From JAMA, Gary Joseph Ordog, MD published:
March 19, 2020 COVID-19: Can We Expedite Treatment? Gary Ordog, MD, DABMT, DABEM | County of Los Angeles, Physician Specialist, Retired The authors discuss human rights pertaining to avoiding infection during the next 18 months. We are supposed to wait while a vaccine is tested for dosing schedule. "Flattening the curve" may only prolong the inevitable infection with the virus. What are our rights to preventative and curing treatments? The most vulnerable of our population currently appear to be older and medically compromised individuals. Also, the most severely ill will require ventilators, ICU beds and critical care staff, and all are currently utilized to capacity, resulting in an increasing number of newsworthy disasters already. I suggest that prophylaxis and treatment should be made available, as a medical right, in this time of impending catastrophe. Treatments that have not had time to advance to final approval may be beneficial for saving life or limb, with those patients on the exponential end of " the curve" probably glad to sign a 'waiver of liability.' As far as prophylaxis and treatment, I refer first to the vaccines that are being tested correctly and for dosage. With a century of vaccine research, I think they have a pretty good estimate of the required dose. Can we not ramp up production and start giving it to the most vulnerable, at least? Secondly, there are currently thousands of patients who have recovered from COVID-19, can these not be a source of gamma globulin for the more serious ill, at least? Stem cell lines are another possible therqpy. Thirdly, there are various antiviral drugs which are safe and possibly effective but obviously have not had the time to be tested. For example, remdesivir appears to be effective against other Corona viruses, probably would have some effect against Covid-19. Could we not ramp up production of these agents and allow our vulnerable patients to have access to them, when otherwise it looks like high mortality and morbidity, with our only treatment available being "social distancing?" Thank you for allowing me to make these comments.
Yes you are right. Vaccine is the biggest hope to restore economy of the whole world.
Vaccines need to be safe in order for population to be vaccinated..i don't want the cure to be worse than the disease.
Here is how and why the vaccine is slow: A modified quote from JAMA today July 10, 2020:
Prevention and Vaccine Development COVID-19 is a potentially preventable disease. The relationship between the intensity of public health action and the control of transmission is clear from the epidemiology of infection around the world.25,101,102 However, because most countries have implemented multiple infection control measures, it is difficult to determine the relative benefit of each.103,104 This question is increasingly important because continued interventions will be required until effective vaccines or treatments become available. In general, these interventions can be divided into those consisting of personal actions (eg, physical distancing, personal hygiene, and use of protective equipment), case and contact identification (eg, test trace-track-isolate, reactive school or workplace closure), regulatory actions (eg, governmental limits on sizes of gatherings or business capacity; stay-at-home orders; proactive school, workplace, and public transport closure or restriction; cordon sanitaire or internal border closures), and international border measures (eg, border closure or enforced quarantine). A key priority is to identify the combination of measures that minimizes societal and economic disruption while adequately controlling infection. Optimal measures may vary between countries based on resource limitations, geography (eg, island nations and international border measures), population, and political factors (eg, health literacy, trust in government, cultural and linguistic diversity). The evidence underlying these public health interventions has not changed since the 1918 flu pandemic.105 Mathematical modeling studies and empirical evidence support that public health interventions, including home quarantine after infection, restricting mass gatherings, travel restrictions, and social distancing, are associated with reduced rates of transmission.101,102,106 Risk of resurgence follows when these interventions are lifted. A human vaccine is currently not available for SARS-CoV-2, but approximately 120 candidates are under development. Approaches include the use of nucleic acids (DNA or RNA), inactivated or live attenuated virus, viral vectors, and recombinant proteins or virus particles.107,108 Challenges to developing an effective vaccine consist of technical barriers (eg, whether S or receptor binding domain proteins provoke more protective antibodies, prior exposure to adenovirus serotype 5 [which impairs immunogenicity in the viral vector vaccine], need for adjuvant), feasibility of largescale production and regulation (eg, ensuring safety and effectiveness), and legal barriers (eg, technology transfer and licensure agreements). The SARS-CoV-2 S protein appears to be a promising immunogen for protection, but whether targeting the full-length protein or only the receptor-binding domain is sufficient to prevent transmission remains unclear.108 Other considerations include the potential duration of immunity and thus the number of vaccine doses. Coronavirus Disease 2019 (COVID-19)—Epidemiology, Diagnosis, and Treatment Review Clinical Review & Education jama.com (Reprinted) JAMA Published online July 10, 2020 E9 © 2020 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ by Gary Ordog on 07/10/2020 needed to confer immunity. More than a dozen candidate SARSCoV-2 vaccines are currently being tested in phase 1-3 trials. Other approaches to prevention are likely to emerge in the coming months, including monoclonal antibodies, hyperimmune globulin, and convalescent titer. If proved effective, these approaches could be used in high-risk individuals, including health care workers, other essential workers, and older adults (particularly those in nursing homes or long-term care facilities). Thank you and stay safe; Gary Ordog, MD
The economic impact of the current pandemic is undeniable.
Article Economy or Health, Constant Dilemma in Times of Pandemic: Th...
Article Enfermedad por Coronavirus 2019 (COVID-19): ¿Prevalecerá la ...
I think that the development of a vaccine is vital, however, I am somewhat pessimistic about the fact that it will take time, and that even, as soon as it is approved, it will also take several months to reach the entire population of the world. This way the consequences will be present, including the economic ones.
July 24, 2020: As shown by CT Scan that 97% of people who are positive for COVID-19 by RT-PCR developed pneumonia; in the following study:
Hope, MD, Raptis, CA, et al: A Role for CT in COVID 19? What data really tells us so far. Lancet 2020: 395; 1189-1190.
So, almost invariably, anyone positive for the virus by PCR will have "pneumonia" by CT Scan of the chest, and thus some degree of pulmonary injury, loss of function, lung scarring, and perhaps metaplasia formation. This was even present in non-clinical and sub-clinical cases. More evidence that one should not promote "herd-immunity" before the vaccine is given. Vaccine production is slow, mainly due to the amount of testing required. This best vaccine (out of potentially hundreds being worked on, is currently our "best hope." Stay safe, thank you;
Gary Ordog, MD
Said with caution. The infection itself seems to only provide short-lived immunity, if at all. We do not have the vaccine experience for over a few months yet. It may be short-lived as well. Time will tell. In the meantime, work with other methods of vaccination should be ongoing. A more robust T-cell response may be desirable for long-term immunity. Maybe even the one based upon the carrier pseudorabies. Note that Pasteur's initial rabies vaccine which he derived from phenol attenuated live rabies virus still works well after almost 200 years! Hundreds of vaccine choices hopefully will be available and we can choose the best one, or several? Be safe, thank you again. July 30, 2020; Gary Ordog, MD
I cannot recommend herd-immunity at this time for this novel virus, for multiple reasons. First, herd-immunity for this virus is probably not attainable. The immune response to infections appears to be short-lived, possibly in the range of 3 months. Thus re-infection may occur repeatedly, thus no "herd-immunity." Secondly, If the immune response is short-lived with probably re-infection frequent, then there is no real immunity to transfer to the "herd." Thirdly, there appears to be a myriad of complications of the viral infection, both in symptomatic and asymptomatic patients, in the majority of those infected with the virus, no matter the age. This ranges from lung scarring, diminished pulmonary function, lung metaplasia, immune dysfunction, neurological injury, cardiac, and rheumatological injury, etc. Fourthly, the virus may be carcinogenic, combined with the immune suppression of the cancer surveillance system it causes, is worrisome for those who are infected with the virus. (There are many other viruses with similar effects, so this would not be unique.) Fifthly, there are many patients with autoimmune diseases stated to be idiopathic, which in fact, may have been associated with other viral infections, and this new one has the same worries for us. Conclusion: A good vaccine, that offers humoral as well as cellular immunity, even if it is not permanent is a much better way to go, rather than "herd-immunity." Thank you for your support and stay safe. July 31, 2020. Gary Ordog, MD
Update August 20, 2020:
COVID-19: Death toll passes 787,000 globally According to the European Centre for Disease Prevention and Control (ECDC), since 31 December 2019 and as of 20 August 2020, 22,431 929 cases of COVID-19 have been reported, including 787,773 deaths. Comments 300801007 replied on Thu, 08/20/2020 - 14:34 The death rate is still significant, evidence that the "flattening of the curve" will result in the same 'area' under the curve, at least until an effective vaccine is given. COVID-19 has not 'disappeared.' Stay safe, thank you, Gary Ordog MD. Reference: https://www.ecdc.europa.eu/en/geographical-distribution-2019-ncov-cases
August 29, 2020 Update:
Yes the vaccine may be expedited; called "Fast-tracking" by FDA Commissioner Hahn. Thank you for applying my advice.
White House USA Dr. Brix statement on the vaccine as of September 03, 2020:
September 16, 2020: Some possible early answers in the news today:
Pfizer reports 'potential' of COVID-19 candidate vaccine after expanding trial to 44,000 people
Karen Weintraub, USA TODAY
Pfizer, one of the front-runners in the quest for a COVID-19 vaccine, said its candidate vaccine looks safe, and the company expects to have data next month on how well it protects people against the coronavirus.
Pfizer CEO Albert Bourla said Tuesday that he is intentionally revealing more information about the COVID-19 candidate vaccine than he would about any other vaccine under development, because he wants the process to be open and transparent.
"Transparency is a must, particularly given this situation and the politicization of the vaccine," he said in a Q&A with journalists.
The company said Saturday that it was expanding its trial from 30,000 to 44,000 people to include teenagers, ages 16-18, as well as people with diseases such as HIV and hepatitis A, B or C. Tuesday, Bourla said the expansion took place because the vaccine appeared to be extremely safe, and the trial could be expanded without delaying the timeline for completion. The first patient enrolled in Pfizer's COVID-19 vaccine clinical trial at the University of Maryland School of Medicine in Baltimore receives an injection May 4.
Warp speed? Why a coronavirus vaccine is more than a year away, despite medical researchers' progress
In data released Tuesday, the company showed that participants – both younger people and senior citizens – complained of only minor side effects, such as headaches and sore arms. The data included about 6,000 people; some who received the active vaccine and others the placebo. The company – which is developing its vaccine, called BNT162, in collaboration with German vaccine developer BioNTech – does not know which participant got which.
An independent Data Safety Commission does know who got the active vaccine and has been checking regularly to make sure there are no health concerns, Pfizer executives said.
There probably have been some serious health issues during the trial, but the safety panel "concluded that none are vaccine-related," said Kathrin Jansen, Pfizer senior vice president and head of vaccine research and development.
The larger numbers should allow the company to look more closely at subgroups of participants, such as those with underlying health conditions such as HIV, and those who had the virus when they received the vaccine, she said.
A final report on the safety and effectiveness of the vaccine should be ready for regulators to review next month.
'It's not at all unprecedented': AstraZeneca's COVID-19 vaccine trial stopped after illness
The vaccine must be at least 50% effective – protecting on average at least half the people who take it – for it to win federal approval and be given to the public. Pfizer manufactures BNT162 in three plants in the USA – in Kalamazoo, Michigan; St. Louis; and Andover, Massachusetts – as well as in Germany and Belgium.
It is not clear how long the vaccine's protection will last. The company is preparing for three possibilities: that people will need an annual shot, as with the flu; that they will need a vaccine every few years, as with tetanus; or that it will be one-and-done, like the polio vaccine, said Dr. Mikael Dolsten, the company's chief scientific officer.
"We think this vaccine has the potential to give reasonable and good protection, but we need to monitor [it]," Dolsten said. "It's reasonable also to assume that we need maybe in the future a boost, because this is a real pandemic and there's going to be a lot of virus circulating even after global [vaccination] campaigns."
Jansen said that although Pfizer is committed to and "very happy with its current vaccine candidate," the company is already working on a second generation.
Pfizer hopes to make two improvements in the next generation, she said: eliminating the need to keep the vaccine frozen and altering the technology so only one dose will be needed, instead of two.
BNT162 uses technology called messenger RNA, which trains the person's cells to make a protein on the surface of the coronavirus that causes COVID-19. Once the immune system learns to recognize this protein, it will attack when it sees it again on the virus.
Achieving herd immunity: How vaccines and masks are the keys to fight coronavirus
In a next-generation vaccine, Jansen said, she could envision a messenger RNA that could amplify itself. "There may be an opportunity that with such an approach, you would be able to only need a single shot" that would provide both "the priming and the boosting effect."
The vaccine needs to be kept frozen at minus-80 degrees, the temperature of dry ice. Pfizer ships BNT162 in coolers that maintain the ultra-cold temperature. The cooler can be fed with dry ice to keep the vaccine frozen for 15 days, then it can be refrigerated for up to five more days before being diluted and injected, said Angela Hwang, president of the Pfizer Biopharmaceuticals Group.
Because the company expects high demand for the vaccine, and its shipping network is efficient, Hwang said the vaccine shouldn't suffer heat damage. "No dose is going to be lying around for very long," she said.
A second-generation vaccine that did not require such cold conditions would be an improvement, Dolsten said.
Bourla, speaking at the end of a two-day conference for investors, bemoaned the politicization of COVID-19 vaccine and drug development.
But he said he thinks the pharmaceutical industry is "rising to the occasion" of the pandemic and hopes that will boost the industry's public image.
"I don't want to declare any victory, just because we're going to bring a vaccine or a treatment that works, that we're going to come back to where we deserve to be, but I think it will be a very good step," he said. "Then we need to continue doing the right thing."
He had one concluding thought as he ended the Q&A: "Science will win," he said.
Thank you and stay safe; Gary Ordog, MD September 16, 2020.
Here is an update on why the vaccine is so difficult. Note that they are saying that multiple vaccinations will be required for COVID-19 alone!!
OCTOBER 14, 2020
Review sums up current knowledge about SARS-CoV-2 immunity, application to vaccine development
In a review published in The Lancet, researchers discussed what is currently known about human humoral and cellular immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and their application to the coronavirus disease 2019 (COVID-19) vaccines currently in phase 3 clinical trials, based on a search performed on PubMed for articles published up till September 24, 2020.
“There is little knowledge of post-infection immunity to SARS-CoV-2, and the biological and genetic factors responsible for the broad spectrum of disease severity remain unclear. Data suggest that uncoordinated or partially neutralizing antibodies, and responses from CD4+ and CD8+ T cells, might be associated with COVID-19 severity, with age being a risk factor,” wrote Gregory A Poland, MD, Mayo Clinic, Rochester, Minnesota, and colleagues.
“Information concerning the durability of immunity to SARS-CoV-2 infection, and the targets of B-cell and T-cell responses, can assist in the continued development of succeeding generations of new vaccines and therapeutics,” they added.
Humoral immunity to SARS-CoV-2
The authors said most patients with COVID-19 or those who are convalescent have virus-specific IgM, IgA, and IgG responses in the days after infection, suggesting that antibodies mediate protective immunity to SARS-CoV-2. The overall kinetics of the antibody response against SARS-CoV-2 are analogous to those for SARS-CoV-1, which are characterized by robust seroconversion (IgM and IgG) 7–14 days following symptom onset and antibody concentrations persisting for weeks to months after infection and viral clearance.
“Additional longitudinal studies are necessary to further understand the dynamics of SARS-CoV-2-induced antibodies in populations and the role that these antibodies have in the risk and severity of COVID-19. Such knowledge is relevant to diagnosing patients with COVID-19 early and for examining the incidence of infections (clinical and subclinical) in different populations. It is important to understand whether, and how, other factors (eg, age, race, ethnicity, sex, body-mass index, and smoking status) might influence serological and immune responses during SARS-CoV-2 infection,” the authors wrote.
Cellular immunity to SARS-CoV-2
According to the authors, initial reports on cellular immunity to SARS-CoV-2 have consisted of case reports with small numbers of patients, which have indicated that the proportion of CD38+ , HLA-DR+ T cells (both CD4+ and CD8+) increases during the first 7–10 days of COVID-19 symptoms and begins to return to baseline around day 20. In addition, SARS-CoV-2- specific T cells express perforin 1 and granzymes upon in vitro re-stimulation with viral antigens. Meanwhile, in some reports but not others, the increase in the proportion of SARS-CoV-2-specific T cells seemed to correlate with disease severity. “This finding represents an important unanswered question that could affect vaccine development,” the authors said. “Serious illness has also been linked to a greater reduction in peripheral CD4+ and CD8+ T cell counts compared with non-serious illness, suggesting a link between disease severity and the size of the cellular immune response; however, larger studies are necessary to further support a correlation.”
Overall, the current data show that both CD4+ T-cell and CD8+ T-cell responses occur in most patients infected by SARS-CoV-2 within 1–2 weeks after symptom onset and produce mainly Th1 cytokines. The frequency of CD4+ T cells targeted to the spike glycoprotein correlates with neutralizing antibody titers, suggesting that the T-cell response might also vary among individuals with different disease severities.
The authors noted that the contribution of cellular immunity to protection against COVID-19 is not currently clear; however, a balanced immune response consisting of high titers of neutralizing antibodies and Th1-biased T cells will probably be optimal. The role of CD8+ T-cell responses in protection against COVID-19 is also unclear, with some evidence suggesting that CD8+ T-cell responses are stronger in patients with mild disease than in patients with severe disease. Additional research into the cellular immune response to SARS-CoV-2 and COVID-19 vaccines will be necessary to test this hypothesis.
Vaccines against SARS-CoV-2
Various candidate vaccines are being developed and tested, including nucleic acid vaccines, inactivated virus vaccines, live attenuated vaccines, protein or peptide subunit vaccines, and viral-vectored vaccines. According to the authors, the front runner candidates are all administered by the intramuscular route. “Therefore, focus is on evaluating immune responses in the blood rather than those in the mucosal surfaces. The role of mucosal immunity should not be discounted, and several intranasal vaccine formulations are under investigation,” they added.
Vaccine candidates currently in phase 3 trials include a chimpanzee adenovirus (ChAdOx1/AXD1222) vaccine, mRNA-based vaccines (mRNA-1273, BNT162b1, BNT162b2), adenovirus serotype 26 vector (Ad26.COV2.S), adenovirus serotype 5 vector and adenovirus serotype 26 vector (Sputnik V), adenovirus serotype 5 vector (Ad5CoV), inactivated virus vaccines (CoronaVac, BBIBP-CorV).
“Much remains to be learned regarding coronavirus immunity in general and SARS-CoV-2 immunity in particular, including the protective immunity induced by vaccines and the maintenance of immunity against this virus. Furthermore, multiple vaccine types will probably be needed across different populations (eg, immune-immature infants, children, pregnant women, immuno-compromised individuals, and immunosenescent individuals aged ≥65 years),” the authors noted.
“In addition to the adaptive immune response, there are some data suggesting that trained innate immunity might also have a role in protection against COVID-19. Multiple clinical trials are examining whether unrelated vaccines, such as the measles, mumps, and rubella vaccine and the Bacillus Calmette–Guérin vaccine, can elicit trained innate immunity and confer protection against COVID-19,” the authors said. “It is crucial that research focuses on understanding the genetic drivers of infection and vaccine induced humoral and cellular immunity to SARS-CoV-2, defining detailed targets of humoral and cellular immune responses at the epitope level, characterizing the B-cell receptor and T-cell receptor repertoire elicited by infection or vaccination, and establishing the long-term durability, and maintenance, of protective immunity after infection or vaccination.”
Reference: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32137-1/fulltextSOURCE: The Lancet
Multiple vaccines will be required! Until then, please stay safe.
Thank you October 14, 2020; Gary Joseph Ordog, MD.
October 16, 2020: Here is today's CDC report for California on COVID-19 in California's Healthcare workers.
" As of October 13, local health departments have reported 41,575 confirmed positive cases in health care workers and 193 deaths statewide. "
These are healthcare workers that I would have to assume to be working must have started out healthy and fit to work. So, in California alone, 193 have died needlessly in nature's process of natural herd immunity.
This is evidence against pursuing natural herd immunity, rather than giving a good vaccine against the virus.
Thank you for your support and please stay safe, we need a good vaccine as soon as possible. October 16, 2020; Gary Ordog, MD.
A major concern published in JAMA today. Apparently, the vaccines for COVID-19 will not stop the worrying. Here is part of the story:
Can Vaccinated People Stop Worrying About COVID-19?
While a vaccine will help protect individual patients and those around them, a large proportion of the population must be immunized and protected before transmission is substantially reduced. Especially for 2-dose regimens, this will take months. No vaccine will be 100% effective and a vaccine that protects against developing clinical illness may not prevent transmission to others. Also, the duration of naturally occurring immunity to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown and may wane with time.9 Therefore, the likely duration of protection by new COVID-19 vaccines is unknown.
For these reasons, even after vaccines become available, SARS-CoV-2 will be a continuing concern. Effective public health measures, such as social distancing, limiting the size of gatherings, and wearing masks, will be needed for at least several more months, and potentially longer.
Conclusions
Many individuals are hesitant about receiving COVID-19 vaccines. Reasons include the novelty and rapid development of the vaccines, as well as the politicization of the pandemic and inconsistent messages from scientists and government leaders. It is critical that clinicians stay well informed about emerging data so that they can help patients make sound decisions about the vaccines needed to help end the pandemic.
Article Information
Corresponding Author: Jesse L. Goodman, MD, MPH, Medicine and Infectious Disease, Georgetown University School of Medicine, 3900 Reservoir Rd, Washington, DC 20057 ([email protected]).
Published Online: October 16, 2020. doi:10.1001/jama.2020.20590
So, apparently life will continue on like this even after we are given the vaccines. We were all hoping to get back to normal. Looks like masks, gloves, sanitizer, social distancing are in effect permanently. I say once again, please stay safe, and thank you for your support, October 16, 2020; Gary Ordog, MD.
We are getting closer to an answer. I published this in JAMA today, November 25, 2020.
November 25, 2020
SARS-CoV-2: Natural Herd Immunity and Complications
Gary Ordog, MD, DABMT, DABEM | County of Los Angeles, Department of Health Services, (retired)
Thank you for the excellent article and comments, being both timely and important. Natural herd immunity probably will not stop the virus. The answer is a good vaccine, several of which that are high efficiency should be available soon. There must be a major effort to implement worldwide vaccination administration next. These discussions, so far, have not mentioned a major reason for advising against natural herd immunity. The COVID-19 mortality rate is quite obvious, but the other concerning metrics of complications were not presented. A major reason to avoid this virus is the high percentage (estimated at least 97%) of complications including immunological, neurological, respiratory, renal, and most other systems, with the potential for long term sequelae. Prudent advice at this time seems to be to avoid exposure this (and probably any) virus, avoid natural herd immunity, and rely upon the administration of good vaccines.
Thank you and stay safe.
CONFLICT OF INTEREST: None Reported
JAMA Insights
October 19, 2020
Herd Immunity and Implications for SARS-CoV-2 Control
Saad B. Omer, MBBS, MPH, PhD1,2; Inci Yildirim, MD, PhD, MSc1,3; Howard P. Forman, MD, MBA4,5
Author Affiliations Article Information
JAMA. 2020;324(20):2095-2096. doi:10.1001/jama.2020.20892
COVID-19 Resource Center
Herd Immunity as a Coronavirus Pandemic Strategy
Herd immunity, also known as indirect protection, community immunity, or community protection, refers to the protection of susceptible individuals against an infection when a sufficiently large proportion of immune individuals exist in a population. In other words, herd immunity is the inability of infected individuals to propagate an epidemic outbreak due to lack of contact with sufficient numbers of susceptible individuals. It stems from the individual immunity that may be gained through natural infection or through vaccination. The term herd immunity was initially introduced more than a century ago. In the latter half of the 20th century, the use of the term became more prevalent with the expansion of immunization programs and the need for describing targets for immunization coverage, discussions on disease eradication, and cost-effectiveness analyses of vaccination programs.1
Eradication of smallpox and sustained reductions in disease incidence in adults and those who are not vaccinated following routine childhood immunization with conjugated Haemophilus influenzae type B and pneumococcal vaccines are successful examples of the effects of vaccine-induced herd immunity.1
Herd Immunity Threshold
The herd immunity threshold is defined as the proportion of individuals in a population who, having acquired immunity, can no longer participate in the chain of transmission. If the proportion of immune individuals in a population is above this threshold, current outbreaks will extinguish and endemic transmission of the pathogen will be interrupted. In the simplest model, the herd immunity threshold depends on the basic reproduction number (R0; the average number of persons infected by an infected person in a fully susceptible population) and is calculated as 1 − 1/R0 (Figure).2,3 The effective reproduction number incorporates partially immune populations and accounts for dynamic changes in the proportion of susceptible individuals in a population, such as seen during an outbreak or following mass immunizations. A highly communicable pathogen, such as measles, will have a high R0 (12-18) and a high proportion of the population must be immune to decrease sustained transmission. Since the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, most of the studies estimated the SARS-CoV-2 R0 to be in the range of 2 to 3.2 Assuming no population immunity and that all individuals are equally susceptible and equally infectious, the herd immunity threshold for SARS-CoV-2 would be expected to range between 50% and 67% in the absence of any interventions.
Figure. Herd Immunity Thresholds by Disease
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Herd Immunity Thresholds by Disease
The locations included are the locations in which the threshold was measured.
Duration of Protection
For both naturally acquired and vaccine-induced immunity, the durability of immune memory is a critical factor in determining population-level protection and sustaining herd immunity. In the case of measles, varicella, and rubella, long-term immunity has been achieved both with infection as well as vaccination. With seasonal coronaviruses, durable immunity has not been observed or has been short lived.4 For infections that produce transient immunity, the pool of susceptible individuals soon increases in the absence of a vaccine and outbreaks reappear. With an effective vaccine and vaccine program, herd immunity can be sustained (even if periodic vaccination is required to do so) and outbreaks can be curtailed as long as the community maintains the necessary levels.
Role of Heterogeneity
Nominal herd immunity thresholds assume random mixing between individuals in a population. However, daily life is more complicated; individuals mix nonrandomly and some individuals have higher numbers of interactions than others. Empirically validated network models have shown that individuals who have higher numbers of interactions get infected earlier in outbreaks.5 This may contribute to slowing of community spread of an infection before reaching the nominal herd immunity threshold. However, there is uncertainty regarding the precise effect of heterogeneity in social mixing on herd immunity against SARS-CoV-2.
T-Cell Cross-reactivity
T-cells are important mediators of immunity. Recent reports have suggested that cross-reactivity with other coronaviruses may confer relative protection of the population from coronavirus disease 2019 (COVID-19).6 It is less clear that T-cell cross-reactivity could provide sterilizing immunity (ie, that the host could not carry nor transmit infection) as opposed to reducing the severity of illness.
Infection-Based Herd Immunity as Policy
An infection-based herd immunity approach (ie, letting the low-risk groups become infected while “sequestering” the susceptible groups) has been proposed to slow the spread of SARS-CoV-2. However, such a strategy is fraught with risks. For example, even with modest infection fatality ratios, a new pathogen will result in substantial mortality because most, if not all, of the population would not have immunity to the pathogen. Sequestering the high-risk populations is impractical because infections that initially transmit in low-mortality populations can spread to high-mortality populations. Moreover, so far, there is no example of a large-scale successful intentional infection-based herd immunity strategy.
There are only rare instances of seemingly sustained herd immunity being achieved through infection. The most recent and well-documented example relates to Zika in Salvador, Brazil. Early in the COVID-19 pandemic, as other countries in Europe were locking down in late February and early March of 2020, Sweden made a decision against lockdown. Initially, some local authorities and journalists described this as the herd immunity strategy: Sweden would do its best to protect the most vulnerable, but otherwise aim to see sufficient numbers of citizens become infected with the goal of achieving true infection-based herd immunity. By late March 2020, Sweden abandoned this strategy in favor of active interventions; most universities and high schools were closed to students, travel restrictions were put in place, work from home was encouraged, and bans on groups of more than 50 individuals were enacted. Far from achieving herd immunity, the seroprevalence in Stockholm, Sweden, was reported to be less than 8% in April 2020,7 which is comparable to several other cities (ie, Geneva, Switzerland,8 and Barcelona, Spain9).
The population of the United States is about 330 million. Based on World Health Organization estimates of an infection fatality rate of 0.5%, about 198 million individuals in the United States are needed to be immune to reach a herd immunity threshold of approximately 60%, which would lead to several hundred thousand additional deaths. Assuming that less than 10% of the population has been infected so far,10 with an infection-induced immunity lasting 2 to 3 years (duration unknown), infection-induced herd immunity is not realistic at this point to control the pandemic. SARS-CoV-2 vaccines will help to reach the herd immunity threshold, but the effectiveness of the vaccine(s) and the vaccine coverage are to be seen.
Conclusions
Herd immunity is an important defense against outbreaks and has shown success in regions with satisfactory vaccination rates. Importantly, even small deviations from protective levels can allow for significant outbreaks due to local clusters of susceptible individuals, as has been seen with measles over the past few years. Therefore, vaccines must not only be effective, but vaccination programs must be efficient and broadly adopted to ensure that those who cannot be directly protected will nonetheless derive relative protections.
Back to topArticle Information
Corresponding Author: Saad B. Omer, MBBS, MPH, PhD, Yale University, 1 Church St, New Haven, CT 06510 ([email protected]).
Published Online: October 19, 2020. doi:10.1001/jama.2020.20892
Conflict of Interest Disclosures: Dr Yildirim reported being a member of the mRNA-1273 Study Group. No other disclosures were reported.
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Comment
4 Comments for this article
October 20, 2020
Estimated Infections in US
Tom Kocsis, BS ME, MS Telecom | Private Citizen
The statement "assuming that less than 10% of the population has been infected so far" is open to question. That statement is made based on a study of "Prevalence of SARS-CoV-2 antibodies in a large nationwide sample of patients on dialysis in the USA" (the paper's reference 10). That seems a very limited and narrow group of individuals from which to base the 10% assumption. Further, the existence of antibodies is not the sole confirmation of whether an individual had a SARS-CoV-2 infection previously. I continue to meet people who believe they had SARS-CoV-2 in the Jan-Apr 2020timeframe before testing was widely available. Some of those folks went for an antibody test later in the Aug-Sep timeframe and their tests came back negative. I think there's still much to be learned on what is a good test for prior infection. Further, there's the entire subject of "asymptomatic" individuals. How many of these individuals never even go in for a test later on since they won't know or suspect they've been infected? I do appreciate this article and its insights despite the criticism stated above and hope that the research community discovers more about this virus and how it is resisted by the human immune system in asymptomatic individuals and that it would lead to a much more effective and revealing test to possibly arrive at a more accurate picture of infection across the US. Also, I'd really like to see new research on how this virus is mutating over time and whether its "deadliness" is declining based on the death rates that we see in the US as having declined and flattened since early Aug while the number of infections has continued to increase at a high rate. Is this due to the virus becoming less "deadly" as it spreads thru the population or is it because of the treatments that are being administered now? Appreciate all the research and work to battle this new virus.CONFLICT OF INTEREST: None Reported
October 20, 2020
The Myth of SARS-CoV-2 Control
Paul von Ebers, MBA Health Administration | Health care consultant, insurance executive
Omir, Yildrim, and Forman argue that herd immunity in the absence of an effective vaccine is not a realistic strategy for SARS-CoV-2 control. They leave open the question of what a realistic strategy would be. Common wisdom is that masking, handwashing, social distancing, and avoiding large gatherings is the strategy that will bring an end to the pandemic. This argument has merit, given reductions in infection rates following the implementation of these strategies in various places around the world. However, a key, unanswered question is whether this strategy is sustainable.
The authors,for example, state what appears to be true: "Importantly, even small deviations from protective levels can allow for significant outbreaks due to local clusters of susceptible individuals." Human behavior has probably changed more dramatically in response to Covid than any other health issue in recent history and yet it has not been enough to stop the virus. Renewed outbreaks are happening even in locations where significant restrictions on person to person contact were put in place for considerable periods of time. Indeed, now the White House coronavirus task force is warning about small family gatherings for holidays as a major risk factor.
Assuming we are as far from herd immunity as the authors state, it appears that the authors are arguing for protracted periods of social isolation and reduced normal human behavior unless an effective vaccine is developed. And the authors have some doubt about how soon and how effective a vaccine will be.
The authors argue that protecting the vulnerable while allowing the virus to burn out in the less vulnerable population is not possible. Even if they are right, they fail to consider social determinants of health impacted by the common wisdom strategy. We know that unnecessary non-Covid deaths are occurring due to reductions in needed care. Preventive care and chronic disease management has been reduced. Low income children are losing valuable school experience and food support due to school closings. Low income parents are losing their incomes due to business closures. Income and health disparities are growing as a direct result of the social isolation strategy. Elderly patients at the end of life without Covid are dying without the comfort of their families. Covid restrictions are not only "an inconvenience" as many public health experts have claimed. They are affecting the morbidity, mortality and lifetime economic prospects (which is correlated to health) of millions of people worldwide.CONFLICT OF INTEREST: None ReportedREAD MORE
October 22, 2020
Is herd immunity even possible
Garreth Debiegun, MD | Maine Medical Center
This article states that infection-based herd immunity has never actually been achieved. I was aware of this before and hypothesize that it can never be achieved because, as the proportion of susceptible individuals decreases, so will the prevalence of the virus. This will continue until a balance is left that enables the virus to persist in the community at lower levels. Otherwise many viruses and other illnesses we see regularly would cease to exist. I’m not an epidemiologist or virologist, is this true? Is infection-achieved herd immunity actually possible?
CONFLICT OF INTEREST: None Reported
November 25, 2020
SARS-CoV-2: Natural Herd Immunity and Complications
Gary Ordog, MD, DABMT, DABEM | County of Los Angeles, Department of Health Services, (retired)
Thank you for the excellent article and comments, being both timely and important. Natural herd immunity probably will not stop the virus. The answer is a good vaccine, several of which that are high efficiency should be available soon. There must be a major effort to implement worldwide vaccination administration next. These discussions, so far, have not mentioned a major reason for advising against natural herd immunity. The COVID-19 mortality rate is quite obvious, but the other concerning metrics of complications were not presented. A major reason to avoid this virus is the high percentage (estimated at least 97%) of complications including immunological, neurological, respiratory, renal, and most other systems, with the potential for long term sequelae. Prudent advice at this time seems to be to avoid exposure this (and probably any) virus, avoid natural herd immunity, and rely upon the administration of good vaccines.
Thank you and stay safe.
CONFLICT OF INTEREST: None Reported
Happy New Year 2021. Here is the latest CDC numbers report, with the new definition of death due to COVID-19 or more specifically SARS-CoV-2:FEBRUARY 4, 2021COVID-19: Case count in US rises by close to 117,000According to CDC's update on February 3, 2021 12:26 pm ET, the case count of COVID-19 in the US stands at 26,277,125* cases, including 445,264* deaths, in 55 (50 states, District of Columbia, Puerto Rico, Guam, Northern Marianas, and US Virgin Islands) jurisdictions. The CDC noted that this represents an increase of 116,915 cases and 3,433 deaths compared to the update on the preceding day. * As of April 14, 2020, CDC case counts and death counts include both confirmed and probable cases and deaths. This change was made to reflect an interim COVID-19 position statement issued by the Council for State and Territorial Epidemiologists on April 5, 2020. The position statement included a case definition and made COVID-19 a nationally notifiable disease.A confirmed case or death is defined by meeting confirmatory laboratory evidence for COVID-19.A probable case or death is defined by one of the following:
- Meeting clinical criteria AND epidemiologic evidence with no confirmatory laboratory testing performed for COVID-19
- Meeting presumptive laboratory evidence AND either clinical criteria OR epidemiologic evidence
- Meeting vital records criteria with no confirmatory laboratory testing performed for COVID-19
- Stay safe it is still not good even though the vaccines have been out for 2 months, but their distribution is failing!!. As it may be another year before we all get our vaccinations, this may well portend the death of a million in the US alone by COVID-19 by then. Remember, only 10% of the US population has been shown to be infected to date. Many of those infected have already reverted back to non-immune status and can get it again. Let alone the new mutations that are re-infective too. Nasty situation getting worse. These numbers will actually approach those of 1918, by 2022, at the rate that things are going now. Poor vaccine roll-out has allowed history to repeat itself again!
- Gary Joseph Ordog, MD.
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