Dr. Sean O’Leary and the American Academy of Pediatrics (AAP) are recommending school children to be physically present in school from this fall. In an interview with the New York Times, Dr. O’Leary explained: “Kids seem to be both less likely to catch the infection and less likely to spread the infection. We have to balance (Covid-19) with the overall health of children. Every district is making major consideration for its teachers, trying to figure out how to keep them safe. If they are taking as many precautions as they can, I think the risk is pretty low” [1]. But many people and many federal and state health officials are at odds with the AAP’s interim guidance on school reopening. There were more than 273 comments over the interview, and some worried about opening schools in this pandemic and felt that “guidance for reopening should come from an expert group” [1]. There is an abundance of articles about COVID-19, but many of them are competing with each other over the issue of treatment for COVID-19, and it is very hard not only for the general population but also for doctors to clearly identify the beneficial methods to handle COVID-19. In this context, a scientific and easy-to-understand guideline is needed to clear the way to help children physically attend schools and to prepare parents to be physically and mentally equipped to overcome COVID-19.

To overcome the pandemic of COVID-19, a combination of pharmacologic and nonpharmacologic preventive methods and adequate treatment methods to cure COVID-19 patients would be needed. As for the non-pharmacologic prevention, the CDC recommendations [2] can be classified into 6 categories as seen in Table 1 by the COVID-19 evidences of the Theodor Roosevelt aircraft carrier [3] and of the WHO-funded study [4]. If you follow the CDC guidelines, you can reduce the possibility of transmission significantly by 28.6% or by 34.2%. (facial mask 11.6% + social distancing 9.4% + avoiding contaminated places 7.6% = 28.6%, p < 0.05) [3] or (facial mask 14.3% + wearing eye protection 10.6% + social distancing 10.2% = 35.1%, p = 0.09) [4]. In addition, Hand washing and Work station cleansing can provide additional 41% risk reduction if more people participate in these prevention methods.

The most effective pharmacologic prevention would be COVID-19 vaccines. However waiting for COVID-19 vaccines cannot be the only hopeful strategy for reopening schools this fall, when considering the fact that among half of the 228 ELISA positive participants, only a few participants had detectable neutralizing antibodies, which would inhibit SARS-CoV-2 infections, over 40 days after onset of symptoms [3], and that the increasing D614G mutated strain of SARS-CoV-2 showed the Spike variant, which may require some modifications of 10 vaccine candidates which used only classic D614 Spike protein segments [5]. The D614G mutated strain of SARS-CoV-2 is more active in colon (x2.4), lung (x4.6), and liver (x7.7) than the original SARS-CoV-2 virus is [5], thus persons with gastrointestinal diseases, lung diseases, and liver diseases can be high risk patients.

The epidemiologic report of the China CDC showed an overall case fatality rate of 2.3%, mild to moderate cases of 80.9%, severe cases of 13.8%, critical cases of 4.7%, and death occurred only in critical cases [6]. The severity of symptoms variable of the China CDC was changed to Tiers in the Triangle of Tiers of COVID-19 USA (Figure 1). Triangle of Tiers of COVID-19 USA has 7 tiers: Tier 1: Expired in the Critical Cases (with ECMO or invasive oxygenations for respiratory failure, septic shock/cytokine storm, and/or multiple organ dysfunction/failure); Tier 2: Survived in the Critical Cases; Tier 3: Severe Cases (with dyspnea, respiratory frequency ≥ 30/min, blood oxygen saturation ≤ 93%, PaO2/FiO2 ratio < 300, non-invasive oxygenation, and/or lung infiltrates > 50% within 24-48 hours), Tier 4: moderate cases(Some are hospitalized, but mostly are not hospitalized, tolerable dyspnea and no-oxygenation is needed, lung infiltration < 50%, 24 ≤ respiration rate ≤ 29 /min, SpO2 ≥ 94%, and/or with risk factors), Tier 5: mild cases (No need for hospitalization, fever, diarrhea, bizarre headache, lethargy, loss of appetite, shortness of breath, strange heart and/or peripheral muscle aches and pains, or coughing, respiration rate < 24 and without risk factors). The prevalence rate of COVID-19 (population of COVID-19 patients and SARS-CoV-2 carriers/ total population of the United States) can be calculated based upon the number of confirmed COVID-19 cases (4,032,430), number of deceased cases (144,167), and number of recovered persons (1,233,269) [7]: the estimated prevalence rate (rate of persons who have SARS-COV-2 viruses in the body on/as of July 24th, 2020) of the United States (total population of 330,000,000) is about 0.00805 (or 2,654,994/330,000,000) i.e., 805 persons/100,000 persons as of July 24th, 2020 [7]. The case mortality rate is about 3.58%. Statistically speaking, about 2,123,995 (or 2,654,994x0.8) persons belong to Tier 4 or Tier 5. The rest 530,999 (or 2,654,994x0.2) persons may belong to Tier 1, Tier 2, or Tier 3, and are being admitted to a hospital on the July 24th, 2020 to be treated by dexamethasone injections, High Dose Intravenous Vit C (HDIVC) injections, convalescent sera, or remdesivir as seen in Figure 1 (Please note that the numbers in the figure 1 are cumulative numbers until July 24th, 2020.). China CDC showed the rates among the Critical Cases and expired: Critical Cases and survived: Severe cases: Mild to Moderate cases were 2.3%: 2.4%: 13.8%: 80.9% in China [6]. When those rates are applied to the COVID-19 data of the United States, it becomes heavy () on the top of the triangle, and it could be 3.58%: 3.5%: 12.9%: 80% in the United States. It means that the Unites States had not done well in the COVID-19 task and lots of Americans faced preventable premature deaths. It looks like at least 1~1.5% of the COVID-19 cases or 60,000 (or 4,032,430 x 0.015) persons died prematurely. Tier 6 is Undiagnosed Cases (but will be SAR-CoV-2 positive if tested), and Tier 7 (Normal population without SARS-CoV-2 viruses, and/or could have convalescent antibodies to SARS-CoV-2). The “Testing Data in the US” of the CDC shows 10% positive test rate of the total reported tests [2], and this means the Undiagnosed Tier 6 cases (who will be positive if tested) could be 10% (or 33,000,000) of the total population (of 330,000,000). The confirmed 4,032,430 cases (as of July 24, 2020, [7]) is just one-nineths (1.22%/10%) portion of an iceberg of the undiagnosed (Tier 6) SARS-CoV-2 infection. Then the real case mortality rate would be less than 1%. The true cumulative case mortality rate would be 0.44% (or 144,167/33,000,000) and less severe than we thought.

Figure 1:

In the treatment aspects, most reported COVID-19 articles mainly dealt with approximately 20% of the total COVID-19/SARS-CoV-2 persons who were admitted to hospitals ( i.e., the patients of Tier 1, Tier 2, Tier 3, and some portions of Tier 4), but they neglected the major remnant of 80% of SARS-CoV-2 positive cases who showed no symptoms or showed only mild to moderate symptoms ( i.e., lots of patients of Tier 4 and all the patients of Tier 5). We need to look at the Tiers of patients who participated in a study to delineate the differences of and/or to interpret correctly the study results.

RECOVERY Collaborative Groups found out that dexamethasone reduced mortality by 11.7% (from 40.7% to 29.0%, p < 0.001) for the patients of Tier 1 & Tier 2, and by 3.5% (from 25.0% to 21.5%, p < 0.002) for the patients of Tier 3, but was not effective for the patients of Tier 4 [8]. For the patients from Tier 1 to Tier 4, remdesivir significantly shortened the recovery by 4 days (from 15 days to 11 days, p < 0.001), but it could not reduce the mortality rate (p > 0.05 or 95% CI 0.47 ~ 1.04) [9]. (For the classification of the study-participated patients, the study used the Ordinal Scale of the Adaptive COVID-19 Treatment Trial. Ordinal Scale 8 is equivalent to Tier 5, Ordinal scale 5 & 6 to Tier 4, Ordinal scale 3 & 4 & 7 to Tier 3, Ordinal scale 2 to Tier 2, and Ordinal scale 1 to Tier 1. But there are no Ordinal scales equivalent to Tier 6 and Tier 7) [9]. Convalescent sera (Con Sera) showed encouraging results for the patients from Tier 1 to Tier 3: three recovered and two stabilized among five patients at Shenzhen Third People’s Hospital; and three patients recovered and seven were improved among 10 patients at Wuhan, China [10]. Recently an antibody “Cocktail” neutralized the SARS-CoV-2 virus both in vitro and with hamsters [11].

Daegu in South Korea and Wuhan in China were endemic areas of COVID-19. Truckload Vitamin C was used in those areas and Shanghai Expert Group reported that 50 patients in Tier 3 and Tier 4 were treated with High Dose Intravenous Vit C (100 mg/Kg over 24 hours or 200mg/Kg in “cytokine storm”), who shortened hospital stays by three to five days over control groups [12].

Related with mean Vit D serum levels from Tier 1 to Tier 5 patients, it was known that countries of high incidence rate and high mortality rate of COVID-19 like Italy, Spain, and UK had lower levels than less severely damaged countries had. Northwestern University study found a significant negative correlation between the mean serum levels of Vit D and the number of COVID-19 cases (-0.443, p = 0.05) and another significant negative correlation between the mean serum levels of Vit D and the mortality rate (-0.437, p = 0.05) [13].

A case report of a 60-year old woman, who broke out COVID-19 during Hydroxychloroquine maintenance, introduced concerns about the Hydroxychloroquine’s role as a prophylactic oral medication against COVID-19 because the case had high concentrations of Hydroxychloroquine in the serum (280 µg/L) and in the saliva (4,890 µg/L) [14]. Paradoxically, however, the report may also present a generalized prophylactic role of, if not complete, Hydroxychloroquine against COVID-19 (for persons from Tier 6 to Tier 7), because it means that there are so many rheumatoid or malaria-related patients maintaining with Hydroxychloroquine over many years without being infected with SARS-CoV-2 that it could become a rare “case report”. In addition to the preventive effect of the HCQ, recent research identified the therapeutic effect of it: Henry Ford COVID-19 Task Force found out that HCQ and combination of HCQ +AZM helped COVID-19 patients (from Tier 1 to Tier 4) when they were administered at early stages of patients’ admission: overall, in-hospital hazard ratio with HCQ alone was 0.340 (p < 0.001), HCQ + AZM was 0.294 (p < 0.001), age of over 65 was 2.579 (p < 0.001), Caucasian race was 1.738 (p < 0.001), chronic kidney disease was 1.699 (p < 0.001), and low oxygen saturation < 95% was 1.488 (p < 0.021), [15].

Hydroxychloroquine (HCQ) and Zinc (Zn) have the inhibiting action on viral RNA dependent RNA polymerase, and HCQ acts as an ionophore to help Zn come into a cell to make innate and adaptive immune responses [16]. A retrospective analysis of the role of Zn in COVID-19 was conducted at the New York University Langone Health hospitals: the addition of Zn to HCQ + AZM regimen signifi cantly decreased mortality or transition to hospice by 55% (OR 0.449, 95% CI 0.271 ~ 0.744, p = 0.002) compared to HCQ + AZM therapy for COVID-19 patients of Tier 1, Tier 2, Tier 3, and some of Tier 4 who were hospitalized [16].

Once a person falls into a pool of SARS-CoV-2 positives, it is hard to know whether the person will belong to the 80% group (Tier 4 or Tier 5: asymptomatic or mild to moderate symptoms) or to the 20% group (from Tier 1 to Tier 3: ranging from hospital admission to intensive care unit, ICU). This is the moment when a cocktail of oral medications of Vit C, Vit D, Zn (Zinc), Hydroxychloroquine (HCQ), and Azithromycin (AZM) is recommended [17]. A cocktail of oral medications has elements that can, synergistically [15,16] and/or independently [12-14], prevent the replications of SARS-CoV-2 and the progression of the COVID-19 from causing a person to be admitted to a hospital or to an ICU or to be added to the total mortality rate; a cocktail of oral medications can prevent a person from stepping up the Triangle of Tiers of COVID-19 U.S.A. of Figure 1. Hydroxychloroquine was confirmed to be effective in reducing hazard ratio in Tier 3 and Tier 4 patients when taken in the early stages (or as soon as possible) of COVID-19 [15,16]. Indirectly, it was suggested that HCQ could prevent COVID-19 for people (Tier 7), if not complete [14]. If the American society had adopted HCQ therapy or a cocktail of oral medications at the early stages of each Tiers of COVID-19, especially at Tier 3 and Tier 4, it could have saved unnecessary premature deaths of 60,000 persons (1.5% of the confirmed SARS-COV-2 positives). But it neglected scientific & medical evidences and chose political correctness instead. It may cost more lives if the society does not will to change its rules to cope with COVID-19; a Cocktail of oral medications (Vit C + VIt D + Zn + HCQ + AZM) is recommended ASAP (as soon as possible) for patients from Tier 3 to Tier 5, and the table 1 recommendations will be a guide for persons from Tier 6 to Tier 7.

Table 1: A scientific and easy-to-understand guideline for the prevention and early treatment of COVID-19: a combination of pharmacologic and nonpharmacologic preventive methods.

If people decide to stick to a scientific guideline, and if we can reduce the hazard ratio of COVID-19 by just 30% every 15 days, even not by the expected much more advantages as seen in the Table 1 with non pharmacological (28.6%, p < 0.05 [3] or 35.1%, p = 0.09 [4]) and pharmacological prevention (Vit C + Vit D 50% + Zn 55% + HCQ) [12,13,16] with early treatment (HCQ 66% + additional 5% with AZM, p < 0.001) [15], the hazard ratio will be 0.118 in the end of 3 months compared to the current hazard of 1 (one). The United States can reduce the total mortality rate of COVID-19 from 3.58% [7] further to about 2% or even less and the prevalence rate from 0.00805 i.e., 805 persons/100,000 persons [7] further to 0.001 (or even to 0.000950), i.e., 100 persons/100,000 persons (or even to 95 persons/ 100,000 persons) in three months.

A scientific and easy-to-understand guideline for the prevention and early treatment for COVID-19:

1. When you meet a SARS-CoV-2 negative person , (probability of 992/1,000) [7], there is no transmission. But remember that there could be contamination on elevator buttons, benches, or other common items.

2. The high-risk group for original SARS-CoV-2 includes persons over age 65, Caucasians, those with chronic kidney disease, or have a low oxygen saturation (< 95%) [15]. In the future environment of the D614G mutated strain of SARS-CoV-2 [5], persons with gastrointestinal diseases, lung diseases, or liver diseases will be high risk persons. If possible, it is best to abstain from smoking and drinking. Exercise regularly, rest adequately, and take nutritionally well-balanced foods with a cocktail of oral medications.

3. If you follow the CDC guidelines, you can reduce the possibility of transmission significantly by 28.6% [3] or by 35.1% [4]. In addition, Hand washing and Work station cleansing can provide additional 41% risk reduction if more people participate in these prevention methods.

4. Please look at table 1. If you think you are in a group that may contain SARS-CoV-2 carriers , (probability of 8/1,000) [7], take a cocktail of oral medications of Vit C + Vit D + Zn, wear a mask, keep a social distance of 6 feet, and wear a facial protector/goggle. Have a shower and change clothes after returning to your home. Some of you may need your doctor’s guidance, when taking a Vit C + Vit D + Zn cocktail of oral medications.

5. If you are a volunteer/worker for COVID-19 persons or a high-risk for COVID-19 , if you are an inmate/worker of a large facility such as a nursing home or a prison, or if you suspect that you met a person with SARS-CoV-2 , you are recommended to take HCQ (Hydroxychloroquine) because HCQ was proved to reduce the hazard ratio by 66% when you are already with COVID-19 [15] or it provides a partial preventive effect against COVID-10 [14]. But you need to visit or call your doctor and get your doctor’s prescription.

6. Even if when you find out that you are SARS-CoV-2 positive or have symptoms (such as fever, diarrhea, bizarre headache, strange muscle pain, lethargy, loss of appetite, shortness of breath, or coughing) after contact with SAR-CoV-2 carriers , don’t panic. Keep on oral intake of Vit C + Vit D + Zn and visit your doctor to get your doctor’s prescription of HCQ + AZM for 5 days. You can reduce your hazard ratio significantly by 71% (HCQ 66% +additional 5% with AZM) [15].

7. If people stick to this guideline, and if we can reduce the hazard ratio of COVID-19 by just 30% every 15 days, the United States can reduce the total mortality rate of COVID-19 from 3.58% [7] further to about 2% and the prevalence rate from 0.00805 i.e., 805 persons/100,000 persons [7] further to 0.001 (or even to 0.000950), i.e., 100 persons/100,000 persons (or even to 95 persons/ 100,000 persons) in three months.

1. Sean O’Leary. Why a Pediatric Group is pushing to reopen schools this fall. New York Times. Jun 30, 2020. https://nyti.ms/2Xciula
2. Coronavirus Disease 2019 (COVID-19). CDC. https://bit.ly/3hTeBJT   
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9. Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, et al. Remdesivir for the treatment of Covid-19-preliminary report. NEJM. May 22, 2020. DOI: 10.1056/NEJMoa2007764
10. Cormac Sheridan. Convalescent serum lines up as first-choice treatment for coronavirus. Nature. May 01, 2020. Retrieved on July 25, 2020. https://go.nature.com/3jWDOFh
11. Caffery M. Antibody “Cocktail” could offer potent treatment, prevention of COVID-19. American Journal of Managed Care [AJMC] Newsroom. July 23, 2020. https://bit.ly/2PdbZKA
12. Saul AW. News media attacks Vitamin C treatment of COVID-19 coronavirus: Yet Ascorbate is a proven, powerful antiviral. Orthomolecular Medicine News Service. March 1, 2020. https://bit.ly/30ilU8e
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16. Carlucci P, Ahuja T, Petrilli CM, Rajagopalan H, Jones S, Rhimian J. Hydroxychloroquine and Azithromycin plus zinc vs Hydroxychloroquine and Azithromycin alone: Outcomes in hospitalized COVID-19 patients. July 13, 2020. DOI: 10.1101/2020.05.02.20080036
17. Ki-Yeob Jeon. Problems of not-using Hydroxychloroquine (HCQ) for COVID-19 patients. American J Epidemiol Public Health. 2020; 4: 059-061. DOI: 10.37871/ajeph.id31