It is said that “the retrospectoscope is always 20/20.” Judgments regarding standard of care and deviation from standard must, however, be made in prospect, i.e., in consideration only of what was known and knowable at the time in question. This is where a medical literature COVID timeline could be a useful resource.

Many factors contribute to the concept of ‘Standard of Care.’ Textbooks, medical school curricula, consensus of colleagues, and accepted societal ethics all are pertinent to varying degrees. In this context, medical literature can be dynamic, timely, and sometimes authoritative when there is both scholarly agreement and evidentiary basis, i.e., accepted fact. It can also reveal uncertainty and lack of agreement.

While no single article in a peer reviewed journal can be the sole determinate of standard of care, there is consensus among physicians and the media that several journals are generally regarded as reliable and authoritative. The readership of these journals is notably not limited to the concerns of a particular specialty and they are thus widely read across the house of medicine and in the broader community. These publications include the New England Journal of Medicine (NEJM), The Journal of the American Medical Association (JAMA), and the Morbidity and Mortality Weekly Report (MMWR) which is a CDC publication for physicians and other practitioners. Other journals, which may be useful in the proposed database include American Family Practice and Annals of Internal Medicine as most physicians caring for patients in primary and long-term care settings are either internists or family practitioners and these publications are widely read.

Using the medical chronology of ‘Sally COVID’ as a hypothetical point of departure, I sequentially reviewed the issues of the NEJM and the MMWR published January through March of 2020. What emerges is the impression that there was minimal understanding and little consensus about the nature of COVID-19; its infectivity, mode of transmission, clinical presentation, asymptomatic and pre-symptomatic viral shedding, risk factors, and prognosis. All were evolving concepts at the time. It was only at the end of March 2020 that any coherent understanding begins to emerge, but much was still unknown.

The first mention of SARS-COV2 in the NEJM appears in the February 20, 2020 issue (1) and includes statements that “its ability to spread among humans remains unknown” and “we do not know where SARS-COV2 falls on the scale of human-to-human transmissibility.”

Other articles in this issue (2,3) describe some critical cases in Wuhan, China and speculate that spread occurs “probably by large droplets based on our experience with SARS-I and MERS” i.e., through sneezing and coughing primarily. This would later prove not to be the case.

On March 5, 2020, NEJM reports on the first U.S. case identified in Washington state (4). High viral loads in both nasopharynx and stool are noted and suggest the possibility of high potential for transmissibility. The article concludes that “transmission dynamics and the full spectrum of illness are not fully understood” and that “current understanding of the clinical spectrum is very limited.” The authors also note that “COVID-19 may be indistinguishable from other common respiratory illnesses early in the course.”

A separate and very important article in the March 5, 2020 NEJM issue reports on ‘transmission of COVID-19 from asymptomatic contacts’ (5) in Munich, Germany. The article notes that “transmission appears to have occurred during the incubation period” and that this finding “may warrant a reassessment of transmission dynamics of the current outbreak.” This represents the first documentation of that finding which is a key parameter for public health and makes the epidemic much more difficult to control in nursing homes and society at large.

On March 12, 2020, various case reports from Asia (6,7) suggest increased risk of transmission indoors and in enclosed spaces. The March 19, 2020 issue noted that high viral load in the nose and nasopharynx were similar in both symptomatic and asymptomatic patients. (8)

Finally, on March 26, 2020 (the day before ‘Sally’ gets a fever), the NEJM published the first real retrospective clinical series which reviewed the Wuhan experience. (9) The article delineates several critical clinical parameters which would greatly influence diagnosis, management, policy, and procedure. These included data on mean incubation from exposure to clinical symptoms, time from onset of symptoms to seeking medical attention, and time from symptom onset to hospitalization.  None of this had been previously described or understood.

In this same issue, a related editorial (10) by Anthony Fauci, M.D., et al., was entitled “COVID-19 – Navigating the Uncharted.” Dr. Fauci discusses “the limitation associated with reporting in real time the evolution of an emerging pathogen in its earliest stages.” He remarks that “we should be prepared for COVID-19 to gain a foothold in the United States.”

Chronological review of the MMWR reveals a similarly gradual evolution of understanding. The February 28, 2020 issue (11) reports on 53 cases in the U.S. and states that “currently COVID-19 is not recognized to be spreading in U.S. communities” and also asserts that “symptoms are similar to influenza.” Both of these statements would later prove to be wrong. This issue also states that “further clarification is needed regarding incubation period, viral shedding, relative importance of various modes of transmission, case fatality ratio, immunologic response, and the role of asymptomatic infection in transmission.”

The March 27, 2020 issue (the day ‘Sally COVID’ develops a fever) features a report entitled “COVID-19 in a long-term care facility in Washington” (12) where they note that “limitations in effective infection control and staff working in multiple locations contributed to the spread.” A set of ‘comprehensive prevention measures’ is proposed including visitor screening and restriction, monitoring of residents symptoms and body temperature, etc.

What emerges from this retrospective chronologic review is a remarkable insight into how little was known and agreed upon regarding COVID-19 in March 2020 while Sally was infected, became sick, and was then hospitalized. Much was unclear regarding clinical presentation and risk factors, diagnosis, transmissibility, and asymptomatic carriage. This bears directly on any assertions of deviation from standard of care and proximate cause of harm during the period in question. If there is no agreed upon set of medical facts, it can be effectively argued that standard of care becomes what is ‘reasonable and prudent.’ At that time, compliance with standard of care would also depend on demonstration of good intent, good faith effort, and adequate documentation of same.

I hope this exercise demonstrates the value of adding a selected ‘medical literature chronology’ to your existing COVID-19 Comprehensive Database. These articles provide greater context and convey much greater nuance and uncertainty than contemporaneous CDC/federal guidelines. The Sally COVID case has obvious medico-legal weaknesses including poor documentation, poor follow-up of abnormal vital signs, and apparently significant delay in appropriate diagnosis and transfer. This would also have been the case in the ‘pre COVID’ world of negligence claims. What is new here, are a variety of questions which might possibly arise about resource allocation, pandemic/quarantine staffing, patient risk factors for higher morbidity and mortality for COVID, visitor screening, visitation policy, masking policy, isolation procedure and capability, etc. Charting omissions and late entries also become more prevalent during chaotic circumstances.

Unfortunately, CDC and federal guidelines often seem aspirational and not reflective of real-life conditions ‘on the ground.’ They create the impression that everyone has adequate access to resources and adequate capability and grasp of the situation. The reality, in terms of physician/public health understanding of COVID-19 and how to deal with it was much more uncertain and problematic in March 2020 than governmental proclamation would suggest.

Finally, relevant topics for a medical literature timeline might include evolving concepts of:

• • Transmissibility: infectivity and spread by droplet vs aerosol vs fomite
  • Asymptomatic carriage and viral shedding
  • Utility and value of masking
  • Variation in clinical presentations and pathologic manifestation i.e. heart, liver kidney, neurologic
  • Evolving concept of relevant or suspicious symptomatology; ex: rhinitis, diarrhea/nausea/vomiting, loss of taste and/or smell, chest pain, profound fatigue, headache, myalgias, change in mental status, stroke
  • Recognition of ‘happy hypoxia’ and how this phenomenon alters medical assessment and decision-making
  • Use of pulse oximeter as early predictor of severe illness
  • Interpreting and misinterpreting test results and the implications of false negatives

References

1. Munster, Ph.D., et al. – Feb. 20, 2020, N Engl J of Med, V382: pp. 692-694 ‘A New Coronavirus Emerging in China’

2. Zhu, Ph.D., et al. – Feb. 20, 2020, N Engl J of Med, V382: pp. 727-733 ‘A Novel Coronavirus from Patients with Pneumonia in China’

3. Perlman, M.D., Ph.D. – Feb. 20, 2020, N Engl J of Med, V382: pp. 760-762 ‘Another Decade, Another Coronavirus’

4. Holshue, M.P.H. – Mar. 5, 2020, N Engl J of Med, V382: pp. 929-936 ‘First Case of 2019 Novel Coronavirus in the United States’

5. Roth, M.D., et al. – Mar. 5, 2020, N Engl J of Med, V382: pp. 970-971 ‘Transmission of 2019 nCoV Infection from an Asymptomatic Contact in Germany

6. Pongpirul, M.D., et al. – Mar. 12, 2020, N Engl J of Med, V382: pp. 1067-1068 ‘Journey of a Thai Taxi Driver and Novel Coronavirus’

7. Liu, M.D., et al. – Mar. 12, 2020, N Engl J of Med, V382: pp. 1070-1072 ‘A Locally Transmitted Case of SARS-CoV-2 Infection in Taiwan’

8. Lirong, M.Sc., et al. – Mar. 19, 2020, N Engl J of Med, V382: pp. 1177-1179 ‘SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients’

9. Li, M.Med., et al. – Mar. 26, 2020, N Engl J of Med, V382: pp. 1199-1207 ‘Early Transmission Dynamics in Wuhan, China of Novel Coronavirus-Infected Pneumonia’

10. Fauci, M.D., et al. – Mar. 26, 2020, N Engl J of Med, V382: pp. 1268-1269 ‘Covid-19 – Navigating the Uncharted’

11. Jernigan, M.D., et al. – Feb. 25, 2020, Morbidity and Mortality Weekly Report, V69(8): pp. 216-219 ‘Public Health Response to the Coronavirus Disease 2019 Outbreak’

12. McMichael, Ph.D., et al. – Feb. 27, 2020 – Mar. 9, 2020, Morbidity and Mortality Weekly Report, V69(12), pp. 339-342 ‘COVID-19 in a Long-Term Care Facility – King County, Washington’