Top 10: October 1

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By Christian Hoffmann &
Bernd S. Kamps

1 October

Epidemiology

Laxminarayan R, Dudala SR, Gopal K, et al. Epidemiology and transmission dynamics of COVID-19 in two Indian states. Science 30 Sep 2020: eabd7672. Full-text: https://doi.org/10.1126/science.abd7672

A detailed view into SARS-CoV-2 transmission pathways and mortality in India. Among 102,569 cases in Tamil Nadu and 22,315 cases in Andhra Pradesh who tested positive at least 30 days before the end of the study follow-up period, the overall case-fatality ratio was 2.06%. Reported cases and deaths have been concentrated in younger cohorts than expected from observations in higher-income countries, even after accounting for demographic differences across settings. Among 575,071 individuals exposed to 84,965 confirmed cases, infection probabilities ranged from 4.7-10.7% for low-risk and high-risk contact types. Same-age contacts were associated with the greatest infection risk.

 

Immunology, Vaccine

Prévost J, Gasser R, Beaudoin-Bussières G. Cross-sectional evaluation of humoral responses against SARS-CoV-2 Spike. Cell Rep Med 2020, September 29, 2020. Full-text: https://doi.org/10.1016/j.xcrm.2020.100126

Another cross-sectional study on 106 different SARS-CoV-2-infected individuals to evaluate humoral responses against SARS-CoV-2 Spike. The vast majority of infected individuals showed anti-Spike antibodies within 2 weeks after the onset of symptoms. While most individuals develop neutralizing antibodies within two weeks of infection, the level of neutralizing activity significantly decreased over time. Interestingly, anti-RBD IgM presented a stronger correlation with neutralization than IgG and IgA, suggesting that at least part of the neutralizing activity is mediated by IgM. However, it remains unclear whether this reduced level of neutralizing activity would remain sufficient to protect from re-infection.

 

Burki T. The online anti-vaccine movement in the age of COVID-19. Lancet Digit Health. 2020 Oct;2(10):e504-e505. PubMed: https://pubmed.gov/32984795. Full-text: https://doi.org/10.1016/S2589-7500(20)30227-2

About 31 million people follow anti-vaccine groups on Facebook, with 17 million people subscribing to similar accounts on YouTube. Within a decade, the anti-vaccination movement could overwhelm pro-vaccination voices online. If that came to pass, the consequences would stretch far beyond COVID-19. This article discusses some strategies.

 

Clinical

Clark KEN, Nevin WD, Mahungu T, Lachmann H, Singh A. Assessment of the Haemophagocytic lymphohistiocytosis HScore in patients with COVID-19. Clin Infect Dis. 2020 Sep 28:ciaa1463. PubMed: https://pubmed.gov/32985664. Full-text: https://doi.org/10.1093/cid/ciaa1463

Secondary hemophagocytic lymphohistiocytosis (HLH) is a rare hyperinflammatory syndrome characterized by hypercytokinemia with multiorgan failure. Given the parallel in cytokine profile between HLH and COVID-19, it has been suggested that utilizing the HScore may help identify those patients with the most severe disease, and heightened inflammatory state, who may be more likely to benefit from immunosuppression. In this cohort, the HScore didn’t work. The score did not identify those patients with COVID-19 most at risk of requiring higher levels of care, or at risk of deterioration and death.

 

Dowd JB, Rotondi V, Mills MC. Dangerous to claim “no clear association” between intergenerational relationships and COVID-19. PNAS September 29, 2020. Full-text: https://doi.org/10.1073/pnas.2016831117

Do intergenerational relationships (e.g., co-residence and contacts between family members of different generations) play a major role in the spread and lethality of COVID-19? A previous study from Italy (where case fatality rate was very high earlier this year) found no clear association. The authors doubt this to be the case. It remains crucial to be mindful of risks to older adults physically interacting with younger relatives.

 

Comorbidities, Collateral damage

Li L, Li F, Fortunati F, et al. Association of a Prior Psychiatric Diagnosis With Mortality Among Hospitalized Patients With Coronavirus Disease 2019 (COVID-19) Infection. JAMA Netw Open September 30, 2020; 3(9):e2023282. Full-text: https://doi.org/10.1001/jamanetworkopen.2020.23282

Among a total of 1685 patients who were hospitalized with COVID-19, 473 (28%) received psychiatric diagnoses prior to hospitalization. After controlling for demographic characteristics, other medical comorbidities, and hospital location, the risk of death remained significantly greater among patients with a psychiatric disorder (hazard ratio, 1.5; 95% CI, 1.1-1.9; P = .003). Reasons are unclear. Psychiatric symptoms may arise as a marker of systemic pathophysiologic processes such as inflammation, that may, in turn, predispose to mortality. Similarly, psychiatric disorders may augment systemic inflammation and compromise the function of the immune system, while psychotropic medications may also be associated with mortality risk. Or is there confounding?

 

Toor J, Adams ER, Aliee M, et al. Predicted Impact of COVID-19 on Neglected Tropical Disease Programs and the Opportunity for Innovation. Clin Infect Dis. 2020 Sep 28:ciaa933. PubMed: https://pubmed.gov/32984870. Full-text: https://doi.org/10.1093/cid/ciaa933

Due to the COVID-19 pandemic, many key neglected tropical disease (NTD) activities have been postponed. However, disruption will vary amongst the diseases and there are ways to mitigate the impact and accelerate progress towards the ambitious WHO 2030 goals.

 

Diagnostics

Mina MJ, Parker R, Larremore DB. Rethinking Covid-19 Test Sensitivity — A Strategy for Containment. NEJM September 30, 2020. Full-text: https://doi.org/10.1056/NEJMp2025631

Strong statement (overdue, IMHO): the frequent use of cheap, simple, rapid tests are essential, even if their analytic sensitivities are vastly inferior to those of benchmark tests. The key question is not how well molecules can be detected in a single sample – but how effectively infections can be detected in a population by the repeated use of a given test as part of an overall testing strategy – the sensitivity of the testing regimen.

 

Treatment

Abella BS, Jolkovsky EL, Biney BT, et al. Efficacy and Safety of Hydroxychloroquine vs Placebo for Pre-exposure SARS-CoV-2 Prophylaxis Among Health Care Workers: A Randomized Clinical Trial. JAMA Intern Med September 30, 2020. Full-text: https://doi.org/10.1001/jamainternmed.2020.6319

This was one of the last open questions regarding hydroxychloroquine (HCQ): Does a regimen of 600 mg per day reduce the transmission of SARS-CoV-2 as a pre-exposure prophylaxis strategy when taken by hospital-based health care workers? The answer is clear: No. In this double-blind, placebo-controlled randomized clinical trial that included 132 HCW and was terminated early, there was not a significant difference in PCR–confirmed SARS-CoV-2 incidence between hydroxychloroquine and placebo cohorts. Mild adverse events were more common in participants taking hydroxychloroquine compared with placebo (45% vs 26%; p = .04).

 

French

If you understand French, listen to Duval K. Nouvelle religion : le covidisme. YouTube 2020, published 29 September. Video (4:44): https://www.youtube.com/watch?v=_48gKagPaB0

“Portez le masque, la foi viendra.” JC (et un peu, beaucoup moi, aussi). By Karim Duval.