pediatrics
Stonoga ETS, Lanzoni LA, Rebutini PZ, Olveira ALP, Chiste JA, Fugaça CA, et al. Intrauterine transmission of SARS-CoV-2. Emerg Infect Dis. 2021 February. Full-text: https://doi.org/10.3201/eid2702.203824
A case of fetal death associated with intrauterine transmission of SARS-CoV-2 in a 42 yr old woman at 27 weeks’ gestation. Placenta and fetal tissue showed chronic histiocytic intervillositis, maternal and fetal vascular malperfusion, microglial hyperplasia, and lymphocytic infiltrates. Placenta and umbilical cord blood tested positive for the virus by PCR, confirming transplacental transmission.
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