RESEARCH BRIEFING – WEEK IN REVIEW

Many have worried that any immunity to SARS-CoV-2 after infection or vaccination may be short-lived. The abiding concern is that vaccines like Moderna's mRNA-1273, which was announced to have an efficacy rate of 94.5 percent in preventing covid-19, might not be enough to end this crisis. The vaccine's investigators shared further data suggesting promising immune responses from the vaccinated subjects collected 119 days after the initial inoculation (90 days after the second dose). In a letter printed in the New England Journal of Medicinethe authors describe the most recent immune response data from the participants enrolled in the phase 1 trial that previously demonstrated a strong immune response in all 34 participants at 57 days. Most promising in this data was the comparison between the phase 1 participants and a group of 41 control participants, all of whom had been naturally infected with SARS-CoV-2. The concentration of antibodies for the vaccine participants exceeded those of the control group, implying that the vaccinated group developed more robust immunity than was generated after a naturally occurring immune response to covid-19 infection. While there was a slight decline in the titer over time, this was expected. The reported levels show promise for long-lasting immunity with Moderna's vaccine. Additionally, no serious adverse events have been attributed to the vaccine over this time period, and the investigators will continue to monitor the phase 1 participants and assess long term immunity. This new data adds to a growing body of promising literature suggesting that the forthcoming vaccine candidates will change the way the United States, and the world, proceed with tackling the covid-19 pandemic. Nevertheless, it will be important to stay vigilant with public health measures such as social distancing and mask use for the foreseeable future. Abbreviated from Brief19 for 4 December 2020.

As of September, over 1,700 healthcare workers in the United States had died of covid-19. Nurses are among the most at-risk, as their work requires repeated and prolonged close contact with patients with active SARS-CoV-2 infection. While difficult to quantify, it seems probable that nurses have more routine exposure to the pandemic illness than virtually any other members of heathcare teams. The National Nurses United (NNU) released a notable report this past September highlighting racial inequalities among health care worker mortality; NNU is the largest union and professional organization of registered nurses. In its data, which includes statistics through September 16th, 2020, the NNU reports that there have been 213 registered nurse (RN) deaths from covid-19 and related complications. Of those deaths, 58 percent of the covid-19 deaths occurred among nurses of color. This is particularly concerning, as just under 1 in 4 nurses in the United States are people of color. Even more concerning is that a staggering 31.5 percent of covid-19 nurse deaths are among the Filipino population, though they make up just 4 percent of the total RNs in the United States. This means that more than half of all non-White nurse deaths have come from the Filipino demographic. The next highest mortality is among Black RNs who have accounted for 18 percent of covid-19 deaths among RNs, while making up for only 12 percent of the total nursing workforce. The NNU also published that approximately 30 percent of healthcare worker fatalities happened amongst those who worked in the hospital setting, while the remaining 70 percent worked in nursing homes, EMS, and other medical practices. The state with the highest number of both healthcare worker and nursing deaths was New York, followed by New Jersey and California. Included in this report is a memorial to all the known RN deaths with names, ages and employers listed. Given this report is from a large nursing union, the underlying goals and reporting biases should be acknowledged, but that does little to reassure us as to the meanings of these data. Hopefully, the dissemination of this information will help target interventions to protect particularly vulnerable professionals in the nursing profession. 2 December 2020.

A new letter to the editor was published in The New England Journal of Medicine that provides some important preliminary evidence that could change hospital practices and covid-19 isolation and quarantine guidelines, especially as related to persons with incompletely functioning immune systems, known as "immunocompromised" or "immune-suppressed" states. Such patients may be those with cancer receiving chemotherapy or other advanced diseases such as AIDS. Fortunately, some autoimmune conditions (in which the body attacks its own immune system) like multiple sclerosis, have not been shown to be associated with worse disease, though contagion itself was not assessed. What about patients with far less intact immune systems?

First some background. Recommendations from the US Centers for Disease Control and Prevention (CDC) currently state that for persons with uncompromised ("normal") immune systems, SARS-CoV-2 infections are considered potentially contagious for 10 to 14 days after the onset of symptoms in mild or moderate cases. The agency further states that those with severe or critical covid-19 (or with incompletely functioning immune symptoms—though what qualifies is not defined), it is possible that infected persons might be able to infect others for up to 20 days. More recent evidence has suggested the possibility of shorter contagious periods for patients with non-severe disease; 10 days after the onset of symptoms, as infectious viral particles have rarely been recovered after that timeframe, leading some to suggest that shorter isolation periods might be preferable guidance, simply because people might be more likely to faithfully complete shorter isolation and quarantine periods. Meanwhile, "typical" patients with covid-19 can continue to have positive nasopharyngeal swabs for SARS-CoV-2 for up to 3 months after illness onset, but most of these persons are considered not contagious after the initial couple of weeks, as the virus cannot usually replicate at that point and the tests are detecting leftover viral genetic material, rather than contagious virus particles.

But what about profoundly "immune-compromised" patients? Now, new data quantifying this is finally available. Researchers at Memorial Sloan Kettering Cancer Center in New York City enrolled 20 immunocompromised patients into their study. All 20 patients had cancer, with 18 of the 20 patients receiving either bone marrow transplant or "CAR-T cell" therapy. The average age of patients was 61 years of age with 11 patients (55 percent) having severe covid-19. Twenty percent (4 patients) died within 30 days.

From each of these patients, serial nasopharyngeal samples were collected throughout the hospital stay. The average time from covid-19 symptom onset to confirmed diagnosis was 3 days. The results are short and to the point: viable (i.e. contagious) SARS-CoV-2 was able to replicate and remained detectable in five patients who were followed-up. In five of those patients, the virus grew for 8, 17, 25, 26, and 61 days after the onset of symptoms.

Yes, this was a very small sample and there was no "immune intact" control group for comparison. Are the results generalizable to all immunocompromised patients? That remains to be determined, as these were very sick individuals at baseline. But the top-line message is clear: patients with SARS-CoV-2 who were or are significantly immunocompromised/immune-suppressed can be contagious for up to two months. More research is needed in this patient population. In the meantime, guidelines for isolation and quarantine may need to be adjusted based solely on these new findings. 1 December 2020.