In his weekly clinical update Dr. Griffin discusses high demand for Amoxicillin causing shortages amid child RSV surge, epidemiologic and clinical features of children and adolescents aged <18 years with monkeypox, low risk of SARS-Cov-2 transmission by fomites, nucleocapsid antigenemia is a marker of acute SARS-CoV-2 infection, impact of community masking on COVID-19, protection against Omicron from vaccination and previous infection in a prison system, Nirmatrelvir and the risk of post-acute sequelae of COVID-19, Bebtelovimab for high-risk outpatients with early COVID-19 in a large US health system, imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution, can SARS-CoV-2 trigger new onset of autoimmune disease in adults? A case-based review, and retrospectively modeling the effects of increased global vaccine sharing on the COVID-19 pandemic.
By David Tuller, DrPH
A few prominent news articles have recently drawn welcome attention to the links and overlaps between ME/CFS and long Covid. One key overlap is the core ME/CFS symptom generally known as “post-exertional malaise” (PEM). This term is so embedded in conversations in the ME and ME/CFS worlds that it is easy to forget others outside that bubble have no idea what it is or what it means or how devastating the experience is for patients.
Infectious Disease physician Jake Scott joins TWiV to provide a west coast clinical perspective on the evolution of the COVID-19 pandemic with respect to the impact of vaccines, antivirals, variants of concern and mortality.
Guest: Jake Scott
In his weekly clinical update Dr. Griffin discusses Influenza incidence and vaccine effectiveness during the southern hemisphere influenza season in Chile, Nirsevimab for prevention of RSV infection in healthy late-preterm and term infants, severe Monkeypox in hospitalized patients, reinfections with different SARS-CoV-2 Omicron subvariants, impact of community masking on COVID-19 in Bangladesh, unadjuvanted intranasal spike vaccine elicits protective mucosal immunity against sarbecoviruses, antibody responses to Omicron BA.4/BA.5 bivalent mRNA vaccine booster shot, immunogenicity of bivalent mRNA vaccine boosters, long-term gastrointestinal sequelae following COVID-19, evaluation of an automated text message–based program to reduce use of acute health care resources after hospital discharge, and how in adults with COVID-19, melatonin was assessed for effects on inflammatory markers, clinical signs and symptoms, and mortality.
by Gertrud U. Rey
You are fully vaccinated against SARS-CoV-2 and have presumably never been infected with the virus. But how can you know for sure? One way to find out is by testing your blood for the presence of antibodies against the viral nucleocapsid protein, which can only be encountered during natural infection. This is because all of the SARS-CoV-2 vaccines used in the U.S. only encode the viral spike protein (none encode nucleocapsid [N] protein), and thus they only stimulate production of antibodies against spike. This approach differentiates between vaccine- and virus infection-induced antibodies and allows one to accurately determine whether a vaccinated person was naturally infected. Or so we thought until now.
Two recent letters to the editor of the Journal of Infection note that not every natural infection induces production of anti-nucleocapsid (or, “anti-N”) antibodies. The letters cast doubt on whether these antibodies are reliable markers for a prior SARS-CoV-2 infection.
The authors of the first letter measured antibody responses in 4,111 vaccinated and 974 unvaccinated Irish healthcare workers. Only 23 of the vaccinated participants, all of whom had received two doses of the Pfizer mRNA vaccine, experienced a SARS-CoV-2 infection at some time after vaccination. As expected, each of the 23 individuals had antibodies against the spike protein, but surprisingly, only six (26%) had detectable anti-N antibodies. In contrast, 82% of unvaccinated participants with a previous PCR-confirmed infection had detectable anti-N antibodies. This result suggests that anti-N antibodies may not be the most accurate indicators of a prior natural infection in vaccinated people; and it further implies that vaccinated individuals may neutralize incoming viruses early during infection, thus preventing and/or limiting their ability to develop antibodies against nucleocapsid protein.
The second letter, which was written in response to the first letter, confirmed and further substantiated these results. Citing data from serosurveys done in Japan, the authors showed that patients who were infected within two months of a third dose of the Pfizer mRNA vaccine were less likely to experience COVID-19 symptoms than patients who were infected 4-8 months after the third dose. These findings are in line with our current understanding of sterilizing immunity, a type of immunity that prevents both disease and infection, which appears to occur most often during the months following vaccination, when high levels of vaccine-induced antibodies probably sequester an incoming virus before it has a chance to infect cells. The authors also showed that participants infected within two months of their third vaccine dose had significantly lower levels of anti-N antibodies than those infected several months later. Although this result seems surprising at first, it actually further supports the notion that vaccination only induces sterilizing immunity for a short time after vaccination, when existing vaccine-induced anti-spike antibodies neutralize incoming virus before the immune system has a chance to respond to the virus and produce antibodies specific to the nucleocapsid protein.
The authors of both letters further mention that COVID-19 patients who experienced symptoms were more likely to have detectable anti-N antibodies than were patients without symptoms, an observation that is in agreement with serological surveys done before vaccines became available. This finding suggests that patients who developed symptoms did not have sterilizing immunity and were subject to a productive viral infection that led to the development of symptoms and production of antibodies to nucleocapsid and other viral proteins.
These two studies provide an interesting perspective of antibody responses to SARS-CoV-2 infection in vaccinated people, and they may inform better strategies for gauging infection after vaccination.
By David Tuller, DrPH
[*See correction in third paragraph]
Three Norwegian researchers recently published an attack on critics of cognitive behavior therapy and graded exercise therapy as treatments for ME. The article, called “Facts and Myths about ME,” was published by the news organization Aftenposten. The authors, from the Scandinavian arm of the CBT/GET ideological brigades, asserted that “the cause of ME is most likely a combination of biological, psychological and social factors”—but they provided no convincing evidence for this causal claim. (I don’t read Norwegian, so I am relying on Google translate here. I apologize if the translation does not accurately convey the authors’ meaning.)
They also asserted the following: “Cognitive behavioral therapy and graded activity adjustment [an alternative term for GET] can make many ME patients healthier…This claim is thoroughly documented. It is fraudulent to claim that there is scientific evidence that such treatments make patients sicker.”