COVID-19’s Endlessly Shifting Landscape

Experts from the Harvard Medical School-led Massachusetts Consortium on Pathogen Readiness, or MassCPR, respond to ongoing questions about the COVID-19 pandemic.

  •  Amy Barczak, assistant professor of medicine at HMS and infectious disease specialist at Massachusetts General Hospital and the Ragon Institute of MGH, MIT and Harvard
  • Bronwyn MacInnis, director of pathogen genomic surveillance at the Broad Institute of MIT and Harvard
  • Jacob Lemieux, HMS instructor in medicine at Mass General; co-lead of the MassCPR viral variants program

Harvard Medicine News: What does the COVID-19 “weather report” look like for the United States and for the region against the backdrop of rising cases in other parts of the world? Are we out of the woods?

Lemieux: In terms of absolute numbers, we’re in a much better place now than we were two months ago. Cases are way down, and hospitalizations are way down. Deaths are still, on an absolute scale, at a really high number—on average, over 1,000 people a day dying of COVID-19—but are dropping rapidly.

The major event over the last two months has been the emergence of an omicron subvariant, BA.2. There are many countries that have had significant BA.2 outbreaks. In many places, including the U.S., there are still major BA.1 outbreaks, but what we are seeing is a gradual transition that’s been taking place over the course of a month or two from BA.1 to BA.2. Although we are in a relative lull, we see signs that we may have reached the nadir and are on the upslope in a few places. The big question before us is what will happen next.

There are two scenarios. Many places have bad outbreaks by case numbers, particularly in parts of Asia and in Western Europe. One possibility is that, as we transition to a predominantly BA. 2 outbreak in the United States, what happens here will be similar to what’s happening in Hong Kong, where the emergence of the BA.2 variant led to a complete loss of control over the epidemic and a massive surge in cases. The other possibility is that we’d see almost nothing, and that’s what happened in South Africa, where there was a severe BA.1 wave, then BA.2 took over with a low level of transmission but no surge. I want to emphasize that we do not know what factors influence what a BA.2 outbreak looks like in a given place.

MacInnis: Our most recent data, based on samples collected on March 8, show 45 percent prevalence of BA.2, so we think that by now, the majority of infections in Massachusetts and in New England are BA.2, perhaps close to 60 percent or even greater, with the proportion of BA.2 cases doubling every 6 to 7 days or so.

Thus far, in Massachusetts, there is no indication that the increase in the proportion of BA.2 infections has led to a corresponding increase in case numbers, hospitalizations, and deaths, but we continue to keep a close eye on this as things may change. It’s just too soon to know whether the increase in BA.2 infections is going to lead to a surge in cases, hospitalizations, and deaths. Aside from BA.2, so far, no new variant of concern has descended from the previous dominant variant of concern. While we’re all watching omicron and BA.2, there could very well be another curveball coming our way. Recombinant variants are a new flavor of this dynamic that we need to grapple with.

HMNewsWhat is the anticipated impact of scaled back testing regulations and testing capacity during this new phase?

MacInnis: This is tricky time because as we are seeing an increase in BA.2 infections, there are also massive changes in the way we are testing and to the underlying infrastructure for doing this type of work. There are also changes in behavioral patterns as the case counts drop and people start reducing masking and gathering more. Many of the federally and state-supported testing programs have begun to wind down. Add to this the fact that many people are testing at home now, so the diagnostic and genomic data from these tests is, unfortunately, lost, and this is going to be one of the challenges going forward. The national genomic testing program that’s been supported by the CDC is also undergoing a transition and ramping down this program. All of this represents a substantial reduction in our intelligence and surveillance system for tracing of what’s out there. As we move away from large-scale surveillance testing, away from PCR-based testing, and toward more home testing, our ability to detect new threats may be challenged.

Barczak: It’s worrisome because our ability to redeploy masking and other protective measures relies on our ability to detect the early warning signals that, with scaled back testing, will become few and far in between. Certainly, it’ll be harder to detect emerging variants of concern. The other thing that is worrisome beyond testing to me, as a practicing infectious disease doctor, is that this pandemic has disproportionately impacted vulnerable populations, both in the United States and globally. Discontinuing free testing and discontinuing subsidized vaccination and subsidized medications will continue to have a disproportionate impact on those very populations.

Lemieux: Transitions are always the most difficult to navigate, and we are in a transition right now. It’s totally appropriate that as cases have fallen, restrictions have liberalized, but that doesn’t mean we shouldn’t start preparing for the likelihood that cases will go up, and when cases go up, hospitalizations and deaths will likely follow. That will require a response.

It is critical that Congress fund ongoing emergency response by state and other governmental authorities to COVID. That funding has stalled and it’s difficult for states and cities to continue to offer preventive therapies and measures when they don’t have the money to do it. Now is the time to be easing up on restrictions, but it is not the time to be easing up on every aspect of testing and treatment. We are likely to see cases rebound. We need to be prepared for that. You get out of a curve, you get straight on the road, and you can go faster. It doesn’t mean you go faster and stop looking at the road. It means you go faster and keep focused on the road, preparing for a possible curve. If there’s one thing that we know about this virus, it’s that there are curves coming.

HMNews: How do we transition into an endemic phase? How do we manage individual risk and make decisions during this period of uncertainty?

Barczak: Many COVID restrictions, including mask mandates, have been removed, but there are no clear contingencies for when these restrictions should be restarted. Many vulnerable populations remain—immunosuppressed individuals, older people, children under 5 who are not yet eligible for vaccination, as well as the unvaccinated.

It is very likely that new variants will emerge and inevitably there is a lag between when we see them appear and when we fully understand them. These variants differ in how susceptible they are to vaccine-conferred immunity and immunity from past infections.

We are also learning in real time how durable vaccine immunity is. As far as tools that can help us during this transition, we have a number of them in our arsenal. Vaccines remain the most important one, especially in terms of protection against severe disease if you should get infected. We have monoclonal antibodies, which can offer protection both to unvaccinated individuals as well as to vaccinated individuals who may be immunocompromised or unlikely to mount a good response to vaccines. Antiviral medications used for treatment of active COVID are most effective when given very soon after infection. We have important nonpharmacological interventions that are effective across variants—masking, ventilation, and gathering outdoors whenever possible, all reduce the risk for infection.

HMNews: How do we apply the toolkit in this very moment?

Barczak: First and foremost, get vaccinated and get boosted. This continues to the best protection you can get.

Vaccines do not prevent infections 100 percent of the time, and you can still transmit infection to others, but in the hospital, we are still seeing severe infections and complications at much higher rates in the unvaccinated.

Also, be aware of local case rates. If you are getting together with loved ones, particularly individuals at high risk of severe disease, get tested. If you develop coldlike symptoms, even if relatively mild, mask, test, isolate. If you have a known COVID exposure, mask and test five to seven days after the exposure if you have no symptoms. If you do develop symptoms, test right away. If you do get COVID, isolate and contact your physician to determine whether you might benefit from antiviral or other treatment even if you are vaccinated.

Whether any one individual is eligible for treatment will be based on several factors—the circulating variants in their community and which treatments may be more effective against these particular variants, the individual’s overall health status, and local availability of specific treatments. Remember, both monoclonal antibodies and antiviral treatments are most effective when given early, within 48 to 72 hours of onset of symptoms.

Decisions about managing risk will depend on your individual circumstances and the people around you. If you are a vulnerable individual, if you’re immunosuppressed, if you’re very elderly, you want to be pretty conservative in your choices. For others, it’s more a question of awareness about who you come in contact with, such as people with very young kids that cannot yet be vaccinated or people who are immunosuppressed. Following these recommendations is also about being conscientious about others’ well-being.

Lemieux: People need to go back to their normal lives. That’s the reason why the government and all of us on the pandemic response front should be working as hard as possible to make sure that going back to normal can be done as safely and as effectively as possible. This is why now is the time to be making sure we have systems in place to ensure people can be diagnosed quickly and treated quickly so there’s as little disruption as possible to the return to normal life.

We need to do two things simultaneously: ease restrictions and intensify public health response and health care response to allow people to return to their normal lives. I think it’s imperative that organizations put in place sensible policies and that people adhere to these policies because the sniffles for one person could be life-threatening for someone else.

We, as a society, need to find ways to return to normal life while protecting the vulnerable among us. That is going to be one of, it not, the most critical challenges over the coming months and years.

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