Delta breakthrough infections elicit potent, broad and durable neutralizing antibody responses (preprint)

The SARS-CoV-2 Delta variant is currently responsible for most infections worldwide, including among vaccinated individuals. Although these latter infections lead to milder COVID-19 disease relative to unvaccinated subjects, the specificity and durability of antibody responses elicited by Delta breakthrough cases remain unknown. Here, we demonstrate that breakthrough infections induce serum binding and neutralizing antibody responses that are markedly more potent, durable and resilient to spike mutations observed in variants than those observed in subjects who were infected only or received only two doses of vaccine. We show that Delta breakthrough cases, subjects who were vaccinated after infection and individuals vaccinated three times (without infection) have serum neutralizing activity of comparable magnitude and breadth, indicating that multiple types of exposure or increased number of exposures to SARS-CoV-2 antigen(s) enhance antibody responses. Neutralization of SARS-CoV, however, was moderate, underscoring the importance of developing vaccines eliciting broad sarbecovirus immunity for pandemic preparedness.

Survival and outcomes of tocilizumab use in severe and critically ill Covid-19 patients not responding to steroids (preprint)

BackgroundMortality and morbidity are highest in severe and critically ill patients with COVID -19 pneumonia. Recently corticosteroids have shown a definite mortality benefit in these patients. In this study we used interleukin -6 inhibitor, tocilizumab in patients who failed to show any clinical improvement after initial treatment with steroids. Patients and methodsThis is a retrospective observational study conducted at a tertiary care referral hospital in India. Severe and critical COVID 19 patients, who got admitted to intensive care unit and subsequently received tocilizumab were included. Patients who worsened clinically or had no change in oxygen requirement even after 24hrs of receiving Intravenous methylprednisolone at a dose of 1-2mg/kg/day received a maximum total dose of 800mg of intravenous tocilizumab. The day 28 all cause mortality and progression to mechanical ventilation were the primary outcome measures. Clinical improvement and oxygen requirements after tocilizumab administration along with trends in inflammatory markers were secondary outcome. Secondary infections rates and other drug related side effects were also noted. ResultsA total of 51 patients who did not show clinical improvement even after 24 hours of intravenous steroids and received tocilizumab were included. In these patients, there was a significant decrease in oxygen requirement by day 3 and clinical improvement by day 7 of tocilizumab administration. Among the inflammatory markers, we observed elevated median baseline values of CRP (114.2 mg/L), IL-6 (55.4 pg/ml) and Neutrophil to Lymphocyte Ratio (12.4). Out of these only CRP showed a significant decrease after the drug administration. 13 (26.5%) of the 49 patients who were on non-invasive or conventional oxygen support progressed to mechanical ventilation. The day 28 all-cause mortality rate was 10/51(19.6%). 10(19.6%) of the 51 patients had life threatening infections, 5/51 had thrombocytopenia, 3/51 had pneumo-mediastenum/pneumothorax, 1 patient had colonic perforation and 1 patient had transaminitis following tocilizumab administration. ConclusionEarly and timely administration of tocilizumab only in selected severe and critical covid patients not responding to initial steroids appears to increase the survival. Further randomized controlled trials are required to confirm this finding.

The World Is at a Dangerous Crossroads on 'China Virus' and US 'Political Virus' (preprint)

As of 17 October 2020, the novel coronavirus without vaccination has resulted in 1,109,654 deaths; the United States is leader in total cases of 8,288,278 and 223,644 deaths with the mortality rate of 2.7%. While the virus is in its 2nd wave of resurgence, this is a crucial time for unity to fight against the invisible coronavirus, and this is the only way to defeat it. Leaders of nations across the world (President Trump in particular) should be extra careful at a time like this and avoid using xenophobic language that may create stigma. Attaching a disease caused by a virus to a nation and calling it “China virus”, “Wuhan virus”, “Chinese virus”, or “Asian virus” is an ugly case of US ‘bullying’ and US ‘political virus’. Coronavirus (also known as COVID-19, and in virology defined as SARS-CoV-2) recognizes no borders, ethnicities, or skin colors; moreover, the virus spares no people and nations based on levels of wealth and economic status. Political leaders, government officials, and medical experts commit an unlawful act by describing the novel coronavirus as China virus, trying to influence others with words without accuracy and empathy will only result in a dangerous spike in abhorrence, racism, aggression, stigma, and xenophobic attacks. Although unilateral economic sanctions have become the centerpiece of U.S. foreign policy under the Trump administration, this low cost/low risk combatant has been ineffective in exerting the “maximum economic pressure” on rogue nations to deter their malign activities. Abundance of research on the topic shows that unwarranted sanctions without multilateral support do not work well as a security tool. Iran and North Korea are two examples that the increased US abuse of sanctions and its use of the dollar as a weapon of mass economic destruction have produced trivial results, not mentioning that all parties involved have been adversely affected.