October 2020 Edition

On October 15, I became one of the ~30 million confirmed cases that has recovered from SARS-CoV-2. There is a great deal of comfort knowing that I was able to beat this virus that has killed over 1 million people worldwide. Naturally, my attention shifted to what’s next. What are my risks now? I have narrowed it down to two questions:

What is the risk of reinfection?

What are the long term consequences of SARS-CoV-2?

This post is my attempt at trying to get close to an answer to those two questions. A little bit about myself: I am not a virologist, immunologist, or epidemiologist. I’m just a regular guy who trusts science. Everything in this post aside from my conclusions will be backed up by publications and case studies from reputable sources. My goal is to sort through the vast amount of information out there, find reliable research, and arrive at a rational conclusion.

One last thing: There is a large amount of ongoing studies and research on this subject. If you’re reading this post in February 2021, it is likely that the information presented is stale. I might do a monthly post on this subject to keep things fresh.

What is the risk of reinfection?

Doing some Googling online about SARS-CoV-2 reinfections leads to a plethora of anecdotal cases of potential reinfections. I was more interested in how scientists arrive at the conclusion that there is a confirmed case of reinfection. Right now, in order for a reinfection case to be considered as confirmed, there must be two positive tests with different genome sequencing. This proves that the host was indeed infected with two different strains of SARS-CoV-2. Why is this important? Because there is always a probability that your body never truly beat the original strain, and the virus lays dormant for a period of time before it resurfaces.

OK, so the next question is: Does every confirmed positive PCR-RT test get sequenced? The answer is sadly, no. Sequencing is time consuming and expensive, so it is only being done in studies. The largest repository of SARS-CoV-2 genome sequences that I found was the GISAID. According to their website, there have been over 147,000 viral genomic sequences shared with them. Not a small number, but far less than the ~40 million confirmed positive cases today.

So how many confirmed cases of reinfection are there today?

Twenty-four, with one reinfection leading to death. Lets look at two of the cases:

25 year old man from Reno, Nevada

Findings

The patient had two positive tests for SARS-CoV-2, the first on April 18, 2020, and the second on June 5, 2020, separated by two negative tests done during follow-up in May, 2020. Genomic analysis of SARS-CoV-2 showed genetically significant differences between each variant associated with each instance of infection. The second infection was symptomatically more severe than the first.

The individual associated with these two SARS-CoV-2 infections had no immunological disorders that would imply facilitation of reinfection. They were not taking any immunosuppressive drugs. The individual was negative for HIV by antibody and RNA testing (data not shown) and had no obvious cell count abnormalities. 

I can conclude based on the case study that the subject was a perfectly healthy 25 year old that was reinfected twice in a span of 48 days.

89 year old woman from The Netherlands

She presented to the emergency department with fever and severe cough and a lymphocyte count of 0.4x109 /L. An in-house SARS-CoV-2 RT-qPCR (E-gen),[2] on a nasopharyngeal swab was positive (Cq 26.2). She was discharged after 5 days and besides some persisting fatigue her symptoms subsided completely.

Two days after a new chemotherapy treatment, fifty-nine days after the start of the first COVID-19 episode, the patient developed fever, cough, and dyspnea. At admission, her oxygen saturation was 90% with a respiratory rate of 40/min. The SARS-CoV-2 RT-qPCR on a nasopharyngeal swab was positive (E-gen; Cq 25.2). At days 4 and 6, serum was tested for SARS-CoV-2 antibodies, using the WANTAI SARS-CoV-2 Ab and IgM ELISA, both were negative. At day 8, the condition of the patient deteriorated. She died two weeks later.

Our patient was immunocompromised, because of Waldenström’s macroglobulinemia treated with B-cell-depleting therapy, resulting in a declined humoral immunity.

This is more of a unique case. This 89 year old woman was fighting a rare form of Leukemia before her first infection. Furthermore, unlike the Reno subject, she never tested negative between infections.

So what did I conclude regarding reinfection risk?

There is a risk of reinfection. However based on the numbers, I can conclude that at the moment reinfections are extremely rare and they point more to an anomaly rather than a commonality. In order for me to feel even more confident that reinfection risk is actually an anomaly, more genome sequencing needs to be done on first time positive PCR-RT tests, so that potential reinfections can be confirmed.

If you want to read a more technical write up regarding immunity and reinfection risk, there is an excellent blog post by Derek Lowe on the subject.

What are the long tern consequences of SARS-CoV-2 ?

Just like the previous question, there is a vast amount of anecdotal information regarding long term symptoms, issues, and problems after recovering from SARS-CoV-2 . This problem is exacerbated by the fact that long term is poorly defined. Less than a year has elapsed since the first subject recovered from SARS-CoV-2.

I decided to look into whether other coronaviruses that affected humans led to long term consequences. This paper from 2009 did a follow up study on SARS survivors from Hong Kong.

Results  Of 369 SARS survivors, 233 (63.1%) participated in the study (mean period of time after SARS, 41.3 months). Over 40% of the respondents had active psychiatric illnesses, 40.3% reported a chronic fatigue problem, and 27.1% met the modified 1994 Centers for Disease Control and Prevention criteria for chronic fatigue syndrome.

Almost three and half years after their infection, a significant amount of survivors reported having long term consequences after recovering from SARS.

Apart from psychiatric disorders, complaint of prominent chronic fatigue was common among the SARS survivors. The high prevalence of chronic fatigue problems in SARS survivors with both psychiatric and nonpsychiatric disorders suggested that psychiatric disorders per se did not fully account for the chronic fatigue problems. Our study found that application to the SARS survivors fund was associated with chronic fatigue, even after controlling for psychiatric morbidities.

The paper concludes that chronic fatigue problems are independent of psychiatric disorders. Interesting.

Based on this study, I can conclude with a high degree of confidence that a decently high percentage of SARS survivors did have long term consequences following their infection. How about SARS-CoV-2?

Most of the studies and papers I found conclude that there is indeed evidence of persistence in symptoms of SARS-CoV-2. However, there is a high degree of skepticism, since a lot of this evidence is self reported. Some of these reports come from people who believed they had SARS-CoV-2, but never received a clinical confirmation through testing.

This paper summarizes well why there is a need for more rigorous research in studying long-term consequences of SARS-CoV-2.

Support for research is needed on the trajectory of people recovering from COVID-19. To avoid the problems we have witnessed in the research of the acute phase of the disease, a clear definition of patient inclusion criteria, a common protocol, and uniform definitions of outcomes and ways to measure them are required. Additionally, data should be collected in real time and computational tools are needed to be able to do this.

The participation of an international and interdisciplinary group of researchers is essential. Multisite and multinational projects are needed because a description from one group or one site cannot discern between universal features and features of the local health system or the local population. By comparing data from different sites and countries we can learn which characteristics of the disease are universal and which are local. 

So what did I conclude regarding long term consequences of SARS-CoV-2?

There is some evidence that there might be long term consequences after recovering from SARS-CoV-2. However more rigorous studies have to be done in order to confirm that there is indeed a probability that I and others that have recovered might face long term consequences from being infected with this virus. Finally, more time has to elapse in order for the research on this question to be more rigorous. The fact that only 10 months have passed since the first confirmed recovery of SARS-CoV-2 (and roughly 7 months since the virus spread worldwide) poises a problem to answering this question.

I have a vested interest in continuing to try to answer these two questions. Over time, I am hoping that more resources go into research and studies that will bring clarity to whether there is a high probability of getting reinfected and whether it is likely that there will be long term consequences of being infected with this virus.

In the most ideal scenario, I hope that reinfections of SARS-CoV-2 are anomalies, which would mean that there is indeed some immunity from recovering from the virus. I also hope that long term consequences, if any, are proven to be very rare, unlike the long term consequences of SARS survivors.