[This article deals with a constantly evolving situation. It was written by Norbert Gleicher, MD, on June 27, 2020 and published on June 29, 2020. For a list of all COVID-19 Bulletins, scroll to the bottom.]
Not at all unexpected, COVID-19 infections have significantly rebounded with, unquestionably, a very profound degree of community spread being the underlying cause. The reason why this is _not _surprising is that this increase in case numbers follows reopening of the economy: States that initially had relatively low infection rates reopened their economies earlier than more affected states, like New York and New Jersey, and, therefore, can also be expected the demonstrate consequences of reopening earlier. This applies specially to states like California, Florida, Texas, Arizona, etc.
Does this mean that these states reopened too early? That seems unlikely (see also below: An expected wave of unintended consequences) - though they may have underestimated how infectious this virus is and, therefore, insufficiently educated the population that reopening of the economy does not negate the continuous need for social distancing and, at all times, use of appropriate face masks in public. The latter two points require reemphasis because they, unquestionably, have been only poorly communicated to the public, as also witnessed in New York City (NYC) by how many people do not wear masks at all in public, use poorly fitting or on purpose poorly positioned masks (covering mouth but not nose) or pretending to use protective gear which, very obviously, is unable to prevent viral transmission. COVID-19 is not only profoundly infectious but also highly unconventional in its infectivity.
The unconventionality of this virus becomes apparent in the current wave of infections, which is quite contradictory in itself: Though final judgments are still difficult to reach, contrary to expectations, mass demonstrations in most major cities, starting at the beginning of June, apparently did not affect disease prevalence, despite spurious masking and practically no social distancing by demonstrators. Over three weeks removed, NYC, Minneapolis, Baltimore, Washington, DC and similar cities, where demonstrations were the biggest, have not witnessed significant increases in COVID-19 cases. That so-far happened only in states defined by geographic location and timing of economic reopening.
That all the states so affected are warmer climate states is also contradictive because viruses generally do not like heat, and increased temperatures are, therefore, widely considered protective from most respiratory viruses. What then is causing the increase in case numbers and hospital admissions in the South-West? Aside from inadequate social distancing and face masking, there must be other reasons since, otherwise, one also would have expected increases following the demonstrations. Though such additional causes have so-far not been clearly identified, an interesting hypothesis has recently been offered by a prominent public health specialist who speculated that the virus may be easily transmittable through air-conditioning systems. With increasing temperatures in the south-western states, people would increasingly avoid the outdoors and, instead, spend more time in closed, air-conditioned spaces. Demonstrators, of course, did not spend time indoors. Moreover, NYC data quite a time ago unequivocally demonstrated that most infections happen indoors. Guidelines in our opinion should, therefore, stress the importance of being outdoors as much as possible, while maintaining social distancing and wearing protective face gear.
These Bulletins have repeatedly addressed the concept of herd immunity. Two very recent papers in highly prestigious science journals are very relevant. By way of background, herd immunity is the level of immunity against a virus in a given geographic region that starves viruses of enough further human targets for infection and, therefore, leads to the “burning out” of the viral infection in that population. The level of anti-viral immunity needed in a population to reach this goal has been for most viruses been estimated at ca. 60%. Historically, these levels of immunity in a population have been based on detection of antibodies to a given virus, which an individual will only demonstrate after exposure to that virus.
Recently, however, several studies, a most recent one in CellPress (Grifoni et al., https:// doi.org/ 10.1016/j.cell.2020.05.015), have convincingly demonstrated that antiviral immunity is not only based on production of antibodies but also on so-called cellular immunity. In above noted study in the journal Cell, SARS-CoV-2 specific CD8+ MHC class I-restricted T cells, including cytotoxic and suppressor T cells) and CD4+ T cells (antibody-producing helper T cells) were identified in most COVID-19 patients in recovery after infection. Responses of CD4+ to the spike epitope (which is mostly used in efforts to develop a vaccine), was strong and related to IgG and IgA antibody titers to the virus. Even more fascinatingly, however, reactive CD4+ T cells to the virus were also found in approximately half of individuals never exposed to _this _virus, suggesting that other viruses, like common cold coronaviruses and SARS-CoV-2, in many individuals sometimes in the past produced cross-reactive T-cell recognition with COVID-19. In other words, a significant portion of the population does have already such immunity that also, at least partially, may protect against COVID-19.
This information may explain why some people get infected very easily and others, despite close proximity and with no history of prior COVID-19 infection, do not. Even more importantly, this observation suggests that the number of individuals with COVID-19 immunity in the population may be much higher than standard antibody tests suggest.
And here is why all of this theoretical detail is of such enormous importance when it comes to herd immunity: We noted above that herd immunity is usually reached when approximately 60% of a population demonstrates immunity to a virus. The highest levels of immunity measured several weeks ago in Manhattan, N.Y., and Stockholm, Sweden, were in the 20s (%), which, of course, is still quite far away from 60%. But, considering the influences of population heterogeneity and likelihood of T cell immunity, investigators just published a new mathematical model for herd immunity in association with COVID-19 in the very prestigious journal Science, in which they reached the conclusion that herd immunity levels may be reached for this virus already at around ca. 43% community spread (Britton et al., Science 2020; http://10.1126/science.abc6810). Though readers of our Bulletins will be aware of our skepticism toward modelling studies, the authors conclusions in this case correspond well with above noted report by Grifoni et al. Assuming that this model is, indeed, correct or close to reality, places like Manhattan and Stockholm may not be too far away from herd immunity, while cities with very low prior infection rates may have a much longer way to go. This, of course, could be, yet, another reason, why south-western states are now experiencing significant increases in disease prevalence.
As paradoxical as this statement may sound, as long as new cases are mostly restricted to young and, therefore, low-risk patients for mortality from COVID-19, it actually is, likely, correct. The mortality risk in young individuals is generally considered below 0.1%. Though every death is tragic, this death risk is lower than many other causes of death in such young individuals. Concomitantly, high risk patients, including individuals above age 60, but also younger people with obesity, diabetes, heart disease and/or immuno-suppressive treatments, must be strongly protected. In this context it is noteworthy that even Richard Horton, the editor-in-chief of the prestigious British medical journal The Lancet in a recent editorial expressed cautious support for the concept of allowing, maybe even furthering, infections of low-risk populations to be able to better protect higher risk populations through development of herd immunity (Horton R. Lancet 2020;l935:1894).
Within this context, it is interesting to note that newly infected patients in the country’s South-West, indeed, appear to be comparably younger to patients in the first wave. Moreover, despite significant increases in case numbers and some increase in hospitalizations, mortality rates from COVID-19, so far, all over the U.S., are continuing to drop. What is currently happening may, therefore, only be the catch-up the population of the country’s south-west needs in reaching adequate immunity levels after, in the first wave, experiencing much less disease than many other states. The hysteria expressed by much of the media about increasing COVID-19 rates in young people is, therefore, once again only too obvious and, as always, either is, simply, political or, again, a demonstration of professional incompetence in adding up facts.
At the same time, hardly anybody in the media is talking about what is coming toward us in unintended consequences because of how this country (and, indeed, most of the world) have managed the COVID-19 pandemic. Gart Graham, vice president of community health at health care company giant CVS Health recently made the point at conference organized by the Milken Institute that, “a huge, massive wave is coming at us because people have delayed vital care in terms of cancer, diabetes and heart disease.”
One, of course, could add several other health care needs that have been delays because of the COVID-19 pandemic, infertility services among those, as most fertility centers, simply, closed down. Other participants were particularly concerned about arising gaps among minority groups, also disproportionally affected by the COVID-19 virus (see also the next paragraph) . The numbers are rather stark: 42% fewer people visited emergency rooms during April and, paradoxically, calls to emergency services dropped by 26%. Experts were especially concerned on the long-term effect on cancer care and there was unanimity that the longer treatments were being withheld for lack of accessibility, the higher the consequential death rates from all of these conditions would be. In other words, protecting the country from the COVID-19 virus cannot be viewed in isolation. Yes, COVID-19 even kills children and young people; but it does so very rarely and, indeed, in these populations more rarely than many flu viruses. But delaying routine health care (and immunizations in children), unquestionably, causes excessive deaths.
Two important studies were just published on both sides of the Atlantic, in the UK and here in the US. Both for the first-time report that minorities are more severely affected by the virus during pregnancy. That minorities demonstrate higher mortality has been known since almost the beginning of the pandemic. But that black women and other minorities are at increased risk for hospitalization and admission into ICUs has not been known.
A British report, published in the British Medical Journal (Knight et al., BMJ 2020;369:m2107) reported that more than half of women admitted with COVID-19 in pregnancy were either black or other ethnic minorities. Most were admitted in the third trimester of pregnancy and, fortunately, were not severely ill. The study, however, also offered relatively good news: mortality was low and, as earlier studies had suggested and we here reported, severity of disease did not seem aggravated by pregnancy (as it is in cases of flu during pregnancy). Also, though the study claimed that transmission of infection between mother and infant can occur, it seems to be a very rare event.
An even much larger study was reported in the Morbidity and Mortality Weekly report by Ellington et al from the CDC (https://www.cdc.gov/mmwr/volumes/69/wr/mm6925a1.htm?scid=mm6925a1 w#suggestedcitation). Here Hispanic and non-Hispanic black pregnant women did appear disporportionally affected by COVID-19 in that they were more frequently hospitalized and demonstrated increased chances of being admitted into ICUs and receive mechanical ventilation but they did not demonstrate increased risk of death.
Both studies, therefore, describe yet another area in medicine where the COVID-19 virus disproportionally appears to affect black patient and other minorities.
Norbert Gleicher, MD, leads CHR’s clinical and research efforts as Medical Director and Chief Scientist. A world-renowned specialist in reproductive endocrinology, Dr. Gleicher has published hundreds of peer-reviewed papers and lectured globally while keeping an active clinical career focused on ovarian aging, immunological issues and other difficult cases of infertility.
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