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THIRD DOSE RECOMMENDED FOR TRANSPLANT PATIENTS
On August 13, 2021, The Advisory Committee on Immunization Practices (ACIP) unanimously passed a resolution recommending vaccination with an additional dose of Pfizer-BioNTech or Moderna COVID-19 mRNA vaccines for moderately and severely immunocompromised people. This included those who were recipients of solid-organ or hematopoietic stem cell transplants. Immunocompromised people should continue to wear a mask, social distance and avoid crowds in poorly ventilated indoor spaces after receiving the third dose.

Receptor Binding Domain (RBD) antibodies one month after the 3rd dose rose to 55% in the Moderna vaccinated vs. 18% in the placebo group. There were no serious adverse events [Hall VG, Ferreira VH, Ku T, Ierullo M, Majchrzak-Kita B, Chaparro C, et al. Randomized Trial of a Third Dose of mRNA-1273 Vaccine in Transplant Recipients. N Engl J Med. 2021.].

4 weeks after a third dose of the Pfizer BNT162b2 vaccine. antibodies rose to 68% from 40% in solid-organ transplant recipients without any Covid-19 cases reported. 
[Kamar N, Abravanel F, Marion O, Couat C, Izopet J, Del Bello A. Three Doses of an mRNA Covid-19 Vaccine in Solid-Organ Transplant Recipients. N Engl J Med. 2021;385(7):661-2.].

COVID-19

This page discusses the Coronavirus pandemic that has been spreading rapidly around the world. In the short time that it has existed, we have learned a great deal about it, but our knowledge is still evolving. Vaccinations, more efficient testing and therapy are under investigation. We have learned that public health measures such as wearing a mask in public, social distancing and sanitizing our hands will help enormously to keep us safe. Kidney disease, especially when accompanied by diabetes or heart disease, puts people at higher risk for hospitalization. Also, acute kidney injury is a common problem in ill COVID-19 patients. Kidney Associates is very interested in this disease and in trying to mitigate its course.

Please click on the highlighted green areas with your mouse to open each section.



INTRODUCTION

In mid-November, 2019 a visitor to the Huanan Seafood Market in Wuhan City in the Hubei province in China became ill and transmitted an unusual type of pneumonia to others. The outbreak grew slowly, and by December 15 there were 27 cases. By the end of December, the World Health Organization (WHO) was notified of 44 cases. China isolated the new virus, a coronavirus similar to the SARS virus of 2003, by January 7 and within the week the genetic code was shared internationally. Named SARS-CoV-2, the virus caused a new and all too often lethal disease, COVID-19. It was felt to have originated in bats, and although the route of transmission was uncertain, began to spread rapidly around the world. There is yet no definitive cure or vaccine for COVID-19, and in most cases, symptoms such as fever and cough are mild. It was shown to spread while completely asymptomatic and to be highly contagious, spreading through air droplets from one’s breath.

Vaccination, masking, social distancing, avoiding crowds have all been shown to decrease the spread of COVID-19.

WHAT IS A VIRUS?

We are made up of trillions of cells. Bacteria are made up of one cell. Viruses aren’t even cells; they are smaller than bacteria and are parasites on other cells. They are made up of genetic material that is surrounded by an outer protein coat. They hijack our cells and reassemble replicating their RNA or DNA and repackaging it to make baby viruses that can spread. Viral infections are not new and have been the source of plagues and pandemics all throughout recorded history. The word “corona” comes from the Latin for garland or crown. Coronaviruses are a large family of viruses – with spikes like a crown.

CURRENT TOPICS OF CONCERN

    • What are the variants?

The major threat from COVID-19 is from emerging variants that either may be more infective, may be resistant to existing vaccines, or may be more lethal with surprising new properties. Viruses mutate frequently, and if the mutation confers a survival advantage for the virus, it crowds out the original virus. The variants are being closely monitored by epidemiologists: 1) Alpha from the United Kingdom (B.1.1.7); 2) Beta from South Africa (B.1.351); 3) Gamma from Japan and Brazil variant (P.1); and 4) Delta (B.1.617.2 from India. All these variants have now been reported in the US, as has the 5) Lambda variant (C.37) spreading from South America. The Lambda variant is now the dominant mutation in Peru, Argentina, Chile, and Columbia. It may be more transmissible than the Alpha, Beta, and Gamma strains, but has yet to be compared to the Delta variant.

In the United Kingdom, the Alpha or B.1.1.7 variant was up to 70 percent more communicable than previous strains, although not more lethal. The vaccines seem effective against this variant.
The Beta variant, B.1.351, from South Africa both reduced the efficacy of vaccines. The Brazil P.1 Gamma variant also reduced neutralization by the vaccine. It was reported that 73.9 percent of deaths carried a portion of the variant labeled G25088T. It is the Delta variant, B.1.617.2 that has dominated in the USA. That is because it is highly effective. It does respond to the vaccine, however. Its infectivity has accounted for the surge in COVID-19 cases in late summer, 2021. It is expected that the virus will continue to mutate, and may be either more infective or dangerous. newer strains may evade vaccination, and could have different pathogenesis altogether.

With respect to the Delta variant, states, where a high percentage of patients were vaccinated were compared with those where the vaccinations were relatively few. In one state with a population of 700,000 70% of patients were vaccinated, and the total cases per week were only 130. However, in a state where only 30% of the residents were vaccinated, there were 5,114 cases among the population of 300,000. The majority of cases are among the unvaccinated in both states. Among patients who were vaccinated, both the Beta and Delta variants have a variable effect on reducing antibody neutralization activity, and thus some effect on vaccine effectiveness. SOURCE:CDC

    • Does immunity last?

All recipients of vaccines experience a decline in neutralizing antibodies over time. The mean titer is 235,228 in those 18-55 at day 119 post-second dose, 151,761 in those 56-70, and 157,946 in those over 71 (https://www.nejm.org/doi/full/10.1056/NEJMc2032195 – Widge AT, Rouphael NG, Jackson LA, Anderson EJ, Roberts PC, Makhene M, et al. Durability of Responses after SARS-CoV-2 mRNA-1273 Vaccination. N Engl J Med. 2020;384(1):80-2.). In 1497 healthcare workers who received the Pfizer BNT162B2 vaccine, 39 had breakthrough infections. In that group, lower neutralizing antibody titers were found at four months. Most breakthrough cases were mild. 85% of the cases were the alpha (B.1.1.7) variant. (Bergwerk M, Gonen T, Lustig Y, Amit S, Lipsitch M, Cohen C, et al. Covid-19 Breakthrough Infections in Vaccinated Health Care Workers. N Engl J Med. 2021). The antibodies persist 8 months after infection and 6 months after the second mRNA vaccine and 8 months after receiving a single Janssen (J&J) dose. There is decreased protection against the Beta and Gamma strains 6 months post vaccine in 50% of those given the Moderna vaccine. 50% who were protected by the vaccine against the original strain lose neutralizing antibodies in 6 months later.

    • Do patients develop cellular immunity?

An article published March 19, 2021 in Nature Communications, reported that virus-specific cellular (T cell) memory can be demonstrated in SARS-COV-2 virus patients and their close contacts. The close contacts gain immunity despite never exhibiting a detectable infection.
(Wang Z, Yang X, Zhong J, et al. Exposure to SARS-CoV-2 generates T-cell memory in the absence of a detectable viral infection. Nat Commun. 2021;12:1724.) This has been confirmed by additional studies. Post infection assays of up to 317 days shows that memory cells are long lasting after infection. This should also hold for patients who are vaccinated (Jung JH, Rha M-S, Sa M, Choi HK, Jeon JH, Seok H, et al. SARS-CoV-2-specific T cell memory is sustained in COVID-19 convalescent patients for 10 months with successful development of stem cell-like memory T cells. Nature Communications. 2021;12(1):4043).

    • Should children returning to school wear a mask?

Children under 12 are currently ineligible for a vaccination although studies are exploring the safety and effectiveness of vaccinating this population. A Duke study of 7,000 children and adults who acquired COVID-19 found that there was a low rate of transmission of only 363 additional children in an environment where all wore masks (https://www.nytimes.com/2021/08/10/opinion/covid-schools-masks.html). 

    • Should elderly persons, health care workers, nursing home residents, and those with chronic diseases receive a booster dose.

A recent study demonstrated that giving a booster vaccination 6 months after duo-vaccinations restores neutralizing antibodies in two weeks (Wu K, Choi A, Koch M, Ma L, Hill A, Nunna N, et al. Preliminary Analysis of Safety and Immunogenicity of a SARS-CoV-2 Variant Vaccine Booster. medRxiv. 2021:2021.05.05.21256716.) Britain, Germany, and Israel are all offering the third COVID-19 vaccine to vulnerable patients. This includes persons over 50 years of age. They are also giving booster vaccines to health care workers and care home staff. The Advisory Committee for Immunological Practices will take up this issue in the coming months. The vaccines are being considered for the elderly, those who are vulnerable, and also health care workers. A consideration with health care personnel is the heightened need to prevent even mild or asymptomatic infections in order to mitigate the risk of spread to high-risk patients.

    • Should a vaccine be mandated?

Health care environments such as Houston Methodist Hospital, as well as our clinical practice, are requiring vaccines, many businesses can and will require that their patrons be vaccinated, particularly when they must congregate in a crowded environment. There are instances where a vaccine may not be warranted, those with high neutralizing antibodies, or those who have had a severe vaccination reaction. Although there are those who feel that the imposition of a government rule that individuals receive any vaccine infringes on personal rights, there is also the concern that an individual who refuses a vaccination violates the rights of others by passing along a dangerous infection. The precedents for a mandate are polio, required by each state, and smallpox. The Supreme Court of 1905 upheld that the government had the authority to reasonably infringe upon personal freedoms during a public health crisis, requiring individuals to get the smallpox vaccine or pay a fine (https://www.history.com/news/smallpox-vaccine-supreme-court). The smallpox vaccine completely eradicated a disease that plagued civilization for 400 years. Two alternatives to a mandate are that those refusing to receive a vaccine either isolate from the vulnerable or incur liability if it can be demonstrated they caused an infection. A far more favorable alternative is that a major effort is made to educate all individuals that the vaccines are safe, protect those receiving them, and as well those with whom they are in contact.

SARS-CoV-2 RESOURCE

SARS-CoV-2 is a coronavirus discovered in 2019 that spreads through droplets and contact. It came from bats and is thought to have originated from a market in Wuhan City in the Hubei province in China. By the end of December 2019, there were 44 cases in China, 11 of whom were severely ill. By January 3 there were 41 confirmed COVID-19 cases admitted to Wuhan hospitals. 32% had diabetes, hypertension, or cardiovascular disease. The median age was 49, and 27 had been exposed in the Huanan Seafood Market. Fever was present in 98% of cases and cough 76%. 55% developed shortness of breath within 8 days and 63% had lymphopenia. All had abnormal chest CT findings. Complications included acute respiratory distress syndrome (29%), and acute cardiac injury (12%). 6 (15%) of the patients died (Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506).

Within a few days, there had been 4,593 cases in several countries including Australia, North America, and Europe. On January 9 the mysterious disease was announced by WHO. By January 20 there were 6 deaths (see above) and the next day WHO acknowledged that the disease spread person to person. As the disease was spreading throughout China the Centers for Disease Control and Prevention (CDC) announced that US airports would screen for the disease. The first case appeared in the United States on January 21 in Washington state, a recent traveler from Wuhan City. Contact tracing was then deployed in Washington state. Wuhan went into quarantine – the city and region strictly locked down 18 million people.

A global health emergency was declared by WHO on January 31, 2020, as the disease was spreading in the United States, Germany, and Asia. In 2019 14,000 persons traveled to the United States from China each day, but with 10,000 confirmed cases in China global air travel to the United States from China had to be suspended. On January 31, the United States declared the disease a national public health emergency. In another week deaths from the disease, now officially named COVID-19 would surpass those of SARs from 2003.  COVID-19 was declared a pandemic on March 11 and a national emergency on March 13. Between March 13 and March 20, a survey of attitudes and awareness was conducted in Chicago hospitals. The survey showed that 24.6% of patients were worried about getting the coronavirus. 65.9% thought they would possibly get sick but 24.6% felt it was not at all likely. 71.1% correctly identified three symptoms and 58/6% significantly changed their lifestyles. The mean age of the group was 62.1 years of age. 23.4% had heart disease and 24.6% diabetes. 54.4% were diabetic, 75.2% hypertension, and 20% were organ transplant recipients. (Wolf, Michael S, Serper Marina, Opsasnick, Lauren et al. Awareness, Attitudes and Actions Related to COVID-19 Among Adults with Chronic Conditions at the Onset of the US Outbreak. Ann Intern Med 2020;173:100-109).

On March 13, 2020 a travel ban from Europe went into effect. Between March 19 and April 3 states went into lockdown, as each created stay-at-home rules curtailing nonessential activities. We saw travel between nations and even between cities and states come to a halt and an entire nation sheltered in place, avoiding social gatherings and working from home. Restaurants, schools, and shops closed. Elective surgery halted.

Telemedicine was used by physicians to care for patients unable to come to the clinic and was approved by the Center for Medicare and Medicaid Services (CMS). Kidney Associates was an early adapter of telemedicine, and patients can see us from home to avoid possible exposure. As patients now can see their doctors through telemedicine portals, Zoom, Facetime and WebEx have become standard methods of communication. Binging television series became a national pastime. Major meetings, travel plans, and even the Tokyo summer Olympics were canceled or postponed. The White House developed social distancing guidelines through April 30. Sheltering in place worked. The National Bureau of Economic Statistics determined that as a result of the executive order in California to avoid nonessential activities, the case rate dropped by 125.5 cases/100,000 between March 19 and April 20. The economic study also estimated that 400 jobs were lost for each life saved. (Friedson AI, McNichols D, Sabia JJ, Dave D. Did California’s Shelter in Place Order Work? 2020. Available from: NBER).

On March 27, 2020 the CARES Act was signed into law to help offset the impact isolation would have on the economy. The disease continued to escalate and surpassed one million by April 4. By April 11 the death rates in the United States exceeded those of all other nations. Mathematical models were showing that a shutdown would delay disease spread, and proved right. As states reopened and gatherings took place, the disease surged. The shutdown that lasted approximately two months saw states starting to lift restrictions by May 20.

Sheltering in place became lax as the nation fatigued of it. National protests of COVID-19 restrictions put pressure on public officials to relax controls over working conditions. Demonstrations to fight police injustice against African Americans were sparked by the May 25, 2020, choking death of George Floyd during an arrest in Minneapolis. As a video taken by a bystander emerged, protests erupted in Minneapolis and other large cities starting that Tuesday and grew in intensity. During this period social distancing was all but forgotten. The large protests did not create a population spike in COVID-19 cases and deaths because during the periods of unrest, mainly because of nonparticipant behavior. But, as people celebrated holidays and gatherings, the disease surged. Meanwhile, grave economic impact forced political divisions in the United States as heated discussions and controversies grew around wearking a mask v personal freedom, opening restaurants, bars, and places of congregation to avoid financial ruin for many proprietors, and when to reopen schools. By June 30, the NIAID chief, Anthony Fauci, predicted that COVID-19 cases could escalate from 40,000 cases to 100,000 new cases per day.

Cases resurged since late June 2020. During July serious debate took place between medical experts and sports associations, local and national leadership. The conflict was the same – how to balance safety with a halt in our lifestyles and economy. In the South records for the number of cases and the number of deaths was shattered. In mid-July, the disease claimed over 140,000 lives with Florida announcing 10,000 new cases per day. As a flood of misinformation hit social media, doubt and fear were coupled with economic devastation and sickness. On July 19 Miami Beach, Florida imposed a curfew.

In the middle of July 2020 Arizona surged to the extent that the city of Tuscon was down to 17 free ICU beds. When the state escaped a large outbreak in April and May, bars and restaurants reopened, testing efforts grew lax and the state leaders and citizens assumed the danger had passed. But by the middle of July, nearly 27% of the tests taken over the past week returned positive. The surge was coupled with anger and blame, and a flow of mixed messages. As the surge worsened the state shut down public gathering places like restaurants, bars, and gyms.

Most restaurants and other gathering places have not fully reopened. Zoom conferencing and working from home are commonplace. World and local travel have significantly decreased with many summer vacations canceled. Political events such as the Democratic and Republican National Conventions took different approaches to gather and social distancing. The RNC was lax with less masking and distancing. The DNC was for the most part virtual. By the end of the summer, the number of cases in five counties was over 100,000 each. These included Harris County (107,490 cases; CFR 2208 deaths; CFR 0.02) Cook County (126,992 cases; 5065 deaths; CFR 0.03988), Maricopa County (134,004 cases; 2,976 deaths; CFR 0.022), Miami-Dade (159,059 cases; 2,537 deaths; CFR 0.0159) and Los Angeles County (242,521 cases; 5,829 deaths; 0.024). The highest number of deaths in the nation was in Queens, 5,992 deaths. The USA leads the world in deaths, 185,744 but has had 6,114,406 cases, and has a CFR of 0.0326 which is 9th worldwide. The USA has 56.4 deaths per 100,000.

The CDC predicted up to 211,000 deaths by September 26, 2020. In the USA vaccines produced by Astra Zeneca, Moderna and Pfizer were in phase 3 testing, but on September 8, Astra Zeneca halted the clinical trial on one of them because of a serious adverse event (SAE) that needed to be resolved. Rapid testing kits for both antigen and antibody were being deployed. Remdesivir, dexamethasone, and convalescent serum all showed promise. School openings across the globe experienced the most feared problem – that the disease would spread on campus as many students partied and ignored health warnings. Debate ensued whether to send infected students back to their homes or contain them in quarantine on campus.

The month of October 2020 saw a steady spike in new cases of COVID-19 across the USA. October 1 had 46,418 new cases with a steady rise that peaked at 85,085 new cases on October 23. (Source:NYT) The month started with President Trump announcing on Friday, October 2 that he and his wife, Melania, tested positive. Several members of his immediate staff also tested positive. He was transferred to Walter Reed National Military Medical Center after “not feeling so well” and was discharged on October 5. During his hospital stay, he was reportedly febrile with two episodes of oxygen desaturation and was treated with Remdesevir and Regeneron. He also received dexamethasone. He remained ambulatory and was photographed working during his stay in the Presidential Suite of the hospital. After his October 5 discharge, he returned to the White House and was back in the Oval Office by October 7. By October 12, his test was negative and he energetically resumed his campaign. The political campaign was polarized by the extreme opposite views surrounding COVID-19 with Trump’s opponents skeptical, and highly critical of his role in preparing the nation for this crisis. Trump was criticized for pushing a sense of normalcy while the disease was progressing. The Trump team took an opposing highly positive view, emphasizing the upcoming vaccine therapy and monoclonal antibodies (He received Regeneron through compassionate use). He stressed that opening up businesses and sustaining the economy was essential and that COVID-19 could be contained while the economy normalized. Trump continued to hold public rallies, but Trump and his supporters were now more prone to wearing masks.

The spread during October 2020 was nationwide, even in sparsely populated areas such as the Dakotas. The US surpassed 225,000 COVID-19 deaths with hospitalizations trending up. The third wave also occurred in Europe. The reasons for increased transmission were apparent – more congregating as students returned to schools and patrons returned to restaurants. COVID fatigue and laxity prevailed.

In December 2020 vaccinations became available. None of these were live vaccines, Two were messenger RNA (mRNA), and the third was a viral vector. The Pfizer BNT162b2 dual vaccine was administered in the deltoid muscle three weeks, and the Moderna mRNA1273 four weeks apart. They had few safety issues and were considered 95 and 94% effective. The J&J viral vector JNJ-78436735 was a single-dose vaccine that was 66.3% effective but 85% in preventing severe disease. As the virus mutated, concerns were raised about its effectiveness against variants. While many refused vaccinations, those who did were able to drive the incidence of the virus down for the first half of 2021. Many businesses reopened and life people started to resume usual activities. However, the emergence of the delta variant became problematic. This variant was more infective even if less lethal. Between July 1 and August 15 there was a 700% increase in the number of cases. Many new cases were among those who were never vaccinated, but breakthrough cases occurred among those vaccinated. By August 2021 over 140 million individuals completed either a 2 dose series of Moderna or Pfizer vaccine or the Janssen vaccine.

Vaccine hesitancy was associated with anti-vaccine sentiment, distrust of the media, those with less formal education, and Blacks, Pacific Islanders, and Native Americans (COVID-19 vaccine hesitancy among individuals with cancer, autoimmune diseases, and other serious comorbid conditions (medrxiv.org)

References frequently reviewed:

  • cdc.gov
  • The Economist
  • cnn.com
  • cbsn.com
  • foxnews.com
  • reuters.com
  • New York Times (NYT)
  • New York Post
  • The Guardian
  • Politico
  • The Hill
  • wired.com
  • nber.org
  • statnews.com
  • nbcmiami.com July 20,2020
  • Clickorlando.com July 31,2020
  • Wall Street Journal, July 15,2020

NEW YORK

New York City was hit particularly hard and deserves special mention because of how people must move about – elevators and subways. It is no wonder that 5,700 persons were hospitalized there from March 1 through April 4, 2020. The mean age was 63 and many had hypertension, obesity, and diabetes. 14.2% were in the ICU and 12.2% were on assisted ventilation. 3.2% required dialysis. In the end, 2,634 people or 21% of the hospitalized died.

Between March 1 and May 16, 2020, there were 191,392 confirmed COVID-19 cases and 20,141 deaths. While the overall infection fatality risk was 1.45% (CI 1.09-1.87). But, when age was taken into consideration, the infection fatality rate was 17% for those over 75 years old, and the risk was 6.1% for those 65-75 years of age (Richardson S, Hirsch JS, Narasimhan M, et al. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area [published online ahead of print, 2020 Apr 22] [published correction appears in doi: 10.1001/jama.2020.7681]. JAMA. 2020;323(20):2052-2059. doi:10.1001/jama.2020.6775) and Wan Yang, Sasikiran Kandula, Mary Huynh, et al. Estimating the infection fatality risk of COVID-19 in New York City, March 1-May 16, 2020. medRxiv preprint server)

HOUSTON

The first case of COVID-19 in Houston was March 4, 2020, identified as a Fort Bend County man in his 70s who had traveled to Egypt. By March 11 the Houston Livestock Show and Rodeo was cancelled as a result of a 40 year old Montgomery County man developing it from person to person spread, and not through travel abroad. The NRG Park was shut down and the county declared a public health emergency. This case was traced to the February 28 Bar-B-Que cookoff at the Houston Livestock and Rodeo. The contest that day was potentially attended by 73,433 persons. The Rodeo is a major Houston event and was scheduled to run until March 22. Houston had 14 cases on March 11. Two days later the President issued a federal emergency declaration to free up public funds and enable the Federal Emergency Management Association to coordinate the pandemic.

By March 16, 2020 County Judge Lina Hidalgo ordered schools closed, restaurants closed for dining, bars closed. Takeout from restaurants was permitted. On March 19 the Texas Governor, Greg Abbott ordered limiting social gatherings to 10 people or less. Schools, bars, and gyms remained closed and restaurants limited to takeout. He also banned visitation at nursing homes. Texas was declared a public health disaster. Hospitals stopped elective surgery. A stay at home order was put into place for Harris County and Houston on March 24. On March 31, churches in Texas were permitted to stay open per Governor Greg Abbott. On April 17 the ban on elective surgery was lifted and state parks were allowed to open. Around that period there were 252 new cases per day in Harris County. 96 people in Houston had died from COVID-19.

On April 27 masks were required in all public places in Harris Country. The stay-at-home order was lifted on May 1 as the state testing was only 14,000 per day. This was felt inadequate by health authorities. The state was now reporting 50 COVID-19 deaths per day. The Harris Country Stay at home order was extended through May 20. Violation in public health orders would not be punished by jail time. The state governor and Harris County/Houston officials clashed on coronavirus restrictions, with Governor Abbott feeling they were too restrictive. By May 18 all stay-at-home orders were lifted by the state, allowing businesses to reopen gradually. The death toll for the state was 58 cases per day. At the of May the percent new cases in Houston were 5.4. There had been 299 deaths thus far.

The May 25 Memorial Day was celebrated with partying, especially with social gatherings at beaches and ignoring the rules of wearing masks. In Minneapolis, however, the brutal murder of Houstonian, George Floyd by a police officer sparked protests around the country. On June 3, 60,000 protested in Houston, but many ignored social distancing and the wearing of masks. Restaurants increased capacity from 25 to 50% capacity by June 3 and Houston traffic increased. Despite rules regarding social distancing and the wearing of masks, many either wore their masks improperly or not at all. With an incubation period of 3-7 days, it was no wonder that over the next week the number of cases in Houston started rising. Despite over 2000 hospitalizations per day throughout the state, by June 12 businesses were operating at 75% capacity. Many stores in Houston required their customers to wear masks.

On June 19 many amusement parks opened at 50% capacity as the state testing rate approached 10%. By June 24 the rate approached 12% as hospitals felt they were reaching crisis levels of admissions. On June 15 there were 3,820 patients in Houston area hospitals were on June 1 there were only 519. The county averages 338 cases per day and Houston sustained 422 deaths. The surge in hospitalizations threatened that Houston would have to close back down. The following day elective surgeries in local hospitals were ordered postponed. Despite the surge in hospitalizations, the Lieutenant Governor stated that the increased number of cases was because of increased testing. Restaurant capacity was again rolled back, but many at home, ordering take out and grocery deliveries. The percent new cases rose from 6.71 on June 15 to 16.89% on July 15. As most people celebrated the Fourth of July in front of the television, Governor Abbott ordered masks to be worn in public throughout the state. On Independence Day, 7,890 persons in the state were in hospital beds with COVID-19, the number of admissions doubling from the week before. Over the month of July, the number of hospitalizations in Harris Country rose. It reached 2,672 on July 15, but by Aug 6 was at 1,559. The number of new cases in Harris county continues to rise, 1685 on August 6. School openings were delayed and many Houston Independent Schools are offering home learning. Houston’s deaths were up to 1866.

Although the Rt for Houston had been less than 1 for several days, by the end of August it was once again greater than 1. By September 2 the number of patients hospitalized in Houston hospitals 717, with 348 patients in Intensive Care. The hospitalization rate for Texas Medical Center was also increased – 114/day. The week prior it was 96/day, but the previous month it was 165 hospitalizations per day. By September 2, there were 2,954 deaths in Houston. On September 2, 2020, there were 1001 new cases in Harris Country.

Over the months that followed the city remain pretty much shut down. Masking closed business and zooming to work remained the alternative to a regular lifestyle. In December 2020, Houstons started to receive vaccinations. As they became more widely available, the seriousness of the disease and the number of cases decreased. On June 20, 2021, there were no new cases; the city had opened back up. Traffic congestion, air travel, and packed restaurants signaled hope. Concerns remained for the coming school year since children under 12 were not excluded from receiving vaccinations. The lull was short-lived. On August 11, 2021, there were 4538 new cases in Harris County. The majority of these cases were the Delta variant.

UNDERSTANDING THE SCIENCE

Viral infections are not new and have been the source of plagues and pandemics throughout all recorded history. A virus is a life form that includes DNA or RNA, molecular chains that can cause amino acids sequencing and manufacture proteins. They can also replicate. A virus is protected by an envelope of proteins and sugars that will allow it to migrate through the environment. The characteristics of the virus determine how it attacks human cells. Since they multiply in great numbers the frequency of mutations may be very high.

We are all too familiar with viruses – smallpox, influenza, measles, polio, rhinovirus, adenovirus, and even other coronaviruses. The coronavirus known as SARS-CoV-2 is unique for it has protein spikes on its envelope. The tip of the spike, known as the receptor-binding domain (RBD) has mutated so that it attacks a specific receptor on the cell. This is known as the ACE2 receptor and is found in many organs, particularly lungs, kidneys, heart, pancreas and blood vessels. When the virus attacks, the body responds through an innate immunity system, recruiting a type of lymphocyte known as a T helper cell to the vicinity. The helper cell then recruits a number of other cells types through the release of cytokines – hormones on a cellular level. The reaction to these hormones plays a key role in what happens next. It is ideal for helpers to recruit killer cells that destroy the virus, and regulatory cells that modulate the response so that normal body cells are not injured. Cells that will make antibodies are also recruited, as these antibodies will be necessary to neutralize the virus in there is recurrent exposure. In the elderly and in patients with diabetes, CKD, heart or lung disease, as well as those with any type of immune compromise, the immune system may not react to a virus properly. Either the virus multiplies unchecked or the cytokines are overly destructive, or the body cannot make antibodies that will protect the person from another attack. For these reasons people who are vulnerable have a greater odd of becoming critically ill or being overcome by the infection. (AAKP Renalife – Fadem 2020).

FROM BATS TO MAN

THE ACE2 BINDING REGION The SARS-CoV-2 virus specifically binds a receptor known as the ACE2 binding region. In the bat, the ACE2 binding region is SCH014 and differs from the human ACE2 binding region. This was demonstrated by combining human ACE2 binding molecules with the retrovirus, HIV, along with cell lines from the Horseshoe bat and civets. An insert region between aa310 and aa518 allowed non-ACE2 binding to human ACE2 receptors showing there is compatibility (1).

Six receptor-binding-domain amino acids are critical for binding to ACE2 receptors. Although the coordinates in the earlier SARS-CoV virus correspond to SARS-CoV-2, five differ. These coordinates still have a high affinity for binding, but it is possible that natural selection to an ideal binding ligand happened in humans. The genetic data demonstrate that SARS-Cov-2 does not come from a previously used virus and developed in the human.

SARS-CoV-2 is optimized for binding to the human ACE2 receptor, and once anchored activates a transmembrane protease. serine subfamily 2 (TMPRSS2) The S protein has subunits – the S1 contains the Receptor Binding Domain (RBD) while the S2 has the fusion protein necessary to bind to the protein. The S protein is activated by this serine protease and activates fusion. It also separates the receptor. Furin is also active at cleavage sites on the S12/S2 boundary of the SARS-CoV-2 virus. Furin is also a protease that plays a role in infectivity. Furin is not species-specific. (2)

That SARS-CoV could be infective was predicted in 2015. An infective virus was created in the laboratory and demonstrated that viral particles could mutate in alveoli. This research was performed by a collaboration of leading investigators from around the world led by the University of North Carolina. (1. Department of Epidemiology, the University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. 2. Department of Microbiology and Immunology, the University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. 3. National Center for Toxicological Research, Food and Drug Administration, Jefferson, Arkansas, USA. 4. Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China. 5. Department of Cell Biology and Physiology, the University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. 6. Cystic Fibrosis Center, Marsico Lung Institute, the University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. 7. Institute for Research in Biomedicine, Bellinzona Institute of Microbiology, Zurich, Switzerland. 8. Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA. 9. Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA. Correspondence should be addressed to R.S.B. (rbaric@email.unc.edu) or V.D.M. (vineet@email.unc.edu).) (3)

The observation that the virus can mutate in the lung suggests that the bat virus first infected man and underwent a series of mutations while replicating in the lungs of man. This led to the perfect spike domain region to attack the ACE2 receptor.

References:

1. Ren W, Qu X, Li W, Han Z, Yu M, Zhou P, et al. Difference in receptor usage between severe acute respiratory syndrome (SARS) coronavirus and SARS-like coronavirus of bat origin. J Virol. 2008;82(4):1899-907.

2. Andersen, K.G., Rambaut, A., Lipkin, W.I. et al. The proximal origin of SARS-CoV-2.Nat Med 26, 450–452 (2020).

3. Menachery VD, Yount BL, Jr., Debbink K, Agnihothram S, Gralinski LE, Plante JA, et al. A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence. Nature medicine. 2015;21(12):1508-13.

SIMPLE TERMS TO KNOW

glossary
  • COViD-19-Corona Viral Disease 2019
  • Cytokines – intracellular hormones that activate body processes
  • Cytokine storm – a rapid innate response that can lead to tissue damage
  • Epidemic – when the disease spreads within a large community
  • Fomite – the towel or surface or tissue that contains the living virus
  • Host – You and I – we host the virus while it hijacks our cells and makes baby viruses
  • Immunity – either immediate (innate) or adaptive (specific) – body mechanisms of defense against foreign substance
  • Outbreak – a few new cases in a community
  • Pandemic – When the disease spreads over the whole world
  • R0 The reproduction rate – fixed how many people will one person theoretically infect
  • Rt The transmission rate – how many people one person will theoretically infect (varies with disease number)
  • SARS – Severe Acute Respiratory Syndrome
  • SARS-CoV-2 – The novel coronavirus discovered in 2019
  • T cells – Cells that are part of the body’s defense against virus and bacteria
  • Vector – the animal that spreads the disease (Bat, Pangolin)

RISKS - AGE - HYPERTENSION - DIABETES

Risk of severe illness
  1. Age over 65
  2. Nursing home or long-term care facility resident
  3. Uncontrolled underlying medical condition:
    • Chronic lung disease or asthma
    • Heart disease
    • Immunocompromised – immune deficiencies – HIV, Corticosteroids
    • Cancer therapy
    • Smoker
    • Bone marrow or organ transplantation
    • Severe obesity (body mass index [BMI] of 40 or higher)
    • Diabetes
    • Chronic kidney disease
    • Liver disease

THERAPY

Therapy
  1. Remdesivir
  2. Convalescent serum
  3. Dexamethasone
  4. Monoclonal antibodies
  5. The hydroxychloroquine story
  6. Il6 blockers – Tocilizamab

REVIEW PMC7307820

Remdesivir – Remdesivir inhibits how the viral particle RNA replicates. 10-day courses were tried in compassionate use. Although the mortality in this critically ill group was 18% there was a 68% improvement in oxygenation and a 57% rate of improvement in the patients who were on mechanical ventilators (1).

Further studies have been completed. A meta-analysis of randomized controlled trials with remdesivir does show benefit over placebo (OR=0.61 95% CI 0.45-0.82; P=0.001) https://www.medrxiv.org/content/10.1101/2020.08.21.20179200v2 (2).

The Solidarity Trial is a huge international 405 hospital and 30 country open-label randomized trial of remdesivir, hydroxychloroquine*, lopinavir*, interferon plus lopinavir, interferon only, and no study drug. The mortality of ventilated patients was 39% and Kaplan-Meier (KM) 28-day mortality was 12%. The RR of Remdesivir was (0.95 CI .81-1.11 p=50) and none of the drugs had any benefit with regard to hospital stay or initiation of ventilation. (*dropped) https://www.medrxiv.org/content/10.1101/2020.10.15.20209817v1 (3).

The New Engl J Med study https://www.nejm.org/doi/full/10.1056/NEJMoa2007764 was a double-blind randomized trial – 541 randomized to remdesivir and 521 randomized to placebo. 903 of the patients had severe disease but the benefit was greater when the drug was given earlier. There were 60 trial sites. Recovery time was shortened by 5 days. KM was 6.7% for remdesivir v 11.9% for placebo. Since the NEJM study, had blinded controls and was placebo-based it should be weighted higher than the Solidarity Trial (4).

References:

1. Grein J, Ohmagari N, Shin D, Diaz G, Asperges E, Castagna A, et al. Compassionate Use of Remdesivir for Patients with Severe Covid-19. The New England journal of medicine. 2020.

2. Sarfraz A, Sarfraz Z, Sanchez-Gonzalez M, Michel J, Michel G, Frontela O, et al. Randomized Controlled Trials of Remdesivir in Hospitalized COVID-19 Patients: A Systematic Review and Meta-Analysis. medRxiv. 2020:2020.08.21.20179200.
3. Pan H, Peto R, Abdool Karim Q, Alejandria M, Henao Restrepo AM, Hernandez Garcia C, et al. Repurposed antiviral drugs for COVID-19; interim WHO SOLIDARITY trial results. medRxiv. 2020:2020.10.15.20209817.
4. Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, et al. Remdesivir for the Treatment of Covid-19 — Final Report. New England Journal of Medicine. 2020.

Convalescent serum – The plasma of patients who recovered from COVID-19 will contain antibodies that can neutralize the virus in other patients. While this does not stimulate the patient to develop their own antibodies, it is useful for the treatment of critically ill patients. In a recent study, it reversed the respiratory distress, and in 3 out of 5 patients studied allowed the patients to be successfully discharged from the hospital. The remaining 2 patients were upgraded to stable condition and improving at the time the paper was published.(1)

Reference:

1. Shen C, Wang Z, Zhao F, Yang Y, Li J, Yuan J, et al. Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. Jama. 2020;323(16):1582-9.

Dexamethasone A large United Kingdom Study published in the New England Journal of Medicine a randomized controlled trial of 2,104 hospitalized patients assigned to receive dexamethasone (DXM) and 4,321 patients assigned to receive usual care – the usual care group (UCG). The mortality within 28 days in the DXM group was 482 patients (22.9%) contrasted with 1110 patients in the UCG (25.7%). The age-adjusted rate ratio was 0.83 (95%CI 0.75-0.93;P<0.001). The death rate was also lower in the DXM group than the UCG in patients requiring assisted mechanical ventilation (29.3% vs 41.4% RR 0.64, 95%CI 0.51-0.81). DXM results were not different among those who dod not require respiratory support at randomization.(1)

Reference:

1. Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report. New England Journal of Medicine. 2020.

Monoclonal Antibodies – Taking it a step beyond serum, specific antibodies that are produced by memory B cells are specific for the receptor-binding domain of the SARS-CoV-2 virus can neutralize the virus. This is a promising new therapy but more research must be done before it is ready for human use.(1)

Reference:

1. Ye L, Chen X, Li R, Pan Z, Qian C, Yang Y, et al. Human monoclonal antibodies block the binding of SARS-CoV-2 spike protein to angiotensin-converting enzyme 2 receptor. medRxiv. 2020:2020.04.06.20055475.

The Hydroxychloroquine Story – Hydroxychloroquine is a malaria drug that is in use today for the treatment of lupus. It is generally safe when used by physicians, but it can prolong the QT portion of the heart rhythm and may potentiate a fatal arrhythmia. The drug was found in vitro to inhibit the viral activity. Recommendations to use the drug as therapy before clinical trials were completed in the management of COVID-19 were premature and led to high expectations that were never met. On March 20 Raoult’s team published 20 cases of COVID-19 in a case-control open observational study. This observation revealed viral load reduction in the nasal carriage at day 6, particularly when azithromycin was added. The study was not randomized, was underpowered, and did not provide a long follow up period. (1) Around that time other clinical trials were in progress. The University of Minnesota launched a multi-center randomized, double blind, placebo-controlled clinical trial to determine if hydroxychloroquine could prevent patient who were exposed to COVID-19 from getting symptomatic. On March 30, the FDA granted emergency use authorization for hydroxychloroquine in patients with COVID-19. However evidence was emerging that Hydroxychloroquine was not meeting expectations. But political pressure and false hopes publicly challenged scientific research, and on June 4, Lancet retracted a previously published paper that demonstrated the drug was not effective in ill COVID-19 patients. This was followed by a retraction in the New England Journal of Medicine. On June 18 WHO ended its study of hydroxychloroquine after it was shown not to reduce mortality. The NIH also halted its study on June 20 citing it was ineffective.(2,3)

The ORCHID Trial NCT04332991 had started enrolling on April 2. It was sponsored by Massachusetts General Hospital. This multicenter, blinded randomized trial of hydroxychloroquine v placebo was designed to study the treatment of hospitalized COVID-19 patients. On June 20 the Data Safety Monitoring Board halted the ORCHID trial because there had been no demonstrated benefit.(4)

The RECOVERY Trial enrolled 11,000 patients from 175 National Health Service Hospitals in the United Kingdom. This is a large randomized trial to assess therapy, including hydroxychloroquine. However, the Data Monitoring Committee halted this trial on June 8 when it was determined that there was no benefit. In this trial 3,132 patients were randomized to the usual care group (UCG) and 1,542 to hydroxychloroquine (HCQ). All patients were hospitalized. With respect to HCQ, the mortality rate was not different – 25.7% for the HCQ and 23.5% for the UCG (HR 1.11 95%CI .98-1.260p=0.10.(5)

The French open-label multi-center adaptive randomized DiSCoVeRy Trial began March 24. It halted its hydroxychloroquine arm on May 24. It was designed to evaluate therapy in patients with low pulmonary saturation or respiratory failure secondary to COVID-19.(6) Thus far several well designed randomized controlled trials have failed to show benefit.

CLINICAL TRIAL NCT04326725 (7) is currently ongoing in Istanbul and is using a very low dose of hydroxychloroquine (200 mg every three weeks) given along with zinc. It should end soon and the results released. It is a prospective, case control study that is not blinded and not randomized. Also the people it is being given to are health care workers who are asymptomatic but have no known direct exposure to COVID-19. Zinc was given along with hydroxychloroquine, so we won’t be able to determine whether it is the zinc or the hydroxychloroquine or nothing that helped. If the results are negative then it confirms that hydroxychloroquine is not of value in the early clinical management of patients with COVID-19. The incidence of COVID-19 among health care workers in our institutions who wear masks and social distance has dropped and is very low. Since the Istanbul trial has only 80 subjects, it will be difficult to show any effect when compared with the current low rates today, and it may only demonstrate that hydroxychloroquine is not necessary if patients or health care workers wear a mask and distance when possible.

A blinded, randomized controlled trial was published in the New England Journal of Medicine on June 4. In this study patients exposed to COVID-19 who were without symptoms were randomized to a group treated with large doses of HCQ and a control group treated with a placebo. The incidence was 11.8% in the treated and 14.3% in placebo group; this was not significant.This study was confirmed July 26 by a large study from Spain that randomized 2,314 healthy contacts of COVID-19 patients to hydroxychloroquine or usual care. There was no benefit of treatment with HCQ (6.2% usual care vs. 5.7% HCQ; RR 0.89 [ CI 0.54-1.46]), nor was there evidence that HCQ could prevent SARS-CoV-2 transmission. (17.8% usual care vs. 18.7% HCQ). Adverse events were 5.9% in the usual care and 51.6% in the HCQ group; there were no deaths or hospitalizations in either group.(8,9)

On July 4, 2020 the SOLIDARITY Trial Steering Committee discontinued its arms on hydroxychloroquine (HCQ) and lopinavir/ritonavir in light of evidence presented at a HCQ WHO summit on July 2. The SOLIDARITY Trial is sponsored by WHO.(10)

References:

1. Gautret P, Lagier J-C, Parola P, Hoang VT, Meddeb L, Mailhe M, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. International Journal of Antimicrobial Agents. 2020;56(1):105949.
2. Mehra MR, Desai SS, Ruschitzka F, Patel AN. RETRACTED: Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis. Lancet. 2020.
3. Mehra MR, Desai SS, Kuy S, Henry TD, Patel AN. Retraction: Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19. N Engl J Med. DOI: 10.1056/NEJMoa2007621. New England Journal of Medicine. 2020.
4. A href=”https://clinicaltrials.gov/ct2/show/NCT04332991″> Clinical Trial NCT04332991 (ORCHID TRIAL)

5. Torjesen I. Covid-19: Hydroxychloroquine does not benefit hospitalised patients, UK trial finds. BMJ. 2020;369:m2263.
6. Clinical Trial NCT04315948 (DisCoVeRy TRIAL)
7. Proflaxis Using Hydroxychloroquine Plus Vitamins-Zinc During COIVD-19 Pandemic (Mehmet Mahir Ozmen)
8. Boulware DR, Pullen MF, Bangdiwala AS, Pastick KA, Lofgren SM, Okafor EC, et al. A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19. New England Journal of Medicine. 2020.
9. Mitja O, Ubals M, Corbacho M, Alemany A, Suner C, Tebe C, et al. A Cluster-Randomized Trial of Hydroxychloroquine as Prevention of Covid-19 Transmission and Disease. medRxiv. 2020:2020.07.20.20157651.
10.SOLIDARITY TRIAL

HOME REMEDIES

home remedies
  1. Vitamin C
  2. Zinc
  3. Vitamin D
  4. Avoid PPI
  5. Selenium
  6. Melatonin https://www.sciencedirect.com/science/article/pii/S0024320520303313?via%3Dihub

Vitamin C – Vitamin C is an antioxidant that removes the free radicals that can damage other cells. It thus has antiinflammatory properties and can stimulate the immune system. It may protect the blood vessel walls from damage. Since patients who have a severe illness like COVID-19 may require increased vitamin D, it is being studied and data from large trials should be available soon. there are 15 clinical trials that are pending for both critically ill and asymptomatic patients. There are thus far no trials that either recommend using or not using vitamin C in asymptomatic patients.

Vitamin D – Vitamin D deficiency is very common in the United States, particularly among the elderly and persons with a darker complexion. Vitamin D supplements may modulate T cell regulatory activity and protect against respiratory tract infection. The effects of vitamin D in patients with COVID-19 are not known but 8 clinical trials are ongoing.

Zinc– Zinc has been shown to be able to enter cells and interfere with viral replication. While there is no data to recommend either for or against its use in the treatment of COVID-19, there are ongoing clinical trials investigating this. However, zinc use above the recommended dose can cause copper deficiency, may cause hematological abnormalities and can cause irreversible neurological disorders. So, at this time it is not recommended that persons not enrolled in a clinical trial exceed the recommended dose of zinc.

REFERENCES:

    • Carr AC. A new clinical trial to test high-dose vitamin C in patients with COVID-19. Critical care (London, England).
    • Grant WB, Lahore H, McDonnell SL, Baggerly CA, French CB, Aliano JL, et al. Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths. Nutrients. 2020;12(4).
    • https://www.thelancet.com/retrieve/pii/S2213858720301832 – great article on vitamin D
    • Carr AC. A new clinical trial to test high-dose vitamin C in patients with COVID-19. Critical care (London, England).
    • Grant WB, Lahore H, McDonnell SL, Baggerly CA, French CB, Aliano JL, et al. Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths. Nutrients. 2020;12(4).
    • https://www.thelancet.com/retrieve/pii/S2213858720301832 – great article on vitamin D
    • Zabetakis I, Lordan R, Norton C, Tsoupras A. COVID-19: The Inflammation Link and the Role of Nutrition in Potential Mitigation. Nutrients. 2020;12(5).

HERD IMMUNITY

Herd immunity occurs when a percentage of the population has become immune to the virus, having either been vaccinated or acquiring the disease and developed neutralizing antibodies or cellular immunity to the virus. At the point of immunity the transmission rate is no longer exponential, and this is represented mathematically. It is the point at which the disease ceases to be an epidemic, but will not be 100% of the population for SARS-CoV-2. Once herd immunity is reached, it is unlikely that those patients who were not candidates for vaccination will acquire the disease. We are not yet at the point where herd immunity can be achieved, and until then the focus should be on protecting the vulnerable from exposure.

There are many questions that surround the development of immunity. For instance, does the detection of antibodies mean that immunity is conferred and for how long. Can people who have had been exposed to previous coronaviruses through upper respiratory infections in the past have some sort of immunity? Can people who have undetectable antibodies still have a cellular immunity to the disease, and when exposed have a killer C cell response? As these questions are answered we will have more firm evidence on how we can achieve herd immunity. (Randolph HE, Barreiro LB. Herd Immunity: Understanding COVID-19. Immunity. 2020;52(5):737-41).

ANGIOTENSIN BLOCKERS AND ACE INHIBITORS

The renin-angiotensin system is designed to be a protective mechanism from stress. Renin is secreted from the juxtaglomerular apparatus in the kidney in response to low sodium, low blood pressure or neurogenic stimuli. It then causes the breakdown of angiotensinogen to the 10 amino acid peptide, angiotensin 1. Angiotensin I is activated to angiotensin II, an 8 amino acid peptide by converting enzyme 1, for which their is a receptor – the ACE1 receptor. There is also a receptor for the enzyme’s deflation product, ACE 2. It is the ACE 2 receptor that is the target for SARS-CoV-2. Angiotensin 2 is accountable for vasoconstriction, blood pressure elevation, inflammation and fibrosis. Since it is activated during illnesses involving the kidney, it is associated with progressive kidney disease. The angiotensin II receptor blockers block the receptor for AII, not ACE2. Because angiotensin is a potent stimulator of blood pressure, its blockade is a major treatment for hypertension.

ACE2 receptors are on many cells, particularly the heart, lungs, and kidneys. There are most prevalent in the lung. They are actually upregulated with the antihypertensives like converting enzyme inhibitors and angiotensin receptor blockers. Since they have a beneficial effect of blocking the formation of AII, their up-regulation is beneficial. When SARS-CoV-2 attacks the receptors, the theory is that does not fully saturate them in patients on medications, and is less dangerous.

A study has shown that older patients taking ACE inhibitors have a lower risk for hospitalization from COVID-19. However current recommendations are to continue ACE and ARB therapy if already on it, but neither drug should be added for the care of COVID-19 patients pending further evidence. (Khera R, Clark C, Lu Y, Guo Y, Ren S, Truax B, et al. Association of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers with the Risk of Hospitalization and Death in Hypertensive Patients with Coronavirus Disease-19. medRxiv. 2020:2020.05.17.20104943).

MASK AND SOCIAL DISTANCE - WHAT CAN WE DO TO STAY SAFE?

Since the droplets are contained in our breath, we must wear a mask to limit the spread. These are generally procedure masks as are used in surgery. Cloth masks are acceptable in the community so long as they cover the nostrils and mouth. These masks are loosely fitting, comfortable, but do not protect the wearer; they protect those who are nearby. We protect others when we wear a mask.

The virus attacks the body through receptors on targeted cells and can easily enter through our mouth and nasal passages. Viral particles may linger without symptoms for a few days in the throat, and the person may be asymptomatic, but still infected. The receptors for SARS-CoV-2 are known as ACE2 receptors and are on the heart, lungs, and kidney, especially the lungs. If the virus defeats our protective mechanisms, it can drop to the lungs and initiate a powerful innate immune response. This be accompanied by powerful cytokines that can destroy lung tissue as well as the virus.

The droplets from SARS-CoV-2 are generally thought to be greater than 5um and expected to fall onto a surface after traveling 6 feet when a mask is not worn. With a mask they can be contained to less than 8 inches. The problem is if the virus is aerosolized and the droplets are less than 5 um. Then they can travel farther. During bronchoscopies and even nasal testing, the droplets may be aerosolized. Therefore, instead of a procedure mask, health workers should wear a special N95 fitted respirator when working in special circumstances where aerosolization is possible

A virus spreads by a transmission rate that is calculated by how many persons will be infected. The Ro transmission rate for SARS-CoV-2 is between 2.3 to 2.6. We also look at the Rt – or transmission rate in a community. That will fall as persons contain the spread. The disease has an incubation period of 5 days give or take 2. That means that if exposed to the disease, you may become symptomatic in less than 7 days. You will be contagious until you are free of the disease, usually less than two weeks or less. (SOURCE: CDC).

DOES SHELTERING IN PLACE WORK?

A study by the National Bureau of Economic Statistics determined that as the result of the March 19 executive order in California to shelter in place for nonessential activities COVID-19 cases were reduced by 125.5 cases per 100,000 population to 219.7 per 100,000 by April 20. This resulted in 1661 fewer COVID-19 deaths but resulted in 400 jobs lost for each life saved during the month. ( Friedson AI, McNichols D, Sabia JJ, Dave D. Did California’s Shelter in Place Order Work?2020. Available from: https://www.nber.org/papers/w26992.pdf.)

TESTING

The SARS tests are generally for the antigen, an indicator of the disease, or the antibody. Some tests can give results within a few moments, others take a few days. Here is a review from the CDC – https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/testing.html

VACCINES AND VARIANTS

From Issues in Kidney Disease – Acute Kidney Injury – Acute Kidney Injury in COVID-19 – Stephen Z. Fadem:

There were currently three vaccines available in the USA; two are messenger RNA (mRNA) varieties; the third is a viral vector vaccine. None of these vaccines are live viruses. mRNA vaccines induce the immune system to make antibodies that will attack a future virus. The Pfizer BNT162b2 vaccine is administered in the deltoid over two injections three weeks apart. In a large clinical trial, 43,548 participants were randomized to receive either the placebo control or vaccination. 8 cases of COVID-19 occurred 7 days after receiving the second vaccine dose in contrast to 162 cases among those who received the placebo; it was considered 95% effective. Side effects were headache, fatigue and injection site pain, and symptoms were short-lived. The occurrence of serious adverse events between the control and placebo group was similar (Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. The New England journal of medicine. 2020;383(27):2603-15.).

The Moderna mRNA1273 vaccine is administered in two injections four weeks apart and has no concerning safety issues. 30,420 volunteers randomized to either placebo-control or vaccination group demonstrated an incidence of symptomatic COVID-19 cases after the second dose of the vaccine 94.1% lower than placebo. Of the 185 cases of symptomatic COVID-19 in the placebo group, 30 were severe. In the 11 cases of post-vaccine COVID-19, none were severe. Local reactions included mild arm pain, headache, fatigue and muscle aches. (Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, et al. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. The New England journal of medicine. 2021;384(5):403-16.).

The Johnson & Johnson (Janssen) vaccine Janssen’s product, JNJ-78436735, is a viral vector vaccine that can be administered in either one or two doses. The single-dose trial enrolled over 44,000 participants and was conducted in areas where variants were emerging. Its reported side effects included local arm pain, redness, and swelling as well as generalized fatigue, headache, muscle pain, fever, nausea, and chills. It was 66.3% effective at preventing illness, and protection was noted two weeks post-vaccine. It was 85% effective against preventing severe disease and completely protective against COVID-19 related hospitalizations and death.

As the virus infects more and more patients, it mutates, particularly in the spike protein area in response to neutralizing antibodies. This creates the potential for resistant strains. The two major variants are the B1.351 and the P.1 variant, both of which evolved during neutralizing antibody selection pressure. The B.1.351 variant is partially resistant to the Moderna, Pfizer, and Novavax vaccinations. In South Africa, the JNJ vaccine was 95% effective against the B.1.351 variant. It is 69% effective against the P.2. variant in Brazil. In the USA it was 96% effective against the dominant D614G variant. It is not clear whether the vaccine is effective against the B.1.1.7 variant from the UK. All leading vaccine companies are in the process of redesigning their vaccines to counter the new variants (Moore JP. Approaches for Optimal Use of Different COVID-19 Vaccines: Issues of Viral Variants and Vaccine Efficacy. (Boyarsky BJ, Werbel WA, Avery RK, Tobian AAR, Massie AB, Segev DL, et al. Immunogenicity of a Single Dose of SARS-CoV-2 Messenger RNA Vaccine in Solid Organ Transplant Recipients. JAMA. 2021).

When Boyarsky, et. al, studied 658 transplant recipients who received 2 doses of SARS-CoV-2 mRNA vaccine antibody was detectable in 15% of the participants after the first dose, and at a median of 29 days after the second dose, the antibody was detected in 54% of participants. (Boyarsky BJ, Werbel WA, Avery RK, Tobian AAR, Massie AB, Segev DL, Garonzik-Wang JM. Antibody Response to 2-Dose SARS-CoV-2 mRNA Vaccine Series in Solid Organ Transplant Recipients. JAMA. 2021 Jun 1;325(21):2204-2206.)

The Advisory Committee for Immunization Practices (ACIP) met following the FDA EUA. It was noted that because of lowered vaccine effectiveness 40-44% of hospitalized breakthrough cases were in immunocompromised people such as those receiving kidney transplantations. The emergency of the delta variant, which is more infective, made it essential to develop a solution. In a randomized trial of a third dose of Moderna vaccine in 120 transplant recipients, 55% of patients had an antibody binding domain rise to greater than or equal to 100 U/ml at one month. No serious adverse events or acute rejection episodes resulted from the third dose. (Hall et al. (2021) NEJM. Randomized Trial of a Third Dose of mRNA-1273 Vaccine in Transplant Recipients. DOI: 10.1056/NEJMc2111462) Among 59 patients who were seronegative prior to the third dose, 44% became seropositive at four weeks following the third dose. Factors that negatively influenced the response were age, a higher degree of immunosuppression, and a lower eGFR. No patients developed critical side effects or required hospitalizations. (Kamar et al. (2021) NEJM Three Doses of an mRNA Covid-19 Vaccine in Solid-Organ Transplant Recipients (nejm.org). On August 13, 2021 ACIP recommended that transplant recipients and those immunocompromised because of solid organ tumors or other immunodeficiency disorders receive a third dose of the same vaccine they had received previously.

COVID HAS WORSE OUTCOMES IN KIDNEY PATIENTS

(From AAKP RENALIFE – ASK THE DOCTOR) Geisinger Clinic evaluated findings from 12,971 individuals who were tested for SARS-CoV-2. There were 1604 positive patients of which 354 required hospitalization. Kidney disease was identified as the leading risk factor for hospitalization. A high rate of hospitalization was noted in Stage 4 CKD (Odds Ratio 2.90, 95% CI: 1.47 to 5.74), Stage 5 CKD/dialysis (OR 8.83, CI: 2.76 to 28.27), and kidney transplant (OR 14.98, CI: 2.77 to 80.8) patients. Stage 3 CKD patients were not at high risk.

RESOURCES